Theme 21. Differential diagnosis and nemergency states in viral hepatitis in children

 

VIRAL HEPATITIS

 

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 A THROUGH E

 

DEFINITION. Viral hepatitis is a major health problem ideveloping and developed countries. Recent advances in the field of molecular nbiology have aided identification and understanding of the pathogenesis of the nfive viruses that are now known to cause hepatitis as their primary disease nmanifestation. These hepatotropic viruses are designated hepatitis A, B, C, D, nand E. Many other viruses can cause hepatitis as part of their clinical nspectrum including herpes simplex, cytomegalovirus, Epstein-Barr, varicella, nhuman immunodeficiency, adenovirus enteroviruses, and arboviruses. Hepatic ninvolvement with these viruses is usually only one component of a multisystem ndisease.

 

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 (HAV) nappears to cause most cases of hepatitis in children. Hepatitis B probably naccounts for about one third of cases in children, whereas hepatitis C is found nin approximately 20%. Hepatitis D occurs in only a small percentage of childrewho must also have active hepatitis B virus (HBV) infection. Hepatitis E has nnot been reported in children who have lived and traveled only in the United nStates.

 

HEPATITIS A

ETIOLOGY. HAV is a 27-nm diameter, RNA-containing virus that is na member of the Picornavirus family. It was isolated originally from stools of ninfected patients. Laboratory strains of HAV have been propagated in tissue nculture. Acute infection is diagnosed by detecting immunoglobulin (Ig)M (IgM) nantibodies (anti-HAV) by radioimmunoassay or, rarely, by identifying viral nparticles in stool.

 

EPIDEMIOLOGY. HAV infections occur throughout the world but are nmost common in developing countries, where the prevalence rate approaches 100% nin children by the age of 5 yr. In the United States, approximately 30% of the nadult population have evidence for previous HAV infection; the rates of ninfection are similar in the 1st, 2nd, and 3rd decades of life. Hepatitis A ncauses only acute hepatitis. The illness is much more likely to be symptomatic nin adults; most infections in children younger than 5 yr are asymptomatic or nhave mild, nonspecific manifestations. The transmission of HAV is almost always nby person-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 nfoodborne and waterborne outbreaks have occurred, including several resulting nfrom contaminated 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 nresponse of the liver to HAV is similar to that of the other four hepatitis nviruses. The entire liver is involved with necrosis, most marked in the ncentrilobular areas, and increased cellularity, which is predominant in the nportal areas. The lobular architecture remains intact, although balloodegeneration and necrosis of parenchymal cells occur initially. Fatty change is nrare. A diffuse mononuclear cell inflammatory reaction causes expansion in the nportal tracts; bile duct proliferation is common, but bile duct damage is not noften found. Diffuse Kupffer cell hyperplasia is present in the sinusoids along nwith infiltration of polymorphonuclear leukocytes and eosinophils. Neonates nrespond to hepatic injury by forming giant cells. In fulminant hepatitis, total ndestruction of the parenchyma occurs, leaving only connective tissue septa. By n3 months after the onset of acute hepatitis resulting from HAV, the liver nusually is normal morphologically.

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 nhepatitis is caused by several mechanisms. The initial injury in hepatitis A is nthought to be cytopathic. Regardless of the mechanism of initial injury to the nliver, damage from the five hepatitis viruses is evident in three main ways. nThe first is a reflection of injury to the hepatocytes, which release alanine naminotransferase (ALT, formerly serum glutamate pyruvate transaminase) and naspartate aminotransferase (AST, formerly serum glutamic-oxaloacetic ntransaminase) into the bloodstream. The ALT is more specific to the liver thathe AST, which also can be elevated after injury to erythrocytes, skeletal nmuscle, or myocardial cells. The height of elevation does not correlate with nthe extent of hepatocellular necrosis and has little prognostic value. In some ncases, a falling aminotransferase level may predict a poor outcome if the ndecline occurs in conjunction with a rising bilirubin and prolonged prothrombitime (PT). This combination of findings indicates that massive hepatic injury nhas occurred, resulting in few functioning hepatocytes. Another enzyme, lactate ndehydrogenase is even less specific to liver than AST and usually is not nhelpful in evaluating liver injury. Viral hepatitis is also associated with ncholestatic jaundice, in which both direct and indirect bilirubin levels are nelevated. Jaundice results from obstruction of biliary flow and damage to nhepatocytes. Elevations of serum alkaline phosphatase, 5-nucleotidase, ng-glutamyl transpeptidase, and urobilinogen all can reflect injury to the nbiliary system. Abnormal protein synthesis by hepatocytes is reflected by nincreased PT. Because of the short half-life of these proteins, the PT is a nsensitive indicator of damage to the liver. Serum albumin is another nliver-manufactured serum protein, but its longer half-life limits its relevance nfor monitoring acute liver injury. Cholestasis results in a decreased nintestinal bile acid pool and decreased absorption of fat-soluble vitamins. nHepatic injury also may result in changes in carbohydrate, ammonia, and drug nmetabolism.

 

CLINICAL MANIFESTATIONS.

 

The onset of HAV ninfection usually is abrupt and is accompanied by systemic complaints of fever, nmalaise, nausea, emesis, anorexia, and abdominal discomfort. This prodrome may nbe mild and often goes unnoticed in infants and preschool-age children. nDiarrhea often occurs in children, but constipation is more common in adults. nJaundice may be so subtle in young children that it can be detected only by nlaboratory tests. When they occur, jaundice and dark urine usually develop nafter the systemic symptoms. In contrast to HAV infections in children, most nHAV infections in adults are symptomatic and can be severe. Symptoms of HAV ninfection include right upper quadrant pain, dark-colored urine, and jaundice. nThe duration of symptoms usually is less than 1 mo, and appetite, exercise ntolerance, and a feeling of well-being gradually return. Almost all patients nwith HAV infection will recover completely, but a relapsing course can occur nfor several months. Fulminant hepatitis leading to death is rare, and chronic ninfection does not occur.

 

DIAGNOSIS. The diagnosis of HAV infection should be considered nwhen a history of jaundice exists in family contacts, friends, schoolmates, nday-care playmates, or school personnel or if the child or family has traveled nto an endemic area. The diagnosis is made by serologic criteria; liver biopsies nrarely are performed. Anti-HAV is detected at the onset of symptoms of acute nhepatitis A and persists for life. The acute infection is diagnosed by the npresence of IgM anti-HAV, which can be detected for 3–12 mo; thereafter, IgG anti-HAV nis found. The virus is excreted in stools from 2 wk before to 1 wk after the nonset of illness. Rises are almost universally found in ALT, AST, bilirubin, nalkaline phosphatase 5´-nucleotidase, and g-glutamyl transpeptidase and ndo not help to differentiate the cause. The PT should always be measured in a nchild with hepatitis to help assess the extent of liver injury; prolongation is na serious sign mandating hospitalization.

 

DIFFERENTIAL DIAGNOSIS.

 

 The possible causes of hepatitis vary somewhat nby age. Physiologic jaundice, hemolytic disease, and sepsis ieonates usually nare distinguished easily from hepatitis. After the immediate newborn period, ninfection remains an important cause of hyperbilirubinemia, but metabolic and nanatomic causes (biliary atresia and choledochal cysts) also must be nconsidered. The introduction of pigmented vegetables into the infant’s diet may nresult in carotenemia, which may be mistaken for jaundice.

 

In later infancy nand childhood, hemolytic-uremic syndrome may be mistaken initially for nhepatitis. Reye and Reye-like syndromes present in a similar fashion to acute nfulminating hepatitis. Jaundice also may occur with malaria, leptospirosis, and nbrucellosis and with severe infection in older children, particularly in those nwith malignant disorders or with immunodeficiency. Gallstones may obstruct nbiliary drainage and cause jaundice in adolescents as well as in children with nchronic hemolytic processes. Hepatitis may be the initial presentation of nWilson disease, cystic fibrosis, a-1-antitrypsin deficiency, and Jamaicavomiting sickness. The liver may be involved in collagen vascular diseases nincluding systemic 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 nalways recover from HAV infection. Rarely, fulminant hepatitis can occur, iwhich a progressive rise in serum bilirubin is accompanied by an initial rise nin aminotransferases followed by a fall to normal or low values. Hepatic nsynthetic function decreases and the PT becomes prolonged, often accompanied by nbleeding. The serum albumin falls, causing edema and ascites. The ammonia nusually rises and the sensorium becomes altered, progressing from drowsiness to nstupor and then deep coma. Progression to end-stage disease and death can occur nin less than 1 wk, or can develop more insidiously.

 

PREVENTION. The recent development of highly immunogenic and safe nformalin-killed vaccines marks a major advance in the prevention of hepatitis nA. Vaccination of young children in endemic areas is unnecessary because the ndisease is almost always asymptomatic or mild and confers lifelong immunity. Iindustrialized countries, vaccination of high-risk children may be of benefit nbecause these children can become carriers of the disease and could infect nolder siblings and parents who are at greater risk for more severe disease. nVaccination will be of special value to unexposed travelers from developed ncountries when they travel to 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, continent nchildren, but their stools and fecally contaminated materials should be treated nwith 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 nbeen school centered. When HAV occurs in a child-care center with childreot nyet toilet 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 ninfection are subSaharan Africa, China, parts of the middle East, the Amazobasin, and the Pacific Islands. In the United States, the Eskimo population iAlaska has the highest prevalence rate. An estimated 300,000 new cases of HBV ninfection occur in the United States each year, with the 20- to 39-yr age group nat greatest risk. The number of new cases in children is low but is difficult nto estimate because the majority of infections in children are asymptomatic. nThe risk of chronic infection is related inversely to age; although less tha10% of infections occur in children, these infections account for 20–30% of all nchronic 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 ntransmission occurred at the time of delivery; virus contained in amniotic nfluid or in maternal feces or blood may be the source. Although most infants nborn to infected mothers become antigenemic from 2–5 mo of age, some infants of nHBsAg-positive mothers are not affected until later ages.

 

HBsAg has beedemonstrated inconsistently in milk of infected mothers. Breast-feeding of nunimmunized infants by infected mothers does not appear to confer a greater nrisk of hepatitis on offspring than does artificial feeding despite the npossibility that cracked nipples may result in the ingestion of contaminated nmaternal 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 nresponse of the liver to HBV is the same as that for all the hepatitis viruses. nPersistence of histologic changes in patients with hepatitis B, C, or D nindicates development of chronic liver disease.

 

PATHOGENESIS.

 

Hepatitis B, nunlike the other hepatitis viruses, is a noncytopathic virus that probably ncauses injury by immune-mediated mechanisms. The first step in the process of nacute hepatitis is infection of hepatocytes by HBV, resulting in the appearance nof viral antigens on the cell surface. The most important of these viral antigens nmay be the nucleocapsid antigens, HBcAg and HBeAg, a cleavage product of HBcAg. nThese antigens, in combination with class I major histocompatibility (MHC) nproteins, make the cell a target for cytotoxic T-cell lysis.

 

The mechanism nfor development of chronic hepatitis is less well understood. To permit nhepatocytes to continue to be infected, the core protein or MHC class I proteimay not be recognized, the cytotoxic lymphocytes may not be activated, or some nother as yet unknown mechanism may interfere with destruction of hepatocytes. nFor cell-to-cell infection to continue, some virus-containing hepatocytes must nsurvive.

 

Immune-mediated nmechanisms also are involved in the extrahepatic conditions that can be nassociated with HBV infections. Circulating immune complexes containing HBsAg ncan occur in patients who experience associated polyarteritis, nglomerulonephritis, polymyalgia rheumatica, mixed cryoglobulinemia, and the nGuillain-Barré syndrome.

 

Mutations of HBV nare more common than for the usual DNA viruses, and a series of mutant strains nhave been recognized. The most important is one that results in failure to nexpress HBeAg and has been associated with development of severe hepatitis and nperhaps more severe exacerbations of chronic HBV infection.

 

CLINICAL MANIFESTATIONS.

 

Many cases of nHBV infection are asymptomatic, as evidenced by the high carriage rate of serum nmarkers in persons who have no history of acute hepatitis. The usual acute, nsymptomatic episode is similar to HAV and hepatitis C virus (HCV) infections nbut may be more severe and is more likely to include involvement of skin and njoints. The first clinical evidence of HBV infection is elevation of ALT, which nbegins to rise just before the development of lethargy, anorexia, and malaise, nabout 6–7 wk after exposure. The illness may be preceded in a few children by a nserum sickness–like prodrome including arthralgia or skin lesions, including nurticarial, purpuric, macular, or maculopapular rashes. Papular acrodermatitis, nthe Gianotti-Crosti syndrome, also may occur. Other extrahepatic conditions nassociated with HBV infections include polyarteritis, glomerulonephritis, and naplastic anemia. Jaundice, which is present in about 25% of infected nindividuals, usually begins about 8 wk after exposure and lasts for about 4 wk. nIn the usual course of resolving HBV infection, symptoms are present for 6–8 nwk. The percentage of people in whom clinical evidence of hepatitis develops is nhigher for hepatitis B than for hepatitis A, and the rate of fulminant hepatitis nalso is greater. Chronic hepatitis also occurs, and the chronic active form caresult in cirrhosis and hepatocellular carcinoma.

 

On physical nexamination, skin and mucous membranes are icteric, especially the sclera and nthe mucosa under the tongue. The liver usually is enlarged and tender to npalpation. When the liver is not palpable below the costal margin, tenderness ncan be demonstrated by striking the rib cage over the liver gently with a nclosed fist. Splenomegaly and lymphadenopathy are common.

 

DIAGNOSIS.

 

 The serologic pattern for HBV is more complex nthan for HAV and differs depending on whether the disease is acute, nsubclinical, or chronic.

 

Routine nscreening for hepatitis B requires assay of at least two serologic markers. nHBsAg is the first serologic marker of infection to appear and is found ialmost all infected persons; its rise coincides closely with the onset of nsymptoms. HBeAg is often present during the acute phase and indicates a highly ninfectious state. Because HBsAg levels fall before the end of symptoms, IgM nantibody to hepatitis B core antigen (IgM anti-HBcAg) also is required because nit rises early after infection and persists for many months before being nreplaced by IgG anti-HBcAg, which persists for years. IgM anti-HBcAg usually is nnot present in perinatal HBV infections. Anti-HBcAg is the most valuable single nserologic marker of acute HBV infection because it is present almost as early nas HBsAg and continues to be present later in the course of the disease wheHBsAg has disappeared. Only anti-HBsAg is present in persons immunized with nhepatitis B vaccine, whereas anti-HBsAg and anti-HBcAg are detected in persons nwith 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 nalso can result in chronic hepatitis, which can lead to cirrhosis and primary nhepatocellular carcinoma. Interferon alpha-2b is available for treatment of nchronic hepatitis B in persons 18 years of age or older with compensated liver ndisease and HBV replication. Membranous glomerulonephritis with deposition of ncomplement and HBeAg in glomerular capillaries is a rare complication of HBV ninfection.

 

PREVENTION.

 

Universal nimmunization of infants with hepatitis B vaccine is now recommended by the nAmerican Academy 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 nUnited States; both have proven to be highly immunogenic in children. The noriginal plasma-derived vaccine is equally immunogenic but is no longer nmanufactured in the United States.

 

Infants born to nHBsAg-positive women should receive vaccine at birth, 1 mo, and 6 mo of age. nThe first dose should be accompanied by administration of 0.5 mL of hepatitis B nimmunoglobulin (HBIG) as soon after delivery as possible because the neffectiveness decreases rapidly with increased time after birth. The AAP nrecommends that infants born to HBsAg-negative women receive the first dose of nvaccine at birth, the second at 1–2 mo of age, and the third between 6 and 18 nmo 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 nthe parenterally acquired cases of what was previously known as non-A, non-B nhepatitis. The virus has not been isolated but has been cloned using nrecombinant DNA technology. Molecular biologic analysis has demonstrated that nHCV is a single-strand RNA virus that has been classified as a separate genus nwithin the Flaviviridae family. HCV is an enveloped virus, 50–60 nm in size, nthat is transmitted mainly by blood or blood products, intravenous drug use, nand sexual contact. Chronic liver disease is common in infected individuals.

 

EPIDEMIOLOGY.

The most nimportant risk factors for HCV transmission in the United States are the use of nintravenous drugs (40%), transfusions (10%), and occupational and sexual nexposure (10%). The remaining 40% of patients have no known associated risk nfactors. Perinatal transmission has been described but is uncommon except whethe mother is HIV infected or has a high titer of HCV RNA. Although HCV testing nhas made blood transfusions much safer, testing of blood may result in only a nmodest decline in HCV cases because transfusions account for only a small npercentage of HCV infections. Large population serosurveys in the 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 nother hepatitis viruses. In chronic cases, lymphoid aggregates or follicles iportal tracts are seen either alone or as part of a general inflammatory ninfiltration of the tracts.

 

PATHOGENESIS. HCV appears to cause injury primarily by cytopathic nmechanisms, but immune-mediated injury also may occur. The cytopathic component nappears to be mild, because the acute form is typically the least severe of all nhepatitis virus infections; HCV rarely is fulminant.

 

CLINICAL MANIFESTATIONS.

The clinical npattern of the acute infection is usually similar to that of the other nhepatitis viruses. HCV is the most likely hepatitis virus to cause chronic ninfection; about two thirds of post-transfusion infections and about one third nof sporadic, community-acquired cases will become chronic. Typically, a nfluctuating pattern of aminotransferase elevations occurs in about 80% of those nin whom chronic HCV develops. Although chronic elevations of aminotransferase nlevels are common, chronic HCV will progress to cirrhosis in only about half of nthe patients, or about 25% of all those initially infected. Primary hepatocellular ncarcinoma can develop in patients with cirrhosis, but HCV is less effective nthan HBV in causing primary hepatocellular carcinoma. The hepatocellular ncarcinoma associated with HCV probably results from chronic inflammation and nnecrosis rather than an oncogenic effect of the virus.

Hepatitis C in the newborn

 

DIAGNOSIS.

The clinically navailable serologic assays for HCV are based on development of antibodies to nHCV antigens because no detectable antigens have been found in blood. The nassays are used mainly for detection of chronic hepatitis C because they remainegative for at least 1–3 mo after the clinical onset of illness. The nsecond-generation assays are the current standard and test for three of the nfive known antigenic epitopes. They have improved sensitivity over the nfirst-generation tests but still have a 10% false-negative rate. Assays for nviral RNA (polymerase chain reaction [PCR], in situ hybridization) are costly, ntime consuming, and available only in research situations.

 

COMPLICATIONS.

The risk of nfulminant hepatitis is low with HCV, but the risk for chronic hepatitis is the nhighest among the hepatitis viruses. The usual chronic course is mild even whecirrhosis develops; long-term follow-up indicates that the overall mortality of npersons with transfusion-acquired HCV is no different from that of noninfected ncontrols. Interferon alpha-2b is available for treatment of chronic hepatitis nin persons 18 yr of age or older with compensated liver disease who have a nhistory of blood or blood product exposure or who are HCV antibody positive or nboth.

 

PREVENTION.

There is no nvaccine available, and none may be developed because animal studies suggest nthat HCV infection does not lead to protective immunity; the same individual ncan be infected multiple times with the same virus. Ig has not proven to be of nbenefit. Ig manufactured in the United States does not contain antibodies to nHCV because blood and plasma donors are screened for anti-HCV, and exclusion of nthe HCV positive persons from the donor pool is recommended.

 

 

HEPATITIS D

 

 ETIOLOGY.

Hepatitis D nvirus (HDV), the smallest known animal virus, is considered defective because nit cannot produce infection without a concurrent HBV infection. The 36-nm ndiameter virus is incapable of making its own coat protein; its outer coat is ncomposed of excess HBsAg from HBV. The inner core of the virus is nsingle-stranded circular RNA, which expresses the HDV antigen.

 

EPIDEMIOLOGY. HDV infection cannot occur without HBV as a helper nvirus. Two patterns of infection are seen. Transmission usually occurs by nintrafamilial or intimate contact in areas of high prevalence, which are nprimarily developing countries. In areas of low prevalence, such as the United nStates, the percutaneous route is far more common. Hepatitis D infections are nuncommon in children in the United States but must be considered when fulminant nhepatitis occurs. In the United States, HDV infection is found most frequently nin parenteral drug abusers, hemophiliacs, and persons immigrating from southerItaly, parts of eastern Europe, South America, Africa, and the Middle East. The nincubation period for HDV superinfection is about 2–8 wk; with coinfection, the nincubation period is similar to that of HBV infection.

 

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

 

PATHOPHYSIOLOGY.

In contrast to nHBV, HDV causes injury directly by cytopathic mechanisms. Many of the most nsevere cases of hepatitis B appear to be due to combined infection with HBV and nHDV. Coinfection with HBV and HDV occurs most frequently in areas of high nprevalence. The second mechanism of pathogenesis is superinfection of a persowho has chronic HBV, which is more common in developed countries.

 

CLINICAL MANIFESTATIONS.

The symptoms of nhepatitis D infection are similar to but usually more severe than those of the nother hepatitis viruses. The clinical outcome for HDV infection depends on the nmechanism of infection. In coinfection, acute hepatitis, which is much more nsevere than for HBV alone, is common, but the risk for chronic hepatitis is nlow. In superinfections, acute illness is rare, whereas chronic hepatitis is ncommon. However, the risk of fulminant hepatitis is highest in superinfection. nHepatitis D should be considered in any child who experiences acute hepatic nfailure.

 

DIAGNOSIS.

The virus has nnot been isolated, and no circulating antigen has been identified. The ndiagnosis is made by detecting IgM antibody to HDV; the antibodies to HDV ndevelop about 2–4 wk after coinfection and about 10 wk after superinfection. nPCR assays for viral RNA are available but only as a research tool.

 

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

 

PREVENTION. There is no vaccine for hepatitis D. However, because nHDV cannot occur without hepatitis B infection, HBV prevention eliminates HDV. nHBIG and hepatitis B vaccines are used for the same indications as hepatitis B.

 

HEPATITIS E

 

 ETIOLOGY. Hepatitis E virus (HEV) has not been isolated but has nbeen cloned using molecular techniques. This RNA virus has a nonenveloped, nsphere shape with spikes and is similar to the caliciviruses. Infection is nassociated with shedding of 27- to 34-nm particles in the stool.

 

 

EPIDEMIOLOGY. Hepatitis E is the epidemic form of what was formally ncalled non-A, non-B hepatitis. Infection is transmitted enterically, the nhighest prevalence has been reported in the Indian subcontinent, the Middle nEast, and Southeast Asia, especially in areas with poor sanitation. In the United nStates, the only reported cases have been in persons who have visited or nemigrated from endemic areas. The mean incubation period is about 40 days n(range, 15–60 days).

 

PATHOLOGY. The pathologic findings are similar to those of the nother hepatitis viruses.

 

PATHOGENESIS. HEV appears to act as a cytopathic virus.

 

CLINICAL nMANIFESTATIONS. The nclinical illness in hepatitis E is similar to that of hepatitis A, the other nenterically transmitted virus, but it is often more severe. Both viruses nproduce only acute disease; chronic illness does not occur. In addition to ncausing more severe illness than HAV, hepatitis E affects older patients, with na peak incidence between 15 and 34 yr. Another important clinical difference is nthat HEV has a high fatality rate in pregnant women.

 

DIAGNOSIS.

Recombinant DNA ntechnology has resulted in the development of an antibody to HEV particles, but nserologic tests are not yet commercially available. IgM antibody to viral nantigen becomes positive after about 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 statement of the material

Acute hepatitis is a continuing hepatic inflammatory process manifested by elevated nhepatic transaminase level, lasting less than 6 mo and accompanied with pain, ndyspeptic, 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 nfamily;

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

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

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

 

Epidemiology:

Source of infection – carries of viruses, ill person;

Way of spreading – alimentary for HAV and HEV;

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

 

HAV, HEV      

ü  nthe source is a patient nwith typical and atypical forms of infection, and viral carrier;

ü  the mechanism of transmissiois fecal-oral, usually realized by the contaminated food, water and by direct ncontact;

ü  nreceptivity – HAV 70-80 % (children elder than 1 nyear), HEV is probably high.

HBV, nHCV, HDV

ü  nsource – viral carriers, patients with acute nand chronic  forms;

ü  mechanism of ntransmission:  

ü  parenteral;

•  vertical (transplacental, at breast nfeeding);

•  sexual (micro trauma);

•  domestic (micro trauma);

ü  nreceptivity is the greatest at children of early age, npeople elder than 30 years.

 

Pathogenesis:

Hepatitis A, E

1.     nInoculatioof the pathogen (entrance gate – small intestine).

2.     nViremia.

3.     nViral nfixation on hepatocytes, intracellular localization.

4.     nPrimary nreplication of the virus.

5.     nExcretiowith a goal to intestine.

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

7.     nActivatioof immune system, that causes cytolysis, mesenchimal inflammation and cholestasis.

8.     nImmune nresponse, elimination of the virus.

Hepatitis B

1.     nInoculatioof the pathogen.

2.     nViremia. n

3.     nViral nintegration and replication in hepatocytes, also may be in blood cells, bone nmarrow, lymph nodes, spleen.

4.     nActivatioof immune system, that causes cytolysis, mesenchimal inflammation and ncholestasis.

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

Hepatitis C

1.     nInoculatioof the pathogen.

2.     nViremia. n

3.     nViral nintegration and replication in hepatocytes, also may be in blood cells, bone nmarrow, lymph nodes, spleen.

4.     nActivatioof immune system with low immune response.

5.     nMutatiochangeability of the virus.

6.     nPersistence nof the virus.

Hepatitis D

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

 

Classification

Type:          –

ü typical (jaundice);

ü atypical:

§  without jaundice (unicteric nhepatitis);

§     effaced;

§  nsubclinical hepatitis.

§  nCholestatic hepatitis

§  Fulminant hepatitis

Severity:     

ü nmild

ü nmoderate

ü severe

Course:

ü acute n(2-3 months);

ü prolonged n(3-6 months);

ü chronic.

        

Periods:     

•         nIncubation

•         nPre-icteric

•         nIcteric

•         nPost-icteric

•         nConvalescent

Diagnostic ncriterions of incubation period

·        nabsence of clinical signs

·        nviral antigens are present iblood

·        nalanine aminotranspherase, naspartate aminotranspherase may be enlarged.

Prodromal (prejaundice, preicteric) nperiod

·        nheadache

·        nrashes (often iHBV-hepatitis)           

·        nArthralgias                                         nCarole’s triad

·        n“flu like syndrome”

·        ndyspepsia

·        nhepatomegaly, pain in right ncostochondrial rib, epigastrium

·        nin the end – appearing of nclay-colored stools

·        nEnlargement of ALAT and ASAT, nurobilinuria, special hepatitis markers.

 

Jaundice (icteric) period

·        nJaundice of mucous membranes, nsclera, and skin (photo).

·        nUrobilinuria, bilirubinuria.

·        nHepatomegaly (photo), ntenderness of liver.

·        nALAT and ASAT are maximally nenlarged.

·        nHyperbilirubinemia with nconjugate bilirubin prevalence.

·        nskin rashes

·        nhemorrhagic syndrome

·        nsplenomegaly

 

Laboratory ntests

Prodromal period

·        nEnlargement of ALAT and ASAT, urobilinuria.

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

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

·        nHBsAg, nHBeAg, HBV-DNA, anti-НВс IgM and nHDVAg, HDV-RNA (hepatitis delta ncoinfection).

·        nHCV-RNA n(hepatitis nC).

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

 

Jaundice period

 Nonspecific ntests

·        nenlargement of ALAT and ASAT ,

·        nhyperbilirubinemia with conjugate bilirubin prevalence,

·        nmarking  of bile npigment in urine,

·        nincreased sediment tymol test

·        ndecreased sulemic test (severe hepatitis B)

·        ndecreased prothrombine index, fibrinogen

·        nin cholestasis alkaline phosphatase, cholesterol, GGTP nare increased

 Specific ntests (markers)

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

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

·        nHBsAg, nHBeAg, HBV-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 E).

 

 

 

 

 

 

 

Severity criterions (iicteric period)

 

 

Posticteric period

·   nUrine becomes lighter

·   nStools darker

·   nJaundice fades

·   nDecreasing ALAT, ASAT

·   nDecreasing of the liver nsizes

·        nNormalization of bilirubin,  ALAT and ASAT, other indexes, later – nsediment tymol test

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

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

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

·        nAnti-HCVcore nIgG (past hepatitis C).

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

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

·        nAnti-HEV Ig G (hepatitis E).

 

Fulminant form criteria:

ü nAcute nfailure of the liver

ü nConfusioand drowsiness

ü nDelirium nand convulsions

ü nLiver ngets smaller

ü nComa nI-II ESG is abnormal

ü nHepatic nsmell

ü nHemorrhagic nsyndrome

ü nEncephalopathy n

ü nDecreasing nof diuresis

ü nTotal nbilirubin  is increased

ü nProtrombitime is prolonged

ü nDecreasing n of nALAT, ASAT

ü nDecreasing nof proteins

 

Atypical (unicteric, effaced, nsubclinical) forms criteria:

ü nContact with patient who had nhepatitis

ü nHepatomegaly

ü nincreasing  of ALAT, ASAT, tymol test

 

Outcome of disease

For HAV, HEV

ü       nRecovering

ü       Residual fibrosis of liver n(posthepatitis hepatomegaly)

ü       nBiliary dyskinesia

ü       nChronic cholecystitis and cholecystocholangitis

 For HBV, HCV , HDV

ü       nRecovering

ü       Residual fibrosis of liver n(posthepatitis hepatomegaly)

ü       nBiliary dyskinesia

ü       nChronic cholecystitis and cholecystocholangitis

ü ntransition in chronic hepatitis;

ü ncirrhosis

ü nhepatic 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 nviral hepatitis

 

 

Treatment:

Basic treatment:

ü   bed nregimen up to intoxication disappear,

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

ü   nspecial diet (diet N 5),

o        nExclude heavy fats (like pork), nspices, 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 baked nare 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,

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

– 0.9 % NaCl, Ringer’s solution,

– Ringer’s lactate solution,

– 5 % glucose,

– albumin 5 ml/kg;

• enterosorption 2-3 wks,

• lactulose for 10-14 days,

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

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

• Hepatoprotectors in severe cases in posticteric period

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

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

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

• Hepabene 1-2 dragee 3 times a day,

• Thiotriazolinum 1 tabl. 3 times a day,

• Chophytol 1-2 tabl. 3 times a day.

 

Treatment of fulminant form

• straight bed regimen,

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

• intravenously:

• prednizone 10-15 mg/kg/day divided in 4 equal doses,

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

• 0.9 % NaCl, Ringer’s solution,

• Ringer’s lactate solution,

• 5 % glucose,

• albumin 5 ml/kg;

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

• hyperbaric oxygenation,

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

• K-serving diuretics (verospiron, triampur),

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

• Heparin 100-300 IU/kg in possibility of DIC-syndrome development,

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

• Antibacterial therapy for bacterial complication prevention (less nhepatotoxic medicine),

• Enema and stomach-washing,

• Lactulose for 10-14 days.

 

Discharge from the hospital, nsupervision, control:

ü patients with mild and nmoderate forms 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 nisolation of ill person.

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

·        nPersonal nhygiene.

·        nDisinfectioin the epidemic focus.

·        nPassive nprophylaxis by human immune globulin.

 

Prophylaxis of parenteral hepatitis

·        nEarly nisolation of ill person.

·        nSterilizatioof instrument.

·        nPassive nprophylaxis by human immune globulin.

For hepatitis B active prophylaxis: after the birth, i1, 6 months. When mother is HBs Ag positive – after the birth, in 1, 2, n12 months.

 

 

 

 

 

SHIGELLA

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 nmkm, without sporing and incapsulation, product endotoxin, resistant to the nenvironment (in milk, water, food stay for several days, in soil –for several nweeks), stable to the freezing, but sensitive for boiling. By antigen structure nand biochemical properties shigella are devided into 4 subgroups: A, B, C, D:

·        nSh.dysenteriae n– belongs to group A

·        nSh. nflexneri – belongs to group B

·        nSh.boydii n– belongs to group C

·        nSh.sonnei n– belongs to group D

Sh. flexneri and Sh.sonnei are the most often agents nfor bacterial dysentery nowadays.

 

 

Epidemiology: n

Source nof infection –

•         nContagious npatient

•         nBacillus ncarrier

Shigella is spread through fecal-oral nmechanism of transmission.

The nway of transmission

•         nContact

•         nAlimentary

•        nWatery

Susceptibility: 60-70% especially infants and preschoolers.

Seasonality is summer-autumn.

 

Pathogenesis:

1.     nEntrance nShigella to gastrointestinal tract.

2.     nDestructioof them under the influence of ferments.

3.     nToxemia.

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

5.     nLocal ninflammatory process (due to colonizing of distal part of the colon).

6.     nDiarrhea.

 

Morphological nchanges in shigellosis

 

Classification

      nI.            nClinical nForm

Typical

•         nWith ndominance of toxicosis

•         nwith ndominance of local inflammation

•         nmixed n

Atypical

•        nEffaced

•        nDyspeptic

•        nSubclinical

•        nHypertoxic

   II.            n Severity (mild, moderate and severe)

III.            nDuration

•         nacute n(up to 1.5 mo)

•         nsubacute n(up to 3 mo)

•         nchronic n(about 3 mo)

ü recurrent

ü constantly recurring

IV.            nCourse

•        nSmooth

•         nUneven (with complication)

V. Bacterium carrier

 

Clinical ncriterions (With dominance of ntoxicosis):

·        nPeriod nof incubation: a few hours to 7 days.

·        nToxicosis nis the first sing even may be neurotoxicosis (lose of appetite, headache, nfatigue, vomiting, hallucinations, unconsciousness, seizure, febrile ntemperature 39-40°C).

·        nColitis nis secondary (abdominal pain, tenesmus, false urge to defecate, sigmoid colois tender, spastic, anus is open in hard cases. Feces in the form of a spit of nmucus and blood (rectal spit), enlargement of number of defecation).

·        nDehydratioisn’t developed (except infants).

 

Marble skin in toxicosis

 

With dominance of local inflammation

•         nSudden onset of high-grade fever

•         n abdominal ncramping

•         nabdominal pain,

•         ntenesmus,

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

•         nfecal incontinence, and small-volume mucous diarrhea nwith frank blood

 

False urge to defecate

 

 

Typical ncolor of feces in shigellosis, rectal spit

 

Sunkeabdomen

 

Rectal nprolapse

 

Peculiarities nof shigellosis in infants:

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

·        nDistal ncolitis is less common

·        nEnterocolitis nis more often with enterocolitic feces, hemocolitis is rare.

·        nHepato- nand splenomegaly

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

·        nAlways noccurs gaping anus, sphincteritis

·        nDehydratiois more often

·        nProlonged nduration of the disease

 

Criteria of the Shigellosis Severity

Mild nform

•         nConsistent nor acute onset of diarrhea

•         n Stool is 5-8 times per day with mucous and nblood

•         nNot npermanent pain in abdominal region.

•         nThe ntemperature is normal

•         nLoss nof appetites

•         nCabe vomiting 

Moderate nform

•         nAcute nonset of diarrhea

•         nSymptoms nof toxicosis

•         n The temperature is 38-39°C

•         nAnorexia

•         nCrampy nabdominal pain

•         n Stool is 10-15 times per day

•         nPaiduring palpation in left inguinal region

•         nhepatomegaly

Severe nform

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

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

•        nGeneral ncondition is sharply worsened,

•        nquite noften – sopor, loss of the consciousness, cramps,

•        nchanges nin all organs and systems,

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

•        nsignificant nweight loss

 

Laboratory ntests:

•         nThe white blood cell count is noften within reference range, with a high percentage of bands. Occasionally, nleucopenia 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 be nperformed 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 ncontrol for water and food.

·        nIsolatioand sanation of ill person

·        nReconvalescent nmay be discharged from hospital after one negative feces culture ( taken 2 days nafter course of antibiotic therapy)

·        nDispensarizatioof reconvalescent for 1-3 months

·        nFeces nculture in contacts, carriers

·        nLooking nafter contacts for 7 days, quarantine

·        nDisinfectioin epidemic focus

 

 

SALMONELLA INFECTIONS

 

Salmonella infections occur worldwide. Acute gastroenteritis, the most nfrequent presentation, is usually self-limited, although bacteremia and focal nextraintestinal infections may develop, especially in immunocompromised npatients. The latter group has become more important and complex because of the nincreasing number of children who are compromised because of acquired immunodeficiency nsyndrome (AIDS), organ transplant, or chemotherapy. Enteric fever, a severe nsystemic disease typically caused by Salmonella typhi, is found mainly ideveloping countries, but it is seen elsewhere because of international travel.

 

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

 

Salmonellae are motile, nonsporulating, nnonencapsulated, gram-negative rods. Most strains ferment glucose, mannose, and nmannitol to produce acid and gas, but they do not ferment lactose or sucrose. nS. typhi does not produce gas. Salmonella organisms grow aerobically and are ncapable of facultative anaerobic growth. They are resistant to many physical nagents but can be killed by heating to 130º F (54.4º C) for 1 hr or n140º F (60º C) for 15 min. They remain viable at ambient or reduced ntemperatures for days and may survive for weeks in sewage, dried foodstuffs, npharmaceutical agents, and fecal material. Like other members of the Enterobacteriaceae, nSalmonella possesses somatic O antigens and flagellar H antigens. The O nantigens are the heat-stable lipopolysaccharide components of cell wall; the H nantigens are heat-labile proteins that can be present in phase 1 or 2. The nKauffmann-White scheme commonly used to classify salmonellae serotypes is based non O and H antigens. Serotyping nis important clinically because certain serotypes tend to be associated with nspecific clinical syndromes and because the detection of an unusual serotype is nsometimes epidemiologically useful. Another antigen is a virulence (Vi) ncapsular polysaccharide present on S. typhi and rarely found on strains of S. nparatyphi C (S. hirschfeldii).

 

These classification schemes are based on biochemical or serologic nreactions. Molecular technology has enabled classification at the gene level. nDNA hybridizations have proven that all Salmonella organisms are closely nrelated genetically as a single species with six subgroups; most isolates ncausing human or animal disease belong to subgroup 1.

 

EPIDEMIOLOGY.

 

About 50,000 cases of culture-proven salmonellosis, napproximately 98% of which are caused by nontyphoidal salmonellae, are reported nannually in the United States. Because culturing and reporting are incomplete, nthe actual number of cases has been estimated as 1–5 million per year. These figures are higher than those of the 1970s and nmay be related to modern practices of mass food production, which increase the npotential for epidemic salmonellosis. About one half of the reported cases noccur in persons younger than 20 yr of age and one third occur in children 4 yr nof age or younger; the highest isolation rate is for infants younger than 1 yr nof age. Nontyphoidal Salmonella infections have a worldwide distribution, with nan incidence related to water potability, sewage disposal, and food preparatiopractices.

 

Salmonella infections occur with highest frequency in the warm months, nJuly through November in the United States. Although most reported cases of nnontyphoidal salmonellosis occur sporadically, outbreaks are well documented, nusually as foodborne (i.e., “food poisoning”). Each year, about 500 nfoodborne Salmonella outbreaks are reported, representing over 50% of all ngastroenteritis outbreaks with a documented bacterial cause. Some of the nSalmonella outbreaks are widespread—interstate or even international—and affect nthousands of individuals. Refinement of outbreak tracing has improved with the ndevelopment of molecular epidemiology techniques, such as plasmid analysis and nendonucleases digestion of chromosomal genes for recognition of small ndifferences 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 nStates include S. typhimurium, S. enteritidis, S. heidelberg, and S. newport.

 

The major reservoir of nontyphoidal salmonellae is ninfected animals, which constitute the principal source of human disease. nInfected animals are often asymptomatic. Salmonella organisms have beeisolated from many animals, including poultry (i.e., chickens, turkeys, ducks), nsheep, cows, pigs, pets, and birds. Animal-to-animal transmission may occur. nAnimal feeds containing fish meal or bone meal contaminated with Salmonella are nan important source of infection for animals. Moreover, subtherapeutic nconcentrations of antibiotics are often added to animal feed. Such practices npromote the emergence of antibiotic-resistant bacteria, including Salmonella, nin the gut flora of the animals. During slaughtering, these gut organisms may ncontaminate the meat, which is subsequently consumed by humans. Data suggest nthat animal antibiotic exposure may be responsible for antibiotic-resistant nSalmonella infections in man.

 

Studies of outbreaks have enabled the collection of numeric data nregarding the sources of human salmonellosis. Poultry and poultry products n(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 nto cause symptomatic disease in healthy adults is 106–108 Salmonella organisms. nIn infants 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 contaminated medical ninstruments (particularly endoscopes) and diagnostic or pharmacologic npreparations, particularly those of animal origin (e.g., pancreatic extracts, npituitary extracts, bile salts, pepsin, gelatin, vitamins, carmine dye). nFoodborne nosocomial transmission is also possible. Hospitalized patients are nat increased risk of severe and complicated Salmonella infections. Intravenous ntransmission by platelet transfusion has been reported.

 

After infection, nontyphoidal salmonellae are excreted in feces for a nmedian of 5 wk. In young children and in individuals with symptomatic ninfections, the excretion period is longer. Prolonged carriage of Salmonella norganisms is rare in healthy children but has been reported in those with nunderlying immune deficiency. During the period of Salmonella excretion, the nindividual may infect others, directly by the fecal-oral route or indirectly by ncontaminating foods. If one household member becomes infected, the probability nthat another will also become infected is about 60%.

 

PATHOLOGY.

 

Enterocolitis is the typical disorder caused by nnontyphoidal Salmonella infection. Findings include diffuse mucosal ninflammation and edema, sometimes with erosions and microabscesses. Although nSalmonella organisms are capable of penetrating the intestinal mucosa, neither ndestruction of epithelial cells nor production of ulcers is usually seen. nIntestinal inflammation, with polymorphonuclear leukocytes and macrophages, nusually involves the lamina propria. Underlying intestinal lymphoid tissue and nmesenteric lymph nodes enlarge and may develop small areas of necrosis. Such nlymphoid hypertrophy may cause interference with the blood supply to the gut nmucosa. Hyperplasia of the reticuloendothelial system is seen also within the nliver and spleen. If bacteremia develops, it may lead to localized infectioand suppuration (with polymorphonuclear leukocyte response) of almost any norgan.

 

 

PATHOGENESIS. The development of disease after infection with nSalmonella depends on the number of infecting organisms, on their virulence ntraits, and on several host defense factors. Ingested Salmonella organisms nreach the stomach, where acidity is the first protective barrier. The acidity ninhibits multiplication of the salmonellae, and when gastric pH reaches 2.0, nmost organisms are rapidly killed. Achlorhydria, buffering medications, rapid ngastric emptying after gastrectomy or gastroenterostomy, and a large inoculum nenable viable organisms to reach the small intestine. Neonates and young ninfants have hypochlorhydria and rapid gastric emptying, which contribute to ntheir increased vulnerability to symptomatic salmonellosis. Because the transit ntime through the stomach is faster for drinks than for foods, a lower inoculum nmay cause disease in waterborne infection.

In the small and large intestines, salmonellae have to ncompete with normal bacterial flora to multiply and cause disease; prior nantibiotic therapy disrupts this competitive relationship. Decreased intestinal nmotility due to anatomic causes or medications increases the contact time of nthe ingested salmonellae with the mucosa and the likelihood of symptomatic ndisease. After multiplication within the lumen, the organisms penetrate the nmucosa, typically at the distal part of the ileum and the proximal part of the ncolon, with subsequent localization in the Peyer patches. The penetratioprocess includes specific attachment to the luminal surface of epithelial ncells, internalization into the cell by receptor-mediated endocytosis, ncytoplasmic translocation of the infected endosome to the basal epithelial nmembrane, and release of the salmonellae in the lamina propria. The role of ncytotoxins, which are produced by most salmonellae, is uncertain. Penetratiousually occurs without destroying epithelial cells, and ulcers are not nproduced.

 

 

Heat-labile, cholera-like enterotoxin is produced by many Salmonella nisolates. This toxin and the prostaglandins that are produced locally increase ncyclic adenosine monophosphate levels within intestinal crypts, causing a net nefflux of electrolytes and water into the intestinal lumen.

 

Genes code for adherence to epithelial cells, invasion of epithelial ncells, a cholera toxin–like enterotoxin, spread beyond the Peyer patches to nmesenteric lymph nodes, intracellular growth in the liver and spleen, survival nin macrophages, serum resistance, and complement resistance. Some of these ntraits are shared by all salmonellae, but others are serotype restricted. These nvirulence traits have been defined in tissue culture and murine models; it is nlikely that clinical features of human Salmonella infection will eventually be nrelated to specific DNA sequences.

 

With most diarrhea-associated nontyphoidal salmonelloses, nthe infection does not extend beyond the lamina propria and the local nlymphatics. S. dublin and S. choleraesuis rapidly invade the bloodstream with nlittle or no intestinal involvement. Specific virulence genes are related to nthe ability to cause bacteremia. These genes are found significantly more oftein strains of S. typhimurium isolated from the blood than the feces of humans. nBacteremia, however, is theoretically possible with any Salmonella strain, nespecially in individuals with reduced host defenses. An impaired nreticuloendothelial or cellular immune response is important. Children with nchronic 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, nSchistosoma mansoni hepatosplenic involvement, and urinary tract Schistosoma nhematobium infection. Localized infections are more common in areas with nimpaired local defenses (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 nan incubation period of 6–72 hr (mean, 24 hr), there is an abrupt onset of nnausea, vomiting, and crampy abdominal pain primarily in the periumbilical area nand right lower quadrant, followed by mild to severe watery diarrhea and nsometimes by dysenteric 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 ngastroenteritis is distinct. Neonates, young infants, and children with primary nor secondary immune deficiency may have symptoms persisting for several weeks. nIn patients with AIDS, the infection may become widespread and overwhelming, ncausing multisystem involvement, septic shock, and death. In patients with ninflammatory bowel disease, especially active ulcerative colitis, Salmonella ngastroenteritis may cause invasion of the bowel with rapid development of toxic nmegacolon, systemic toxicity, and death. Patients with schistosomiasis have nincreased susceptibility to salmonellosis and exhibit persistence of infectiounless the schistosomiasis is also treated. Salmonella organisms are able to nmultiply within the schistosomes, where they are protected from antibiotics.

 

Bacteremia. Transient bacteremia during nontyphoidal Salmonella ngastroenteritis is thought to occur in 1–5% of patients. The precise incidence nis unclear, because blood cultures often are not obtained from patients with nSalmonella gastroenteritis, especially those who are not hospitalized, and nbecause most studies are retrospective. Salmonella bacteremia is associated nwith fever, chills, and often with a toxic appearance. Bacteremia has beedocumented, however, in afebrile, well-looking children, especially neonates. nProlonged or intermittent bacteremia is associated with low-grade fever, nanorexia, weight loss, diaphoresis, and myalgias. Children with certaiunderlying conditions who have Salmonella gastroenteritis are at increased risk nof bacteremia, which may lead to extraintestinal infection. Recurrent nSalmonella septicemia is one of the criteria for diagnosing AIDS according to nthe Centers for Disease Control and Prevention (CDC) case definition. In these npatients, recurrent septicemia appears despite antibiotic therapy, often with a nnegative stool culture for Salmonella and sometimes with no identifiable focus nof infection. Prolonged or recurrent bacteremia is also seen in patients with nschistosomiasis. Hemolytic anemias, malaria, and bartonellosis are associated nwith an increased risk of bacteremia, presumably because of reticuloendothelial nsystem dysfunction. In pregnancy, Salmonella septicemia and fetal loss have nbeen reported. S. typhimurium is the most common serotype causing Salmonella nbacteremia in the United States.

 

Extraintestinal Focal Infections. 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 ichildren with sickle cell disease. Salmonella osteomyelitis and suppurative arthritis nalso occur in sites of previous trauma or skeletal prosthesis. Reactive narthritis may follow Salmonella gastroenteritis, usually in children with the nHLA-B27 antigen. Meningitis appears mainly in infants. Patients usually present nwith little or no fever and minimal symptoms, but rapid deterioration, a high nmortality rate (~50%), and neurologic sequelae occur despite appropriate nantibiotic therapy. Salmonella meningitis occurs also in patients with AIDS, nfor whom the mortality rate is more than 50%, and relapse and brain abscesses ncan occur. Persistent bacteremia suggests endocarditis, arteritis, or ainfected aneurysm. The serotypes causing most extraintestinal focal infections nare S. typhimurium and S. choleraesuis.

 

Asymptomatic Infection. Asymptomatic fecal excretion of salmonellae after ninfection with these organisms has been documented, for instance, as part of aoutbreak investigation. The precise incidence is unclear. After clinical nrecovery from Salmonella gastroenteritis, asymptomatic fecal excretion of nsalmonellae occurs for several weeks. A chronic carrier state is defined as nasymptomatic excretion of Salmonella organisms for more than 1 yr. Although the ncarrier state does occur after nontyphoidal salmonellosis, it is rare (<1%), nand it develops especially in patients with biliary tract disease. The only nsignificance of asymptomatic fecal excretion of nontyphoidal Salmonella is the npotential transmission of the infection to other individuals.

 

DIAGNOSIS.

 

Definitive diagnosis of the various clinical syndromes nis still based on culturing and subsequent identification of Salmonella norganisms. In children with gastroenteritis, cultures of stools have higher nyields than rectal swabs. In patients with sites of local suppuration, naspirated specimens should be used for Gram staining and culture. Salmonella norganisms grow well oonselective or enriched media, such as blood agar, nchocolate agar, or nutrient broth. Normally sterile body fluids (e.g., ncerebrospinal fluid, joint fluid, urine) can be cultured on any of these. For nspecimens normally containing bacterial flora (e.g., stools), selective media, nsuch as MacConkey, XLD, bismuth sulfite (BBL) or Salmonella-Shigella (SS) agar, nwhich inhibit the growth of normal flora, should be used.

 

Several methods are being developed to answer the need for rapid ndiagnosis. Two tests, based on latex agglutination and fluorescence, are ncommercially available for the rapid diagnosis of Salmonella colonies growing nin stool culture enrichment broth or culture plates. Clinical experience is nlimited. Alternatively, chromosomal fragments that are unique to the genus nSalmonella have been employed as DNA probes to detect Salmonella species. The nmethod is still experimental and needs evaluation with clinical specimens. Serologic nassay for detecting antibodies against S. typhimurium and S. enteritidis has nbeen reported, but clinical usefulness is still unclear.

 

DIFFERENTIAL DIAGNOSIS.

 

Salmonella gastroenteritis should be differentiated nfrom other bacterial, viral, and parasitic causes of diarrhea. The presentatioof inflammatory diarrhea with moderate fever should be particularly ndifferentiated from Shigella, enteroinvasive Escherichia coli, Yersinia nenterocolitica, and Clostridium difficile infections. Rotavirus infections iinfants can mimic Salmonella enterocolitis. Etiologic diagnosis on the basis of nthe clinical picture is not possible. Epidemiologic data may be helpful. If nabdominal pain and tenderness are severe, appendicitis, perforated viscus, and nulcerative colitis merit consideration in the differential diagnosis.

 

PREVENTION.

 

Chlorinated water, proper sanitary systems, and nadequate food hygiene practices are necessary to prevent nontyphoidal nsalmonellosis in humans. Handwashing is of paramount importance in controlling nperson-to-person transmission by means of food. In hospitalized patients, nenteric precautions should be used for the duration of illness. Individuals nwith symptomatic or asymptomatic excretion of Salmonella strains should be nexcluded from activities that involve food preparation or child care until nrepeated stool cultures are negative. Promotion of breast-feeding may reduce ninfection, especially in developing communities.

 

Control of the transmission of Salmonella infections nto humans requires control of the infection in the animal reservoir, judicious nuse of antibiotics in dairy and livestock farming, prevention of contaminatioof foodstuffs prepared from animals, and use of appropriate standards in food nprocessing in commercial and private kitchens. Whenever cooking practices nprevent food from reaching a temperature greater than 150º F (65.5º nC) for more than 12 min, salmonellosis may be transmitted. Because large noutbreaks are often related to mass food production, it should be recognized nthat contamination of just one piece of machinery used in food processing may ncause an outbreak; meticulous cleaning of the equipment is essential. No nvaccine against nontyphoidal Salmonella infections is available.

 

TREATMENT.

 

Proper therapy depends on the specific clinical presentation of nSalmonella infection. Assessment of the hydration status, correction of ndehydration and electrolyte disturbances, and supportive care (see Chapter 60) nare the most important aspects of managing Salmonella gastroenteritis ichildren. Antimotility agents prolong intestinal transit time and are thought nto increase the risk of invasion; they should not be used when salmonellosis is nsuspected. In patients with gastroenteritis, antimicrobial agents do not nshorten the clinical course, nor do they eliminate fecal excretion of nSalmonella. By suppressing normal intestinal flora, antimicrobial agents may nprolong the excretion of Salmonella and increase the risk of creating the nchronic carrier state. Antibiotics therefore are not indicated routinely itreating Salmonella gastroenteritis. They should be used in young infants and nother children who are at increased risk of a disseminated disease and in those nwith a severe or protracted course.

 

Children with bacteremia or extraintestinal focal nSalmonella infections should receive antimicrobial therapy. Ampicillin (200 nmg/kg/24 hr in four divided doses) is efficacious and used to be the drug of nchoice; trimethoprim-sulfamethoxazole (TMP-SMX; 10–50 mg/kg/24 hr in two ndivided doses) and chloramphenicol (75 mg/kg/24 hr in four divided doses) are nalso effective. Because of the increasing worldwide antibiotic resistance of nSalmonella strains, it is necessary to perform susceptibility tests on all nhuman isolates. About 20% of Salmonella isolates in the United States are nresistant to ampicillin. Multiresistance to ampicillin, TMP-SMX, and nchloramphenicol has been reported. The third-generation cephalosporins, ncefotaxime (150–200 mg/kg/24 hr in three to four divided doses) or ceftriaxone n(100 mg/kg/24 hr in one or two doses), are effective in these cases, although nclinical experience is still limited. Quinolones are also effective, but they nare not approved for use in children because of the potential damage to growing ncartilage. In children with severe disease, initial treatment with a nthird-generation cephalosporin is recommended until antibiotic susceptibility nis known. Thereafter, antibiotics should be changed accordingly.

 

The duration of antimicrobial therapy is 10–14 days ichildren with bacteremia, 4–6 wks for acute osteomyelitis, and 4 wk for nmeningitis. In a child with a focal suppurative process, surgical drainage is nnecessary in addition to antibiotic treatment. Surgical intervention is oftenecessary in intravascular Salmonella infections (e.g., repair of aneurysm, nreplacement of valve) and in cases of chronic osteomyelitis.

 

PROGNOSIS. Complete recovery is the rule in healthy children who ndevelop Salmonella gastroenteritis. Young infants and immunocompromised npatients often have systemic involvement, a prolonged course, and ncomplications. The prognosis is poor for children with Salmonella meningitis n(~50% mortality rate) or endocarditis.

 

Short statement of the material

Salmonellosis is an acute infectious ndisease of human and animals, that is caused by the numerous strains of nSalmonella and more frequent courses as gastro-intestinal, rare – as typhoid nand septic forms

 

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

•         nS. typhimurium

•         nS. enteritidis

•         nS. java

•         nS. anatum and other

Bacteria are stable in the environment (for months and nyears they live in 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.     Massive entering nof bacteria to the alimentary canal.

2.     Destruction of salmonella in the upper departments of alimentary canal.

3.     Toxemia → vomit (as a nprotective factor).

4.     Entering of other bacteria into thiintestinum, colon, colonization of epitheliocytes.

5.     Local inflammatory process, ndysperistalsis, digestion and suction imparement, biologically active substance naccumulation, which impare absorption of water, electrolytes n(diarrhea, dehydration).

6.     Damage of nthe intestinal, lymphatic barriers (septic form of salmonellosis).

7.     nBacteriemia.

8.     nForming of septic focuses.

 

Classification

1.     nLocal form

•         nGastrointestinal nform

•         n Bacterium carrying

2.     nGeneral form

•         nTyphoid fever – like

•         nSepsis

3.     nAsymptomatic form

    nII.            nSeverity (mild, moderate and severe)

III.            nDuration

•         nAcute (up to 1.5 mo)

•         nSubacute (up to 3 nmo)

•         nChronic (more than 3 mo)

IV.            nCourse

•        nSmooth

•         nUneven (with complication)

V. Bacterium carrier

 

Clinical diagnostic 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 npain;

·       ndiarrhea, nusually 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, nhallucinations;

·       n“Typhoid” ntongue;

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

·       nskirash (roseols) on the trunk;

·       ndiarrhea; n

·       ntenderness nin the right inguinal part of abdomen.

 

Septic form

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

·       nUsually noccurs iewborns, infants with predisposal factors (hypotrophy, rickets so non).

·       nAcute nbeginning from fever that becomes hectic.

·       nSeptic nfocus: meningitis, pneumonia, osteomyelitis, pyelonephritis, enterocolitis);

·       nhepatosplenomegaly; n

·       nhemorrhagic nsyndrome;

·       ndevelopment nof toxic-dystrophic syndrome;

·       nrelapses, n

·       nlongitude nduration, formation of carrying;

·       nhigh nmortality;

·       nantibiotic nresistance, nosocomeal strains of Salmonella;

·       ncontact nway of spreading.

 

Salmonellosis Features in the newborns

·        nGeneralized form, high lethality.

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

·        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 ndifferential

•         nCultures: Isolatioof Salmonella from cultures of stool, blood, urine, or bone marrow is ndiagnostic. 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:

·       Salmonellosis (S. enteritidis), ntypical local gastrointestinal form (enterocolitis), moderate degree, acute nduration. Complication: isotonic dehydration, n1st degree.

·       Salmonellosis (S. typhimurium), ntypical generalized septic form (enterocolitis, meningitis, bilateral npneumonia, left humeral bone osteomyelitis), severe degree, subacute duration. Complication: malnutrition, 2^nd degree.

 

Differential ndiagnosis should be performed with: functional ndiarrhea, shigellosis, escherichiosis, klebsiellosis, typhoid fever, and sepsis nof 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.

 

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 ncoli, and is characterized by localization of npathological process in Gastro-intestinal tract with development of toxic and ndiarrhea syndromes, rarer – defeat of other organs or generalization of the nprocess up to sepsis or failure to thrive development.

 

Etiology: enterotoxigenic, enteropathogenic, enteroinvasive, nenterohemorrhagic Escherichia Coli. Escherichia coli, a facultative nanaerobic gram-negative bacillus, is a major component of the normal intestinal nflora and ubiquitous in the human environment.

They well grow in ordinary  environments, ave a difficult antigestructure. Microbes contain a somatic 0-antigen, flagellate Н-antigeand superficial somatic O-antigen. Distinctions in a 0-antigen devide bacteria ninto number of 0-groups (serological groups) Different pathogenic effects, ncaused 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. ncoli that cause diarrhea are known: enterotoxigenic, enteropathogenic, enteroinvasive, nenterohemorrhagic, enteroadgesive (enteroadherrent).

 

Epidemiology:

·       Source of infection – ill person or carrier;

·       Way of spreading – orally – Fecal (by water, milk, food); by direct ncontact;

·       nSusceptible organism: children, especially before 2 nyears of old.

 

Pathogenesis:

1.     Invasioof bacteria in GIT

2.     Reproduction of bacteria, nselection of toxins

·        nEPE on the enterocytes surface

·        nETE on the enterocytes microvilli surface

·        nEIE, EHE in the colon epithelial cells

3.     Local inflammatory process n(EPE, EIE), toxemia (EPE, EIE)

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

5.     Diarrhea

6.     In severe cases: bacteremia (sepsis)

 

 

Clinical features

Enteropathogenic diarrhea nis usually self – limited in older children and adults. Nausea, vomiting, ncramps and voluminous diarrhea without blood and mucus are common. Diarrhea nlasting 2 weeks or longer in infants.

Enterotoxigenic diarrhea nincludes nausea, vomiting, cramps and frequent watery stools. There no fecal nleukocytes in the stool. This syndrome is usually self – limited and lasts nabout 5 days.

Enteroinvasive nstrains are associated with a clinical picture comparable to those observed nwith shigella. Nausea and vomiting frequently accompany abdominal pain. The ndiarrhea is less in volume than that seen with ETEC strains and contains mucus nand blood. Fever, headache, and myalgia are common.

Enterohemorrhagic nescherichiosis is associated with severe abdominal cramps, low – grade fever, ngrossly bloody stools, nausea and vomiting. This organism also has been found nin association with hemolytic uremic syndrome (HUS).

5. nEnteroadgesive (enteroadherrent) Е. coli  nwere primary selected in 1985. They have not invasive activity, does not nform cytotoxins and does not have a plasmide adhesive factor. The category of nEAEC while is not represented by any serological group.

 

Enteropathogenic nE.coli infection criteria

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

·        nAccordingly: gradual or acute illness beginning.

·        nThe watery massive yellow-orange feces with the ntoo-bit of mucus the green color 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, nDIC-syndrome, infectious-toxic shock.

Massive yellow-orange feces

 

Enteropathogenic nE.coli infection peculiarities iewborns

·        nhospital infection caused by resistant cultures.

·        ninfection generalization with development of sepsis.

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

·        nRarely occurs diarrhea.

·        nHigh lethality.

 

Enteroinvasive E.coli infectiocriteria

·        nLatent period is 1-3 days.

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

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

·        nAbdomen is tender by the colon way, infiltrated nsigmoid colon, tenesms are absent.

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

 

Enteroinvasive nE.coli infection peculiarities 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 E.coli infectiocriteria

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

·        nAcute beginning from the repeated vomiting, watery ndiarrhea.

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

·        ngrumbling along thin intestine during palpation.

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

·        nDevelopment of severe dehydration

·        nDuratioof the disease is not more than 5-10 days.

 

Enterohemorrhagic Е. coli  infection criteria

·        nLatent period is n1-7 days, rarer 9-10 days.

·        nA disease has nmoderate or severe course.

·        nAcute nbeginning.

·        nCrampy pain in epigastrium or in all abdomenm.

·        nDevelopment of secretory diarrhea nin the first days.

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

·        nAbsence of febrile nfever.

·        nComplications:

o   hemolytic-uremic nsyndrome at 2-7%, at the end of the first – beginning of the second week of ndisease

o   acute kidney insufficiency,

o   hemolytic nanaemia,

o   thrombocytopenia,

o   Cramps and other neurological disorders (up to nblindness).

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

·        nLetality nis  1-2%. In HUS – 5-10%.

 

Enteroadgesive n(enteroadherrent) escherichiosis is not ngood studied

 

Laboratory test

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

– A culture of the stools

– Serologic reaction (IHAR in dynamics nwith fourfold title increasing in 10-14 days) in children elder than 1 year if nfecal culture is negative.

Diarrhea Classification

 

n

Diarrhea’s type	Diagnostic’s criteria	Severity	Main 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 nperformed among acute non infection diarrheas, salmonellosis, shigellosis, nstaphylococcal diarrhea, viral diarrhea, and cholera.

Diagnosis example:

E.coli infection (caused by nEnterotoxigenic strain), typical form, severe degree.

Complication: hypertonic dehydration, n3^rd degree.

 

Treatment

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

Dehydration: Dehydration means the body does not have enough fluids nto function at an optimal level. Dehydration can be caused by fluid loss n(through vomiting, diarrhea or excessive urination), inadequate intake, or a ncombination of both. The most common cause of dehydration in infants and nchildren is acute gastroenteritis, nwith its associated vomiting and diarrhea.

 

 

 

 

1. Rehydration 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	Childre aged before 3 yrs	3-5%	6-9%	10% and more
	Childre 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 sunken	Sunken
Eyeballs		Not changed	Soft	Sunken expressively
Mucus membranes of the mouth		Moist	Slightly dry	Dry
Ski 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 nrehydration is most effective, when is performed from the first hours of the ndisease. Oral rehydration must be the first aid at home when the disease nbegins. It doesn’t have any contraindications.

Iaccordance with recommendations of WHO optimum composition of solutions for noral rehydration is:

sodium n- 60 mmol/l;

potassium n- 20 mmol/l;

bicarbonates n- 10 mmol/l;

glucose n- 110 mmol/l;

osmolarity nis – 250 mosmol/l.

Content nof sodium and potassium in solutions for oral rehydration must correspond their naverage losses at an acute intestinal infection. The concentration of glucose nin them must help water resorptioot only in an intestine but also ikidneys. Because high osmolarity it is not recommended to give fruit juices, nsweet drinks (Coca-cola, and others like that) during the oral rehydration.

The nmethod of oral rehydration have to start immediately, because dehydratiobegins after the first liquid, watery emptying, yet long before appearance of nclinical signs of dehydration. Valuable rehydration therapy is performed i2 stages.

The 1^st nstage is nrehydration therapy which is carried out during 4-6 hours for proceeding of the nlost liquid volume. During the mild dehydration – 30-50 ml/kg, at moderate ndegree – 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 nof liquid introduction through a mouth is 5 ml/kg/hour.

Criteria of the n1^st stage efficiency: (are estimated in 4-6 hours)

·        ndisappearance of thirst,

·        nimprovement of the tissues turgor,

·        nmoistening of mucus membranes,

·        nincrease of diuresis,

·        ndisappearance of microcirculation violation signs.

Choice of nsubsequent tactic:

1.     nif signs of dehydration have disappeared – continue the 2^nd nstage of rehydration therapy.

2.     nthe signs of dehydration have diminished, but still are present – it is nneeded to continue to give solution through a mouth during the following 4-6 nhours in a previous volume.

3.     nthe signs of dehydration have increased – parenteral rehydration should nbe start.

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

Method nof the 2^nd stage:

Supporting noral rehydration means that to the child for every following 6 hours is entered nso many rehydration solution, as he has lost during previous 6 hours.

Oriented nvolume of solution for supporting rehydration for children before 2 yrs is n50-100 ml, children elder than 2 yrs – 100-200 ml or 10 ml/kg of solution after nevery emptying. On this stage oral rehydration solution is possible to nalternate with fruit or vegetable sugar free decoctions,  or tea, especially green. At vomit rehydratiotherapy is continued after 10-minute pauses. In the hospital in case the child nrefuse to drink or at presence of vomit tube rehydration should be done. nNasogastric tube rehydration can be done continuously with a help of the system nfor intravenous infusion, with maximal speed 10 ml/min.

 

Parenteral rehydration

 

At nacute intestinal infections, which are accompanied by the 3^rd stage nof dehydration, with multiple vomits, anorexia, waiver of drink, oral nrehydration is combined with the parenteral rehydration.

Solutions for nparenteral rehydration:

·        nRinger’s lactat,

·        nRinger’s acetate,

·        nIsotonic glucose solution,

·        nIsotonic sodium chloride solution.

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

To nthe children of early age it is necessary to eliminate solutions, which contaiplenty of sodium, chlorine, glucose (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 n(sodium, potassium, magnesium, calcium) or acid-base balance changes it is need nto correct them.

 To nperform parenterally rehydration it is necessary to define:

·        nDay’s requirement of liquid and electrolytes.

·        nType and degree of dehydration.

·        nLevel of liquid deficit.

·        nCurrent losses of liquid.

Principle of nvolume calculation for the infusion therapy:

Day’s nvolume of liquid in case of dehydration consists of:

a)     ndeficit of liquid before the treatment (a loss of body weight during the ndisease),

b)    nphysiologic liquid’s requirement,

c)     ncurrent pathological losses.

a) For the calculation of physiologic nliquid’s requirement it is possible to recommend the method of Holiday Segar that is used nthe most widely in the world (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% nof dehydration = 10 ml/kg

1 kg of weight loss = 1 liter

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

The expected nvolume of liquid is entered during a day.

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

Liquid’s nrequirement per hour of the infusion is more physiologic:

New-born: n

1-st nday of life – 2 ml/kg/hour;

2-nd nday of life – 3 ml/kg/hour;

3-rd nday of life – 4 ml/kg/hour;

Elder nchildren:

weight nup to 10 kg n- 4 ml/kg/hour;

weight nfrom 10 to 20 kg n- 40 ml/hour + 2 ml for every kg over 10 kg;

weight nmore than 20 kg n- 60 ml/hour + 1 ml on every kg of weight of body over 20 kg

A calculation of nsalts requirements:

Special nattention should be paid to the correction of sodium and potassium deficit, losses of which can be considerable. It nis necessary to remember, that sodium na child will get with crystalloid solutions which are entered in certaicorrelations with glucose depending type and severity of dehydration. If nlaboratory control is not done, potassium nis entered according the physiologic necessity (1-2 mmol/kg/day). Maximal daily namount must 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 0.3-0.5% n(maximally 6 ml 7.5% KCl on 100 ml of glucose). 1 ml of 7.5% KCl solutiocontains 1 mmol of K⁺. Before entering potassium it is necessary to nrestore urination, as anuria or severe oliguria is contra-indication for nintravenous potassium infusion. Blood potassium in plasma as 6.5 mmol/l is nthreatened for the life, in concentration 7 mmol/l hemodialysis is needed.

Determinatioof salts deficit is based on laboratory information.

Acute nintestinal infections in children mainly are accompanied by isotonic type of ndehydration, that’s why determination of blood electrolytes to all childrewith diarrhea is not necessary. Determination of Na+ and K+ is necessary at 3^rd ndegree of dehydration and for children with 2^nd degree of ndehydration, in which general condition severity does not correspond the ndiarhea severity, anamnes is complicated, a rapid effect from the rehydratiotherapy is absent.

A ncalculation of sodium and potassium deficit is done by the following formula:

Iodeficit = (normal ION concentration – patient’s ION concentration) х  M х К, where

M is nweight of the patient

K is na coefficient of intracellular liquid volume.

K = n0.3 – before 1 year

K = n0.2 – after 1 year and for adults.

Thait is necessary to define the amount of sodium and potassium in solutions which nare entered, volume and correlations of which are already expected. A content nof these ions in solutions which are often used, are represented in a table. nAfter the urgent intravenous rehydration it is necessary to check up the level nof sodium and potassium in plasma.

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 solution	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 ninto account importance of magnesium ions for the child’s organism, and also nthat the magnesium losses go parallell with potassium losses on the first stage nof rehydration therapy a 25% solution of magnesium is rotined in the dose of n0,5-0,75 mmol/kg (1 ml of solution = 1 mmol of magnesium).

Ichildren with a severe malnutrition daily necessity in potassium and magnesium nis enlarged (up to 3-4 mmol potassium 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 nml/kg/day on every degree of temperature over 37.0 ^oC;

20 nml/kg/day  in case of vomit;

20-40 nml/kg/day in case of intestinal paresis;

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

30 nml/kg/day for perspiration.

Control nof correct rehydration therapy is frequency of pulse, frequency of breathing, nbody weight and diuresis dynamics.

Rehydration therapy depending the type of ndehydration

It nis necessary to take into account the type of dehydration to choice solutions and ntheir correlations for the rehydration therapy. There are 3 types of ndehydration: isotonic, hypertonic (water deficient) and hypotonic  (salt deficient) (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
Ski	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 nDehydration Types

 

 

At isotonic nrehydration n(Na 130-150 mmol/l) develops as a result of equal losses of salts and water; it nis the most often type of dehydration in children with an acute intestinal ninfection. In the first days (in case of microcirculation maintenance) nrehydration is performed by 5% glucose solution in combination with 0.9% sodium nchloride or Ringer’s lactate solution in correlation (2:1) with parallel ncorrection of electrolytes.

Next ndays of rehydration therapy glucose-saline solutions in a volume which provides nthe physiology liquid’s requirement of organism, remnant volume for the ncompensation of dehydration, current pathological losses, correction of plasma nelectrolytes are performed.

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

Rehydratiotherapy should be done by a 5% glucose solution in combination with 0.9% sodium nchloride solution in correlation (3:1).

During nthe rehydration therapy for patients with hypertonic dehydration it is need to ntake into account daily sodium requirements (2-3 mmol/kg). Thus should be takeinto account sodium in solutions for infusion.

If nthe level of sodium is 140-150 mmol/l, then amount of sodium should be  decreased 2 times from physiology necessities, nand at the increase of it more than 150 mmol/l solutions which contain sodium nare eliminated, except  colloid ones.

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

To nprevent cerebral edema control of plasma osmolarity and body weight is needed. nOn this stage a speed of infusion is 15-20 drops per hour.

Hypotonic ndehydration n(Na < 130 mmol/l) develops as a result of salts losses predominance above nliquid loses, excessive injection of water with small amount of salts. It ndevelopes in case of intestinal infections which are accompanied by frequent nvomit, or during oral rehydration by solutions with small amount of salts.

Rehydratiotherapy is done by 5% glucose solution in combination with 0.9% sodium chloride nin correlation (1:1).

If nthe level of sodium is less than 129 mmol/l it is needed to correct it n(calculate it by formula described before). During the correction of sodium nhypertyonic solutions are avoided. Their infusion can result in acute nintracellular dehydration, first of all cerebral. Except this, anaphylactic nreactions can develop. The correction of sodium is done by 0.9% NaCl, Ringer’s nlactat.

If nit is impossible to investigate blood electrolytes, glucose-saline solutions nare infused in correlation 1:1.

By nthe WHO recommendations (if the fast rehydration is necessary in case of nlaboratory control absence) the volume and speed of 0.9% NaCl, Ringer’s lactat ninfusion on the first rehydration stage should 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 ncondition of the child is checked up each 15-30 minutes to normal pulse filling non a radial artery. If the condition of child does not get better, speed of ninfusion should be increased. After that the condition of the child is estimated nevery hour (abdominal skin fold, consciousness, possibility to drink).

After nall volume is entered the child’s condition should be estimated again:

·        nif the signs of severe dehydration still present – repeat infusion agaiaccording the table 6.

·        nif the child’s condition gets better, but there are signs of moderate ndehydration – continue oral rtehyderation according the table 2. If a child is breast fed, it is recommended to continue nfeeding; numbers of feeding should be increased.

·        nif signs of dehydration are absent, then the duration of feeding should nbe increased. 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.

Supervisioafter children with a severe malnutrition and dehydration during the nrehydration therapy should be done each 30 minutes during the first 2 hours, nand then every hour next 4-10 hours. At signs of hyperhydratation (increase of npulse frequency on 15 per minute, breathing frequency on 5 per minute) nrehydration should be stopped. Than estimate the child’s condition through ahour.

During nparenteral rehydration for such children, and also for children with pneumonia, ntoxic encephalopathy, speed of liquid infusion must not exceed 15 ml/kg/hour. nAt these states daily body weight gain in the first 3 days must not exceed n1-3%.

Icase if dehydration is absent and infectious toxic shock is developed nreanimation measures according the protocol should be done.

 

1.     Antibacterial therapy

 

   

 

Antibacterial ntherapy at invasive diarrhea is given to:

1.     nChildren with severe and moderate forms of disease.

2.     nChildren aged before 3 months independent of the disease severity.

3.     nChildren with the immune deficiency, HIV-infected children,  children, that receive immune suppressive therapy n(chemical, ray), long corticosteroid therapy, children with hemolytic nanemia,  hemoglobinopathies independent nof age and the disease severity.

4.     nChildren with hemocolitis independent of age and the disease severity.

5.     nChildren with the secondary bacterial complications in all age groups.

Antibacterial ntherapy at secretory diarrhea is given to:

1.     nChildren with severe and moderate forms aged before 6 months.

2.     nChildren with the immune deficiency, HIV-infected children, children, nthat receive immune suppressive therapy (chemical, ray), long corticosteroid ntherapy, children with hemolytic anemia, hemoglobinopathies.

3.     nCholera, parasitogenic diarrhea independent of age and the disease nseverity.

4.     nChildren with the secondary bacterial complications in all age groups.

Antibacterial ntherapy is nnot indicated to:

1.     nChildren with mild, effaced and moderate forms of infections, except for nthose which are listed above.

2.     nChildren with bacterial transmitting of any etiology (transitory, npostinfectional).

3.     nChildren with alimentary dysfunction, as a result of an acute intestinal ninfection (intestine dysbiosis, lactase insufficiency, celiac syndrome, nsecondary enzymopathy etc.).

 

Antibacterial ntherapy if the etiology of an 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	Preparation 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	Erythromyci Ciprofloxaci	Aminoglycosides** Amoxacyllin/сlavulanat Carbapenems (imipenem, carbapenem)
Yersinia enterocolitica	Ceftriaxon Cefotaksim Ciprofloxaci	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

Preparation	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
Ciprofloxaci (through a mouth)	15 mg/kg (maximal dose is 500 mg) Course of treatment 3 days	2 times per day
Ceftriaxon (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
Azythromycin (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
Doxycycli (through a mouth) to children elder than 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 nis recommended to prescribe for empiric therapy of an acute intestinal ninfection (in case of the unknown etiology): Nifuroxazid, nTrimetoprim/sulfamethoxazolum, Cefotaxim, Ceftriaxon, Ciprofloxacin.

At a nnecessity of empiric antibacterial therapy of secretory diarrhea cefalosporins nof 3-4 generations are used.

Diet

Aimportant moment in organization of sick children feeding is a waiver of nwater-tea pauses, as it is well-proven that even at the severe forms of ndiarrhea the digestive function of greater part of intestine is saved, and npauses will decelerate reparation processes, reduce intestine tolerance to the nmeal, and considerably weaken immunity of organism. A volume and composition of nmeal depends from child’s age, weight and severity of diarrhea, character of nprevious diseases. Rational feeding is important for rapid renewal of the nintestinal function.

Ithe acute period of gastroenteritis it is recommended to diminish daily nvolume of meal on 1/2-1/3, in the acute period of colitis – on 1/2-1/4. nPossibly increase of feedings up to 8-10 times per day for infants, especially nat urges on vomit. In this time most physiology is consider early, but gradual nrenewal of feed. Proceeding in high-quality and quantitative composition of nmeal is characteristic for this age of child, carried out in short period after nthe rehydration and disappearance of dehydration (4-5 days). In this period it nis recommended diet for every day. The fat, fried, smoked food and others like nthat are eliminated from a ration in elder children.

If a nchild is breast fed, it is recommended to continue feeding. Children on the nartificial feeding are fed by the same chart, by lactose free formulas.

Products nwith high amount of lactose should be eliminated (milk formulas, milk, fruit njuices). This will decrease secretory diarrhea duration Children on the nartificial feeding are fed by the same chart, by lactose free formulas. Lactose nfree diet should last individually from 1-4 weeks to 1.5-2 months. Porridges nprepared on water are recommended, meet puree should be given earlier. Diary nmilk formulas after 8 month 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, bananas, napple and carrot puree contain large amount of pectins are recommended in case nof 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 nadditional medicine during antibacterial therapy. Probiotics, which contailacto-, bifid bacteria and propineb bacteria. Self eliminate probiotics n(contain saccharomycets) or probiotics which contain lacto bacteria are used iinvasive diarrhea on a background of antibacterial therapy. The last ones are nstable to antibiotics.

 

 

 

To nthe children with the immunodeficiency, those which are treated  in the intensive care units probiotics aren’t nappointed.

The ncourse of therapy lasts for 5-10 days.

 

Enterosorbents

Enterosorbents nare able to fix on their surface hundreds of millions bacteria. Fixed microbes nare ruined and hatch from a sick organism. Together with the bacteria nenerosorbents fix on their surface rotaviruses from the intestine cavity. nExcept for the infectants enerosorption destroy the toxins of microbes and nproducts of their metabolism. They transform toxic matters in less toxic.

The nmost perspective at treatment of an acute intestinal infection in children are n”white”, alumsilicate enerosorbents. Unlike coal sorbents they do not nrequire introduction of high dose of preparation for achievement of therapeutic neffect. Also coal sorbents get to the submucous layer of the intestine and cadamage it.

 

 

Iobedience to WHO recommendations (2006) in auxiliary therapy of an acute nintestinal infection are recommended preparations of zinc (to the childrebefore 6 months – 10 mg per day, children elder than 6 months – 20 mg per day nduring 10-14 days. 

 

Primary nProphylaxis:

•         nSanitary ndisposal of human feces

•         nProtection, npurification and boiling of water

•         nCorrect npreparing and saving of foodstuffs 

•         nPersohygiene

 

Secondary nProphylaxis

Ill Person

•         nIsolation period –until  the stool culture taken 3 days after stopping netiologic treatment is negative

•         nCurrent and terminal disinfection

•         nMedical supervision for 1-3 mo

Contact children   

Stool culture

 

Prophylaxis of acute bowel diseases:

 – Epidemiological control.

 – Isolation and sanation of ill person and ncarriers.

 – Reconvalescent may be discharged from hospital nafter one negative feces culture (taken 2 days after stop of antibiotic ntherapy).

 – 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 nan acute contagious disease of men and animals that is caused by Rotavirus, is npassed by a fecal-oral mechanism, and is characterized by the damage of ngastro-intestinal tract (as gastroenteritis).

 

Etiology:  an agent is Rotavirus nfrom Rheoviridae.

 

Epidemiology:

·                     nthe source of infection is npatient or virus carrier;

·                     nthe mechanism of transmission  is fecal-oral (through the infected water, nfood, 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.     nLatent nperiod is 1-4 days.

2.     nDVF-syndrome n(diarrhea, vomiting, fever):

ü ndiarrhea n(gastroenteritis, enterocolitis) during 3-6 days stools are «sprinkling», ncolorless, watery;

ü nVomits n(precedes or appears together with diarrhea) during 1-3 days;

ü nFever n(moderate) – 2-4 days.

 

Features of nRotavirus infection niew-born

ü nOfteis hospital infection.

ü nAcute nbeginning with the refuse of breast feeding, vomits, diarrhea, development of nthe dehydration ІІ-ІІІ stage

ü nPossible ngradual beginning with growth of degree of dehydration.

Often is lethal.

 

Confirmation of diagnosis

ü nVirology by immune-electronic microscopy, IEА, diffuses precipitation in a ngael.

ü nSerological – NR, CBR, DHAR.

ü nIn koprogram – lymphocytes, impaired enzyme intestinal nfunction.

 

Diagnosis nexample:

Rota-viral ninfection typical form, severe degree.

Complication: nhypotonic dehydration, 2^nd degree.

A ndifferential diagnosis is nperformed with cholera, salmonellosis, enterotoxigenic escherichiosis; acute nintestinal infections caused by relative pathogenic bacteria.

 

Treatment: see treatment of Ecsherichiosis

 

Primary nProphylaxis:

ü Sanitary disposal of human feces

ü nProtection, npurification and boiling of water

ü nCorrect npreparing and saving of foodstuffs 

ü Person hygiene

 

Secondary nProphylaxis

Ill Person

ü nIsolation 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 children   

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.

 

 

 

 

 

 

References:

Main: n     

1.     nAmbulatory pediatric care/ edited by nRobert A. Derchewitz; – 2^nd ed. – Lippincot – Raven, 1992. – p. n404-411, P.425-429.

2.     nCurrent therapy in pediatric ninfections disease – 2/ edited by John D. Nelson, M.D. – B.C. Decker Inc. nToronto, Philadelphia, 1988. – p.74-77, 80-81.

3.     nPrinciples nand Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry nK. Pickering, Charles G. Prober, Philadelphia, Pa: Churchill Livingstone; 1997. n– 1921 p.

 

Additional:

1.                       nCleary TG: Yersinia. In: Behrman RE, Kliegman RM, Jenson HB, eds. NelsoTextbook of Pediatrics. 16th ed. Philadelphia: WB Saunders; 2000: 857-859.

2.                       nPickering L, ed: Yersinia enterocolitica and Yersinia pseudotuberculosis ninfections. In: Red Book: Report of the Committee on Infectious Diseases. 25th ned. Elk Grove Village, Ill: American Academy of Pediatrics; 2000: 642-643.

3.                       nTextbook nof Pediatric Nursing.  Dorothy R. Marlow; nR. N., Ed. D. –London, 1989.-661p.

4.                       nPediatrics ( 2^nd edition, editor – Paul nH.Dworkin, M.D.) – 1992. – 550 pp.

5.                       nBehrman R.E., Kliegman R.M., Jenson H.B. Nelsoextbook of Pediatrics. n- Saunders. – 2004. – 2618 p.

6.                       nCastaneda C. Effects of Saccharomyces boulardii in children with Chronic nDiarrhoea, Especially Due to Giardiasis // Revista Mexicana de Puericultura y nPediatria. – 1995. – V. 12. – P. 1462-1464.

7.                       nGuidelines for control of shigellosis, icluding epidemics due to nShigella type 1/-World Health Organisation, 2005.

8.                       nImplementing the New Recommendation on the Clinical Management of nDiarrhoea. – World Health Organisation, 2006.

9.                       nKlein J.D., Zaoutis T.E. Pediatric Infectious Disease Secrets. – nPhiledelphia: Hanley & Belfus Inc, 2003. – P. 142.