Lesson 6

Theme 6. nShigellae infections. Salmonellae infections. Escherichia infections. nYersiniosis. Rotaviral infection

Theme 7. Viral nhepatitis A, B, С, D et al.

 

SHIGELLA

 

Although dysenteric syndromes have long beerecognized as a scourge of man, it is only in the last 90 yr that the nbacteriology of the most common form of epidemic dysentery has beeappreciated. Four species of Shigella are responsible for illness: S. ndysenteriae (serogroup A), S. flexneri (serogroup B), S. boydii (serogroup C), nand S. sonnei (serogroup D). There are 12 serotypes in group A, 6 serotypes and n13 subserotypes in group B, 18 serotypes in group C, and 1 serotype in group D.

 

PATHOPHYSIOLOGY. The basic virulence trait shared by all shigellae is the ability to ninvade colonic epithelial cells. This characteristic is encoded on a large n(120–140 MD) plasmid that is responsible for synthesis of a group of npolypeptides involved in cell invasion and killing. Shigellae that lose the nvirulence plasmid no longer act as pathogens. Escherichia coli that naturally nor artificially harbor this plasmid behave like shigellae. In addition to the nmajor plasmid-encoded virulence traits, chromosomally encoded factors are also nrequired for full virulence; some of these chromosomal traits are important for nall shigellae (e.g., lipopolysaccharide synthesis), whereas others are nimportant only in some serotypes (e.g., shigatoxin synthesis). Shigatoxin, a npotent protein synthesis–inhibiting exotoxin, is produced in significant namounts only by S. dysenteriae serotype 1 and certain E. coli n(enterohemorrhagic E. coli or shiga-like toxin–producing E. coli). The watery ndiarrhea phase of shigellosis may be caused by unique enterotoxins: shigella nenterotoxin 1 (ShET-1), encoded on the bacterial chromosome, and ShET-2, nencoded on the virulence plasmid.

 

Shigellae require very low inocula to cause illness. nIngestion of as few as 10 S. dysenteriae serotype 1 organisms can cause ndysentery in some susceptible individuals. This is in contrast to organisms nsuch as Vibrio cholerae, which require ingestion of 108–1010 organisms to cause nillness. The inoculum effect explains the ease of person-to-person transmissioof shigellae in contrast to V. cholerae.

 

Immune Responses. Secretory IgA and serum antibodies develop within days to weeks after ninfection with Shigella. Although both antilipopolysaccharide and antivirulence nplasmid polypeptide antibodies have been described, identification of the major ndeterminant of protection against subsequent infection remains unclear. There nis evidence that protection is serotype specific, but there is also the nsuggestion that a degree of cross-protection against all shigellae follows ninfection with a given serotype. Cell-mediated immunity may also play some role nin protection, although it appears to be minor.

 

PATHOLOGY. The npathologic changes of shigellosis take place primarily in the colon, the target norgan for shigellae. The changes are most intense in the distal colon, although npancolitis may occur. Grossly, localized or diffuse mucosal edema, ulcerations, nfriable mucosa, bleeding, and exudate may be seen. Microscopically, nulcerations, pseudomembranes, epithelial cell death, infiltration extending nfrom the mucosa to the muscularis mucosae by polymorphonuclear and mononuclear ncells, and submucosal edema occur.

 

EPIDEMIOLOGY. Infection with shigellae occurs most often during the warm months itemperate climates and during the rainy season in tropical climates. The sexes nare affected equally. Although infection can occur at any age, it is most ncommon in the 2nd and 3rd yr of life. Infection in the first 6 mo is rare for nreasons that are not clear. Breast milk, which in endemic areas contains nantibodies to both virulence plasmid-coded antigens and lipopolysaccharides, nmay partially explain the age-related incidence. Asymptomatic infection of nchildren and adults occurs but is uncommon.

 

In industrialized societies, S. sonnei is the most common cause of nbacillary dysentery, with S. flexneri second in frequency; in preindustrial nsocieties, S. flexneri is most common with S. sonnei second in frequency. S. ndysenteriae serotype 1 tends to occur in massive epidemics, although it is also nendemic in Asia.

 

Contaminated food (often a salad or nother item requiring extensive handling of the ingredients) and water are nimportant vectors. However, person-to-person transmission is probably the major nmechanism of infection in most areas of the world. Spread within families, custodial institutions, and day-care centers ndemonstrates the ability of low numbers of organisms to cause disease on a nperson-to-person basis.

 

CLINICAL MANIFESTATIONS.

 

Bacillary dysentery is clinically similar regardless of whether the ndisease is caused by an enteroinvasive E. coli (see Chapter 184) or any of the nfour species of Shigella; however, there are some clinical differences, nparticularly relating to the severity and risk of complications with S. ndysenteriae serotype 1 infection.

 

After ingestion of shigellae there is an incubation period of several ndays before symptoms ensue. Characteristically, severe abdominal pain, high nfever, emesis, anorexia, generalized toxicity, urgency, and painful defecatiooccur. Physical examination at this point may show abdominal distention and ntenderness, hyperactive bowel sounds, and a tender rectum on digital nexamination.

 

The diarrhea may be watery and of large volume initially, evolving into nfrequent small-volume, bloody mucoid stools; however, some childreever nprogress to the stage of bloody diarrhea, whereas in others the first stools nare bloody. Significant dehydration related to the fluid and electrolyte losses nin both feces and emesis can occur. Untreated diarrhea may last 1–2 wk; only nabout 10% of patients have diarrhea persisting for more than 10 days. Chronic ndiarrhea is uncommon except in malnourished infants.

 

Neurologic findings are among the most common extraintestinal nmanifestations of bacillary dysentery, occurring in as many as 40% of nhospitalized infected children. Convulsions, headache, lethargy, confusion, nnuchal rigidity, or hallucinations may be present before or after the onset of ndiarrhea. The cause of these neurologic findings is not understood. In the npast, these symptoms were attributed to the neurotoxicity of shigatoxin, but it nis now clear that that explanation is wrong. Seizures sometimes occur whelittle fever is present, suggesting that simple febrile convulsions do not nexplain their appearance. Hypocalcemia or hyponatremia may be associated with nseizures in a small number of patients. Although symptoms often suggest central nnervous system infection, and cerebrospinal fluid pleocytosis with minimally nelevated protein levels can occur, meningitis due to shigellae is rare.

 

The most common complication of shigellosis is dehydration with its nattendant risks of renal failure and death (see Chapter 56.1). Inappropriate nsecretion of antidiuretic hormone with profound hyponatremia may complicate ndysentery, particularly when S. dysenteriae is the etiologic agent.

 

Other major complications, particularly in very young, malnourished nchildren, include sepsis and disseminated intravascular coagulation. Given that nthese organisms penetrate the intestinal mucosal barrier, these events are nsurprisingly uncommon. Shigellae and sometimes other gram-negative enterics are nrecovered from blood cultures in 1–5% of cases in whom blood cultures are ntaken; because patients selected for blood cultures represent a biased sample, nthe risk in unselected cases of shigellosis is presumably lower. Bacteremia is nmore common with S. dysenteriae serotype 1 than with other shigellae. The nmortality rate is high (20–50%) when sepsis occurs.

 

In those who have S. dysenteriae serotype 1 infection, hemolysis, nanemia, and hemolytic uremic syndrome are common complications; these events nmay occasionally follow S. flexneri infection. This syndrome is thought to be nrelated to shigatoxin, because those E. coli that produce toxins closely nrelated to shigatoxin (enterohemorrhagic E. coli) also cause hemolytic uremic nsyndrome (see Chapter 184).

 

Rectal prolapse, toxic megacolon or pseudomembranous colitis (usually nassociated with S. dysenteriae), cholestatic hepatitis, conjunctivitis, iritis, ncorneal ulcers, pneumonia, arthritis (usually 2–5 wk after enteritis), Reiter nsyndrome, cystitis, myocarditis, and vaginitis (typically with a blood-tinged ndischarge associated with S. flexneri) are uncommon events. The rare syndrome nof extreme toxicity, convulsions, hyperpyrexia, and headache followed by braiedema and a rapidly fatal outcome without sepsis or significant dehydratio(Ekiri syndrome or “lethal toxic encephalopathy”) is not well nunderstood. Death is a rare outcome in the well-nourished, older child; nmalnutrition, illness in the 1st yr of life, hypothermia, severe dehydration, nthrombocytopenia, hyponatremia, renal failure, and bacteremia are common ichildren who die during bacillary dysentery.

 

DIAGNOSIS. Although nclinical features suggest shigellosis, they are insufficiently specific to nallow confident diagnosis. Infection by Campylobacter jejuni, Salmonella sp, nenteroinvasive E. coli, enterohemorrhagic E. coli, Yersinia enterocolitica, and nEntamoeba histolytica as well as inflammatory bowel disease may cause nconfusion. Unfortunately, the laboratory is ofteot able to confirm the nclinical suspicion of shigellosis even when it is present. Presumptive data nsupporting a diagnosis of bacillary dysentery include the finding of fecal nleukocytes (confirming the presence of colitis) and demonstration in peripheral nblood of leukocytosis with a dramatic left shift (often with more bands thasegmented neutrophils). The total peripheral white blood cell count is usually n5,000–15,000 cells/mm3, although leukopenia and leukemoid reactions occur.

 

Culture of both stool and rectal swab specimens optimizes the chance of ndiagnosing Shigella infection. Culture media should include MacConkey agar as nwell as selective media such as xylose-lysine deoxycholate (XLD) and SS agar. nTransport media should be used if specimens cannot be cultured promptly. nAppropriate media should be used to exclude Campylobacter and other agents. nCulture is the gold standard for diagnosis, but it is not absolute. Stool ncultures of adult volunteers with dysentery after ingestion of shigellae failed nto detect the organism iearly 20% of subjects. Studies of foodborne noutbreaks suggest that a single culture allows diagnosis in about half of nsymptomatic patients with shigellosis. Although additional tools to improve ndiagnosis (e.g., gene probes) are being developed, the diagnostic inadequacy of ncultures makes it incumbent on the clinician to use judgment in the management nof clinical syndromes consistent with shigellosis. In children who appear to be ntoxic, blood cultures should be obtained; this is particularly important ivery young or malnourished infants because of their increased risk of nbacteremia.

 

TREATMENT.

 

As with gastroenteritis of other causes, the first concern about a child nwith suspected shigellosis should be for fluid and electrolyte correction and nmaintenance. Drugs that retard intestinal motility should not be used because nof the risk of prolonging the illness.

 

The next concern is a decision about the use of antibiotics. Although nsome authorities recommend withholding antibacterial therapy because of the nself-limited nature of the infection, the cost of drugs, and the risk of nemergence of resistant organisms, there is a persuasive logic in favor of nempiric treatment of all children in whom shigellosis is suspected. Even if not nfatal, the untreated illness may cause the child to be quite ill for 2 weeks or nmore; chronic or recurrent diarrhea may ensue. There is a risk of malnutritiodeveloping or worsening during prolonged illness, particularly in children ideveloping countries. The risk of continued excretion and subsequent infectioof family contacts further argues against the strategy of withholding nantibiotics.

 

There are major geographic variations in drug susceptibility. In the United States, nshigellae are so frequently resistant to ampicillin that it should not be used nfor empiric therapy; occasional strains are also resistant to ntrimethoprim-sulfamethoxazole (TMP-SMX). Cefixime and ceftriaxone are effective nalternative drugs in areas where TMP-SMX resistance is common. Nalidixic acid nis also an acceptable option in this setting. Resistance to nalidixic acid is nuncommon. With the exception of nalidixic acid, the quinolones that have beerecommended for use in adults have not been used in children (because of the nputative risk of arthropathy). Treatment regimens involve a 5-day course. For strains nknown to be susceptible to ampicillin, this drug is given at 100 mg/kg/24 hr ndivided into four doses each day. The usual empiric choice before the navailability of susceptibility data is TMP-SMX, given at 5–10 mg/kg/24 hr of nthe TMP component in two divided doses. For strains known to be resistant to nthe usual drugs, cefixime (8 mg/kg/24 hr in two divided doses given orally for n5 days), ceftriaxone (50 mg/kg/24 hr as a single daily dose given parenterally nfor 2–5 days), or nalidixic acid (55 mg/kg/24 hr in four divided doses for 5 ndays) can be given. Of these agents, given a susceptible organism, TMP-SMX is npreferred because of the rapidity with which it causes resolution of symptoms. nIn patients too ill to take oral medications, intravenous therapy with TMP-SMX nis effective if the organism is susceptible. Oral first- and second-generatiocephalosporins are inadequate as alternative drugs. Amoxicillin is less neffective than ampicillin in therapy of ampicillin-sensitive strains.

 

Treatment of patients suspected on clinical grounds of having Shigella ninfection should be started when the patient is first examined. Stool culture nis obtained to exclude other pathogens and to assist in antibiotic selectioshould the child fail to respond to empiric therapy. A child who has typical ndysentery and who responds to initial empiric antibiotic treatment should be ncontinued on that drug for a full 5-day course even if the stool culture is nnegative. The logic of this recommendation is based on the difficulty of culturing nShigella and on the fact that enteroinvasive E. coli, which cause dysentery nindistinguishable from that due to shigellae, cannot be diagnosed in routine nclinical microbiology laboratories. In a child who fails to respond to therapy nof a dysenteric syndrome in the presence of initially negative stool cultures, ncultures should be retaken and the child re-evaluated for other possible ndiagnoses.

 

PREVENTION. Two nsimple measures decrease the risk of shigellosis in children. The first is to nencourage prolonged breast-feeding in settings in which shigellosis is common. nBreastfeeding decreases the risk of symptomatic shigellosis and lessens its nseverity in infants who acquire infection despite breast-feeding. The second nmeasure is to educate families in handwashing techniques, especially after ndefecation and before food preparation and consumption. Other public health nmeasures, including water and sewage treatment, are expensive and are unlikely nto be universally available in the near future in developing countries.

 

Short statement of the material

Shigelloses (dysenteries) are nacute human infectious diseases with enteral infection that is characterized by ncolitic syndrome and symptoms of general intoxication, quite often with ndevelopment of primary neurotoxicosis.

 

Etiology: Shigella, gram negative bacteria, immobile, sized 2-3 mkm, without sporing and nincapsulation, product endotoxin, resistant to the environment (in milk, water, nfood stay for several days, in soil –for several weeks), stable to the nfreezing, but sensitive for boiling. By antigen structure and biochemical nproperties shigella are devided into 4 subgroups: A, B, C, D:

·        nSh.dysenteriae – nbelongs to group A

·        nSh. flexneri – nbelongs to group B

·        nSh.boydii – nbelongs to group C

·        nSh.sonnei – nbelongs to group D

Sh. flexneri and Sh.sonnei are the most often agents for bacterial ndysentery nowadays.

 

 

Epidemiology:

Source of ninfection –

•         nContagious patient

•         nBacillus carrier

Shigella is spread through fecal-oral nmechanism of transmission.

The way of ntransmission

•         nContact

•         nAlimentary

•        nWatery

Susceptibility: 60-70% especially infants and preschoolers.

Seasonality is summer-autumn.

 

Pathogenesis:

1.     nEntrance Shigella to gastrointestinal tract.

2.     nDestruction of them under the influence of ferments.

3.     nToxemia.

4.     nToxic changes in organs and systems (especially in CNS).

5.     nLocal inflammatory process (due to colonizing of distal part of the ncolon).

6.     nDiarrhea.

 

Morphological changes in shigellosis

 

 

 

 

 

 

Classification

      nI.            nClinical Form

Typical

•         nWith dominance of toxicosis

•         nwith dominance of local inflammation

•         nmixed

Atypical

•        nEffaced

•        nDyspeptic

•        nSubclinical

•        nHypertoxic

   nII.            n Severity (mild, moderate and severe)

III.            nDuration

•         nacute (up to 1.5 mo)

•         nsubacute (up to 3 mo)

•         nchronic (about 3 mo)

ü nrecurrent

ü nconstantly recurring

IV.            nCourse

•        nSmooth

•         nUneven (with complication)

V. Bacterium carrier

 

Clinical ncriterions (With dominance of ntoxicosis):

·        nPeriod of incubation: a few hours to 7 ndays.

·        nToxicosis is the first sing even may be neurotoxicosis (lose of nappetite, headache, fatigue, vomiting, hallucinations, unconsciousness, nseizure, febrile temperature 39-40°C).

·        nColitis is secondary (abdominal pain, tenesmus, false urge to defecate, nsigmoid colon is tender, spastic, anus is open in hard cases. Feces in the form nof a spit of mucus and blood (rectal spit), enlargement of number of ndefecation).

·        nDehydration isn’t developed (except infants).

 

Marble skin in toxicosis

 

With dominance of local inflammation

•         nSudden onset of high-grade fever

•         n abdominal cramping

•         nabdominal pain,

•         ntenesmus,

•         nand large-volume , mucus, cylindrical epithelial cells diarrhea →

•         nfecal incontinence, and small-volume mucous ndiarrhea with frank blood

 

False urge to defecate

 

Typical color of feces in shigellosis, rectal spit

 

Sunken abdomen

 

Rectal prolapse

 

Peculiarities of nshigellosis in infants:

·        nAcute beginning with slow development of signs and symptoms (for 3-5 ndays).

·        nDistal colitis is less common

·        nEnterocolitis is more often with enterocolitic feces, hemocolitis is nrare.

·        nHepato- and splenomegaly

·        nCrying, anxiety, red face during defecation is equivalent to tenesmus.

·        nAlways occurs gaping anus, sphincteritis

·        nDehydration is more often

·        nProlonged duration of the disease

 

Criteria of the Shigellosis Severity

Mild form

•         nConsistent or acute onset of diarrhea

•         n Stool is 5-8 times per day with nmucous and blood

•         nNot permanent pain in abdominal region.

•         nThe temperature is normal

•         nLoss of appetites

•         nCan be vomiting 

Moderate form

•         nAcute onset of diarrhea

•         nSymptoms of toxicosis

•         n The temperature is 38-39°C

•         nAnorexia

•         nCrampy abdominal pain

•         n Stool is 10-15 times per day

•         nPain during palpation in left inguinal region

•         nhepatomegaly

Severe form

•        nMultiple nvomiting not only after receiving the food, but also independent, can be with nbile, sometimes – as coffee lees,

•        nexcrements – nmore 15 times per day, sometimes – with each diaper, much mucus, there is nblood, sometimes – an intestinal bleeding

•        nGeneral ncondition is sharply worsened,

•        nquite often – nsopor, loss of the consciousness, cramps,

•        nchanges in all norgans and systems,

•        nsevere ntoxicosis, may be dehydration (in infants),

•        nsignificant nweight loss

 

Laboratory ntests:

•         nThe white blood cell count is often within reference range, with a high percentage of bands. nOccasionally, leucopenia or leukemic reactions may be detected.

•         nIn HUS, anemia and thrombocytopenia occur.

•         nStool examination Increasing of red blood cells and leukocytes

•         nStool culture Specimens should be plated lightly onto Endo-Levin, nPloskirev, McConkey, xylose-lysine-deoxycholate, or eosin-methylene blue agars. n

•         nSerological test: (AR, PHAR in dynamics with fourfold title increasing in 10-14 days) nin children elder than 1 year if fecal culture is negative.

Diagnosis example:

•         nShigellosis (Sh. sonnei), typical form (with dominance nof toxicosis), severe degree, acute duration.

•         nShigellosis (Sh. flexneri), typical form (with ndominance of local inflammation), moderate degree, constantly recurring duration, complicated by the rectum prolapse

 

Differential ndiagnosis should nbe performed with: salmonellosis, escherichiosis, acute appendicitis, bowel ninvagination, Krohn’s disease, nonspecific necrotizing colitis.

 

Differential-Diagnostic Criteria of Diarrheal Diseases

 

Treatment: see treatment of Ecsherichiosis below

 

Prophylaxis

·        nEpidemiological control for water and food.

·        nIsolation and sanation of ill person

·        nReconvalescent may be discharged from hospital after one negative feces nculture ( taken 2 days after course of antibiotic therapy)

·        nDispensarization of reconvalescent for 1-3 months

·        nFeces culture in contacts, carriers

·        nLooking after contacts for 7 days, quarantine

·        nDisinfection in epidemic focus

 

SALMONELLA INFECTIONS

 

Salmonella infections occur worldwide. Acute ngastroenteritis, the most frequent presentation, is usually self-limited, although nbacteremia and focal extraintestinal infections may develop, especially iimmunocompromised patients. The latter group has become more important and ncomplex because of the increasing number of children who are compromised nbecause of acquired immunodeficiency syndrome (AIDS), organ transplant, or nchemotherapy. Enteric fever, a severe systemic disease typically caused by nSalmonella typhi, is found mainly in developing countries, but it is seeelsewhere because of international travel.

 

ETIOLOGY. Salmonella nis a genus that belongs to the family Enterobacteriaceae and contains three nspecies: S. typhi, S. choleraesuis, and S. enteritidis. The former two species nhave one serotype each, but S. enteritidis contains more than 1800 distinct nserotypes. For convenience, serotypes are sometimes artificially identified as nif they were Salmonella species (e.g., S. typhimurium).

 

 

Salmonellae are motile, nnonsporulating, nonencapsulated, gram-negative rods. Most strains ferment nglucose, mannose, and mannitol to produce acid and gas, but they do not ferment nlactose or sucrose. S. typhi does not produce gas. Salmonella organisms grow naerobically and are capable of facultative anaerobic growth. They are resistant nto many physical agents but can be killed by heating to 130º F (54.4º nC) for 1 hr or 140º F (60º C) for 15 min. They remain viable at nambient or reduced temperatures for days and may survive for weeks in sewage, ndried foodstuffs, pharmaceutical agents, and fecal material. Like other members nof the Enterobacteriaceae, Salmonella possesses somatic O antigens and nflagellar H antigens. The O antigens are the heat-stable lipopolysaccharide ncomponents of cell wall; the H antigens are heat-labile proteins that can be npresent in phase 1 or 2. The Kauffmann-White scheme commonly used to classify nsalmonellae serotypes is based on O and H antigens. Serotyping is important clinically because certain serotypes tend to be nassociated with specific clinical syndromes and because the detection of aunusual serotype is sometimes epidemiologically useful. Another antigen is a nvirulence (Vi) capsular polysaccharide present on S. typhi and rarely found ostrains of S. paratyphi C (S. hirschfeldii).

 

These classification schemes are based on biochemical nor serologic reactions. Molecular technology has enabled classification at the ngene level. DNA hybridizations have proven that all Salmonella organisms are nclosely related genetically as a single species with six subgroups; most nisolates causing human or animal disease belong to subgroup 1.

 

EPIDEMIOLOGY.

 

About 50,000 cases of nculture-proven salmonellosis, approximately 98% of which are caused by nnontyphoidal salmonellae, are reported annually in the United States. nBecause culturing and reporting are incomplete, the actual number of cases has nbeen estimated as 1–5 million per year. These figures are higher than those of the 1970s and may be related to nmodern practices of mass food production, which increase the potential for nepidemic salmonellosis. About one half of the reported cases occur in persons nyounger than 20 yr of age and one third occur in children 4 yr of age or nyounger; the highest isolation rate is for infants younger than 1 yr of age. nNontyphoidal Salmonella infections have a worldwide distribution, with aincidence related to water potability, sewage disposal, and food preparatiopractices.

 

Salmonella infections occur with highest frequency ithe warm months, July through November in the United States. Although most nreported cases of nontyphoidal salmonellosis occur sporadically, outbreaks are nwell documented, usually as foodborne (i.e., “food poisoning”). Each nyear, about 500 foodborne Salmonella outbreaks are reported, representing over n50% of all gastroenteritis outbreaks with a documented bacterial cause. Some of nthe Salmonella outbreaks are widespread—interstate or even international—and naffect thousands of individuals. Refinement of outbreak tracing has improved nwith the development of molecular epidemiology techniques, such as plasmid nanalysis and endonucleases digestion of chromosomal genes for recognition of nsmall differences in chromosomal structure. These can “fingerprint” a nparticular clone and are especially useful in tracing outbreaks caused by ncommon serotypes. The Salmonella serotypes most often encountered in the United States include S. typhimurium, S. nenteritidis, S. heidelberg, and S. newport.

 

The major reservoir of nontyphoidal salmonellae is infected animals, nwhich constitute the principal source of human disease. Infected animals are noften asymptomatic. Salmonella organisms have been isolated from many animals, nincluding poultry (i.e., chickens, turkeys, ducks), sheep, cows, pigs, pets, nand birds. Animal-to-animal transmission may occur. Animal feeds containing nfish meal or bone meal contaminated with Salmonella are an important source of ninfection for animals. Moreover, subtherapeutic concentrations of antibiotics nare often added to animal feed. Such practices promote the emergence of nantibiotic-resistant bacteria, including Salmonella, in the gut flora of the nanimals. During slaughtering, these gut organisms may contaminate the meat, nwhich is subsequently consumed by humans. Data suggest that animal antibiotic nexposure may be responsible for antibiotic-resistant Salmonella infections iman.

 

Studies of outbreaks have enabled the collection of nnumeric data regarding the sources of human salmonellosis. Poultry and poultry nproducts (mainly eggs) caused about half of the common-source outbreaks. Foods ncontaining raw or undercooked eggs (e.g., Caesar salad, egg-dipped bread, nhomemade eggnog) are of special importance. Salmonella infections in chickens nincrease the risk for contamination of eggs. Salmonellae can contaminate the nshell surface, penetrate the egg, or be transmitted from an ovarian infectiodirectly to the egg yolk. Salmonella serotypes have been isolated in as many as n50% of poultry, 16% of pork, 5% of beef, and 40% of frozen egg products npurchased in retail stores. Meats, especially beef and pork, caused about 13% nof the outbreaks, and raw or powdered milk and dairy products were the source nof about 5% of the outbreaks. Food product–related outbreaks are often caused nby contaminated equipment in processing plants or infected food handlers. Pets, nespecially turtles, caused about 3% of the outbreaks.

 

The estimated number of bacteria that must be ingested to cause nsymptomatic disease in healthy adults is 106–108 Salmonella organisms. Iinfants and in persons with certain underlying conditions, the inoculum size nthat can produce disease is smaller. Because of the relatively high inoculum nsize of Salmonella infection, ingestion of contaminated food, in which the norganisms can multiply, is a major source of human infection. Unlike S. typhi, ninfection with nontyphoidal salmonellae by contaminated water is infrequent. nBecause of the high infecting dose, person-to-person transmission by direct nfecal-oral spread is unusual but can occur, especially in young children who nare not yet toilet-trained and do not maintain proper hygiene. Perinatal ntransmission during vaginal delivery has been reported.

 

Nosocomial infections have been related to ncontaminated medical instruments (particularly endoscopes) and diagnostic or npharmacologic preparations, particularly those of animal origin (e.g., npancreatic extracts, pituitary extracts, bile salts, pepsin, gelatin, vitamins, ncarmine dye). Foodborne nosocomial transmission is also possible. Hospitalized npatients are at increased risk of severe and complicated Salmonella infections. nIntravenous transmission by platelet transfusion has been reported.

 

After infection, nontyphoidal salmonellae are excreted nin feces for a median of 5 wk. In young children and in individuals with nsymptomatic infections, the excretion period is longer. Prolonged carriage of nSalmonella organisms is rare in healthy children but has been reported in those nwith underlying immune deficiency. During the period of Salmonella excretion, nthe individual may infect others, directly by the fecal-oral route or nindirectly by contaminating foods. If one household member becomes infected, nthe probability that another will also become infected is about 60%.

 

PATHOLOGY.

 

Enterocolitis is the typical disorder caused by nontyphoidal Salmonella ninfection. Findings include diffuse mucosal inflammation and edema, sometimes nwith erosions and microabscesses. Although Salmonella organisms are capable of npenetrating the intestinal mucosa, neither destruction of epithelial cells nor nproduction of ulcers is usually seen. Intestinal inflammation, with npolymorphonuclear leukocytes and macrophages, usually involves the lamina npropria. Underlying intestinal lymphoid tissue and mesenteric lymph nodes nenlarge and may develop small areas of necrosis. Such lymphoid hypertrophy may ncause interference with the blood supply to the gut mucosa. Hyperplasia of the nreticuloendothelial system is seen also within the liver and spleen. If nbacteremia develops, it may lead to localized infection and suppuration (with npolymorphonuclear leukocyte response) of almost any organ.

 

PATHOGENESIS. The ndevelopment of disease after infection with Salmonella depends on the number of ninfecting organisms, on their virulence traits, and on several host defense nfactors. Ingested Salmonella organisms reach the stomach, where acidity is the nfirst protective barrier. The acidity inhibits multiplication of the nsalmonellae, and when gastric pH reaches 2.0, most organisms are rapidly nkilled. Achlorhydria, buffering medications, rapid gastric emptying after ngastrectomy or gastroenterostomy, and a large inoculum enable viable organisms nto reach the small intestine. Neonates and young infants have hypochlorhydria nand rapid gastric emptying, which contribute to their increased vulnerability nto symptomatic salmonellosis. Because the transit time through the stomach is nfaster for drinks than for foods, a lower inoculum may cause disease iwaterborne infection.

In the small and large intestines, salmonellae have to compete with nnormal bacterial flora to multiply and cause disease; prior antibiotic therapy ndisrupts this competitive relationship. Decreased intestinal motility due to nanatomic causes or medications increases the contact time of the ingested nsalmonellae with the mucosa and the likelihood of symptomatic disease. After nmultiplication within the lumen, the organisms penetrate the mucosa, typically nat the distal part of the ileum and the proximal part of the colon, with nsubsequent localization in the Peyer patches. The penetration process includes nspecific attachment to the luminal surface of epithelial cells, internalizatiointo the cell by receptor-mediated endocytosis, cytoplasmic translocation of nthe infected endosome to the basal epithelial membrane, and release of the nsalmonellae in the lamina propria. The role of cytotoxins, which are produced nby most salmonellae, is uncertain. Penetration usually occurs without ndestroying epithelial cells, and ulcers are not produced.

 

 

Heat-labile, cholera-like enterotoxin is produced by nmany Salmonella isolates. This toxin and the prostaglandins that are produced nlocally increase cyclic adenosine monophosphate levels within intestinal ncrypts, causing a net efflux of electrolytes and water into the intestinal nlumen.

 

Genes code for adherence to epithelial cells, invasioof epithelial cells, a cholera toxin–like enterotoxin, spread beyond the Peyer npatches to mesenteric lymph nodes, intracellular growth in the liver and nspleen, survival in macrophages, serum resistance, and complement resistance. nSome of these traits are shared by all salmonellae, but others are serotype restricted. nThese virulence traits have been defined in tissue culture and murine models; nit is likely that clinical features of human Salmonella infection will neventually be related to specific DNA sequences.

 

With most diarrhea-associated nontyphoidal salmonelloses, the infectiodoes not extend beyond the lamina propria and the local lymphatics. S. dublin and S. choleraesuis rapidly invade the nbloodstream with little or no intestinal involvement. Specific virulence genes nare related to the ability to cause bacteremia. These genes are found nsignificantly more often in strains of S. typhimurium isolated from the blood nthan the feces of humans. Bacteremia, however, is theoretically possible with nany Salmonella strain, especially in individuals with reduced host defenses. Aimpaired reticuloendothelial or cellular immune response is important. Childrewith chronic granulomatous disease, other white cell disorders, and AIDS are at nincreased risk. Children with sickle cell disease are prone to Salmonella septicemia nand osteomyelitis. The numerous infarcted areas in the gastrointestinal tract, nbones, and reticuloendothelial system may initially permit organisms greater naccess to the circulation from the intestine and then furnish an optimal nenvironment for localization. The decreased phagocytic and opsonizing capacity nof patients with sickle cell disease also contributes to the high infectiorate.

 

Chronic infection is associated with cholelithiasis, Schistosoma mansoni nhepatosplenic involvement, and urinary tract Schistosoma hematobium infection. nLocalized infections are more common in areas with impaired local defenses n(e.g., effusions, tumors, hematomas).

 

CLINICAL MANIFESTATIONS. Several distinct clinical syndromes can develop ichildren infected with nontyphoidal Salmonella, depending on host factors and nthe specific serotype involved.

 

Acute Gastroenteritis. This is the most common clinical presentation. After an incubatioperiod of 6–72 hr (mean, 24 hr), there is an abrupt onset of nausea, vomiting, nand crampy abdominal pain primarily in the periumbilical area and right lower nquadrant, followed by mild to severe watery diarrhea and sometimes by ndysenteric diarrhea, containing blood and mucus. Moderate fever of n101–102º F (38.5–39º C) affects about 70% of patients. Some childredevelop severe disease with high fever, headache, drowsiness, confusion, nmeningismus, seizures, and abdominal distention. Abdominal examination reveals nsome tenderness. The stool, which is usually not bloody, typically contains a moderate nnumber of polymorphonuclear leukocytes and occult blood. Mild leukocytosis may nbe detected. Symptoms subside within 2–7 days in healthy children; fatalities nare rare.

 

Hemocolitis in salmonellosis

 

In certain high-risk groups, the course of Salmonella gastroenteritis is ndistinct. Neonates, young infants, and children with primary or secondary nimmune deficiency may have symptoms persisting for several weeks. In patients nwith AIDS, the infection may become widespread and overwhelming, causing multisystem ninvolvement, septic shock, and death. In patients with inflammatory bowel ndisease, especially active ulcerative colitis, Salmonella gastroenteritis may ncause invasion of the bowel with rapid development of toxic megacolon, systemic ntoxicity, and death. Patients with schistosomiasis have increased nsusceptibility to salmonellosis and exhibit persistence of infection unless the nschistosomiasis is also treated. Salmonella organisms are able to multiply nwithin the schistosomes, where they are protected from antibiotics.

 

Bacteremia. nTransient bacteremia during nontyphoidal Salmonella gastroenteritis is thought nto occur in 1–5% of patients. The precise incidence is unclear, because blood ncultures often are not obtained from patients with Salmonella gastroenteritis, nespecially those who are not hospitalized, and because most studies are nretrospective. Salmonella bacteremia is associated with fever, chills, and noften with a toxic appearance. Bacteremia has been documented, however, iafebrile, well-looking children, especially neonates. Prolonged or intermittent nbacteremia is associated with low-grade fever, anorexia, weight loss, ndiaphoresis, and myalgias. Children with certain underlying conditions who have nSalmonella gastroenteritis are at increased risk of bacteremia, which may lead nto extraintestinal infection. Recurrent Salmonella septicemia is one of the ncriteria for diagnosing AIDS according to the Centers for Disease Control and nPrevention (CDC) case definition. In these patients, recurrent septicemia appears ndespite antibiotic therapy, often with a negative stool culture for Salmonella nand sometimes with no identifiable focus of infection. Prolonged or recurrent nbacteremia is also seen in patients with schistosomiasis. Hemolytic anemias, nmalaria, and bartonellosis are associated with an increased risk of bacteremia, npresumably because of reticuloendothelial system dysfunction. In pregnancy, nSalmonella septicemia and fetal loss have been reported. S. typhimurium is the nmost common serotype causing Salmonella bacteremia in the United States.

 

Extraintestinal Focal nInfections. After salmonellae have entered the nblood stream, they have a unique capability to metastasize and cause a focal, nsuppurative infection of almost any organ. Sites of pre-existing abnormalities nare typically involved. The most common focal infections involve the skeletal nsystem, meninges, and intravascular sites. Salmonella is a common cause of osteomyelitis in children with sickle ncell disease. Salmonella osteomyelitis and suppurative arthritis also occur isites of previous trauma or skeletal prosthesis. Reactive arthritis may follow nSalmonella gastroenteritis, usually in children with the HLA-B27 antigen. nMeningitis appears mainly in infants. Patients usually present with little or no nfever and minimal symptoms, but rapid deterioration, a high mortality rate n(~50%), and neurologic sequelae occur despite appropriate antibiotic therapy. nSalmonella meningitis occurs also in patients with AIDS, for whom the mortality nrate is more than 50%, and relapse and brain abscesses can occur. Persistent nbacteremia suggests endocarditis, arteritis, or an infected aneurysm. The nserotypes causing most extraintestinal focal infections are S. typhimurium and nS. choleraesuis.

 

Asymptomatic Infection. Asymptomatic fecal excretion of salmonellae after infection with these norganisms has been documented, for instance, as part of an outbreak ninvestigation. The precise incidence is unclear. After clinical recovery from nSalmonella gastroenteritis, asymptomatic fecal excretion of salmonellae occurs nfor several weeks. A chronic carrier state is defined as asymptomatic excretioof Salmonella organisms for more than 1 yr. Although the carrier state does noccur after nontyphoidal salmonellosis, it is rare (<1%), and it develops nespecially in patients with biliary tract disease. The only significance of nasymptomatic fecal excretion of nontyphoidal Salmonella is the potential ntransmission of the infection to other individuals.

 

DIAGNOSIS.

 

Definitive diagnosis of the various clinical syndromes is still based oculturing and subsequent identification of Salmonella organisms. In childrewith gastroenteritis, cultures of stools have higher yields than rectal swabs. nIn patients with sites of local suppuration, aspirated specimens should be used nfor Gram staining and culture. Salmonella organisms grow well oonselective nor enriched media, such as blood agar, chocolate agar, or nutrient broth. nNormally sterile body fluids (e.g., cerebrospinal fluid, joint fluid, urine) ncan be cultured on any of these. For specimens normally containing bacterial nflora (e.g., stools), selective media, such as MacConkey, XLD, bismuth sulfite n(BBL) or Salmonella-Shigella (SS) agar, which inhibit the growth of normal nflora, should be used.

 

Several methods are being developed to answer the need nfor rapid diagnosis. Two tests, based on latex agglutination and fluorescence, nare commercially available for the rapid diagnosis of Salmonella colonies ngrowing in stool culture enrichment broth or culture plates. Clinical nexperience is limited. Alternatively, chromosomal fragments that are unique to nthe genus Salmonella have been employed as DNA probes to detect Salmonella nspecies. The method is still experimental and needs evaluation with clinical nspecimens. Serologic assay for detecting antibodies against S. typhimurium and nS. enteritidis has been reported, but clinical usefulness is still unclear.

 

DIFFERENTIAL DIAGNOSIS.

 

Salmonella gastroenteritis should be differentiated from other nbacterial, viral, and parasitic causes of diarrhea. The presentation of ninflammatory diarrhea with moderate fever should be particularly differentiated nfrom Shigella, enteroinvasive Escherichia coli, Yersinia enterocolitica, and nClostridium difficile infections. Rotavirus infections in infants can mimic nSalmonella enterocolitis. Etiologic diagnosis on the basis of the clinical npicture is not possible. Epidemiologic data may be helpful. If abdominal paiand tenderness are severe, appendicitis, perforated viscus, and ulcerative colitis nmerit consideration in the differential diagnosis.

 

PREVENTION.

 

Chlorinated water, proper sanitary systems, and adequate food hygiene npractices are necessary to prevent nontyphoidal salmonellosis in humans. nHandwashing is of paramount importance in controlling person-to-persotransmission by means of food. In hospitalized patients, enteric precautions nshould be used for the duration of illness. Individuals with symptomatic or nasymptomatic excretion of Salmonella strains should be excluded from activities nthat involve food preparation or child care until repeated stool cultures are nnegative. Promotion of breast-feeding may reduce infection, especially ideveloping communities.

 

Control of the transmission of Salmonella infections to humans requires control nof the infection in the animal reservoir, judicious use of antibiotics in dairy nand livestock farming, prevention of contamination of foodstuffs prepared from nanimals, and use of appropriate standards in food processing in commercial and nprivate kitchens. Whenever cooking practices prevent food from reaching a ntemperature greater than 150º F (65.5º C) for more than 12 min, nsalmonellosis may be transmitted. Because large outbreaks are often related to nmass food production, it should be recognized that contamination of just one npiece of machinery used in food processing may cause an outbreak; meticulous ncleaning of the equipment is essential. No vaccine against nontyphoidal nSalmonella infections is available.

 

TREATMENT.

 

Proper therapy depends on the specific clinical npresentation of Salmonella infection. Assessment of the hydration status, ncorrection of dehydration and electrolyte disturbances, and supportive care n(see Chapter 60) are the most important aspects of managing Salmonella ngastroenteritis in children. Antimotility agents prolong intestinal transit ntime and are thought to increase the risk of invasion; they should not be used nwhen salmonellosis is suspected. In patients with gastroenteritis, nantimicrobial agents do not shorten the clinical course, nor do they eliminate nfecal excretion of Salmonella. By suppressing normal intestinal flora, nantimicrobial agents may prolong the excretion of Salmonella and increase the nrisk of creating the chronic carrier state. Antibiotics therefore are not indicated nroutinely in treating Salmonella gastroenteritis. They should be used in young ninfants and other children who are at increased risk of a disseminated disease nand in those with a severe or protracted course.

 

Children with bacteremia or extraintestinal focal Salmonella infections nshould receive antimicrobial therapy. Ampicillin (200 mg/kg/24 hr in four ndivided doses) is efficacious and used to be the drug of choice; ntrimethoprim-sulfamethoxazole (TMP-SMX; 10–50 mg/kg/24 hr in two divided doses) nand chloramphenicol (75 mg/kg/24 hr in four divided doses) are also effective. nBecause of the increasing worldwide antibiotic resistance of Salmonella nstrains, it is necessary to perform susceptibility tests on all human isolates. nAbout 20% of Salmonella isolates in the United States are resistant to nampicillin. Multiresistance to ampicillin, TMP-SMX, and chloramphenicol has nbeen reported. The third-generation cephalosporins, cefotaxime (150–200 nmg/kg/24 hr in three to four divided doses) or ceftriaxone (100 mg/kg/24 hr ione or two doses), are effective in these cases, although clinical experience nis still limited. Quinolones are also effective, but they are not approved for nuse in children because of the potential damage to growing cartilage. Ichildren with severe disease, initial treatment with a third-generatiocephalosporin is recommended until antibiotic susceptibility is known. nThereafter, antibiotics should be changed accordingly.

 

The duration of antimicrobial therapy is 10–14 days in children with nbacteremia, 4–6 wks for acute osteomyelitis, and 4 wk for meningitis. In a nchild with a focal suppurative process, surgical drainage is necessary iaddition to antibiotic treatment. Surgical intervention is ofteecessary iintravascular Salmonella infections (e.g., repair of aneurysm, replacement of nvalve) and in cases of chronic osteomyelitis.

 

PROGNOSIS. Complete nrecovery is the rule in healthy children who develop Salmonella ngastroenteritis. Young infants and immunocompromised patients often have nsystemic involvement, a prolonged course, and complications. The prognosis is npoor for children with Salmonella meningitis (~50% mortality rate) or nendocarditis.

 

Enteric Fever

 

Enteric fever is a systemic clinical syndrome produced by certaiSalmonella organisms. It encompasses the terms typhoid fever, caused by S. ntyphi, and paratyphoid fever, caused by S. paratyphi A, S. schottmuelleri n(formerly S. paratyphi B), S. hirschfeldii (formerly S. paratyphi C), and noccasionally other Salmonella serotypes. Typhoid fever, the most frequent and nbest studied type of enteric fever, tends to be more severe than the other nforms.

 

EPIDEMIOLOGY. The incidence, mode of transmission, and consequences of enteric fever ndiffer significantly in developed and developing countries. The incidence has ndecreased markedly in developed countries. In the UnitedStates, about 400 cases of typhoid fever are reported neach year, giving an annual incidence of less than 0.2 per 100,000, which is nsimilar to that in Western Europe and Japan. In Souther Europe, the annual incidence is 4.3–14.5 per 100,000. In developing ncountries, S. typhi is often the most common Salmonella isolate, with aincidence than can reach 500 per 100,000 (0.5%) and a high mortality rate. The nWorld Health Organization has estimated that 12.5 million cases occur annually nworldwide (excluding China).

 

Because humans are the only natural reservoir of S. ntyphi, direct or indirect contact with an infected person (sick or chronic ncarrier) is necessary for infection. Ingestion of foods or water contaminated nwith human feces is the most common mode of transmission. Waterborne outbreaks ndue to poor sanitation and direct fecal-oral spread due to poor personal nhygiene are seen, mainly in developing countries. Oysters and other shellfish ncultivated in water contaminated by sewage are also a source of widespread ninfection. In the United States, about 65% of the cases result from ninternational travel. Travel to Asia (especially to India) nand Central or South America (especially Mexico) is usually implicated. nDomestically acquired enteric fever is most frequent in the southern and nwestern United States nand is usually caused by consumption of foods contaminated by individuals who nare chronic carriers. Congenital transmission of enteric fever can occur by ntransplacental infection from a bacteremic mother to her fetus. Intrapartum ntransmission is also possible, occurring by a fecal-oral route from a carrier nmother.

 

PATHOLOGY. Iyounger children, the morphologic changes of S. typhi infection are less nprominent than in older children and adults. Hyperplasia of Peyer patches with nnecrosis and sloughing of overlying epithelium, producing ulcers, is typical. nThe mucosa and lymphatic tissue of the intestinal tract are severely inflamed nand necrotic. Ulceration that heals without scarring is common. Strictures and nintestinal obstruction virtually never occur after typhoid fever. Hemorrhages nmay occur. The inflammatory lesion may occasionally penetrate the muscularis nand serosa of the intestine and produce perforation. The mesenteric lymph nnodes, liver, and spleen are hyperemic and generally reveal areas of focal nnecrosis. Hyperplasia of reticuloendothelial tissue with proliferation of nmononuclear cells is the predominant finding. A mononuclear response may be nseen in the bone marrow associated with areas of focal necrosis. Inflammatioof the gallbladder is focal, inconstant, and modest in proportion to the extent nof local bacterial multiplication. Bronchitis is common. Inflammation also may nbe observed in the form of localized abscesses, pneumonia, septic arthritis, nosteomyelitis, pyelonephritis, endophthalmitis, and meningitis.

 

PATHOGENESIS. nBloodstream invasion by S. typhi or occasionally by other serotypes is nnecessary to produce the enteric fever syndrome. The inoculum size required to ncause disease in volunteers is 105–109 S. typhi organisms. These estimates may nbe higher than iaturally acquired infection because the volunteers ingested nthe organisms in milk; stomach acidity is an important determinant of nsusceptibility to salmonella. After attachment to the microvilli of the ileal nbrush borders, the bacteria invade intestinal epithelium, apparently through nthe Peyer patches. Organisms are transported to intestinal lymph follicles, nwhere multiplication takes place within the mononuclear cells. Monocytes, nunable to destroy the bacilli early in the disease process, carry these norganisms into the mesenteric lymph nodes. Organisms then reach the bloodstream nthrough the thoracic duct, causing a transient bacteremia. Circulating norganisms reach the reticuloendothelial cells in the liver, spleen, and bone nmarrow and may seed other organs. After proliferation in the nreticuloendothelial system, the bacteremia recurs. The gallbladder is nparticularly susceptible to being infected from the bloodstream or through the nbiliary system. Local multiplication in the walls of the gallbladder produces nlarge numbers of salmonellae, which secondarily reach the intestine through the nbile.

 

Several virulence factors seem to be important. A surface Vi capsular nantigen is found in most S. typhi and some other serotypes; it interferes with nphagocytosis by preventing the binding of C3 to the surface of the bacterium nand correlates with invasion capability. The sequence of the gene (viaB) nencoding Vi has been defined. The ability of organisms to survive withimacrophages after phagocytosis is an important virulence trait encoded by the nphoP regulon; it may be related to metabolic effects on host cells. Circulating nendotoxin, a lipopolysaccharide component of the bacterial cell wall, is nthought to cause the prolonged fever and toxic symptoms of enteric fever, nalthough its levels in symptomatic patients are low. Alternatively, nendotoxin-induced cytokine production by human macrophages may cause the nsystemic symptoms. The occasional occurrence of diarrhea may be explained by npresence of a toxin related to cholera toxin and E. coli heat-labile nenterotoxin.

 

Cell-mediated immunity is important in protecting the human host against ntyphoid fever. Decreased numbers of T lymphocytes are found in patients who are ncritically ill with typhoid fever. Carriers show impaired cellular reactivity nto S. typhi antigens in the leukocyte migration inhibition test. In carriers, a nlarge number of virulent bacilli pass into the intestine daily and are excreted nin the stool, without entering the epithelium of the host.

 

CLINICAL MANIFESTATIONS. The incubation period is usually 7–14 days, but it nmay range from 3–30 days, depending mainly on the size of the ingested ninoculum. The clinical manifestations of enteric fever depend on age.

 

School-Age Children and Adolescents. The onset of symptoms is insidious. Initial symptoms nof fever, malaise, anorexia, myalgia, headache, and abdominal pain develop over n2–3 days. Although diarrhea having a pea soup consistency may be present during nthe early course of the disease, constipation later becomes a more prominent nsymptom. Nausea and vomiting are uncommon and suggest a complication, nparticularly if occurring in the 2nd or 3rd wk. Cough and epistaxis may be nseen. Severe lethargy may develop in some children. The fever, which rises in a nstep-wise fashion, becomes unremittent and high within 1 wk, often reaching n40º C (104º F).

 

During the 2nd wk of illness, high fever is sustained, and fatigue, nanorexia, cough, and abdominal symptoms increase in severity. The patient nappears acutely ill, disoriented, and lethargic. Delirium and stupor may be nobserved. Physical findings include a relative bradycardia, which is ndisproportionate to the high fever. Hepatomegaly, splenomegaly, and distended nabdomen with diffuse tenderness are very common. In about 50% of patients with nenteric fever, a macular (i.e., rose spots) or maculopapular rash appears oabout the 7th to 10th day. Lesions are usually discrete, erythematous, and 1 to n5 mm idiameter; the lesions are slightly raised, and blanch on pressure. They appear nin crops of 10 to 15 lesions on the lower chest and abdomen and last 2 or 3 ndays. They leave a slight brownish discoloration of the skin on healing. nCultures of the lesions have a 60% yield for Salmonella organisms. Rhonchi and nscattered rales may be heard on auscultation of the chest. If no complications noccur, the symptoms and physical findings gradually resolve within 2–4 wk, but nmalaise and lethargy may persist for an additional 1–2 mo. The patients may be nemaciated by the end of the illness. Enteric fever caused by nontyphoidal nSalmonella is usually milder, with a shorter duration of fever and a lower rate nof complications.

 

Infants and Young Children (<5 yr). Enteric fever is relatively rare in this age group. nAlthough clinical sepsis can occur, the disease is surprisingly mild at npresentation, making the diagnosis difficult and underdiagnosis possible. Mild nfever and malaise, misinterpreted as a viral syndrome, are seen in infants with nculture-proven typhoid fever. Diarrhea is more common in young children with ntyphoid fever than in adults, leading to a diagnosis of acute gastroenteritis. nOthers may present with signs and symptoms of lower respiratory tract ninfection.

 

Neonates. Iaddition to its ability to cause abortion and premature delivery, enteric fever nduring late pregnancy may be transmitted vertically. The neonatal disease nusually begins within 3 days of delivery. Vomiting, diarrhea, and abdominal ndistention are common. Temperature is variable but may be as high as 40.5º nC (105º F). Seizures may occur. Hepatomegaly, jaundice, anorexia, and nweight loss can be marked.

 

LABORATORY FINDINGS. A normochromic, normocytic anemia is often seen after several weeks of nillness and is related to intestinal blood loss or bone marrow suppression. nBlood leukocyte counts are frequently low in relation to the fever and ntoxicity, but there is a wide range in counts; leukopenia, usually not below n2500 cells/mm3, is often seen after the 1st or 2nd wk of illness. When pyogenic nabscesses develop, leukocytosis may reach 20,000–25,000/mm3. Thrombocytopenia nmay be striking and persist for as long as 1 wk. Liver function test results nare often disturbed. Proteinuria is common. Fecal leukocytes and fecal blood nare very common.

 

COMPLICATIONS. Common complications include intestinal perforation, myocarditis, and ncentral nervous system manifestations. Severe intestinal hemorrhage and nintestinal perforation occur in 1–10% and 0.5–3% of the patients, respectively. nThese and most other complications usually occur after the 1st wk of the ndisease. Hemorrhage, which usually precedes perforation, is manifested by a ndrop in temperature and blood pressure and an increase in the pulse rate. nPerforations, which are usually pinpoint size but may be as large as several ncentimeters, typically occur in the distal ileum and are accompanied by a nmarked increase in abdominal pain, tenderness, vomiting, and signs of peritonitis. nSepsis with various enteric aerobic Gram-negative bacilli and anaerobes may ndevelop. Although disturbed liver function test results are found for many npatients with enteric fever, overt hepatitis and cholecystitis are considered ncomplications. An increase in serum amylase levels may be seen sometimes with nclinically obvious pancreatitis.

 

Pneumonia often caused by superinfection with organisms other thaSalmonella is more common in children than in adults. In children, pneumonia or nbronchitis is common (approximately 10%). Toxic myocarditis may be manifested nby arrhythmias, sinoatrial block, ST-T changes on the electrocardiogram, ncardiogenic shock, fatty infiltration, and necrosis of the myocardium. nThrombosis and phlebitis occur rarely. Neurologic complications include nincreased intracranial pressure, cerebral thrombosis, acute cerebellar ataxia, nchorea, aphasia, deafness, psychosis, and transverse myelitis. Peripheral and noptic neuritis have been reported. Permanent sequelae are rare. Other reported ncomplications are fatal bone marrow necrosis, pyelonephritis, nephrotic nsyndrome, meningitis, endocarditis, parotitis, orchitis, and suppurative nlymphadenitis. Although osteomyelitis and septic arthritis can occur in a nnormal host, they are more frequently seen in children with hemoglobinopathies.

 

DIAGNOSIS. Culturing the Salmonella strain involved is usually the basis for the ndiagnosis. Blood cultures are positive in 40–60% of the patients seen early ithe course of the disease, and stool and urine cultures become positive after nthe 1st wk. The stool culture is also occasionally positive during the nincubation period. Because of the intermittent and low-level bacteremia, nrepeated blood cultures should be obtained. Cultures of bone marrow are oftepositive during later stages of the disease, when blood cultures may be nsterile; although seldom obtained, cultures of mesenteric lymph nodes, liver, nand spleen may also be positive at this point. A culture of bone marrow is the nsingle most sensitive method of diagnosis (positive in 85–90%) and is less ninfluenced by prior antimicrobial therapy. Stool and sometimes urine cultures nare positive in chronic carriers. In suspected cases with negative stool ncultures, a culture of aspirated duodenal fluid or of a duodenal string capsule nmay be helpful in confirming infection.

 

Because identification of S. typhi from culture nusually takes at least 3 days, several methods for earlier diagnosis are being ndeveloped. Direct detection of S. typhi–specific antigens in the serum or S. ntyphi Vi antigen in the urine has been attempted by immunologic methods, ofteusing monoclonal antibodies. Polymerase chain reaction (PCR) has been used to namplify specific genes of S. typhi in the blood of patients, enabling diagnosis nwithin a few hours. This method is specific and more sensitive than blood ncultures given the low level of bacteremia in enteric fever. More experience nwith these new methods is needed before they can be endorsed.

 

Serology is of little help in establishing the diagnosis, but it may be nuseful in epidemiologic studies. The classic Widal test measures antibodies nagainst O and H antigens of S. typhi. Because many false-positive and nfalse-negative results occur, diagnosis of typhoid fever by Widal test alone is nprone to error. Experience is still limited with new serologic assays.

 

DIFFERENTIAL DIAGNOSIS. During the initial stage of enteric fever, the clinical diagnosis may nmistakenly be gastroenteritis, viral syndrome, bronchitis, or bronchopneumonia. nSubsequently, the differential diagnosis includes sepsis with other bacterial npathogens; infections caused by intracellular microorganisms, such as ntuberculosis, brucellosis, tularemia, leptospirosis, and rickettsial diseases; nviral infections, such as infectious mononucleosis and anicteric hepatitis; and nmalignancies, such as leukemia and lymphoma.

 

PREVENTION. Iendemic areas, improved sanitation and clean, running water are essential to ncontrol enteric fever. To minimize person-to-person transmission and food ncontamination, personal hygiene measures, handwashing, and attention to food npreparation practices are necessary. Efforts to eradicate S. typhi from ncarriers are recommended, because humans are the only reservoir of S. typhi. nWhen such efforts are unsuccessful, carriers should be prevented from working nin food- or water-processing plants, in kitchens, and in occupations related to npatient care. These individuals should be made aware of the potential ncontagiousness of their condition and the importance of handwashing and personal nhygiene.

 

Several vaccines against S. typhi are available. A nparenteral heat-phenol–inactivated vaccine confers limited protection (51–76% nefficacy) and is associated with adverse effects, including fever, local nreactions, and headache in at least 25% of recipients. Two doses of 0.5 mL nadministered subcutaneously 4 wk or more apart have been recommended for nchildren 10 yr or older; 0.25 mL per dose is recommended for younger children. nA second newly licensed vaccine (Vivotif) is an oral, live-attenuated npreparation of the Ty21a strain of S. typhi. Several large studies have showefficacy (67–82%). Significant adverse effects are rare. Four enteric-coated ncapsules on alternate days are given. The oral vaccine is not recommended for nchildren younger than 6 yr because of limited experience. Infants and toddlers ndo not develop immune responses with this preparation. It should not be used ipersons with immunodeficiency syndromes. Vaccines against typhoid fever made nfrom the Vi capsular polysaccharide, with or without protein conjugation, are nunder investigation.

 

A typhoid vaccine is recommended to travelers to endemic areas, nespecially Latin America, Southeast Asia, and Africa. nSuch travelers need to be cautioned that the vaccine is not a substitute for npersonal hygiene and careful selection of foods and drinks, because neither nvaccine has efficacy approaching 100%. Vaccination is also recommended to nindividuals with intimate exposure to a documented carrier and for control of noutbreaks.

 

TREATMENT.

 

Antimicrobial therapy is essential in treating enteric fever, especially nfor typhoid fever. Because of increasing antibiotic resistance, however, nchoosing the appropriate empiric therapy is problematic and sometimes ncontroversial. Most antibiotic regimens are associated with a 5–20% recurrence nrisk. Chloramphenicol (50 mg/kg/24 hr orally or 75 mg/kg/24 hr, intravenously nin four equal doses), ampicillin (200 mg/kg/24 hr, intravenously in four to six ndoses), amoxicillin (100 mg/kg/24 hr, orally in three doses), and ntrimethoprim-sulfamethoxazole (10 mg of TMP and 50 mg of SMX/kg/24 hr, orally nin two doses) have demonstrated good clinical efficacy. Although nchloramphenicol therapy is associated with a more rapid defervescence and nsterilization of blood, the rate of relapse is somewhat higher, and this agent ncan cause potentially serious adverse effects. Most children become afebrile nwithin 7 days; treatment of uncomplicated patients should be continued for at nleast 14 days or 5–7 days after defervescence. In children with underlying ndisturbances, including severe malnutrition, extending antibiotic therapy for n21 days may reduce the rate of complications.

 

Although antibiotic resistance of S. typhi isolates in the United States nis relatively low (3–4%), most infections are acquired abroad, where resistance noccurs. Increasing rates of plasmid-mediated antibiotic resistance of S. typhi nhave been reported from Southeast Asia, Mexico, nand certain countries in the Middle East. nReports from India ndescribe multiresistance to chloramphenicol, ampicillin, and TMP-SMX in 49–83% nof S. typhi isolates. Resistant strains are usually susceptible to nthird-generation cephalosporins. Cefotaxime (200 mg/kg/24 hr, intravenously ithree to four doses) and ceftriaxone (100 mg/kg/24 hr, intravenously in one to ntwo doses) have been successfully used to treat typhoid fever caused by nresistant strains, although the response to ceftriaxone was somewhat better. nAztreonam has also been successfully used. Fluoroquinolones are efficacious, nbut they are not approved for children. In adults, ciprofloxacin at a dose of n500 mg twice daily for 7–10 days is effective and associated with a low relapse nrate. In patients with suspected resistant strains, we recommend empirical ntherapy with ceftriaxone (or cefotaxime) until antibiotic susceptibility npatterns are available.

 

In addition to antibiotic therapy, a short course of dexamethasone, nusing 3 mg/kg for the initial dose, followed by 1 mg/kg every 6 hr for 48 hr, nimproves the survival rate of patients with shock, obtundation, stupor, or ncoma. This does not increase the incidence of complications if antibiotic ntherapy is adequate. Supportive treatment and maintenance of appropriate fluid nand electrolyte balance are essential. When intestinal hemorrhage is severe, nblood transfusion is needed. Surgical intervention with broad-spectrum nantibiotics is recommended for intestinal perforation. Platelet transfusions nhave been suggested for the treatment of thrombocytopenia that is sufficiently nsevere to cause intestinal hemorrhage in patients for whom surgery is ncontemplated.

 

Although attempts to eradicate chronic carriage of S. typhi are nrecommended for public health considerations, eradication is difficult despite nin vitro susceptibility to the antibiotic used. A course of 4–6 wk of high-dose nampicillin (or amoxicillin) plus probenecid or TMP-SMX results in aapproximately 80% cure rate of carriers if no biliary tract disease is present. nCiprofloxacin has been used successfully in adults. In the presence of cholelithiasis nor cholecystitis, antibiotics alone are unlikely to be successful; ncholecystectomy within 14 days of antibiotic treatment is recommended.

 

PROGNOSIS.

 

The prognosis for a patient with enteric fever depends on prompt ntherapy, the age of the patient, previous state of health, the causative nSalmonella serotype, and the appearance of complications. In developed ncountries, with appropriate antimicrobial therapy, the mortality rate is below n1%. In developing countries, the mortality rate is higher than 10%, usually nbecause of delays in diagnosis, hospitalization, and treatment. Infants younger nthan 1 yr of age and children with underlying debilitating disorders are at nhigher risk. S. typhi causes a more severe disease, with higher rates of ncomplications and death, than other serotypes. The appearance of complications, nsuch as gastrointestinal perforation or severe hemorrhage, meningitis, nendocarditis, and pneumonia, are associated with high morbidity and mortality nrates.

 

Relapse after the initial clinical response occurs i4–8% of the patients who are not treated with antibiotics. In patients who have nreceived appropriate antimicrobial therapy, the clinical manifestations of nrelapse become apparent about 2 wk after stopping antibiotics and resemble the acute nillness. The relapse, however, is usually milder and of shorter duration. nMultiple relapses may occur. Individuals who excrete S. typhi 3 mo or longer nafter infection are usually excretors at 1 yr and defined as chronic carriers. nThe risk of becoming a carrier is low in children and increases with age; of nall patients with typhoid fever, 1–5% become chronic carriers. The incidence of nbiliary tract diseases is higher in chronic carriers than in the general npopulation. Although chronic urinary carriage may also occur, it is rare and nfound mainly in individuals with schistosomiasis.

 

Short statement of the material

Salmonellosis is an acute infectious disease of human and animals, that is caused by nthe numerous strains of Salmonella and more frequent courses as ngastro-intestinal, rare – as typhoid and septic forms

 

Etiology: Salmonella, over 2000 strains, Gramm-negative movable bacili, that don’t form capsules and spores. Their main antigents are O-H-and Vi, by nO-antigen are devided on groups (A, B, C, D, E, F etc.). Most often salmonella ninfection are called by:

•         nS. typhimurium

•         nS. enteritidis

•         nS. java

•         nS. anatum and other

Bacteria are stable in the environment (for months and years they live nin food, water, soil), hot temperature kill them in 1 hour.

 

Epidemiology:

·       nSource of infection: ill person, carrier, ill animals and birds

·       nWay of spreading – alimentary or by water; by direct contact, rare nair-droplet

·       nSusceptible organism: children, especially before 2 years old

 

Pathogenesis

1.     nMassive entering nof bacteria to the nalimentary canal.

2.     nDestruction of salmonella in the upper ndepartments of alimentary canal.

3.     nToxemia n→ vomit (as a protective factor).

4.     nEntering of other bacteria into thin intestinum, colon, ncolonization of epitheliocytes.

5.     nLocal inflammatory process, dysperistalsis, digestioand suction imparement, biologically active substance accumulation, which nimpare absorption of nwater, electrolytes (diarrhea, dehydration).

6.     nDamage nof the intestinal, lymphatic barriers (septic form of salmonellosis).

7.     Bacteriemia.

8.     Forming nof septic focuses.

 

Classification

1.     Local form

•         nGastrointestinal nform

•         n Bacterium carrying

2.     General form

•         nTyphoid nfever – like

•         nSepsis

3.     Asymptomatic form

    nII.            nSeverity (mild, moderate and severe)

III.            nDuration

•         nAcute (up nto 1.5 mo)

•         nSubacute n(up to 3 mo)

•         nChronic (more than 3 mo)

IV.            nCourse

•        nSmooth

•         nUneven (with complication)

V. Bacterium carrier

 

Clinical ndiagnostic criterions

Of local gastro-intestinal forms:

·        nperiod of incubation: hours (for gastritis) – several days (in case of nspreading by direct contact)

·        nacute beginning from: intoxication (nausea, vomiting, high body ntemperature, headache);

·       nabdominal pain;

·       ndiarrhea, usually appears secondary, stools are “muddy” (photo), may be with blood and mucus, abdomen is tender; ndehydration is moderate.

 

 

 “Muddy” stools, hemocolitis

 

Typhoid form

·       nacute beginning from high temperature (39-40˚ C) lasting for 1-2 nweeks,

·       nvomiting, hallucinations;

·       n“Typhoid” tongue;

·       nhepato-, splenomegaly from the 5-6 day of disease;

·       nskin rash (roseols) on the trunk;

·       ndiarrhea;

·       ntenderness in the right inguinal part of abdomen.

 

Septic form

·        nIncubation period is long (5-10 days).

·       nUsually occurs iewborns, infants with predisposal factors n(hypotrophy, rickets so on).

·       nAcute beginning from fever that becomes hectic.

·       nSeptic focus: meningitis, pneumonia, osteomyelitis, pyelonephritis, nenterocolitis);

·       nhepatosplenomegaly;

·       nhemorrhagic syndrome;

·       ndevelopment of toxic-dystrophic syndrome;

·       nrelapses,

·       nlongitude duration, formation of carrying;

·       nhigh mortality;

·       nantibiotic resistance, nosocomeal strains of Salmonella;

·       ncontact way of spreading.

 

Salmonellosis nFeatures in the newborns

·        nGeneralized form, high lethality.

·        nThe mechanism of transmission is contact-domestic (through nursery nfacilities).

·        nSources are mothers, hospital personnel.

·        nAgent – hospital strains of Salmonella.

·        nHigh resistance to antibiotics

·        nProlonged latent period (5-10 days).

·        nGradual beginning with growth of clinical symptoms.

·        nSevere and prolonged intoxication.

·        nProtracted motion, transmitter, relapses.

·        nToxic-dystrophic syndrome development.

 

 Laboratory tests

·       nComplete blood count with differential

•         nCultures: Isolation of Salmonella from cultures of stool, blood, urine, or nbone marrow is diagnostic. Specimens should be plated lightly onto Endo-Lewin, nPloskirev, McConkey, xylose-lysine-deoxycholate, or eosin-methylene blue agars. n

·       nStool examination: Stool may be hemoccult positive and may be stool npositive for fecal polymorphonuclear cells.

·       nChemistry: Electrolyte tests may reveal metabolic acidosis or nother abnormalities consistent with dehydration.

·       nSerologic tests: (AR, PHAR in dynamics with fourfold title increasing in 10-14 ndays) in children elder than 1 year if fecal culture is negative.

 

Diagnosis example:

·       nSalmonellosis (S. enteritidis), typical local ngastrointestinal form (enterocolitis), moderate degree, acute duration. Complication: nisotonic dehydration, 1st degree.

·       nSalmonellosis (S. typhimurium), typical generalized nseptic form (enterocolitis, meningitis, bilateral pneumonia, left humeral bone nosteomyelitis), severe degree, subacute duration. Complication: nmalnutrition, 2^nd degree.

 

Differential diagnosis should be nperformed with: functional diarrhea, shigellosis, escherichiosis, nklebsiellosis, typhoid fever, and sepsis of different etiology.

 

Treatment: see treatment of Ecsherichiosis below

 

Prophylaxis:

 – nEpidemiological control.

 – Isolation and nsanation of ill person and carriers.

 – nReconvalescent may be discharged from hospital after one negative feces culture n(taken 2 days after stop of antibiotic therapy).

 – nDispensarization of reconvalescents for 3 months.

 – Feces culture nin contacts, carriers.

 – Looking after ncontacts for 7 days without quarantine.

 – Disinfectioin epidemic focus.

 

ESCHERICHIA COLI

 

 ETIOLOGY AND PATHOGENESIS.

 

Five classes of E. coli are recognized as agents associated with npediatric gastroenteritis. Because E. coli organisms are normal fecal flora, ndemonstration of virulence characteristics is the only way by which the ndiarrheagenic E. coli can be defined. The mechanism by which E. coli produces ndiarrhea typically involves adherence of organisms to a glycoprotein or nglycolipid receptor, followed by production of some noxious substance that ninjures gut cells or disturbs gut function. The genes for virulence properties nand for antibiotic resistance are often carried on transferable plasmids or nbacteriophages. The current classification is summarized here; the nclassification changes as new virulence genes are cloned and sequenced.

 

 

Enterotoxigenic E. coli (ETEC). These E. coli serogroups produce a heat-labile nenterotoxin (LT) and/or a heat-stable enterotoxin (ST). LT, a large molecule nconsisting of five receptor-binding subunits and one enzymatically active nsubunit, is structurally, functionally, and immunologically related to cholera ntoxin produced by Vibrio cholerae. ST is a small molecule (18–19 amino acids) nnot related to LT or cholera toxin, although it is related to an enterotoxiproduced by some strains of Yersinia enterocolitica. These toxins do not injure nor kill cells; rather, they disturb cyclic nucleotide–regulated fluid and nelectrolyte absorption. ST stimulates guanylate cyclase, resulting in increased ncyclic GMP, but LT (like cholera toxin) stimulates adenylate cyclase, resulting nin increased cyclic AMP. The ETEC typically also possess fimbria or ncolonization factor antigens (CFAs) that allow them to adhere tightly to nintestinal epithelium, thereby efficiently colonizing and delivering toxin to nthe epithelium. Several CFAs have been recognized as important in effecting the nadherence of ETEC to gut mucosal cells. These CFAs are called CFA I, CFA II, nCFA III, CFA IV, CS7, CS17, 2230, 8786, PCF 09, PCF 0166, PCF 0148, and PCF n0159. After colonization of intestinal epithelium, the ETEC release ST or LT. nThe genes for both colonization factors and enterotoxins are typically encoded non the same plasmid. Of the more than 170 E. coli serogroups only a relatively nsmall number typically are ETEC; these serogroups (06, 08, 015, 020, 025, 027, n063, 078, 080, 085, 0115, 0128ac [but not subgroups 0128ab or 0128ad], 0139, n0148, 0153, 0159, and 0167) are generally different from those found in the nother diarrhea-associated E. coli.

 

Enteroinvasive E. coli (EIEC). These E. coli serogroups behave like shigellae in their capacity to ninvade gut epithelium and produce a dysentery-like illness. The EIEC adhere to nand invade gut epithelium. This Shigella-like behavior occurs because these E. ncoli possess a large virulence plasmid closely related to the plasmid that nendows Shigella with its invasiveness (see Chapter 183). As with Shigella, a nsmall group of polypeptides encoded on these plasmids is critical to the ninvasion of intestinal epithelium. Invasion of epithelium causes cell death and na brisk inflammatory response (clinically recognizable as colitis). The bacterial nproduct that kills intestinal cells is not known. EIEC encompass a small number nof serogroups (028ac, 029, 0124, 0136, 0143, 0144, 0152, 0164, 0167, and some nuntypable strains). These serogroups have lipopolysaccharide (LPS) antigens nrelated to Shigella LPS, and, like shigellae, the organisms are nonmotile (they nlack H or flagellar antigens) and are usually nonlactose fermenters.

 

Enteropathogenic E. coli (EPEC). These diarrheagenic E. coli belong to serogroups (O nantigen or lipopolysaccharide antigen) that have been associated with outbreaks nof infantile gastroenteritis but do not produce conventional enterotoxins or ninvade epithelial cells. Low levels of invasion are observed in some assay nsystems. However, organisms within these serogroups also have been isolated nfrom well individuals. The EPEC adhere to the intestinal mucosa in a ndistinctive way. This pattern of adherence, seen on transmission electromicroscopy, has been called “close attaching and effacing” adherence nor “pedestal-forming” adherence. The lesion consists of loss of nmicrovilli with adherence of bacteria to the epithelial cells, which form a cup nor pedestal in which the bacteria can be seen. Chronic inflammation with nflattened villi may also be seen on small bowel biopsy of affected children. nEPEC cause localized or diffuse adherence based on HEp-2 cell assays. EPEC with nlocalized adherence attach loosely to the microvilli of the epithelial cell nthrough ropelike structures called bundle-forming pili, which are encoded on a nplasmid (EAF plasmid), followed by attachment to the epithelial cell through nthe action of the eae gene (E. coli attaching-effacing). Attachment results iincreased intracellular calcium concentration and dense polymerization of actiat the site of attachment. How these cytoskeletal changes cause diarrhea is not nclear. EPEC, which are diffusely adherent in the HEp-2 cell assay system, nproduce an adhesin involved in diffuse adherence (AIDA-I), which has homology nto a S. flexneri protein associated with intercellular spread (VirG). Some nserogroups are associated with localized adherence and are EAF probe positive n(055, 086, 0111, 0119, 0125, 0126, 0127, 0128ab, and 0142) whereas others are nnonadherent or diffusely adherent to HEp-2 cells and are usually EAF probe nnegative (018, 044, 0112, and 0114).

 

Enterohemorrhagic E. coli (EHEC). These E. coli serogroups produce one or more toxins nthat kill mammalian cells. They have also been called enterocytotoxic E. coli, nShiga-like toxin–producing E. coli (SLT-EC), and verotoxin-producing E. coli n(VTEC). Two major toxins are produced by EHEC. One is essentially identical to nshigatoxin, the protein synthesis–inhibiting exotoxin of Shigella dysenteriae nserotype 1. The second is more distantly related to shigatoxin (only 55% amino nacid homology). The first toxin is called SLT-I (VT-1) and the second SLT-II n(VT-2). Multiple variants of these toxins probably exist. Some EHEC produce nonly SLT-I, others only SLT-II, but most EHEC produce both toxins. These toxins nkill cells by cleaving an adenine residue from ribosomal RNA at the site where nelongation factor 1–dependent attachment of aminoacyl t-RNA occurs; the result nis protein synthesis inhibition and cell death. EHEC adhere to intestinal cells nand produce attaching-effacing lesions that resemble, on electron microscopy, nthose seen with EPEC, although they are more restricted in their distributio(being found primarily in the colon) compared with EPEC (which infest the nentire intestine). The protein product of the eae gene of EHEC is closely nrelated but not identical to intimin, the product of the eae gene of EPEC, and nto invasin, produced by Yersinia pseudotuberculosis. The most common serotypes nare E. coli 0157:H7 and E. coli 026:H11, although a number of other serotypes nhave also been described. E. coli 026:H11 was formerly considered an EPEC.

 

Enteroaggregative E. coli (EAggEC). These E. coli serogroups have the ability to adhere nto HEp-2 cells in tissue culture. They are also referred to as nautoagglutinating and enteroadherent-aggregative E. coli. It is likely that nthis group will be further subdivided, and some of these organisms will be nshown to be nonpathogens. EAggEC attach to HEp-2 cells and colonic epithelial ncells by plasmid-encoded aggregative adherence fimbriae (AAF/I). These organisms ndo not possess the eae genes or produce attaching-effacing lesions. A 4.1-kD nheat-stable toxin EAST 1, related to the heat-stable toxin of ETEC, is encoded non a plasmid. A second toxin is a 120-kD heat-labile protein related to the npore-forming cytolytic toxin family, which contains the Bordetella pertussis nadenylate cyclase hemolysin. This heat-labile toxin increases intracellular nlevels of calcium. The role of these toxins in EAggEC pathogenesis is unknown. nEAggEC appear to colonize the colon.

 

EPIDEMIOLOGY.

 

In the developing world, the various diarrheagenic nserogroups of E. coli cause frequent infections in the first few years of life. nThey occur with increased frequency during the warm months in temperate nclimates and during rainy season months in tropical climates. Most E. coli nstrains (except EHEC and perhaps some EPEC) require a large inoculum of norganisms to induce disease; person-to-person spread is atypical, but foodborne nor waterborne illness is common. Infection is most likely when food-handling or nsewage-disposal practices are suboptimal. Although infection occurs in children in the United States, it is more ofteseen in those who live in or have recently visited the developing world. EHEC nand EPEC organisms are transmitted person to person as well as by food, nsuggesting that ingestion of a lower number of these organisms is sufficient to ncause disease. Poorly cooked hamburger is the most common cause of foodborne noutbreaks of EHEC.

 

PATHOLOGY.

 

ETEC cause little or no structural alterations in the gut mucosa. EIEC ncause colonic lesions like those of bacillary dysentery; ulcerations, nhemorrhage, and infiltration of polymorphonuclear leukocytes with mucosal and nsubmucosal edema are typical. EPEC are associated with blunting of villi, inflammatory nchanges and sloughing of superficial mucosal cells on light microscopy, and nattaching and effacing changes on transmission electron microscopy; these nlesions are found from the duodenum through the colon. EHEC affect the colomost severely. These organisms cause edema, fibrin deposits, hemorrhage in the nsubmucosa, mucosal ulceration, neutrophil infiltration, and microvascular nthrombi. Some of these effects may result from a synergistic action of the nShiga-like toxin and the lipid A portion of the LPS. The pathology of EAggEC nconsists of secretory diarrhea caused by heat-stable or heat-labile toxins.

 

CLINICAL MANIFESTATIONS.

 

As might be expected from the different mechanisms of disease nproduction, the clinical features of E. coli–associated diarrhea vary from ngroup to group. ETEC are a major cause of dehydrating infantile diarrhea in the ndeveloping world. The typical signs and symptoms include explosive watery ndiarrhea, abdominal pain, nausea, vomiting, and little or no fever. Resolutiousually occurs in a matter of days. These infections have an untoward effect oinfant nutritional status.

 

EIEC cause an illness that is indistinguishable from classic bacillary ndysentery. Fever, systemic toxicity, crampy abdominal pain, tenesmus, and nurgency with water or bloody diarrhea are characteristic.

 

EPEC usually are isolated from infants and children in the first few nyears of life who have a nonbloody diarrhea with mucus; fever may occur. Unlike nETEC, EIEC, or EHEC, these organisms often cause a prolonged diarrheal disease.

 

EHEC may cause a nondescript diarrheal illness or an illness ncharacterized by abdominal pain with diarrhea that is initially watery but nwithin a few days becomes grossly bloody (hemorrhagic colitis). Although this npattern resembles that of shigellosis or EIEC disease, it differs in that fever nis an uncommon manifestation. The major risk with EHEC is that approximately n10% of symptomatic infections are complicated by development of nhemolytic-uremic syndrome.

 

EAggEC cause significant fluid loss with dehydration, but vomiting and ngrossly bloody stools are relatively infrequent. These organisms, like the nEPEC, are often associated with prolonged diarrhea.

 

COMPLICATIONS.

 

The major complications are those related to ndehydration and electrolyte loss. Some complications are related to specific npathogens. EPEC and EAEC are likely to cause persistent diarrhea. Infectiowith EHEC is frequently associated with the hemolytic-uremic syndrome.

 

DIAGNOSIS.

 

The clinical features of illness are seldom distinctive enough to allow nconfident diagnosis, and routine laboratory studies are of very limited value. nDiagnosis currently depends heavily on laboratory studies that are not readily navailable to the practitioner. Routine stool cultures from which E. coli norganisms are isolated are interpreted as showing “normal flora.” nBiochemical criteria (e.g., fermentation patterns) are of minimal value. EHEC nserotype O157:H7 is suggested by failure of a suspect colony to ferment nsorbitol on MacConkey sorbitol medium; latex agglutination confirms that the norganism contains O157 LPS. The other EHEC cannot be detected in routine nhospital laboratories, although it is likely that assays based on toxidetection will become available. Culture of duodenal fluid may be helpful ithe diagnosis of EPEC because of their tendency to colonize the small nintestine. This study is generally indicated only in the child with chronic ndiarrhea.

 

Other laboratory data are at best nonspecific indicators of etiology. nFecal leukocyte examination of the stool is usually positive with the EIEC but nnegative with all other diarrheagenic E. coli. Blood counts, especially with nEIEC and EHEC, often show an elevated leukocyte count with a left shift. nElectrolyte changes are nonspecific, reflecting only fluid loss.

 

The traditional methods of identification of these organisms require nanimal or tissue culture models that are unacceptably cumbersome and expensive nfor routine use by hospital laboratories. Some of these organisms, especially nthe EPEC, could theoretically be defined serologically. However, the frequency nof cross reactions, the unavailability of suitable reagents, and the ninfrequency with which the serogroup alone is adequate to define a pathogemake these methods unsuitable. DNA probes for genes encoding the various nvirulence traits hold the greatest promise for the future; they are currently nappropriate only in the research laboratory setting. Probes have been developed nfor ETEC, EIEC, EPEC, EAggEC, and EHEC.

 

Suspected organisms should be forwarded to reference or research nlaboratories for definitive evaluation. Such efforts are seldom necessary, but nthey may be critical for correct diagnosis of the child with severe or nlife-threatening complications or for the occasional outbreak investigation.

TREATMENT.

 

The cornerstone of proper management is related to fluid and electrolyte ntherapy. In general, this therapy should include oral replacement and nmaintenance with rehydrating solutions such as those specified by the World nHealth Organization. Early refeeding with breast milk or dilute formula should nbe encouraged as soon as dehydration is corrected. Prolonged withholding of nfeeding frequently leads to chronic diarrhea and malnutrition.

 

Specific antimicrobial therapy of diarrheagenic E. coli is problematic nbecause of the difficulty of making an accurate diagnosis of these pathogens nand the unpredictability of antibiotic susceptibilities. ETEC respond to nantimicrobial agents such as trimethoprim-sulfamethoxazole (TMP-SMX) when the nE. coli strains are susceptible. However, other than for a child recently nreturning from travel to the developing world, empirical treatment of severe nwatery diarrhea with antibiotics is seldom appropriate. Although treatment of nEPEC infection with TMP-SMX (6.4 mg/kg/24 hr of the trimethoprim component ifour divided doses intravenously or orally for 5 days) is effective in speeding nresolution, the lack of a rapid diagnostic test makes treatment decisions ndifficult. EIEC infections are usually treated prior to the availability of nculture results because the clinician typically suspects shigellosis and begins nempirical therapy. If the organisms are susceptible, TMP-SMX is an appropriate nchoice. The EHEC represent a particularly difficult therapeutic dilemma. The data nsuggest that antibiotic treatment, particularly with sulfa-containing regimens, nmay increase the risk of hemolytic-uremic syndrome; however, the lack of nprospective controlled trials makes these observations questionable. It is too nearly to assess the usefulness of antibiotics in the treatment of EAEC.

 

Antibiotic resistance is often encoded on the same plasmids that carry nvirulence properties and continues to make rational decisions about antibiotic ntherapy difficult. Because emergence of resistance to widely used regimens is ntypical, new antimicrobial agents must continue to be evaluated.

 

Prophylactic antibiotic therapy, although effective in adult travelers, nhas not been studied in children and is not generally recommended. Public nhealth measures, including sewage disposal and food-handling practices, have nmade pathogens that require large inocula to produce illness relatively nuncommon in industrialized countries. Foodborne outbreaks of EHEC are a problem nfor which no adequate solution has been found. During the occasional hospital noutbreak of EPEC disease, attention to enteric isolation precautions and ncohorting may be critical.

 

PREVENTION.

 

In the developing world, preventioof disease caused by diarrheogenic E. coli is probably best done by maintaining nprolonged breast-feeding, paying careful attention to personal hygiene, and nfollowing proper food- and water-handling procedures. Children traveling to these places can be best protected by paying ncareful attention to diet, in particular consuming only processed water, nbottled beverages, breads, fruit juices, fruits that can be peeled, or foods nthat are served steaming hot.

 

Short statement of the material

 Escherichia coli infection is nan acute infectious disease mainly of early age children, caused by different npathogenic strains of Escherichia coli, nand is characterized by localization of pathological process iGastro-intestinal tract with development of toxic and diarrhea syndromes, rarer n- defeat of other organs or generalization of the process up to sepsis or nfailure to thrive development.

 

Etiology: nenterotoxigenic, enteropathogenic, enteroinvasive, enterohemorrhagic nEscherichia Coli. Escherichia coli, a facultative anaerobic ngram-negative bacillus, is a major component of the normal intestinal flora and nubiquitous in the human environment.

They well grow in ordinary  environments, ave a difficult antigestructure. Microbes contain a somatic 0-antigen, flagellate Н-antigen and superficial somatic O-antigen. Distinctions in a 0-antigedevide bacteria into number of 0-groups (serological groups) Different npathogenic effects, caused Е. coli, are conditioned by producted nenthero-, cyto- and verotoxins, and also by the adhesive and invasive activity nof bacteria.

Nowadays several categories of Е. coli that cause diarrhea are known: enterotoxigenic, nenteropathogenic, enteroinvasive, enterohemorrhagic, enteroadgesive n(enteroadherrent).

 

Epidemiology:

·       nSource of infection – ill person or carrier;

·       nWay of spreading – orally – Fecal (by water, milk, food); nby direct contact;

·       Susceptible organism: nchildren, especially before 2 years of old.

 

Pathogenesis:

1.     nInvasioof bacteria in GIT

2.     nReproduction of bacteria, selection of toxins

·        nEPE on the enterocytes surface

·        nETE on the enterocytes microvilli surface

·        nEIE, EHE in the coloepithelial cells

3.     nLocal inflammatory process (EPE, EIE), toxemia (EPE, EIE)

4.     nViolation of the surface and membrane digestion, absorption (EPE, EIE), hypersecretion, nviolation of water, and nelectrolytes absorption (ETE)

5.     nDiarrhea

6.     nIn severe cases: bacteremia (sepsis)

 

 

Clinical features

Enteropathogenic diarrhea is usually self – limited in older childreand adults. Nausea, vomiting, cramps and voluminous diarrhea without blood and nmucus are common. Diarrhea lasting 2 weeks or longer in infants.

Enterotoxigenic diarrhea includes nausea, vomiting, cramps and frequent watery stools. nThere no fecal leukocytes in the stool. This syndrome is usually self – limited nand lasts about 5 days.

Enteroinvasive strains are associated with a clinical picture comparable to those nobserved with shigella. Nausea and vomiting frequently accompany abdominal npain. The diarrhea is less in volume than that seen with ETEC strains and ncontains mucus and blood. Fever, headache, and myalgia are common.

Enterohemorrhagic escherichiosis is associated with severe abdominal cramps, low – grade nfever, grossly bloody stools, nausea and vomiting. This organism also has beefound in association with hemolytic uremic syndrome (HUS).

5. Enteroadgesive n(enteroadherrent) Е. coli  were primary selected i1985. They have not invasive activity, does not form cytotoxins and does not nhave a plasmide adhesive factor. The category of EAEC while is not represented nby any serological group.

 

Enteropathogenic E.coli infection criteria

·        nLatent period 5-8 days, iew-born, weakened – 1-2 days.

·        nAccordingly: gradual or acute illness beginning.

·        nThe watery massive yellow-orange feces with the too-bit of mucus the greecolor admixtures sometimes (photo), up to 10-15 times per day.

·        nVomits, regurgitation from the disease beginning.

·        nGradual growth of symptoms up to 5-7 days.

·        nsubfebril temperature.

·        ntoxicosis with dehydration of 2-3 stage

·        nCredible acute kidney or adrenal insufficiency, DIC-syndrome, ninfectious-toxic shock.

Massive yellow-orange feces

 

Enteropathogenic E.coli infection peculiarities iewborns

·        nhospital infection caused by resistant cultures.

·        ninfection generalization with development of sepsis.

·        nFrequent damage of brain-membranes, with development of the remaining nphenomena

·        nRarely occurs diarrhea.

·        nHigh lethality.

 

Enteroinvasive nE.coli infection criteria

·        nLatent period is 1-3 days.

·        nAcute beginning with the severe toxic syndrome, fever (1-3 days), rarer nvomits.

·        nDiarrhea in the 1st day of the disease: feces with the admixtures of mucus nand green, blood 3-5 times per day.

·        nAbdomen is tender by the colon way, infiltrated sigmoid colon, tenesms are nabsent.

·        nRapid recovery, normalization of feces in 3-5 days.

 

Enteroinvasive E.coli infectiopeculiarities in infants

·        nGradual beginning.

·        nsevere toxic syndrome increases during 5-7 days.

·        nenteritis, enterocolitic character of stools.

·        nDehydration develops often.

·        nmoderate or severe disease duration.

·        nThe fever lasts for 5-7 days, sometimes up to 2 weeks.

·        nNormalization of feces delays to 1-2 weeks.

 

Enterotoxigenic nE.coli infection criteria

·        nLatent period from few hours up to 1-2 days.

·        nAcute beginning from the repeated vomiting, watery diarrhea.

·        nIntoxication is absent; body temperature is normal or subfebrile.

·        ngrumbling along thin intestine during palpation.

·        nFeces 15-20 time per days, watery without pathological admixtures, of nrice-water character.

·        nDevelopment of severe dehydration

·        nDuration of the ndisease is not more than 5-10 days.

 

Enterohemorrhagic nЕ. coli  infection criteria

·        nLatent period is 1-7 days, rarer n9-10 days.

·        nA disease has moderate or severe course.

·        nAcute beginning.

·        nCrampy pain in epigastrium or in all abdomenm.

·        nDevelopment of secretory diarrhea in the first ndays.

·        nFuture signs of hemocolitis with frequent defecation, in severe cases up to 20-30 times per day.

·        nAbsence of febrile fever.

·        nComplications:

o   hemolytic-uremic syndrome at n2-7%, at the end of the first – beginning of the second week of disease

o   acute nkidney insufficiency,

o   hemolytic anaemia,

o   thrombocytopenia,

o   Cramps nand other neurological disorders (up to blindness).

·        nLaboratory features – in fecal test ndissociation between large number of erythrocytes and less amount of leucocytes.

·        nLetality is  n1-2%. In HUS n- 5-10%.

 

Enteroadgesive (enteroadherrent) nescherichiosis is not good studied

 

Laboratory test

– The examination of the stool n(koprogram): ninflammatory changes, intestinal enzymopathy

– A culture of the stools

– Serologic reaction (IHAR idynamics with fourfold title increasing in 10-14 days) in children elder than 1 nyear if fecal culture is negative.

Diarrhea Classification

 

n

Diarrhea’s type	Diagnostic’s criteria	Severity	Mai clinical syndrome
Invasive (bacterial)	Liquid excrements with pathological admixture (mucus, verdure, blood)	Mild   Moderate   Severe	·         Primary toxicosis (neurotoxicosis) ·         Toxicosis with dehydration I, II and III degree ·         Infectious-toxic shock ·         Toxic-dystrophic syndrome ·         Hemolytic-uremic syndrome
Secretor (watery)	Excrements are liquid, massive, without pathological admixtures
Prolonged	Long-lasting diarrhea (more 2 weeks) with pathological admixtures
Chronic enzyme-associated	Watery, don’t fermentated excrements without signs of the inflammation in koprogram, associated with food ingredients

 

Criteria of the Diarrhea Severity

 

Differential diagnosis should be performed among acute non infectiodiarrheas, salmonellosis, shigellosis, staphylococcal diarrhea, viral diarrhea, nand cholera.

Diagnosis example:

E.coli infection (caused by Enterotoxigenic strain), ntypical form, severe degree.

Complication: hypertonic dehydration, 3^rd ndegree.

 

Treatment

Therapy of an acute intestinal infectiofor children has 4 constituents: diet, rehydration therapy, antibacterial ntherapy and auxiliary therapy (enerosorption, probiotics).

Dehydration: Dehydratiomeans the body does not have enough fluids to function at an optimal level. nDehydration can be caused by fluid loss (through vomiting, diarrhea or nexcessive urination), inadequate intake, or a combination of both. The most ncommon cause of dehydration in infants and children is acute gastroenteritis, nwith its associated vomiting and diarrhea.

 

 

 

 

1. nRehydration therapy

Timely and adequate rehydration therapy is na near-term and most essential link in treatment of an acute intestinal ninfection, both secretory and invasive. Early application of adequate nrehydration therapy is the main condition of rapid and successful treatment. nRehydration therapy is done according the severity of child’s dehydratio(Table 1).

Table 1

 Clinical signs of dehydration severity n(present 2 or more from the noted signs)

n

Sign		Mild (1st  degree)	Moderate (2nd  degree)	Severe (3rd  degree)
Loss of body weight	Children aged before 3 yrs	3-5%	6-9%	10% and more
	Children aged 3-14 years	To 3%	3-6%	6-9%
General condition		Disturbance	Disturbance or somnolence	Languor, somnolence
Thirst		Drinks voraciously	Drinks voraciously	Does not drink
Anterior fontanel		Not changed	Slightly sunke	Sunken
Eyeballs		Not changed	Soft	Sunken expressively
Mucus membranes of the mouth		Moist	Slightly dry	Dry
Skin fold		Disappears at once	Disappears slowly	It can disappear slowly (> 2 sec.) or does not disappear at all
Arterial pressure		Norm	Hypotonia	Severe hypotonia
Urination		Normal	Decreased	Considerably decreased to 10 ml/kg day

 

Oral rehydration (by mouth)

 

 

 

Oral rehydration is most effective, wheis performed from the first hours of the disease. Oral rehydration must be the nfirst aid at home when the disease begins. It doesn’t have any ncontraindications.

In accordance with recommendations of WHO noptimum composition of solutions for oral rehydration is:

sodium – 60 mmol/l;

potassium – 20 mmol/l;

bicarbonates – 10 mmol/l;

glucose – 110 mmol/l;

osmolarity is – 250 mosmol/l.

Content of sodium and potassium isolutions for oral rehydration must correspond their average losses at an acute nintestinal infection. The concentration of glucose in them must help water nresorptioot only in an intestine but also in kidneys. Because high nosmolarity it is not recommended to give fruit juices, sweet drinks (Coca-cola, nand others like that) during the oral rehydration.

The method of oral rehydration have to nstart immediately, because dehydration begins after the first liquid, watery nemptying, yet long before appearance of clinical signs of dehydration. Valuable nrehydration therapy is performed in 2 stages.

The 1^st stage is rehydration therapy which is carried nout during 4-6 hours for proceeding of the lost liquid volume. During the mild ndehydration – 30-50 ml/kg, at moderate degree – 60-100 ml/kg. 

Table 2

A calculation of oral rehydratiosolutions volume

n

Body weight in kg	An amount of solution for 4-6 hours (ml)
	mild dehydration	moderate dehydration
5	250	400
10	500	800
15	750	1 200
20	1 000	1 600
25	1 250	2 000

Speed of liquid introduction through a mouth is 5 ml/kg/hour.

Criteria of the 1^st stage nefficiency: (are estimated nin 4-6 hours)

·        ndisappearance nof thirst,

·        nimprovement nof the tissues turgor,

·        nmoistening nof mucus membranes,

·        nincrease nof diuresis,

·        ndisappearance nof microcirculation violation signs.

Choice of subsequent tactic:

1.     if signs of dehydration have disappeared – ncontinue the 2^nd stage of rehydration therapy.

2.     the signs of dehydration have diminished, nbut still are present – it is needed to continue to give solution through a nmouth during the following 4-6 hours in a previous volume.

3.     the signs of dehydration have increased – nparenteral rehydration should be start.

The 2^nd stage is supporting therapy, which is done depend the nlosses of liquid, which proceed, with vomit and emptying.

Method of the 2^nd stage:

Supporting oral rehydration means that to nthe child for every following 6 hours is entered so many rehydration solution, nas he has lost during previous 6 hours.

Oriented volume of solution for supporting nrehydration for children before 2 yrs is 50-100 ml, children elder than 2 yrs – n100-200 ml or 10 ml/kg of solution after every emptying. On this stage oral nrehydration solution is possible to alternate with fruit or vegetable sugar nfree decoctions,  or tea, especially ngreen. At vomit rehydration therapy is continued after 10-minute pauses. In the nhospital in case the child refuse to drink or at presence of vomit tube nrehydration should be done. Nasogastric tube rehydration can be done ncontinuously with a help of the system for intravenous infusion, with maximal nspeed 10 ml/min.

 

Parenteral rehydration

 

At acute intestinal infections, which are naccompanied by the 3^rd stage of dehydration, with multiple vomits, nanorexia, waiver of drink, oral rehydration is combined with the parenteral nrehydration.

Solutions for parenteral rehydration:

·        nRinger’s nlactat,

·        nRinger’s nacetate,

·        nIsotonic nglucose solution,

·        nIsotonic nsodium chloride solution.

To the children aged before 3 months is nbetter not to use 0.9% NaCl, so as it has relatively plenty of chlorine (154 nmmol/l) and relatively high osmolarity (308 mosmol/l). Monotherapy by glucose nsolution is not effective. Composition and correlation of solutions depends from nthe type of dehydration.

To the children of early age it is nnecessary to eliminate solutions, which contain plenty of sodium, chlorine, nglucose (solutions of Disol, Trisol, Quartasol, nAcesol, Laktasol, Chlosol and others like that) because of possible nhypernatremia and intracellular edema development.

At presence of some ions deficit in blood plasma (sodium, potassium, nmagnesium, calcium) or acid-base balance changes it is need to correct them.

 To perform nparenterally rehydration it is necessary to define:

·        nDay’s nrequirement of liquid and electrolytes.

·        nType nand degree of dehydration.

·        nLevel nof liquid deficit.

·        nCurrent nlosses of liquid.

Principle of volume calculation for the ninfusion therapy:

Day’s volume of liquid in case of ndehydration consists of:

a)     deficit of liquid before the treatment (a nloss of body weight during the disease),

b)    physiologic liquid’s requirement,

c)     current pathological losses.

a) For the calculation of physiologic liquid’s nrequirement it is possible nto recommend the method of Holiday Segar that is used the most widely in the nworld (Table 3).

Table 3

Determination of physiology requirements nis in a liquid on the method of Holiday Segar

n

Weight	Day’s necessity
1-10 kg	100 ml/kg
10,1-20 kg	1000 ml + 50 ml/kg on every kilogram over 10 kg
more than 20 kg	1500 ml + 20 ml/kg on every kilogram over 20 kg

b) The calculation of liquid’s deficit depends on the degree of dehydration is ndetermined by the clinical signs or weight lost %:

1% of dehydration = 10 ml/kg

1 kg of weight loss = 1 liter

Consequently, at a 1^st degree nof dehydration (5% weight loss) day’s deficit of liquid is 50 ml/kg/day; at 2^nd ndegree (10% weight loss) – 100 ml/kg/day.

The expected volume of liquid is entered during a day.

A liquid is entered in peripheral veins nduring 4-8 hours, repeating infusion if necessary in 12 hours. According to it na patient gets intravenously 1/6 of day’s volume during 4 hours, or 1/3 – nduring 8 hours et cetera). A remained volume is entered through a mouth! n

Liquid’s requirement per hour of the ninfusion is more physiologic:

New-born:

1-st day of life – 2 ml/kg/hour;

2-nd day of life – 3 ml/kg/hour;

3-rd day of life – 4 ml/kg/hour;

Elder children:

weight up to 10 kg – 4 ml/kg/hour;

weight from 10 to 20 kg – 40 ml/hour + 2 ml for nevery kg over 10 kg; n

weight more than 20 kg – 60 ml/hour + 1 ml oevery kg of weight of body over 20kg

A calculation of salts requirements:

Special attention should be paid to the ncorrection of sodium and potassium deficit, losses of which can be considerable. It is necessary nto remember, that sodium a child will nget with crystalloid solutions which are entered in certain correlations with nglucose depending type and severity of dehydration. If laboratory control is nnot done, potassium is entered naccording the physiologic necessity (1-2 mmol/kg/day). Maximal daily amount nmust not exceed 3-4 mmol/kg/day. Medicine, mainly potassium chloride, is entered intravenously droplet on 5% glucose nsolution. Nowadays insulin adding to these solutions is not recommended. A nconcentration of potassium chloride in prepared solution must not exceed n0.3-0.5% (maximally 6 ml 7.5% KCl on 100 ml of glucose). 1 ml of 7.5% KCl nsolution contains 1 mmol of K⁺. Before entering potassium it is nnecessary to restore urination, as anuria or severe oliguria is ncontra-indication for intravenous potassium infusion. Blood potassium in plasma nas 6.5 mmol/l is threatened for the life, in concentration 7 mmol/l nhemodialysis is needed.

Determination of salts deficit is based olaboratory information.

Acute intestinal infections in childremainly are accompanied by isotonic type of dehydration, that’s why determinatioof blood electrolytes to all children with diarrhea is not necessary. nDetermination of Na+ and K+ is necessary at 3^rd degree of ndehydration and for children with 2^nd degree of dehydration, iwhich general condition severity does not correspond the diarhea severity, nanamnes is complicated, a rapid effect from the rehydration therapy is absent.

A calculation of sodium and potassium ndeficit is done by the following formula:

Ion deficit = (normal ION concentration – npatient’s ION concentration) х  M х К, where

M is weight of the patient

K is a coefficient of intracellular liquid nvolume.

K = 0.3 – before 1 year

K = 0.2 – after 1 year and for adults.

Than it is necessary to define the amount nof sodium and potassium in solutions which are entered, volume and correlations nof which are already expected. A content of these ions in solutions which are noften used, are represented in a table. After the urgent intravenous nrehydration it is necessary to check up the level of sodium and potassium in plasma. n

Table 4

Content of ions in crystalloid solutions

n

Content of the ion in mmol/l Osmolarity
SOLUTION	Na+	K+	Cl-	Ca++	Acetate (bicarbonate)	mosmol/l
Physiological solution	154	–	154	–	–	308
Ringer’s solutio	147	4	155	2	–	308
Ringer’s lactat	130	4	109	1,5	28 (bicarbonate)	273
4% NaHCO3	500	–	–	–	500 (bicarbonate)	1000
5% dextrose solution on 0,45% solutio of NaCl	77	–	–	–	–	252

Taking into account importance of nmagnesium ions for the child’s organism, and also that the magnesium losses go nparallell with potassium losses on the first stage of rehydration therapy a 25% nsolution of magnesium is rotined in the dose of 0,5-0,75 mmol/kg (1 ml of nsolution = 1 mmol of magnesium).

In children with a severe malnutritiodaily necessity in potassium and magnesium is enlarged (up to 3-4 mmol npotassium and 0.4-0.6 mmol magnesium).

c) Current pathological losses are determined by weighing of dry and wet ndiapers, determining the amount of the vomit or with a help of calculations:

10 ml/kg/day on every degree of ntemperature over 37.0 ^oC;

20 ml/kg/day  in case of vomit;

20-40 ml/kg/day in case of intestinal nparesis;

25-75 ml/kg/day in case of diarhea;

30 ml/kg/day for perspiration.

Control of correct rehydration therapy is nfrequency of pulse, frequency of breathing, body weight and diuresis dynamics.

Rehydration therapy depending the type of dehydration

It is necessary to take into account the ntype of dehydration to choice solutions and their correlations for the rehydratiotherapy. There are 3 types of dehydration: isotonic, hypertonic (water ndeficient) and hypotonic  (salt ndeficient) (Table 5).

Table 5

Signs of different forms of dehydration

n

Index	Isotonic type of dehydration	Hypotonic type of dehydration	Hypertonic type of dehydration
Breathing	No peculiarities	Hypoventilation	Hyperventilation
Blood pressure	Decreased or increased	Low	Remains normal for a long time
Temperature of the body	Subfebrile	Normal, tendency to the hypothermia	Febrile
Skin	Cold, dry, elasticity is decreased	Cold with a cyanotic tint, elasticity is decreased	Elasticity is stored, warm
Nervous system	Malaise	Excitation, possible cramps	Disturbance, sleeplessness
Diuresis	Diminished	Diminished	For long time it remains normal
Specific gravity of urine	Norm or insignificantly encreased	Decreased to 1010 or low	Encreased to 1035 and more
Osmolality of plasma	Norm	Decreased	Encreased
A level of electrolytes in the blood	Normal	Low	Encreased

 

Main Differential Signs of the Dehydration Types

 

 

At isotonic rehydration (Na 130-150 mmol/l) develops as a result nof equal losses of salts and water; it is the most often type of dehydration ichildren with an acute intestinal infection. In the first days (in case of nmicrocirculation maintenance) rehydration is performed by 5% glucose solutioin combination with 0.9% sodium chloride or Ringer’s lactate solution icorrelation (2:1) with parallel correction of electrolytes.

Next days of rehydration therapy nglucose-saline solutions in a volume which provides the physiology liquid’s nrequirement of organism, remnant volume for the compensation of dehydration, ncurrent pathological losses, correction of plasma electrolytes are performed.

Hypertonic dehydration (Na > 150 mmol/l) develops as a result nof liquid losses predominance above salts loses, inadequate rapid injection of nsalts with small amount of water.

Rehydration therapy should be done by a 5% nglucose solution in combination with 0.9% sodium chloride solution icorrelation (3:1).

During the rehydration therapy for npatients with hypertonic dehydration it is need to take into account daily nsodium requirements (2-3 mmol/kg). Thus should be taken into account sodium isolutions for infusion.

If the level of sodium is 140-150 mmol/l, nthen amount of sodium should be  ndecreased 2 times from physiology necessities, and at the increase of it nmore than 150 mmol/l solutions which contain sodium are eliminated, except  colloid ones.

It is necessary to investigate a potassium nlevel and correct it if it is needed.

To prevent cerebral edema control of nplasma osmolarity and body weight is needed. On this stage a speed of infusiois 15-20 drops per hour.

Hypotonic dehydration (Na < 130 mmol/l) develops as a result nof salts losses predominance above liquid loses, excessive injection of water nwith small amount of salts. It developes in case of intestinal infections which nare accompanied by frequent vomit, or during oral rehydration by solutions with nsmall amount of salts.

Rehydration therapy is done by 5% glucose nsolution in combination with 0.9% sodium chloride in correlation (1:1).

If the level of sodium is less than 129 nmmol/l it is needed to correct it (calculate it by formula described before). nDuring the correction of sodium hypertyonic solutions are avoided. Their ninfusion can result in acute intracellular dehydration, first of all cerebral. nExcept this, anaphylactic reactions can develop. The correction of sodium is ndone by 0.9% NaCl, Ringer’s lactat.

If it is impossible to investigate blood nelectrolytes, glucose-saline solutions are infused in correlation 1:1.

By the WHO recommendations (if the fast nrehydration is necessary in case of laboratory control absence) the volume and nspeed of 0.9% NaCl, Ringer’s lactat infusion on the first rehydration stage nshould be the following (Table 6):

Table 6

Speed of infusion during the rehydratiotherapy

n

Age of the child	Speed of infusion	Speed of infusion
Before 12 months	30 ml/kg for the first 1 hour	70 ml/kg for the next 5 hours
Elder than 12 months	30 ml/kg for the first 30 minutes	70 ml/kg for the next 2.5 hours

 

The condition of the child is checked up neach 15-30 minutes to normal pulse filling on a radial artery. If the conditioof child does not get better, speed of infusion should be increased. After that nthe condition of the child is estimated every hour (abdominal skin fold, consciousness, npossibility to drink).

After all volume is entered the child’s ncondition should be estimated again:

·        nif nthe signs of severe dehydration still present – repeat infusion again according nthe table 6.

·        nif nthe child’s condition gets better, but there are signs of moderate dehydratio– continue oral rtehyderation according the table n2. If a child is breast fed, it is recommended to continue feeding; numbers nof feeding should be increased.

·        nif nsigns of dehydration are absent, then the duration of feeding should be nincreased. At the same time at presence of diarrhea for supporting nrehydration 50-100 ml of oral rehydration solution is given to the childreaged before 2 yrs, 100-200 ml to the children elder than 2 yrs or 10 ml/kg  additionally after every emptying (up to 1/3 nexpected volume for oral rehydration). Children on the artificial feeding are nfed by the same chart, by lactose free formulas.

Supervision after children with a severe nmalnutrition and dehydration during the rehydration therapy should be done each n30 minutes during the first 2 hours, and then every hour next 4-10 hours. At nsigns of hyperhydratation (increase of pulse frequency on 15 per minute, nbreathing frequency on 5 per minute) rehydration should be stopped. Thaestimate the child’s condition through an hour.

During parenteral rehydration for such nchildren, and also for children with pneumonia, toxic encephalopathy, speed of nliquid infusion must not exceed 15 ml/kg/hour. At these states daily body nweight gain in the first 3 days must not exceed 1-3%.

In case if dehydration is absent and ninfectious toxic shock is developed reanimation measures according the protocol nshould be done.

 

1.     Antibacterial ntherapy

 

   

 

Antibacterial therapy at invasive diarrhea nis given to:

1.     Children with severe and moderate forms of ndisease.

2.     Children aged before 3 months independent nof the disease severity.

3.     Children with the immune deficiency, nHIV-infected children,  children, that nreceive immune suppressive therapy (chemical, ray), long corticosteroid ntherapy, children with hemolytic anemia,  nhemoglobinopathies independent of age and the disease severity.

4.     Children with hemocolitis independent of nage and the disease severity.

5.     Children with the secondary bacterial ncomplications in all age groups.

Antibacterial therapy at secretory ndiarrhea is given to:

1.     Children with severe and moderate forms naged before 6 months.

2.     Children with the immune deficiency, nHIV-infected children, children, that receive immune suppressive therapy n(chemical, ray), long corticosteroid therapy, children with hemolytic anemia, nhemoglobinopathies.

3.     Cholera, parasitogenic diarrhea nindependent of age and the disease severity.

4.     Children with the secondary bacterial ncomplications in all age groups.

Antibacterial therapy is not indicated to:

1.     nChildrewith mild, effaced and moderate forms of infections, except for those which are nlisted above.

2.     nChildrewith bacterial transmitting of any etiology (transitory, postinfectional).

3.     nChildrewith alimentary dysfunction, as a result of an acute intestinal infectio(intestine dysbiosis, lactase insufficiency, celiac syndrome, secondary nenzymopathy etc.).

 

Antibacterial therapy if the etiology of nan acute intestinal infection is known

Table 8

Antibacterial preparations which are nrecommended for treatment of an acute intestinal infections for children at the nknown exciter of illness

n

Acute intestinal infection etiology	Starting preparation	Preparatio of reserve
Shigella	Ciprofloxacin* Nifuroxazid	Ceftriaxo Trimetoprim/sulfamethoxazolum  Azythromycin
Salmonella	Ceftriaxon Cefotaxim Nifuroxazid	Trimetoprim/sulfamethoxazolum  Ciprofloxacin Ampycillin** Chlorampheniсol** Azythromycin
Entherotoxigenic E.coli	Trimetoprim/sulfamethoxazolum Doxycycli (to the children elder than 8 years)	Aminoglycosides** Nifuroxazid
Entheroinvasive E.coli***	Nifuroxazid Ciprofloxaci	Trimetoprim/sulfamethoxazolum Ceftriaxon Azythromycin
Kampylobacter	Erythromycin Ciprofloxaci	Aminoglycosides** Amoxacyllin/сlavulanat Carbapenems (imipenem, carbapenem)
Yersinia enterocolitica	Ceftriaxon Cefotaksim Ciprofloxacin	Trimetoprim/sulfamethoxazolum Doxycycli (to the children elder than 8 years) Aminoglycosides** Chloramphenicol**
Vibrio сholerae	Trimetoprim/sulfamethoxazolum Doxycycli (to the children elder than 8 years)	Nifuroxazid Furazolidonum Ciprofloxaci
Clostridium deficile	Methronidazol	Ornidazol Vancomycinum (through a mouth)
Giardia Lamblia	Methronidazol Furazolidonum	Ornidazol
Amoeba hystolitica	Methronidazol Intetrix	Thynidazol

—————

* – other fluorquinolons, except Cyprofloxacin, are not recommended to nthe children.

** – only in case of sensitivity to the nantibiotic.

*** – in case of Entherohemorrhagic E.coli antibiotics ncan provoke hemolytic-uremic syndrome.

Table 9

A dosage of antibacterial preparations for nchildren in case of an acute intestinal infections

n

Preparatio	Dose	Number of receptions per day
Nifuroxazid  (through a mouth)	Suspension: children aged 2-6 months 2,5-5 ml (110-220 mg) 6 month to 6 years – 5 ml (220 mg) elder than 6 years – 5 ml (220 mg) Pills: children aged before 6 yrs – 0,2 g elder than 6 years – 0,2 g Course of treatment 5-7 days	2 times per day 3 times per day 4 times per day   3 times per day 4 times per day
Trimetoprim/sulfamethoxazolum (through a mouth)	children aged 2-5 years – 200 mg of sulfamethoxazolum/ 40 mg of trimetoprim children aged 5-12 years – 400 mg of sulfamethoxazolum/ 80 mg of trimetoprim children elder than 12 years – 800 mg of sulfamethoxazolum/ 160 mg of trimetoprim Course of treatment 3-5 days	2 times per day
Ciprofloxacin (through a mouth)	15 mg/kg (maximal dose is 500 mg) Course of treatment 3 days	2 times per day
Ceftriaxo (IM, IV)	50-100 mg/kg daily dose (a maximal dose is 1-2 g) Course of treatment 2-5 days	onse a day
Cefotaxim (IM, IV)	50-100 mg/kg daily dose (a maximal dose is 1-2 g) Course of treatment 3-5 days	2 times per day
Azythromyci (through a mouth)	6-20 mg/kg Course of treatment 1-5 days	once a day 1-1,5 hours before the meal
Erythromycin (through a mouth)	children aged 1-3 years daily dose 0,4 g children aged 4-6 years – 0,5-0,75 g children aged 6-8 years – 0,75 g children aged 6-8 years – 1 g Course of treatment 7-10 days	4 times per day 1-1,5 hours before the meal
Amoxacyllin/сlavulanat	Through a mouth (suspension) children aged 1-2 years 78 mg children aged 2-7 years 156 mg childre aged 7-12 years 312 mg IV – 30 mg/kg Course of treatment 5-10 days	3 times per day 3-4 times per day
Aminoglycosides (IM, IV)	Gentamycin 2-3 mg/kg/day Amikacin 15 mg/kg/day Netylmycin: children before 1 year 7,5-9 mg/kg children elder 1 year – 6-7,5 mg/kg Course of treatment 5-7 days	2 times per day 2-3 times per day   3 times per day   3 times per day
Furazolidonum (through a mouth)	8-10 mg/kg daily dose Course of treatment 10 days	4 times per day
Doxycyclin (through a mouth) to children elder tha 8 yrs	children aged 9-12 years daily dose – the first day 4 mg/kg, then 2 mg/kg Course of treatment 7-10 days	2 times per day
Vancomycinum (through a mouth)	40 mg/kg daily dose Course of treatment 7-10 days	3-4 times per day
Chloramfenicolum	Through a mouth children before 3 yrs – 10-15 mg/kg children aged 4-8 years – 0,15-0,2 g children elder than 8 yrs – 0,2-0,3 g IM children before 1 year daily dose 25-30 mg/kg children elder 1 year daily dose – 50 mg/kg Course of treatment 5-10 days	3-4 times per day 30 min before the meal         2-3 injections
Methronidazolum (through a mouth)	Amebiasis: children aged 2-5 years – 0,25 g children aged 6-10 years – 0,375g children aged 11-15 years – 0,5g Course of treatment 10 days Giardiasis: children aged 2-5 years – 0,2 g children aged 6-10 years – 0,3 g children aged 11-15 years – 0,4g Course of treatment 5-7 days	once a day during a meal
Ornidazolum (through a mouth)	Giardiasis – 40 mg/kg Course of treatment 1-3 days Amebiasis – 25-30 mg/kg Course of treatment 1-3 days	once a day
Albendazolum (through a mouth)	Giardiasis children elder 2 yrs 400 mg Course of treatment 5 days	once a day
Tinidazolum (through a mouth)	Amebiasis – 30 mg/kg Course of treatment 3 days	once a day
Intetrix (through a mouth)	children after 12 years – 1 capsule Course of treatment 10 days	4 times per day
Carbapenems	Imipenem/cilastatin (IM, IV) children with body weight less than 40 kg – 15 mg/kg (maximal daily dose is 2 g) children with body weight more than 40 kg – 500-1000 mg maximal daily dose is 2 g) Meropenem (IV) 10-12 mg/kg children with body weight more than 50 kg – 500 mg Course of treatment according the evidences	4 times per day   2-4 times per day     3 times per day

 

It is recommended to prescribe for empiric ntherapy of an acute intestinal infection (in case of the unknown etiology): nNifuroxazid, Trimetoprim/sulfamethoxazolum, Cefotaxim, Ceftriaxon, nCiprofloxacin.

At a necessity of empiric antibacterial ntherapy of secretory diarrhea cefalosporins of 3-4 generations are used.

Diet

An important moment in organization of nsick children feeding is a waiver of water-tea pauses, as it is well-provethat even at the severe forms of diarrhea the digestive function of greater npart of intestine is saved, and pauses will decelerate reparation processes, nreduce intestine tolerance to the meal, and considerably weaken immunity of norganism. A volume and composition of meal depends from child’s age, weight and nseverity of diarrhea, character of previous diseases. Rational feeding is nimportant for rapid renewal of the intestinal function.

In the acute period of gastroenteritis nit is recommended to diminish daily volume of meal on 1/2-1/3, in the acute nperiod of colitis – on 1/2-1/4. Possibly increase of feedings up to 8-10 times nper day for infants, especially at urges on vomit. In this time most physiology nis consider early, but gradual renewal of feed. Proceeding in high-quality and nquantitative composition of meal is characteristic for this age of child, ncarried out in short period after the rehydration and disappearance of ndehydration (4-5 days). In this period it is recommended diet for every day. nThe fat, fried, smoked food and others like that are eliminated from a ratioin elder children.

If a child is breast fed, it is nrecommended to continue feeding. Children on the artificial feeding are fed by nthe same chart, by lactose free formulas.

Products with high amount of lactose nshould be eliminated (milk formulas, milk, fruit juices). This will decrease nsecretory diarrhea duration Children on the artificial feeding are fed by the nsame chart, by lactose free formulas. Lactose free diet should last nindividually from 1-4 weeks to 1.5-2 months. Porridges prepared on water are nrecommended, meet puree should be given earlier. Diary milk formulas after 8 nmonth are recommended.

 

   

 Soya containing formulas are not recommended nbecause intestine excessive sensitivity to soy proteins in diarrhea. It is nrisky for protein entheropathy development. Apple prepared in the oven, nbananas, apple and carrot puree contain large amount of pectins are recommended nin case of colitis.

 

Auxiliary therapy of an acute intestinal ninfection 

Probiotics can be applied as independent etiotropic ntreatment (in cases when antibacterial therapy is not indicated) or as additional nmedicine during antibacterial therapy. Probiotics, which contain lacto-, bifid nbacteria and propineb bacteria. Self eliminate probiotics (contaisaccharomycets) or probiotics which contain lacto bacteria are used in invasive ndiarrhea on a background of antibacterial therapy. The last ones are stable to nantibiotics.

 

 

 

To the children with the immunodeficiency, nthose which are treated  in the intensive ncare units probiotics aren’t appointed.

The course of therapy lasts for 5-10 days. n

 

Enterosorbents

Enterosorbents are able to fix on their nsurface hundreds of millions bacteria. Fixed microbes are ruined and hatch from na sick organism. Together with the bacteria enerosorbents fix on their surface nrotaviruses from the intestine cavity. Except for the infectants enerosorptiodestroy the toxins of microbes and products of their metabolism. They transform ntoxic matters in less toxic.

The most perspective at treatment of aacute intestinal infection in children are “white”, alumsilicate nenerosorbents. Unlike coal sorbents they do not require introduction of high ndose of preparation for achievement of therapeutic effect. Also coal sorbents nget to the submucous layer of the intestine and can damage it.

 

 

In obedience to WHO recommendations (2006) nin auxiliary therapy of an acute intestinal infection are recommended npreparations of zinc (to the children before 6 months – 10 mg per day, childreelder than 6 months – 20 mg per day during 10-14 days. 

 

Primary nProphylaxis:

•         nSanitary disposal of human feces

•         nProtection, purification and boiling of water

•         nCorrect preparing and saving of foodstuffs 

•         nPerson hygiene

 

Secondary Prophylaxis

Ill nPerson

•         nIsolation period –until  the stool nculture taken 3 days after stopping etiologic treatment is negative

•         nCurrent and terminal disinfection

•         nMedical supervision for 1-3 mo

Contact nchildren   

Stool culture

 

Prophylaxis of acute bowel diseases:

 – Epidemiological control.

 – Isolation and sanation of ill person and ncarriers.

 – Reconvalescent may be discharged from nhospital after one negative feces culture (taken 2 days after stop of nantibiotic therapy).

 – Dispensarisation of reconvalescents for 3 nmonths.

 – Feces culture in contacts, carriers.

 – Looking after contacts for 7 days without nquarantine.

 – Disinfection in epidemic focus.

 

 

ROTAVIRUS INFECTION

 

Rotavirus infection is an acute contagious ndisease of men and animals that is caused by Rotavirus, is passed by a nfecal-oral mechanism, and is characterized by the damage of gastro-intestinal ntract (as gastroenteritis).

 

Etiology:  an agent is Rotavirus from nRheoviridae.

 

Epidemiology:

·                     nthe source of infection is patient or virus ncarrier;

·                     nthe mechanism of transmission  is nfecal-oral (through the infected water, food, direct contact);

·                     nreceptivity is high in case of decreased immunity.

 

Pathogenesis

1. Virus invasion to the thiintestine epithelial cells (enterocytes).

2. Replication of virus and ndestruction of enterocytes.

3. Increased growth of nimmature cells.

4. Enzyme insufficiency.

5. Violation of digestion and nsuction, accumulation of disaccharides.

6. Overabundance of liquid and nelectrolytes in the intestine.

7. Diarrhea.

 

Diagnostic criteria

1.     Latent period is 1-4 days.

2.     DVF-syndrome (diarrhea, vomiting, fever):

ü diarrhea (gastroenteritis, enterocolitis) during 3-6 ndays stools are «sprinkling», colorless, watery;

ü Vomits (precedes or appears together with diarrhea) nduring 1-3 days;

ü Fever (moderate) – 2-4 days.

 

Features of Rotavirus infection iew-born

ü Often is hospital infection.

ü Acute beginning with the refuse of breast feeding, nvomits, diarrhea, development of the dehydration ІІ-ІІІ stage

ü Possible gradual beginning with growth of degree of ndehydration.

Often is lethal.

 

Confirmation of diagnosis

ü Virology by immune-electronic nmicroscopy, IEА, diffuses precipitation in a gael.

ü Serological – NR, CBR, DHAR.

ü In koprogram – lymphocytes, nimpaired enzyme intestinal function.

 

Diagnosis example:

Rota-viral infection typical form, severe degree.

Complication: hypotonic dehydration, 2^nd degree.

A ndifferential diagnosis is performed with ncholera, salmonellosis, enterotoxigenic escherichiosis; acute intestinal ninfections caused by relative pathogenic bacteria.

 

Treatment: see treatment of Ecsherichiosis

 

Primary Prophylaxis:

ü Sanitary disposal of human feces

ü Protection, purification and boiling of water

ü Correct preparing and saving of foodstuffs 

ü Person hygiene

 

Secondary Prophylaxis

Ill nPerson

ü Isolation period –until  the stool culture taken 3 days after stopping ntreatment is negative

ü Current and terminal ndisinfection

ü Medical supervision for 1-3 nmo

Contact nchildren   

Stool culture

 

For the specific prophylaxis of rotavirus ninfection there are two vaccines . Both accepted oral and contain a weak living nvirus of 1-4^th types.

 

 

 

YERSINIOSIS

 

Yersiniosis is an acute infectious disease caused by Yersinia enterocolitica is ncharacterized by the symptoms of intoxication, GIT, liver, joints, other organs nand systems defeat.

Etiology: Yersinia nenterocolitica, gram-negative bacillus

 

Epidemiology:

·                          nSource of infection– ill human and bacterial carrier n(transmitter), wild and home animals (rats, dogs, foxes, cats and other);

·                          nMechanism of transmission – fecally-oral, contact-domestic

·                          nWay of transmission – alimentary (with infected food, nprodacts), contact;

·                          nSusceptible organism – all age groups, among children – npreschoolers.

 

Pathogenesis:

1.                       nEntering the bacilli to gastrointestinal tract. An entrance gate nis a thin bowel (terminal department and appendix)

2.                       nEnteral phase: invasion of nbacteria in enterocytes, development of local inflammation, diarrhea, nenterotoxin secretion.

3.                       nRegional nlymphadenitis (regional infection).

4.                       nGeneralization (bacteriemia, toxemia) in severe cases.

5.                       nParenhymatous phase: hematogenous distribution of nbacteria with forming of the secondary focus (lungs, liver, spleen, bones).

6.                       nImmunological nresponse, recovering from disease.

7.                       nMay be nsecondary bacteriemia (exacerbations nand relapses), because of possible persistansy in lymph nodes.

 

Diagnostic ncriteria:

ü Latent period 3-20 ndays.

ü Acute (72.2 %) or ngradual (27.8 %) beginning.

ü Polymorphism of nclinical picture.

ü The symptoms of nthe Gastro-intestinal tract defeat come forward on a foreground (nausea, nstomach-aches, tenderness and grumbling in the ileocecal area, diarrhea as igastroenteritis, enteritis),

ü Moderately nexpressed toxic syndrome, prolonged fever for 1-2 wks.

ü Rashes for 6-14 ndays: maculous or maculous-papulous as in measles, nodular erythema, in folds, nround joints, lateral surfaces of trunk, chest;

ü hyperemia of face, nhands and feet (“hood”, “gloves”,”socks” nsymptom)

ü “strawberry” tongue

ü arthralgias, rarer narthritis,

ü hepatomegaly, nsometimes parenchymal hepatitis with icterus

ü mild respirator nsyndrome (pharyngitis, rhinitis)

ü Rarely nmyocarditis, pericarditis,

ü Splenomegaly (to n20 %),

ü Lymphoproliferative nsyndrome (increase of neck, inguinal and other lymph nodes) is insignificantly nexpressed,

ü Toxic damage of nkidneys (at severe degree)

 

Classification

Form:

·                     ntypical

o           ngastro-interstinal,

o           npseudo appendicitis,

o           nseptic (generalized),

o           nhepatic,

o           nnodular erythema,

o           njoint form

·                     natypical (effaced, subclinical)                

Severity:

·                     nmild

·                     nmoderate

·                     nsevere

Course (duration):    n

·   acute:

ü  smooth

ü  relapsed (not smooth, uneven)

·   nchronic

 

Diagnosis example:

·   nYersiniosis, typical joint form, moderate nseverity, chronic relapsed  duration

·   Yersiniosis, typical ngastro-intestinal form, mild severity, acute duration

 

Yersiniosis npeculiarities in infants:

ü more frequent is ngastro-intestinal that generalized (septic) form;

ü high fever, nprotracted, expressed intoxication;

ü dehydratiodevelopment;

ü from the first ndays there is a noticeable lymphoproliferative syndrome, splenomegaly;

ü frequent nrespirator syndrome;

ü seldom develops nhepatitis;

·                          narthritis nis absent.

 

Laboratory finding  n

·              nComplete nblood analysis: leucocytosis, nneutrophilosis with left shift, eosynophylia, ERS is enlarged.

·              nUrinalysis: nslight proteinuria, leucocituria, casts uin small amount in case of toxic damage of nkidneys.

·              nBacteriological n– Yersinia enterocolitica may be found ifeces, urine, blood, pus, lymph nodes and pharyngeal mucus.

·              nCoprogram: Increasing nof red blood sells and leukocytes, mucus.

·              nSerologically – increasing of special antibodies 4 ntimes and more in 2-4 wks in paired sera (IHAR 1:200, AR 1:40 – 1:160).

 

Differential diagnosis with: acute intestinal infections, nby viral hepatitis, scarlatina, measles, enterovirus infection, sepsis, pseudotuberculosis, ntyphoid diseases.

 

Yersiniosis Differential diagnosis nwith Pseudotuberculosis

 

n

Sign	Yersiniosis	Pseudotuberculosis
beginning	Often subacute	Acute
intoxication	moderate, increase	Severe from the beginning
exanthema	Not often (41 %)	Very often (84 %)
“gloves”,  “socks” sign	22 %	48 %
conjunctivitis, scleritis	12,6 %	30,1 %
Arthralgia	20,9 %	40,1 %
Abdominal pain	often	Not often
enteritis, enterocolitis	A leading symptom	Secondary symptom
Neck lymph nodes enlargement	often	rare
Bacteriology	Yersinia enterocolitica	Yersinia pseudotuberculosis

 

Treatment

Regimen

ü    nhalf-bed regimen in mild cases,

ü bed regimen in moderate cases

ü straight bed regimen in severe cases

Diet:

ü Icteric (jaundice) form – N 5

ü Abdominal (intestinal) form – N 4

ü Other forms – N 15

 

1.                nEtiological:

·        nimild cases it’s not used;

·        nimoderate and severe cases – by chloramphenicol 10-20 mg/kg 4 times per day norally during 6-9 days. If not effective – alternative antibiotics: ncefalosporins of the 3^rd-4^th generation 100-150 mg/kg, naminoglycosides of the 3^rd generation.

·        nCourse nof treatment is 7-10 days.

2.                       nPathogenetical: n

·  disintoxication oral to all patient and in case of mild ndehydration, or parenteral: Rheosorbilact, 0.9% NaCl, 5% glucose (moderate and nsevere dehydration);

·  Sorbents: enterosgel 0.5-1 g/kg, polysorb (Silix) n100-200 mg/kg per day in 3 doses for 5-7 days

·  antihistamines: claritin, cetirizin, suprastin, pipolphen 1-3 mg/kg per day,

·  corticosteroids 1-3 mg/kg with a short ncourse (in severe cases, in case of myocarditis),

·  Normalisatioof the intestinal flora: nlinex, bifi-form, acidophilus 1-2 caps 2-3 times per day not less than 2 wks;

·  antipyretics: paracethamol 10 mg/kg not more than 5 ntimes per day,

·  NSAIDs nin case of arthritis, carditis, nodular nerythema (ibuprophen 20 mg/kg per day, aspirin 50-75 mg/kg per day, voltare2-3 mg/kg per day, indomethacin 2-3 mg/kg per day (in average doses).

 

Prophylaxis:

1.    Isolation and treatment of ill person, ndisinfection.

2.           nCorrect nstorage of products, bacteriological control, deratization.

3.           nExaminatioof contact persons from the epidemic focus for 3 wks (measuring the ntemperature, skin, throat and feces inspection), 1 bacteriological ninvestigation of feces.

 

Key worlds nand phrases: Yersiniosis, polymorphism of complaints, rashes, ncatharral syndrome, abdominal syndrome, dyspepsia, hepatosplenomegaly, nlymphadenopathy, arthritis, hepatitis, myocarditis, nephritis, bronchitis and npneumonia, raspberry tongue, ”gloves”, ”socks”, ”hood”- symptoms.

 

 

VIRAL nHEPATITIS

 

Acute hepatite can occur or be mimicked in a variety nof infectious diseases (cytomegalovirus, Epstein-Barr virus, toxoplasmosis, nrubella, scarlet fever, secondary syphilis, salmonellosis, amoebic liver nabscess and malaria) in which the liver is not the primary target of infection. nViral infection is the most frequent cause of hepatite in patients, younger nthan 14 years old. The prophylaxis and treatment of hepatite depends on the nidentity of the viral etiology.

 

HEPATITIS nA THROUGH E

 

DEFINITION. Viral hepatitis is a major health problem in developing and developed ncountries. Recent advances in the field of molecular biology have aided nidentification and understanding of the pathogenesis of the five viruses that nare now known to cause hepatitis as their primary disease manifestation. These nhepatotropic viruses are designated hepatitis A, B, C, D, and E. Many other nviruses can cause hepatitis as part of their clinical spectrum including herpes nsimplex, cytomegalovirus, Epstein-Barr, varicella, human immunodeficiency, nadenovirus enteroviruses, and arboviruses. Hepatic involvement with these nviruses is usually only one component of a multisystem disease.

 

The five hepatitis viruses are a heterogenous group of nviruses that cause similar acute clinical illness. Hepatitis A, C, D, and E are nRNA viruses representing four different families, and hepatitis B is a DNA nvirus.

 

Hepatitis A and E are not known to cause chronic nillness, whereas hepatitis B, C, and D cause important morbidity and mortality nthrough chronic infections. In the United States, hepatitis A virus n(HAV) appears to cause most cases of hepatitis in children. Hepatitis B nprobably accounts for about one third of cases in children, whereas hepatitis C nis found in approximately 20%. Hepatitis D occurs in only a small percentage of nchildren who must also have active hepatitis B virus (HBV) infection. Hepatitis nE has not been reported in children who have lived and traveled only in the United States.

 

HEPATITIS nA

 

ETIOLOGY. HAV is a 27-nm diameter, RNA-containing virus that is a member of the nPicornavirus family. It was isolated originally from stools of infected npatients. Laboratory strains of HAV have been propagated in tissue culture. nAcute infection is diagnosed by detecting immunoglobulin (Ig)M (IgM) antibodies n(anti-HAV) by radioimmunoassay or, rarely, by identifying viral particles istool.

 

EPIDEMIOLOGY. HAV infections occur throughout the world but are most common ideveloping countries, where the prevalence rate approaches 100% in children by nthe age of 5 yr. In the United States, approximately 30% of the adult npopulation have evidence for previous HAV infection; the rates of infection are nsimilar in the 1st, 2nd, and 3rd decades of life. Hepatitis A causes only acute nhepatitis. The illness is much more likely to be symptomatic in adults; most ninfections in children younger than 5 yr are asymptomatic or have mild, nnonspecific manifestations. The transmission of HAV is almost always by nperson-to-person contact. Spread is predominantly by the fecal-oral route; npercutaneous transmission is a rare occurrence and maternal-neonatal ntransmission is not recognized as an epidemiologic entity. HAV infection during npregnancy or at the time of delivery does not appear to result in complications nof pregnancy or clinical disease in the newborn. The infectivity of humasaliva, urine, and semen is unknown. In the United States, increased risk of ninfection is found in households, day-care centers, household contacts of nchildren in day-care centers, and homosexual populations. Common-source foodborne nand waterborne outbreaks have occurred, including several resulting from ncontaminated shellfish. Fecal excretion of the virus occurs late in the nincubation period, reaches its peak just before the onset of symptoms, and is nminimal in the week after the onset of jaundice. The mean incubation period for nHAV is about 4 wk.

 

PATHOLOGY.

 

The acute response of the liver to HAV is similar to nthat of the other four hepatitis viruses. The entire liver is involved with nnecrosis, most marked in the centrilobular areas, and increased cellularity, nwhich is predominant in the portal areas. The lobular architecture remains nintact, although balloon degeneration and necrosis of parenchymal cells occur ninitially. Fatty change is rare. A diffuse mononuclear cell inflammatory nreaction causes expansion in the portal tracts; bile duct proliferation is ncommon, but bile duct damage is not often found. Diffuse Kupffer cell nhyperplasia is present in the sinusoids along with infiltration of npolymorphonuclear leukocytes and eosinophils. Neonates respond to hepatic ninjury by forming giant cells. In fulminant hepatitis, total destruction of the nparenchyma occurs, leaving only connective tissue septa. By 3 months after the nonset of acute hepatitis resulting from HAV, the liver usually is normal nmorphologically.

Hepatocyte

 

Other organ systems can be affected during HAV ninfection. Regional lymph nodes and the spleen may be enlarged. The bone marrow nmay be moderately hypoplastic, and aplastic anemia has been reported. nSmall-intestine tissue may show changes in villous structure, and ulceration of nthe gastrointestinal tract can occur, especially in fatal cases. Acute npancreatitis and myocarditis have been reported rarely, and renal, joint, and nskin involvement may result from circulating immune complexes.

 

PATHOGENESIS.

 

Injury in acute hepatitis is caused by several nmechanisms. The initial injury in hepatitis A is thought to be cytopathic. nRegardless of the mechanism of initial injury to the liver, damage from the nfive hepatitis viruses is evident in three main ways. The first is a reflectioof injury to the hepatocytes, which release alanine aminotransferase (ALT, nformerly serum glutamate pyruvate transaminase) and aspartate aminotransferase n(AST, formerly serum glutamic-oxaloacetic transaminase) into the bloodstream. nThe ALT is more specific to the liver than the AST, which also can be elevated nafter injury to erythrocytes, skeletal muscle, or myocardial cells. The height nof elevation does not correlate with the extent of hepatocellular necrosis and nhas little prognostic value. In some cases, a falling aminotransferase level nmay predict a poor outcome if the decline occurs in conjunction with a rising nbilirubin and prolonged prothrombin time (PT). This combination of findings indicates nthat massive hepatic injury has occurred, resulting in few functioning nhepatocytes. Another enzyme, lactate dehydrogenase is even less specific to nliver than AST and usually is not helpful in evaluating liver injury. Viral nhepatitis is also associated with cholestatic jaundice, in which both direct nand indirect bilirubin levels are elevated. Jaundice results from obstructioof biliary flow and damage to hepatocytes. Elevations of serum alkaline nphosphatase, 5-nucleotidase, g-glutamyl transpeptidase, and urobilinogen all ncan reflect injury to the biliary system. Abnormal protein synthesis by nhepatocytes is reflected by increased PT. Because of the short half-life of nthese proteins, the PT is a sensitive indicator of damage to the liver. Serum nalbumin is another liver-manufactured serum protein, but its longer half-life nlimits its relevance for monitoring acute liver injury. Cholestasis results ia decreased intestinal bile acid pool and decreased absorption of fat-soluble nvitamins. Hepatic injury also may result in changes in carbohydrate, ammonia, nand drug metabolism.

 

CLINICAL MANIFESTATIONS.

 

The onset of HAV infection usually is abrupt and is naccompanied by systemic complaints of fever, malaise, nausea, emesis, anorexia, nand abdominal discomfort. This prodrome may be mild and often goes unnoticed iinfants and preschool-age children. Diarrhea often occurs in children, but nconstipation is more common in adults. Jaundice may be so subtle in young nchildren that it can be detected only by laboratory tests. When they occur, njaundice and dark urine usually develop after the systemic symptoms. Icontrast to HAV infections in children, most HAV infections in adults are nsymptomatic and can be severe. Symptoms of HAV infection include right upper nquadrant pain, dark-colored urine, and jaundice. The duration of symptoms nusually is less than 1 mo, and appetite, exercise tolerance, and a feeling of nwell-being gradually return. Almost all patients with HAV infection will nrecover completely, but a relapsing course can occur for several months. nFulminant hepatitis leading to death is rare, and chronic infection does not noccur.

 

DIAGNOSIS. The diagnosis of HAV infection should be considered when a history of njaundice exists in family contacts, friends, schoolmates, day-care playmates, nor school personnel or if the child or family has traveled to an endemic area. nThe diagnosis is made by serologic criteria; liver biopsies rarely are nperformed. Anti-HAV is detected at the onset of symptoms of acute hepatitis A nand persists for life. The acute infection is diagnosed by the presence of IgM nanti-HAV, which can be detected for 3–12 mo; thereafter, IgG anti-HAV is found. nThe virus is excreted in stools from 2 wk before to 1 wk after the onset of nillness. Rises are almost universally found in ALT, AST, bilirubin, alkaline nphosphatase 5´-nucleotidase, and g-glutamyl transpeptidase and do not nhelp to differentiate the cause. The PT should always be measured in a child nwith hepatitis to help assess the extent of liver injury; prolongation is a nserious sign mandating hospitalization.

 

DIFFERENTIAL DIAGNOSIS.

 

 The possible ncauses of hepatitis vary somewhat by age. Physiologic jaundice, hemolytic ndisease, and sepsis ieonates usually are distinguished easily from nhepatitis. After the immediate newborn period, infection remains an important ncause of hyperbilirubinemia, but metabolic and anatomic causes (biliary atresia nand choledochal cysts) also must be considered. The introduction of pigmented nvegetables into the infant’s diet may result in carotenemia, which may be nmistaken for jaundice.

 

In later infancy and childhood, hemolytic-uremic nsyndrome may be mistaken initially for hepatitis. Reye and Reye-like syndromes npresent in a similar fashion to acute fulminating hepatitis. Jaundice also may noccur with malaria, leptospirosis, and brucellosis and with severe infection iolder children, particularly in those with malignant disorders or with nimmunodeficiency. Gallstones may obstruct biliary drainage and cause jaundice nin adolescents as well as in children with chronic hemolytic processes. nHepatitis may be the initial presentation of Wilson ndisease, cystic fibrosis, a-1-antitrypsin deficiency, and Jamaican vomiting nsickness. The liver may be involved in collagen vascular diseases including nsystemic lupus erythematosus.

 

Medications, including acetaminophen overdose, nvalproic acid, and various hepatotoxins, can be associated with a nhepatitis-like picture. Drugs well tolerated in healthy children may cause nhepatic dysfunction in children with certain illnesses.

 

COMPLICATIONS.

 

Children almost always recover from HAV infection. nRarely, fulminant hepatitis can occur, in which a progressive rise in serum nbilirubin is accompanied by an initial rise in aminotransferases followed by a nfall to normal or low values. Hepatic synthetic function decreases and the PT nbecomes prolonged, often accompanied by bleeding. The serum albumin falls, ncausing edema and ascites. The ammonia usually rises and the sensorium becomes naltered, progressing from drowsiness to stupor and then deep coma. Progressioto end-stage disease and death can occur in less than 1 wk, or can develop more ninsidiously.

 

PREVENTION. The recent development of highly immunogenic and safe formalin-killed nvaccines marks a major advance in the prevention of hepatitis A. Vaccination of nyoung children in endemic areas is unnecessary because the disease is almost nalways asymptomatic or mild and confers lifelong immunity. In industrialized ncountries, vaccination of high-risk children may be of benefit because these nchildren can become carriers of the disease and could infect older siblings and nparents who are at greater risk for more severe disease. Vaccination will be of nspecial value to unexposed travelers from developed countries when they travel nto hepatitis A–endemic areas.

 

Enteric precautions should be observed for nhospitalized, infected patients who are incontinent of stool or who are idiapers. Careful hand washing is necessary, particularly after changing diapers nand before preparing or serving food. Persons infected with HAV are contagious nfor about 1 wk after onset of jaundice. There is no need to isolate older, ncontinent children, but their stools and fecally contaminated materials should nbe treated with precautions, and strict hand washing should be practiced.

 

Standard pooled Ig is effective in modifying clinical nmanifestations of HAV infection. The prophylactic value is greatest when giveearly in the incubation period and declines thereafter. Ig is recommended for nall susceptible individuals traveling to developing countries. Unimmunized nhousehold contacts should receive a single intramuscular dose of Ig as soon as npossible after exposure. This is effective in preventing clinical hepatitis, nalthough infection may still occur. Giving Ig more than 2 wk after exposure is nnot indicated.

 

Ig is not recommended routinely for sporadic, nnonhousehold exposures (e.g., protection of hospital personnel or schoolmates). nMass administration of Ig to schoolchildren has been used when epidemics have beeschool centered. When HAV occurs in a child-care center with childreot yet ntoilet trained, Ig should be administered to all children and personnel. It nalso is advisable to administer Ig to family members of children in diapers.

 

 HEPATITIS B

 

 ETIOLOGY.

HBV is a 42-nm diameter member of the hepadnavirus nfamily, a noncytopathogenic, hepatotropic group of DNA viruses. HBV has a ncircular, partially double-stranded DNA genome composed of approximately 3,200 nnucleotides. Four genes have been identified: the S, C, X, and P genes. The nsurface of the virus includes two particles designated hepatitis B surface nantigen (HBsAg): a 22-nm diameter spherical particle and a 22-nm wide tubular nparticle with a variable length of up to 200 nm. The inner portion of the nvirion contains hepatitis B core antigen (HBcAg) and a nonstructural antigecalled hepatitis B e antigen (HBeAg), a nonparticulate–soluble antigen derived nfrom HBcAg by proteolytic self-cleavage. Replication of HBV occurs npredominantly in the liver but also occurs in lymphocytes, spleen, kidney, and npancreas.

 

 

EPIDEMIOLOGY. Worldwide, the areas of highest prevalence of HBV infection are nsubSaharan Africa, China, nparts of the middle East, the Amazon basin, and the Pacific nIslands. In the United States, nthe Eskimo population in Alaska has the nhighest prevalence rate. An estimated 300,000 new cases of HBV infection occur nin the United States neach year, with the 20- to 39-yr age group at greatest risk. The number of new ncases in children is low but is difficult to estimate because the majority of ninfections in children are asymptomatic. The risk of chronic infection is nrelated inversely to age; although less than 10% of infections occur ichildren, these infections account for 20–30% of all chronic cases.

 

The most important risk factor for acquisition of nhepatitis B infection in children is perinatal exposure to an HBsAg-positive nmother. The risk of transmission is greatest if the mother also is HBeAg npositive; 70–90% of their infants become chronically infected if untreated. nDuring the neonatal period, hepatitis B antigen is present in the blood of 2.5% nof infants born to affected mothers, indicating that intrauterine infectiooccurred. In most cases, antigenemia appears later, suggesting that transmissiooccurred at the time of delivery; virus contained in amniotic fluid or imaternal feces or blood may be the source. Although most infants born to ninfected mothers become antigenemic from 2–5 mo of age, some infants of nHBsAg-positive mothers are not affected until later ages.

 

HBsAg has been demonstrated inconsistently in milk of ninfected mothers. Breast-feeding of unimmunized infants by infected mothers ndoes not appear to confer a greater risk of hepatitis on offspring than does nartificial feeding despite the possibility that cracked nipples may result ithe ingestion of contaminated maternal blood by the nursing infant.

 

Other important risk factors for HBV infection ichildren include intravenous acquisition by drugs or blood products, sexual ncontact, institutional care, and contact with carriers. Chronic HBV infection, nwhich is defined as being HBsAg positive for 6 or more mo, is associated with nchronic liver disease and with primary hepatocellular carcinoma, the most nimportant cause of cancer-related death in the Orient.

 

HBV is present in high concentrations in blood, serum, nand serous exudates and in moderate concentrations in saliva, vaginal fluid, nand semen. For these reasons, efficient transmission occurs through blood nexposure and sexual contact. The incubation period ranges from 45–160 days, nwith a mean of about 100 days.

 

PATHOLOGY.

 

The acute response of the liver to HBV is the same as nthat for all the hepatitis viruses. Persistence of histologic changes ipatients with hepatitis B, C, or D indicates development of chronic liver ndisease.

 

PATHOGENESIS.

 

Hepatitis B, unlike the other hepatitis viruses, is a nnoncytopathic virus that probably causes injury by immune-mediated mechanisms. nThe first step in the process of acute hepatitis is infection of hepatocytes by nHBV, resulting in the appearance of viral antigens on the cell surface. The nmost important of these viral antigens may be the nucleocapsid antigens, HBcAg nand HBeAg, a cleavage product of HBcAg. These antigens, in combination with class nI major histocompatibility (MHC) proteins, make the cell a target for cytotoxic nT-cell lysis.

 

The mechanism for development of chronic hepatitis is nless well understood. To permit hepatocytes to continue to be infected, the ncore protein or MHC class I protein may not be recognized, the cytotoxic nlymphocytes may not be activated, or some other as yet unknown mechanism may ninterfere with destruction of hepatocytes. For cell-to-cell infection to ncontinue, some virus-containing hepatocytes must survive.

 

Immune-mediated mechanisms also are involved in the nextrahepatic conditions that can be associated with HBV infections. Circulating nimmune complexes containing HBsAg can occur in patients who experience nassociated polyarteritis, glomerulonephritis, polymyalgia rheumatica, mixed ncryoglobulinemia, and the Guillain-Barré syndrome.

 

Mutations of HBV are more common than for the usual nDNA viruses, and a series of mutant strains have been recognized. The most nimportant is one that results in failure to express HBeAg and has beeassociated with development of severe hepatitis and perhaps more severe nexacerbations of chronic HBV infection.

 

CLINICAL MANIFESTATIONS.

 

Many cases of HBV infection are asymptomatic, as nevidenced by the high carriage rate of serum markers in persons who have no nhistory of acute hepatitis. The usual acute, symptomatic episode is similar to nHAV and hepatitis C virus (HCV) infections but may be more severe and is more nlikely to include involvement of skin and joints. The first clinical evidence nof HBV infection is elevation of ALT, which begins to rise just before the ndevelopment of lethargy, anorexia, and malaise, about 6–7 wk after exposure. nThe illness may be preceded in a few children by a serum sickness–like prodrome nincluding arthralgia or skin lesions, including urticarial, purpuric, macular, nor maculopapular rashes. Papular acrodermatitis, the Gianotti-Crosti syndrome, nalso may occur. Other extrahepatic conditions associated with HBV infections ninclude polyarteritis, glomerulonephritis, and aplastic anemia. Jaundice, which nis present in about 25% of infected individuals, usually begins about 8 wk nafter exposure and lasts for about 4 wk. In the usual course of resolving HBV ninfection, symptoms are present for 6–8 wk. The percentage of people in whom nclinical evidence of hepatitis develops is higher for hepatitis B than for nhepatitis A, and the rate of fulminant hepatitis also is greater. Chronic nhepatitis also occurs, and the chronic active form can result in cirrhosis and nhepatocellular carcinoma.

 

On physical examination, skin and mucous membranes are nicteric, especially the sclera and the mucosa under the tongue. The liver nusually is enlarged and tender to palpation. When the liver is not palpable nbelow the costal margin, tenderness can be demonstrated by striking the rib ncage over the liver gently with a closed fist. Splenomegaly and lymphadenopathy nare common.

 

DIAGNOSIS.

 

 The serologic npattern for HBV is more complex than for HAV and differs depending on whether nthe disease is acute, subclinical, or chronic.

 

Routine screening for hepatitis B requires assay of at nleast two serologic markers. HBsAg is the first serologic marker of infectioto appear and is found in almost all infected persons; its rise coincides nclosely with the onset of symptoms. HBeAg is often present during the acute nphase and indicates a highly infectious state. Because HBsAg levels fall before nthe end of symptoms, IgM antibody to hepatitis B core antigen (IgM anti-HBcAg) nalso is required because it rises early after infection and persists for many nmonths before being replaced by IgG anti-HBcAg, which persists for years. IgM nanti-HBcAg usually is not present in perinatal HBV infections. Anti-HBcAg is nthe most valuable single serologic marker of acute HBV infection because it is npresent almost as early as HBsAg and continues to be present later in the ncourse of the disease when HBsAg has disappeared. Only anti-HBsAg is present ipersons immunized with hepatitis B vaccine, whereas anti-HBsAg and anti-HBcAg nare detected in persons with resolved infection.

 

COMPLICATIONS.

 

Acute fulminant hepatitis occurs more frequently with nHBV than with the other hepatitis viruses, and the risk of fulminant hepatitis nis further increased when there is coinfection or superinfection with HDV. nMortality from fulminant hepatitis is greater than 30%. Liver transplantatiois the only effective intervention; supportive care aimed at sustaining the npatient while providing the time needed for regeneration of hepatic cells is nthe only other option.

 

HBV infections also can result in chronic hepatitis, nwhich can lead to cirrhosis and primary hepatocellular carcinoma. Interferoalpha-2b is available for treatment of chronic hepatitis B in persons 18 years nof age or older with compensated liver disease and HBV replication. Membranous nglomerulonephritis with deposition of complement and HBeAg in glomerular ncapillaries is a rare complication of HBV infection.

 

PREVENTION.

 

Universal immunization of infants with hepatitis B nvaccine is now recommended by the American nAcademy of Pediatrics (AAP) and the U.S. Public Health Service because nselective strategies failed to prevent the substantial morbidity and mortality nassociated with HBV infection. The neonatal period has been targeted because nmore than 90% of infants who acquire the infection perinatally will become nchronic carriers. The risk of acquiring the chronic carrier state diminishes nwith age; 50% of older children and 10% of adults who become infected will nbecome chronic carriers. Two recombinant DNA vaccines are available in the United States; nboth have proven to be highly immunogenic in children. The original nplasma-derived vaccine is equally immunogenic but is no longer manufactured ithe United States.

 

Infants born to HBsAg-positive women should receive nvaccine at birth, 1 mo, and 6 mo of age. The first dose should be accompanied nby administration of 0.5 mL of hepatitis B immunoglobulin (HBIG) as soon after ndelivery as possible because the effectiveness decreases rapidly with increased ntime after birth. The AAP recommends that infants born to HBsAg-negative womereceive the first dose of vaccine at birth, the second at 1–2 mo of age, and nthe third between 6 and 18 mo of age.

 

The methods of prevention of hepatitis B infectiodepend on the conditions under which the person is exposed to hepatitis B, and nthe dose is dependent on the age of the person.

 

 

HEPATITIS C

 

ETIOLOGY. HCV is now recognized as the cause of almost all of the parenterally nacquired cases of what was previously known as non-A, non-B hepatitis. The nvirus has not been isolated but has been cloned using recombinant DNA ntechnology. Molecular biologic analysis has demonstrated that HCV is a nsingle-strand RNA virus that has been classified as a separate genus within the nFlaviviridae family. HCV is an enveloped virus, 50–60 nm in size, that is ntransmitted mainly by blood or blood products, intravenous drug use, and sexual ncontact. Chronic liver disease is common in infected individuals.

 

EPIDEMIOLOGY.

The most important risk factors for HCV transmissioin the United States nare the use of intravenous drugs (40%), transfusions (10%), and occupational nand sexual exposure (10%). The remaining 40% of patients have no knowassociated risk factors. Perinatal transmission has been described but is nuncommon except when the mother is HIV infected or has a high titer of HCV RNA. nAlthough HCV testing has made blood transfusions much safer, testing of blood nmay result in only a modest decline in HCV cases because transfusions account nfor only a small percentage of HCV infections. Large population serosurveys ithe United States nindicate that approximately 1% of the adult population has evidence for nprevious HCV infection. The incubation period is 7–9 wk (range, 2–24 wk).

 

PATHOLOGY. The pattern of acute injury is similar to that of the other hepatitis nviruses. In chronic cases, lymphoid aggregates or follicles in portal tracts nare seen either alone or as part of a general inflammatory infiltration of the ntracts.

 

PATHOGENESIS. HCV appears to cause injury primarily by cytopathic mechanisms, but nimmune-mediated injury also may occur. The cytopathic component appears to be nmild, because the acute form is typically the least severe of all hepatitis nvirus infections; HCV rarely is fulminant.

 

CLINICAL MANIFESTATIONS.

The clinical pattern of the acute infection is usually nsimilar to that of the other hepatitis viruses. HCV is the most likely nhepatitis virus to cause chronic infection; about two thirds of npost-transfusion infections and about one third of sporadic, community-acquired ncases will become chronic. Typically, a fluctuating pattern of aminotransferase nelevations occurs in about 80% of those in whom chronic HCV develops. Although nchronic elevations of aminotransferase levels are common, chronic HCV will nprogress to cirrhosis in only about half of the patients, or about 25% of all nthose initially infected. Primary hepatocellular carcinoma can develop ipatients with cirrhosis, but HCV is less effective than HBV in causing primary nhepatocellular carcinoma. The hepatocellular carcinoma associated with HCV nprobably results from chronic inflammation and necrosis rather than aoncogenic effect of the virus.

Hepatitis C in the newborn

 

DIAGNOSIS.

The clinically available serologic assays for HCV are nbased on development of antibodies to HCV antigens because no detectable nantigens have been found in blood. The assays are used mainly for detection of nchronic hepatitis C because they remaiegative for at least 1–3 mo after the nclinical onset of illness. The second-generation assays are the current nstandard and test for three of the five known antigenic epitopes. They have nimproved sensitivity over the first-generation tests but still have a 10% nfalse-negative rate. Assays for viral RNA (polymerase chain reaction [PCR], isitu hybridization) are costly, time consuming, and available only in research nsituations.

 

COMPLICATIONS.

The risk of fulminant hepatitis is low with HCV, but nthe risk for chronic hepatitis is the highest among the hepatitis viruses. The nusual chronic course is mild even when cirrhosis develops; long-term follow-up nindicates that the overall mortality of persons with transfusion-acquired HCV nis no different from that of noninfected controls. Interferon alpha-2b is navailable for treatment of chronic hepatitis in persons 18 yr of age or older nwith compensated liver disease who have a history of blood or blood product nexposure or who are HCV antibody positive or both.

 

PREVENTION.

There is no vaccine available, and none may be ndeveloped because animal studies suggest that HCV infection does not lead to nprotective immunity; the same individual can be infected multiple times with nthe same virus. Ig has not proven to be of benefit. Ig manufactured in the United States ndoes not contain antibodies to HCV because blood and plasma donors are screened nfor anti-HCV, and exclusion of the HCV positive persons from the donor pool is nrecommended.

 

 

HEPATITIS nD

 

 ETIOLOGY.

Hepatitis D virus (HDV), the smallest known animal nvirus, is considered defective because it cannot produce infection without a nconcurrent HBV infection. The 36-nm diameter virus is incapable of making its nown coat protein; its outer coat is composed of excess HBsAg from HBV. The ninner core of the virus is single-stranded circular RNA, which expresses the nHDV antigen.

 

EPIDEMIOLOGY. HDV infection cannot occur without HBV as a helper virus. Two patterns nof infection are seen. Transmission usually occurs by intrafamilial or intimate ncontact in areas of high prevalence, which are primarily developing countries. nIn areas of low prevalence, such as the United States, the percutaneous nroute is far more common. Hepatitis D infections are uncommon in children ithe United States nbut must be considered when fulminant hepatitis occurs. In the United States, HDV infection is found most nfrequently in parenteral drug abusers, hemophiliacs, and persons immigrating nfrom southern Italy, parts nof eastern Europe, South America, Africa, and the MiddleEast. The incubation period for HDV superinfection is about 2–8 nwk; with coinfection, the incubation period is similar to that of HBV ninfection.

 

PATHOLOGY. There are no distinguishing features of liver disease in HDV hepatitis nexcept that the damage is usually more severe.

 

PATHOPHYSIOLOGY.

In contrast to HBV, HDV causes injury directly by ncytopathic mechanisms. Many of the most severe cases of hepatitis B appear to nbe due to combined infection with HBV and HDV. Coinfection with HBV and HDV noccurs most frequently in areas of high prevalence. The second mechanism of npathogenesis is superinfection of a person who has chronic HBV, which is more ncommon in developed countries.

 

CLINICAL MANIFESTATIONS.

The symptoms of hepatitis D infection are similar to nbut usually more severe than those of the other hepatitis viruses. The clinical noutcome for HDV infection depends on the mechanism of infection. Icoinfection, acute hepatitis, which is much more severe than for HBV alone, is ncommon, but the risk for chronic hepatitis is low. In superinfections, acute nillness is rare, whereas chronic hepatitis is common. However, the risk of nfulminant hepatitis is highest in superinfection. Hepatitis D should be nconsidered in any child who experiences acute hepatic failure.

 

DIAGNOSIS.

The virus has not been isolated, and no circulating nantigen has been identified. The diagnosis is made by detecting IgM antibody to nHDV; the antibodies to HDV develop about 2–4 wk after coinfection and about 10 nwk after superinfection. PCR assays for viral RNA are available but only as a nresearch tool.

 

COMPLICATIONS. HDV must be considered in all cases of fulminant hepatitis.

 

PREVENTION. There is no vaccine for hepatitis D. However, because HDV cannot occur nwithout hepatitis B infection, HBV prevention eliminates HDV. HBIG and nhepatitis B vaccines are used for the same indications as hepatitis B.

 

HEPATITIS nE

 

 ETIOLOGY. Hepatitis E virus (HEV) has not been isolated but has been cloned using nmolecular techniques. This RNA virus has a nonenveloped, sphere shape with nspikes and is similar to the caliciviruses. Infection is associated with nshedding of 27- to 34-nm particles in the stool.

 

 

EPIDEMIOLOGY. Hepatitis E is the epidemic form of what was formally called non-A, nnon-B hepatitis. Infection is transmitted enterically, the highest prevalence has nbeen reported in the Indian subcontinent, the Middle East, and Southeast Asia, especially in areas with poor sanitation. nIn the United States, nthe only reported cases have been in persons who have visited or emigrated from nendemic areas. The mean incubation period is about 40 days (range, 15–60 days).

 

PATHOLOGY. The pathologic findings are similar to those of the other hepatitis nviruses.

 

PATHOGENESIS. HEV appears to act as a cytopathic virus.

 

CLINICAL MANIFESTATIONS. The clinical illness in hepatitis E is similar to nthat of hepatitis A, the other enterically transmitted virus, but it is oftemore severe. Both viruses produce only acute disease; chronic illness does not noccur. In addition to causing more severe illness than HAV, hepatitis E affects nolder patients, with a peak incidence between 15 and 34 yr. Another important nclinical difference is that HEV has a high fatality rate in pregnant women.

 

DIAGNOSIS.

Recombinant DNA technology has resulted in the ndevelopment of an antibody to HEV particles, but serologic tests are not yet ncommercially available. IgM antibody to viral antigen becomes positive after nabout 1 wk of illness.

 

PREVENTION.

No vaccines are available, and there is no evidence nthat Ig is effective in preventing hepatitis E infections. However, Ig pooled nfrom patients in endemic areas may prove to be effective.

 

Short nstatement of the material

Acute hepatitis is a continuing hepatic inflammatory process nmanifested by elevated hepatic transaminase level, lasting less than 6 mo and naccompanied with pain, dyspeptic, intoxication and cholestatic syndromes

 

Etiology               

·        nHAV is RNA-containing virus 27-30 nm in diameter;

·        nHBV is DNA-containing nvirus from HepaDNA viruses family of, 42 nm in diameter;

·        nHCV is virus 22-60 nm in diameter, probably flavivirus family;

·        nHDV is virus 35-37 nm in diameter with small RNA and HB virus shell;

·        nHEV is virus-like particle of spherical form 27 nm in diameter;

·        nHGV, HFV, TTV – nviruses are insufficiently known.

 

Epidemiology:

Source of infection – carries of viruses, ill person;

Way of spreading – alimentary for HAV and HEV;

parenteral nand vertical, sexual, micro traumas for HBV, HCV, HD, HFV and TTV; Susceptibility is high.

 

HAV, HEV      

ü  the nsource is a patient with typical and atypical forms of infection, and viral ncarrier;

ü  nthe mechanism of transmission is fecal-oral, usually realized by the ncontaminated food, water and by direct contact;

ü  receptivity – HAV 70-80 % n(children elder than 1 year), HEV is probably high.

HBV, HCV, HDV

ü  source – viral carriers, npatients with acute and chronic  forms;

ü  nmechanism of transmission:  

ü  nparenteral;

•  vertical (transplacental, at breast feeding);

•  sexual n(micro trauma);

•  domestic n(micro trauma);

ü  receptivity is the greatest at nchildren of early age, people elder than 30 years.

 

Pathogenesis:

Hepatitis A, E

1.     nInoculation of the pathogen (entrance gate – small intestine).

2.     nViremia.

3.     nViral fixation on hepatocytes, intracellular localization.

4.     nPrimary replication of the virus.

5.     nExcretion with a goal to intestine.

6.     nPart of the viruses caused viremia (prodromal period of the disease).

7.     nActivation of immune system, that causes cytolysis, mesenchimal ninflammation and cholestasis.

8.     nImmune response, elimination of the virus.

Hepatitis B

1.     nInoculation of the pathogen.

2.     nViremia.

3.     nViral integration and replication in hepatocytes, also may be in blood ncells, bone marrow, lymph nodes, spleen.

4.     nActivation of immune system, that causes cytolysis, mesenchimal ninflammation and cholestasis.

5.     nImmune response, elimination or persistence of the virus.

Hepatitis C

1.     nInoculation of the pathogen.

2.     nViremia.

3.     nViral integration and replication in hepatocytes, also may be in blood ncells, bone marrow, lymph nodes, spleen.

4.     nActivation of immune system with low immune response.

5.     nMutation changeability of the virus.

6.     nPersistence of the virus.

Hepatitis D

Need virus hepatitis B for its replication, develops nonly in infected HBV patients.

 

Classification

Type:          –

ü ntypical n(jaundice);

ü natypical:

§  nwithout njaundice (unicteric hepatitis);

§     neffaced;

§  subclinical hepatitis.

§  Cholestatic hepatitis

§  nFulminant nhepatitis

Severity:     

ü mild

ü moderate

ü nsevere

Course:

ü nacute n(2-3 months);

ü nprolonged n(3-6 months);

ü nchronic.

        

Periods:     

•         nIncubatio

•         nPre-icteric n

•         nIcteric n

•         nPost-icteric n

•         nConvalescent n

Diagnostic criterions of incubation period

·        nabsence of clinical signs

·        nviral antigens are present nin blood

·        nalanine aminotranspherase, naspartate aminotranspherase may be enlarged.

Prodromal (prejaundice, preicteric) period

·        nheadache

·        nrashes n(often in HBV-hepatitis)           

·        nArthralgias                                         Carole’s triad

·        n“flu like nsyndrome”

·        ndyspepsia

·        nhepatomegaly, pain iright costochondrial rib, epigastrium

·        nin the end – appearing of nclay-colored stools

·        nEnlargement of ALAT and nASAT, urobilinuria, special hepatitis markers.

 

Jaundice (icteric) period

·        nJaundice of mucous nmembranes, sclera, and skin (photo).

·        nUrobilinuria, nbilirubinuria.

·        nHepatomegaly (photo), ntenderness of liver.

·        nALAT and ASAT are nmaximally enlarged.

·        nHyperbilirubinemia with nconjugate bilirubin prevalence.

·        nskin rashes

·        nhemorrhagic syndrome

·        nsplenomegaly

 

Laboratory tests

Prodromal period

·        nEnlargement of ALAT and ASAT, urobilinuria.

·        nAnti-HAV Ig M, HAV-RNA (hepatitis nA).

·        nHBsAg, HBeAg, HBV-DNA and anti-НВс IgM (hepatitis B).

·        nHBsAg, HBeAg, nHBV-DNA, anti-НВс IgM and HDVAg, nHDV-RNA (hepatitis delta coinfection).

·        nHCV-RNA (hepatitis nC).

·        nAnti-HEV Ig M, HEV-RNA (hepatitis nE).

 

Jaundice period

 Nonspecific ntests

·        nenlargement of ALAT and ASAT ,

·        nhyperbilirubinemia with conjugate bilirubin prevalence,

·        nmarking  of bile pigment in urine,

·        nincreased sediment tymol test

·        ndecreased sulemic test (severe hepatitis B)

·        ndecreased prothrombine index, fibrinogen

·        nin cholestasis alkaline phosphatase, cholesterol, GGTP are increased

 Specific tests (markers)

·        nAnti-HAV Ig M, HAV-RNA (hepatitis nA).

·        nHBsAg, HBeAg, HBV-DNA and anti-НВс IgM (hepatitis B).

·        nHBsAg, HBeAg, nHBV-DNA, anti-НВс IgM  and HDVAg, anti-HDV IgM, HDV-RNA.(hepatitis delta coinfection)

·        nHCV-RNA, nanti-HCVcore IgM and IgG (acute hepatitis C).

·        nAnti-HEV Ig M, HEV-RNA (hepatitis nE).

 

 

 

 

 

 

 

Severity criterions (in icteric period)

 

 

Posticteric period

·   Urine nbecomes lighter

·   Stools ndarker

·   Jaundice nfades

·   Decreasing nALAT, ASAT

·   Decreasing nof the liver sizes

·        nNormalization of bilirubin,  ALAT nand ASAT, other indexes, later – sediment tymol test

·        nAnti-HAV Ig G, HAV-RNA (hepatitis nA).

·        nAnti-НВс IgM , anti-Нве IgM, later- anti-НВс (total) IgM and anti-НВс IgG (hepatitis B).

·        nAnti-НВс IgM , anti-Нве IgM, later- nanti-НВс (total) IgM and nanti-НВс IgG and nanti-HDV IgG (hepatitis D).

·        nAnti-HCVcore IgG n(past hepatitis C).

·        nAnti-HCVcore nIgG, anti-HCV NS  in hepatitis C latent phase. 

·        nAnti-HCVcore IgM nand IgG (with IgM predominance), anti-HCV NS and HCV-RNA in hepatitis C reactivation phase.  n

·        nAnti-HEV Ig G (hepatitis E).

 

Fulminant form criteria:

ü Acute failure of the liver

ü Confusion and drowsiness

ü Delirium and convulsions

ü Liver gets smaller

ü Coma I-II ESG is abnormal

ü Hepatic smell

ü Hemorrhagic syndrome

ü Encephalopathy

ü Decreasing of diuresis

ü Total bilirubin  nis increased

ü Protrombin time is prolonged

ü Decreasing  of nALAT, ASAT

ü Decreasing of proteins

 

Atypical (unicteric, effaced, nsubclinical) forms criteria:

ü Contact with patient who had nhepatitis

ü Hepatomegaly

ü increasing  of nALAT, ASAT, tymol test

 

Outcome of disease

For HAV, HEV

ü       nRecovering

ü       nResidual fibrosis of liver (posthepatitis hepatomegaly)

ü       nBiliary dyskinesia

ü       nChronic cholecystitis and cholecystocholangitis

 For HBV, HCV , HDV

ü       nRecovering

ü       nResidual fibrosis of liver (posthepatitis hepatomegaly)

ü       nBiliary dyskinesia

ü       nChronic cholecystitis and cholecystocholangitis

ü transition in chronic nhepatitis;

ü cirrhosis

ü hepatic carcinoma

ü       ndeath.

 

Diagnosis nexample: Hepatitis nA, typical form, icteric period, mild severity, acute course

 

Differential ndiagnosis

Prejaundice period:

ü      viral nupper respiratory tract infections,

ü      bowel ninfection,

ü      acute nappendicitis,

ü      diseases ncaused by parasites,

ü      acute npancreatitis.

Jaundice period:

ü      suprahepatic nicterus (hemolytic anemia),

ü      hepatic nicterus (Gilbert, Krigler-Nadjar syndrome, infectious mononucleosis, nleptospirosis, pseudotuberculosis, congenital liver diseases, ),

ü      subhepatic nicterus (mechanical jaundice).

 

Differential diagnosis of viral hepatitis

 

 

Treatment:

Basic treatment:

ü   bed nregimen up to intoxication disappear,

ü   half-bed nregimen (up to icterus disappear, normalization of ALAT, ASAT)

ü   special ndiet (diet N 5),

o        nExclude heavy fats (like npork), spices, fried foods, “fast food””; avoid stimulators of ngastrointestinal secretions, the diet must be rich by metionine, lecithin, and ncholine to stimulate synthesis of proteins and enzymes in the liver. Diet with nnormal value of proteins and vitamins, with restriction of fats and ncarbohydrates is administered, also restrict salt.

o        nFoods boiled, steamed and nbaked are recommended; food taking 5 times daily

 

Treatment of mild hepatitis – only nbasic therapy

 

Treatment of moderate hepatitis

ü       basic ntherapy

ü       peroral ndetoxication 40-50 ml/kg with water balance control

ü       enterosorptio1-2 wks (in case of cholestatic variant)

ü       choleretics nfrom the 3-d week of disease

•                      ncholagon

•                      nallocholum

•                      ncholenzym

•                      ngalstena

•                      nhepabene

 

Treatment of nsevere hepatitis

• basic therapy,

• nintravenous detoxication therapy (total – 50-100 ml/kg/day):

– 0.9 % nNaCl, Ringer’s solution,

– Ringer’s nlactate solution,

– 5 % nglucose,

– albumin 5 nml/kg;

• nenterosorption 2-3 wks,

• lactulose nfor 10-14 days,

• ndesoxycholic acid (ursophalk) in case of cholestasis 10 mg/kg,

• prednizone n(in possibility of fulminant form development) and for infants before 1 year nwith unfavorable premorbid background): in daily dose 2-3 mg/kg 4 times per day ndivided in equal doses during 7-10 days,

• Hepatoprotectors nin severe cases in posticteric period

• Heptral n(tabl. – 0.4 g, namp. – 0.4 g) n1-2 tabl. 3 times a day (20-25 mg/kg/day),

• Essentiale n(caps., amp.) 1-2 cap. 3 times a day,

• Carsil n(dragee) 1-2 dragee 3 times a day,

• Hepabene n1-2 dragee 3 times a day,

• nThiotriazolinum 1 tabl. 3 times a day,

• Chophytol n1-2 tabl. 3 times a day.

 

Treatment of nfulminant form

• straight nbed regimen,

• diet N 5a nwith protein restriction up to 40 %,

• nintravenously:

• prednizone n10-15 mg/kg/day divided in 4 equal doses,

• ndetoxication therapy (total – 50-100 ml/kg/day) with diuresis control:

• 0.9 % nNaCl, Ringer’s solution,

• Ringer’s nlactate solution,

• 5 % nglucose,

• albumin 5 nml/kg;

• nextracorporeal detoxication in case of ineffective previous therapy n(plasmapheresis),

• hyperbaric noxygenation,

• in case of nedema, ascytis – water-electrolyte balance correction,

• K-serving ndiuretics (verospiron, triampur),

• Fresh nfrozen plasma 10 ml/kg as coagulation factors donator,

• Hepari100-300 IU/kg in possibility of DIC-syndrome development,

• nProtease-inhibitors (trasilol, contrical, gordox) in case of DIC-syndrome ndevelopment,

• nAntibacterial therapy for bacterial complication prevention (less hepatotoxic nmedicine),

• Enema and nstomach-washing,

• Lactulose nfor 10-14 days.

 

Discharge from the hospital, nsupervision, control:

ü patients with mild and moderate nforms can be treated at home;

ü discharge on 15-20 day of illness with nthe remaining phenomena (hepatomegaly, slight increased ALAT, ASAT, ndysproteinemia);

ü Finish treatment in dispensary ncabinet: first examination – in 7 days, then – in 1, 3, 6 months. In absence of nthe remaining phenomena – stop dispensarization;

ü  can visit school on 40-50 day, release from nphysical education on 3-6 months, sport – 12 months

 

Prophylaxis of A, E hepatitis

·        nEarly isolation of ill person.

·        nLooking after contacts, laboratory test every 10 – 15 days.

·        nPersonal hygiene.

·        nDisinfection in the epidemic focus.

·        nPassive prophylaxis by human immune globulin.

 

Prophylaxis of parenteral hepatitis

·        nEarly isolation of ill person.

·        nSterilization of instrument.

·        nPassive prophylaxis by human immune globulin.

For nhepatitis B active prophylaxis: after nthe birth, in 1, 6 months. When mother is HBs Ag positive – after the nbirth, in 1, 2, 12 months.

 

 

 

 

Key words nand phrases: Viral hepatitis, hepatitis A virus, hepatitis B nvirus, viral antigens, alanine aminotranspherase, aspartate aminotranspherase, nCarole’s triad, “flu like syndrome”,  nclay-colored stools, special hepatitis markers, prodromal period, njaundice period, conjugate bilirubin, bile pigments.

 

References:

1.           nManual nof children’s infectious diseases / O. Ye. Fedortsiv, I. L. Horishna, I. M. Horishniy. – TERNOPІL n: UKRMEDKNYHA, 2010. – 382 p. – ISBN 978-966-673-145-9 n

2.           nManual nof Childhood Infections: The Blue Book (Oxford Specialist Handbooks iPaediatrics) by Mike Sharland, Andrew Cant and al. Published by  Oxford University Press Inc., New York, 2011 n, p. 881  ISBN: 978-019-957-358-5.

3.           nIllustrated nTextbook of Paediatrics, 4th Edition.  nPublished by  Lissauer & nClayden, 2012, p. 552 ISBN: 978-072-343-566-2.

4.           n Nelson Textbook of Pediatrics, 19th EditioKliegman, Behrman. Published by Jenson & Stanton, 2011, 2608.  ISBN: 978-080-892-420-3.

5.           nOxford Textbook of Medicine: Infection by David Warrell, Timothy M. Cox, John Firth and Mili nEstee Torok , Published nby Wiley-Blackwell, 2012

6.           nhttp://www.merckmanuals.com/professional/index.html