Lesson 4
Meningococcal infection. Poliomyelitis. Enteroviral infection.
MENINGOCOCCAL INFECTIONS
Meningococcal disease, first described by Vieusseaux in 1805 as epidemic cerebrospinal fever, remains a significant health problem, particularly in the developing world. Although nasopharyngeal colonization rarely leads to disseminated disease, the fulminant, rapidly fatal course of a child with meningococcemia is not soon forgotten.
ETIOLOGY.
Neisseria meningitidis is a gram-negative diplococcus (0.6 ´0.8 mm) that is often described as biscuit shaped. It is a common commensal organism of the humaasopharynx and has not been isolated from animal or environmental sources. The meningococcus is fastidious, and growth is facilitated in a moist environment at 35–37º C in an atmosphere of 5–10% carbon dioxide. It grows well on several enriched media, including supplemented chocolate agar, Mueller-Hinton agar, blood agar base, and trypticase soy agar. On solid media, colonies are transparent, nonpigmented, and nonhemolytic. N. meningitidis is identified by its ability to ferment glucose and maltose to acid and its inability to ferment sucrose or lactose. Indole and hydrogen sulfide are not formed. The cell wall contains cytochrome oxidase, which results in the positive oxidase test result.
The meningococci have been divided into serogroups based on antigenic differences in their capsular polysaccharides. At least 13 serogroups have been identified, but groups A, B, C, W, and Y account for most meningococcal disease. The other serogroups often colonize the nasopharynx but rarely disseminate. Lipooligosaccharides (e.g., endotoxin) and proteins found in the outer membrane complex are also used to serotype meningococcal strains.
EPIDEMIOLOGY.
Meningococcal dissemination occurs as endemic disease punctuated by outbreaks of cases that are often clustered geographically. True epidemics have become rare in developed countries but remain a significant problem in much of the developing world. Endemic disease appears to be caused by a heterogeneous group of meningococcal serotypes, and epidemics are caused by a single serotype. Analysis with multilocus enzyme genetic methods has confirmed that a meningococcal epidemic is caused by strains derived from a single clonotype.
The Centers for Disease Control (CDC) reported the results of a laboratory-based surveillance for meningococcal disease in a large United States population for the years 1989 through 1991. The average annual rate of invasive disease remained fairly constant at 1.1 per 100,000 members of the population. It was estimated that 2,600 cases of meningococcal disease occurred annually in the United States during this period. The highest attack rates were during the winter and early spring months. Males accounted for 55% of the total cases, and 29% of the cases occurred in children younger than 1 yr of age, with the peak incidence of disease being 26 per 100,000 infants less than 4 mo of age. Forty-six per cent of the cases occurred in children 2 yr of age or younger, and an additional 25% of the cases occurred in persons 30 yr of age or older. Serogroup B and serogroup C meningococci accounted for near-equal proportions of disease (46% and 45%, respectively), but 69% of group C disease occurred in persons older than 2 yr of age. Fifty-eight per cent of the cases were reported to have meningitis. N. meningitidis was isolated from blood in 66% of cases, cerebrospinal fluid (CSF) in 51%, and joint fluid in 1%.
Meningococcal disease, particularly group A, remains a major health problem in much of the developing world. Many areas, such as China and Africa, have an endemic rate of disease of 10–25 per 100,000 persons and major periodic epidemics (100–500 cases/100,000). Epidemic disease typically involves individuals who are older than those with endemic disease.
PATHOGENESIS.
N. meningitidis is thought to be acquired by a respiratory route. Colonization of the nasopharynx with meningococci usually leads to asymptomatic carriage, and only rarely does dissemination occur. Colonization can persist for weeks to months. Carriage rates vary from 2–30% in a normal population during nonepidemic periods but are higher among children in day-care centers and in conditions of crowding. The carriage rate can approach 100% in a closed population during an epidemic.
For colonization to take place, meningococci must evade mucosal IgA and adhere to epithelial cells in the nasopharynx. This is facilitated by the secretion of proteases that cleave the proline-rich hinge region of IgA and render it nonfunctional. Meningococci and gonococci produce this enzyme, but nonpathogenic Neisseria organisms do not. Meningococci then bind selectively to nonciliated epithelial cells. Pili appear to be of major importance in the attachment of meningococci to the humaasopharynx. The bacteria enter nonciliated epithelial cells by a parasite-directed endocytotic process and are carried across the cell in membrane-bound vacuoles.
Meningococci disseminate from the upper respiratory tract through the bloodstream. Serum antibody leading to complement-mediated bacterial lysis has been shown to block this dissemination, and a deficiency of antimeningococcal antibody is associated with the development of meningococcemia. Bactericidal antibody is directed against the capsular polysaccharide, subcapsular protein, and lipooligosaccharide antigens. Newborn infants have protective antibody that is primarily IgG of maternal origin. As this antibody wanes, infants 3–24 mo of age experience the highest incidence of meningococcal disease. By adulthood, most individuals have developed natural immunity against N. meningitidis.
The source of this immunity comes from nasopharyngeal colonization with N. meningitidis and colonization of the gastrointestinal tract with enteric bacteria that express cross-reactive antigens. Infants have a high carriage rate of an unencapsulated, nonpathogenic neisserial strain, N. lactamica, that leads to the development of bactericidal antibody against the meningococcus.
The importance of the complement system in host defense against N. meningitidis is underscored by the fact that individuals with primary or acquired complement deficiency have an increased risk of developing meningococcal disease, and 50–60% of individuals with properdin, factor D, or terminal-component deficiencies develop bacterial infections that are caused almost solely by N. meningitidis. Recurrent infection is common with terminal component deficiencies but is uncommon with properdin deficiency. Acquired complement deficiency also carries an increased risk and can be seen with systemic diseases that deplete serum complement. Examples are systemic lupus erythematosus, nephrotic syndrome, multiple myeloma, and hepatic failure.
The group B capsule is a homopolymer of sialic acid, which is known to inhibit alternative complement pathway activation. Antibody that activates the classic pathway can overcome this inhibition. The lack of specific antibody coupled with the inhibition of the alternative pathway may explain the prevalence of serogroup B meningococcal disease in young children.
PATHOLOGY. Disseminated meningococcal disease is associated with an acute inflammatory response. Hemorrhage and necrosis may be seen in any organ system and appears to be mediated by intravascular coagulation with deposition of fibrin in small vessels. The major organ systems involved in fatal cases of meningococcemia are the heart, central nervous system, skin, mucous and serous membranes, and adrenals. Myocarditis is found in more than 50% of patients who die of meningococcal disease. Cutaneous hemorrhages, ranging from petechiae to purpura, occur in most fatal infections and are associated with acute vasculitis with fibrin deposition in arterioles and capillaries. Diffuse adrenal hemorrhage may occur in patients with fulminant meningococcemia (i.e., Waterhouse-Friderichsen syndrome). Meningitis is characterized by acute inflammatory cells in the leptomeninges and perivascular spaces. Focal cerebral involvement is uncommon.
The interaction of endotoxin released by N. meningitidis and the complement system probably is key in the pathogenesis of the clinical manifestations of meningococcal disease. Complement activation correlates with the concentration of meningococcal lipooligosaccharide in the plasma. The concentration of circulating endotoxin is directly correlated with activation of the fibrinolytic system, development of disseminated intravascular coagulopathy, multiple organ system failure, septic shock, and death. The level of endotoxemia correlates with the concentration of circulating cytokines, which are released from endotoxin-stimulated monocytes and macrophages. The concentrations of tumor necrosis factor-a and interleukins have been directly associated with fatal meningococcal disease.
CLINICAL MANIFESTATIONS. The spectrum of meningococcal disease can vary widely, from fever and occult bacteremia to sepsis, shock, and death. Recognized patterns of disease are bacteremia without sepsis, meningococcemic sepsis without meningitis, meningitis with or without meningococcemia, meningoencephalitis, and infection of specific organs.
A well-recognized entity is occult bacteremia in a febrile child. Upper respiratory or gastrointestinal symptoms or a maculopapular rash can be evident. The child often is sent home oo antibiotics or oral antibiotics for a minor infection. Spontaneous recovery without antibiotics has been reported, but some children have developed meningitis.
Acute meningococcemia can mimic a viral-like illness with pharyngitis, fever, myalgias, weakness, and headache. With widespread hematogenous dissemination, the disease rapidly progresses to septic shock characterized by hypotension, disseminated intravascular coagulation, acidosis, adrenal hemorrhage, renal failure, myocardial failure, and coma. Meningitis may or may not develop. Concomitant pneumonia, myocarditis, purulent pericarditis, and septic arthritis have been described. More often, meningococcal disease manifests as acute meningitis that responds to appropriate antibiotics and supportive therapy. Seizures and focal neurologic signs occur less frequently than in patients with meningitis caused by the pneumococcus or Haemophilus. Rarely, meningoencephalitis can occur with diffuse brain involvement.
Typical rash in typical meningococcemia
rash in purpura (meningococcemia) fulminans
Infant with meningococcal endophthalmitis
Meningeal pose in meningitis
Nuchal rigidity (stiff neck) and positive upper Brudzinsky’s sign
Positive Kernig’s and lower Brudzinsky’s sign
A review of 100 children with invasive meningococcal disease revealed that 71% presented with fever, 4% with hypothermia, and 42% with shock. Skin lesions occurred in 71% of the cases with petechiae and/or purpura, and in 49% with both. Purpura fulminans developed in 16%. Other rashes described were maculopapular, pustular, and bullous lesions. Additional presenting symptoms and signs were irritability in 21%, lethargy in 30%, and emesis in 34%. Diarrhea, cough, rhinorrhea, seizure, and arthritis occurred much less frequently (6–10%). Leukopenia and low platelet counts affected 21% and 14%, respectively, and the white blood cell counts ranged from 0.9 to 46/mm3 ´{times} 103. N. meningitidis was isolated in blood culture from 48% of the children, and meningitis was diagnosed in 55%. Six children had meningococci isolated from CSF in the absence of CSF pleocytosis, hypoglycorrhachia, or organisms detected by Gram stain. Five of eight children who presented with arthritis had N. meningitidis isolated from joint aspiration fluid. Eight per cent of the children had radiographic evidence of pneumonia on presentation.
Uncommon manifestations of meningococcal disease include endocarditis, purulent pericarditis, septic arthritis, endophthalmitis, mesenteric adenitis, and osteomyelitis. Primary purulent conjunctivitis can lead to invasive disease. Sinusitis, otitis media, and periorbital cellulitis also can be caused by the meningococcus. Primary meningococcal pneumonia is a recognized clinical entity that is associated with pleural effusions or empyema in 15% of cases. N. meningitidis is a rare isolate of the genitourinary tract in asymptomatic or symptomatic individuals and has been the causal organism in urethritis, cervicitis, vaginitis, and proctitis.
Chronic meningococcemia is a rare manifestation of meningococcal disease that can occur in children and adults. It is characterized by fever, nontoxic appearance, arthralgias, headache, and rash. The rash resembles that of disseminated gonococcal infection. Symptoms are intermittent, with the rash often appearing with fever. The mean duration of illness is 6–8 wk. Blood cultures may initially be sterile. Without specific therapy, complications such as meningitis can result.
DIAGNOSIS.
Definitive diagnosis of meningococcal disease is made by the isolation of the organism from a usually sterile body fluid such as blood, CSF, or synovial fluid. Isolation of meningococci from the nasopharynx is not diagnostic for disseminated disease. Blood and CSF are the usual sources of organism isolation. The blood culture yields N. meningitidis in about one half of the cases of disseminated disease, and culture or Gram stain usually reveal the organism in those with meningitis. Culture or Gram stain of petechial or papular lesions has been variably successful in identifying meningococci. Occasionally, bacteria can be seen on Gram stain of the buffy coat layer of a spun blood sample.
In meningitis, the morphologic and clinical characteristics of CSF are those of acute bacterial meningitis. CSF cultures can be positive in patients with meningococcemia but without clinical evidence of meningitis or CSF pleocytosis. CSF cultures may be negative if the lumbar puncture has been performed early in the course of disease or if the patient has received previous antibiotic treatment.
lumbar puncture
CSF in meningococcal meningitis
Techniques of counterimmunoelectrophoresis and latex agglutination detect meningococcal capsular polysaccharide in CSF, serum, joint fluid, and urine. False-negative results occur, and specificity may be limited when organisms with cross-reactive antigens are involved, such as Escherichia coli K1, which cross reacts with the group B meningococcus. Antisera and monoclonal antibodies can be used to identify different serogroups of meningococci. These studies are useful early in infection and if the patient has received antibiotics, rendering cultures sterile.
Ancillary data may support a systemic bacterial infection and includes elevated sedimentation rate and C-reactive protein, leukocytopenia or leukocytosis, thrombocytopenia, proteinuria, and hematuria. Patients with disseminated intravascular coagulation may have decreased serum concentrations of prothrombin and fibrinogen. Screening for complement deficiency is recommended for individuals diagnosed with meningococcal disease. In one series of 20 patients with a first episode of meningococcal meningitis, meningococcemia, or meningococcal pericarditis, three had a deficiency of a terminal-pathway component and three had deficiencies of multiple complement components associated with underlying systemic diseases.
DIFFERENTIAL DIAGNOSIS. This includes acute bacterial or viral meningitis, mycoplasma infection, leptospirosis, syphilis, acute hemorrhagic encephalitis, encephalopathies, serum sickness, collagen vascular diseases, Henoch-Schö{umlaut-o}nlein purpura, hemolytic uremic syndrome, and ingestion of various poisons. The petechial or purpuric rash of meningococcemia is similar to that noted in any patient with a disease characterized by generalized vasculitis. These diseases include septicemia due to many gram-negative organisms; overwhelming septicemia with gram-positive organisms; bacterial endocarditis; Rocky Mountain spotted fever; epidemic typhus; Ehrlichia canis infection; infections with echoviruses, particularly types 6, 9, and 16; coxsackievirus infections, predominantly of types A2, A4, A9, and A16; rubella; rubeola and atypical rubeola; Henoch-Schönlein purpura; Kawasaki disease; idiopathic thrombocytopenia; and erythema multiforme or erythema nodosum due to drugs or infectious or noninfectious disease processes. The morbilliform rash occasionally observed may be confused with any macular or maculopapular viral exanthem.
COMPLICATIONS.
Acute complications are related to the inflammatory changes, vasculitis, disseminated intravascular coagulation, and hypotension of invasive meningococcal disease. These can include adrenal hemorrhage, arthritis, myocarditis, pneumonia, lung abscess, peritonitis, and renal infarcts. The vasculitis can lead to skin loss with secondary infection, tissue necrosis, and gangrene. Skin sloughing caecessitate the use of skin grafts. Bone involvement can lead to growth disturbance and late skeletal deformities secondary to epiphyseal avascular necrosis and epiphyseal-metaphyseal defects. Limb amputation has been reported for patients with purpura fulminans.
adrenal hemorrhage (Waterhouse-Frederikson syndrome)
Gangrene in a patient with purpura fulminans
Meningitis rarely is complicated by subdural effusion or empyema or by brain abscess. Deafness is the most frequent neurologic sequelae, but the reported incidence varies from 0–38%. Other rare sequelae include ataxia, seizures, blindness, cranial nerve palsies, hemiparesis or quadriparesis, and obstructive hydrocephalus.
subdural effusion
obstructive hydrocephalus
The late complications of meningococcal disease are thought to be immune complex–mediated and become apparent 4–9 days after the onset of illness. The usual manifestations are arthritis and cutaneous vasculitis. The arthritis is usually monoarticular or oligoarticular. Effusions are usually sterile and respond to nonsteroidal anti-inflammatory agents. Permanent joint deformity is uncommon. Because most patients with meningococcal meningitis are afebrile by the 7th hospital day, the persistence or recrudescence of fever after 5 days of antibiotics warrants an evaluation for immune complex-mediated complications.
PREVENTION.
Close contacts of patients with meningococcal disease are at increased risk of infection and should be carefully monitored and brought to medical attention if fever develops. Prophylaxis is indicated as soon as possible for household, day-care, and nursery school contacts. Prophylaxis is also recommended for persons who have had contact with patients’ oral secretions. Prophylaxis is not routinely recommended for medical personnel except those with intimate exposure, such as with mouth-to-mouth resuscitation, intubation, or suctioning before antibiotic therapy was begun. Rifampin is given (10 mg/kg; maximum dose, 600 mg) orally every 12 hr for 2 days (total of four doses). The dose is reduced to 5 mg/kg for very young infants. If the isolate is known to be sensitive to sulfonamides, suflisoxazole prophylaxis is preferred. Penicillin does not eradicate nasopharyngeal carriage, and patients with meningococcal disease should receive rifampin before discharge.
A quadrivalent vaccine composed of capsular polysaccharide of meningococcal groups A, C, Y, and W-135 is licensed in the United States. The vaccine is immunogenic in adults but is unreliable in children under 2 yr of age. The group B polysaccharide is poorly immunogenic in children and adults, and no vaccine is available against this serogroup. Routine immunization of the United States population is not recommended at this time, but the vaccine is routinely given to all American military recruits.
Immunization is useful to control outbreaks of meningococcal disease of the serogroups represented in the quadravalent vaccine. It is also recommended for travelers to countries with a high incidence of meningococcal disease. Immunization of close contacts of individuals with A, C, Y, or W disease should be considered, because it has been useful in the prevention of secondary cases. Individuals with anatomic or functional asplenia and those with complement component deficiencies should be immunized.
Polysaccharide-protein conjugate vaccines are being developed for the prevention of meningococcal disease, and subcapsular proteins and detoxified lipooligosaccharides are being investigated as possible vaccines.
TREATMENT.
Aqueous penicillin G is the drug of choice and should be given in doses of 250,000 to 300,000 U/kg/24 hr, administered intravenously in six divided doses. Chloramphenicol sodium succinate (75–100 mg/kg/24 hr, intravenously in four divided doses) provides effective treatment for patients who are allergic to penicillin. Cefotaxime (200/mg/24 hr) and ceftriaxone (100 mg/kg/24 hr) are effective empirical therapy for meningococcal disease and may be useful in patients who are allergic to penicillin. Therapy is continued for 7 days.
Isolates of N. meningitidis have been reported from Spain, South Africa, and Canada as being relatively resistant to penicillin, defined as having a minimal inhibitory concentration of penicillin of 0.1–1.0 m{mu}g/mL. Moderate resistance is caused, at least in part, by altered penicillin-binding protein 2. High-level resistance due to b-lactamase production has been reported from South Africa. The CDC estimated that about 4% of meningococcal disease in
PROGNOSIS.
Despite the use of appropriate antibiotics, the mortality rate for disseminated meningococcal disease remains at 8–12% in the United States. Poor prognostic factors include hypothermia, hypotension, purpura fulminans, seizures or shock on presentation, leukopenia, thrombocytopenia, and high circulating levels of endotoxin and tumor necrosis factor. Some studies have included the development of petechiae within 12 hr of admission, hyperpyrexia, and the absence of meningitis.
Short statement of the material
Meningococcal infection is an acute infectious disease that is caused by neisseria meningitidis and is characterized by the variety of clinical forms: from nasopharyngitis and healthy carrying to generalized forms (meningococcemia, meningitis, and meningoencephalitis).
Etiology: Neisseria meningitidis, Gram negative diplococci.
Epidemiology:
· Source of infection – ill person or carrier.
· Way of spreading – droplet with nasopharyngeal mucus during sneezing, coughing, speaking. –
· Susceptibility is high in children 6 mouths -5 years old. Only 15% of contact persons may be infected, 98% of them become carriers, only 2% – ill.
Classification:
Localized forms
· Meningococcal carrying,
· acute nasopharyngitis;
Generalized forms
· Meningococcemia (typical, fulminant and chronic),
· Meningitis,
· Meningoencephalitis.
Rare forms
· Meningococcal endocarditis,
· Arthritis,
· Pneumonia,
· Iridocyclitis.
More usual combined forms (meningitis + meningococcemia or meningoencephalitis + meningococcemia).
Pathogenesis
1. Inoculation and reproduction of bacteria in upper respiratory tract.
2. Development of local inflammation, lymphoid tissue hyperplasia (nasopharyngitis)
3. Bacteraemia, dissemination
4. Toxemia (meningococcemia) in fulminant form: massive bacteriemia, disintegration of microbes, endotoxemia ® infectious-toxic shock (violation of microcirculation ® DIC-syndrome ® metabolic disorders)
5. Rupture of hematoencephalic barrier meningitis, meningoencephalitis.
Diagnostic criterions
Nasopharyngitis:
· intoxication (headache, malaise, pain, fever);
· catarrhal syndrome (cough, sore throat, corryza, conjunctive hyperaemia);
· insignificant hyperemia of tonsils, soft palate, palatal arch, bright, swollen, covered by mucus back pharyngeal wall with hyper pleased follicles.
Meningococcemia is characterised by:
· acute beginning from intoxication, high temperature (39-
· prime maculopapulous rashes on the 1 day (like in measles);
· typical rashes on the 1-2nd day: purpura or petechia lesions (photo), bruises (photo). Petechia are pinpoint, may have a raised vesicular or pustular centre. Lesions are more common on the trunk and extremities but may also occurs on the palms, soles and mucosa. More fulminant meningococcal infections are often associated with extensive purpura lesions and with large, well circumscribed ecchymotic patches covering large areas of the body (photo). Necrotic bulla may develop within the ecchymotic patches with resultant sloughing. Rashes are resolved by necrosis, scarring;
· hemorrhagic syndrome (nasal bleeding, bloody vomits, hematuria).
· Other features – irritability, myalgia, arthralgia and hypotension.
Exanthema at meningococcemia
Exanthema and bruises at meningococcemia
Fulminant form:
· rapid beginning, severe toxic syndrome;
· considerable defeats from the beginning (hemorrhagic syndrome; hemorrhage in mucus membranes, skin (photo), adrenal glands, necrosis of adrenal glands known as Waterhouse-Frederixen syndrome (photo) with development of acute adrenal insufficiency, severe toxic shock syndrome);
· high lethality (at inadequate treatment).
Exanthema at fulminant meningococcemia
fulminant meningococcemia, hypostases
adrenal hemorrhage (Waterhouse-Frederikson syndrome)
Meningitis has
· sudden onset (with previous nasopharyngitis 2-3 days before in 1/3 of patients);
· toxic syndrome (hyperpyrexia);
· general cerebral syndrome:
· central repeated vomiting without nausea,
· severe diffuse headache, or in the forehead or occiput, it increases during the head movements, bright light or loud sounds;
· irritability or lethargy
· Meningeal syndrome (meningeal pose, hyperesthesia, stiff neck, positive Kerning’s and Brudzinsky’s signs, tenderness in sites of trigeminal nerve endings, suppression of skin rephlexes).
· Lethargy and obtundation usually develop and may progress to stupor or even coma.
· Cerebrospinal fluid (CSF) examination show: -polymorphonuclear pleocytosis, protein enlargement, high pressure of CSF, glucose and chlorides are low decreased or normal.
· local symptoms damage of 8th, 3rd, 6th, or 7th pairs of cerebral nerves, tonic-clonic seizures (brain edema), is quickly regressing;
· Infectious-toxic damage of myocardium;
· Dyspepsia: coated tongue, loss of appetite, constipation.
Features of meningitis in infants:
· intoxication, fever;
· expressed hyperesthesia (crying in case if diaper changing, taking the child);
· cerebral scream (equivalent of headache);
· Lesage’s symptom (other meningeal sins are not expressed);
· meningeal pose or head extension;
· depression of abdominal reflexes;
· expulsion and tension of large fontanel;
· diarrhea
Complications:
• infectious-toxic shock;
• acute edema-swelling of the brain;
• restriction (wedging) of oblong brain into the great cervical opening;
• convulsive syndrome;
• ependimatitis;
• DIC (disseminated intravascular coagulation) syndrome;
• pluriglandular insufficiency;
• convulsive syndrome.
Phenomena that remain:
· cerebral asthenia;
· epileptiform syndrome;
· physical and intellect retardation;
· deafness;
· blindness;
· hydrocephalus;
· Palsies, paralyses.
obstructive hydrocephalus
Laboratory tests
· Complete blood test: leucocytosis with neutrophyllosis and left shift, increased ESR
· Bacteriological investigation of nasopharyngeal mucus, blood, CSF; Bacterioscopy of blood (thick drop) and CSF;
· Clinical investigation of CSF: neutrophyl pleocytosis, protein increase, positive Pandy test, elevated pressure, slight decrease of glucose level.
· Serological IHAR, immunological methods, latex-agglutination test (presence of N.meningitidis antigens).
· Coagulogram – hyper coagulation or coagulopathy
Diagnosis example:
· Meningococcal infection, typical localized form (meningococcal carrying)
· Meningococcal infection, typical generalized combined form (meningitis + meningococcemia), complicated by toxic shock syndrome, 2nd degree
Differential diagnosis for meningococcemia should be performed with measles, scarlet fever, pseudotuberculosis; thrombocytopenia, purpura fulminance, sepsis acquired by Gram-negative strains. For meningoencephalitis differential diagnosis should be performed with meningismus in influenza; spasmophylia; viral meningitis in influenza, measles; tuberculosis meningitis.
Differential diagnosis of meningitis
|
Signs |
Meningismus |
Viral meningitis |
Tuberculosis meningitis |
Purulent bacterial meningitis |
Subarachnoid hemorrhage |
|
Color, transparence |
Colorless, transparent |
Colorless, transparent or opalescent |
Colorless, xanthochromic or opalescent |
White-yellow or green, muddy |
bloody, after settling – xanthochromic |
|
Pressure (mm. H2O), flow out speed (drops per 1 minute) |
below 180-200 50-80 |
200-300 60-90 |
250-500 60-90 |
250-500 jet, sometimes rare drops |
250-400 > 70 or jet |
|
cytosis (in 1 mkl.) |
2-12 |
20-800 |
200-700 |
500-1000 and more |
It is hard to count in the first days, from 5-7 day 15-120 |
|
cytogram lymphocytes, % neutrophyls, % |
80-85 15-20 |
80-100 0-20 |
40-60 20-50 |
0-30 30-100 |
from 5-7 day lymphocytes prevail |
|
protein, g/l |
0.16-0.33 |
0.33-1.0 |
1.0-3.3 |
0.66-16.0 |
0.66-16.0 |
|
sedimentation tests (Pandy) |
– |
+(++) |
+++(++++) |
+++(++++) |
+++ |
|
Dissociations |
Absent |
cellular-protein on the low level (from 8-10 day – protein-cellular) |
protein-cellular |
cellular-protein on the high level |
– |
|
Fibrin pellicle |
– |
– in 3-5 % |
Often rough in 30-40 % |
Often as a sediment |
Rare |
|
glucose, mmol/l |
2.2-3.3 |
2.2-3.3 |
For 2-3 weeks 1.0-2.0 |
Normal or slightly less thaormal |
normal |
Differential diagnosis of meningococcemia
|
Signs |
Measles |
Rubella |
Scarlet fever |
|
Initial symptoms |
catarrhal signs from upper airways, conjunctives during 2-4 days, intoxication |
Increase of occipital lymph nodes, small catarrhal signs and intoxication |
Acutely – intoxication, angina, regional lymphadenitis |
|
Time of the rashes’ beginning |
on 4-5 days of the disease, with stages |
1 day, seldom 2 |
1 day (in 20% – 2) |
|
Morphology |
maculopapulous |
small-papulous, |
small point-like |
|
Sizes of elements |
middle, large |
small, middle |
small |
|
Localization |
1 day – on the face 2 – on the face, trunk; 3 – on the face, trunk, limbs |
on whole body, mainly on unbending surfaces of the limbs |
mainly on bending surfaces of limbs, down the abdomen, lumbar region, face, lateral surfaces of the trunk, pale nose-labial triangle |
|
Brightness and color of elements |
bright red |
pale-rose |
bright |
|
Further rashes’ development |
pigmentation, slight hulling |
disappear on 3-4 days |
gradually turn pale for 4-5 days, small, lamellar hulling |
|
Catarrhal phenomena |
expressed in first 5-6 days |
small, short for 1-2 days |
Not typical, |
|
Oral mucous membranes |
hyperemied, friable, enanthema, Koplick’s spots |
clear, sometimes single elements of enanthema |
marked off, bright hyperemia, enanthema on palate, angina |
|
Intoxication |
significant, lasts 5-7 days |
small or being absent |
proportional to local signs, short for 1-3 days |
|
Other symptoms |
Complications (respiratory, digestive, nervous, urinary systems, eye, ears, skin) |
increased and painful posterior neck and occipital lymph nodes |
angina, changes on the tongue (raid, from 4-5 days “strawberry”), complications on 2-3 weeks |
|
Laboratory criteria |
leucopenia, lymphocytosis, aneosynophylia, serological reaction with measles antigen (+) |
leucopenia, lymphocytosis, increase of the plasmatic cells’ number, serological reactions with rubella antigen (+) |
leucocytosis, shift to the left, neutrophyllosis, enlarged ESR, in pharyngeal, nasal swabs – streptococci |
|
Signs |
Pseudotubercullosis |
Meningococcemia |
Chickenpox |
|
Initial symptoms |
acutely with many symptoms (intoxication, intestinal changes, seldom – catarrhal signs |
intoxication, develops very acutely, initial measles-like rash |
Acutely, observing catarrh, intoxication, rash |
|
Time of the rashes’ beginning |
on 2-8 day |
first hours of the disease |
On 1-2 days, appear next 3-5 days as pushes |
|
Morphology |
puncture-like, small spots, erythema |
hemorrhagic “star-like” with necrosis in the centre |
Polymorphic (spots, papules, vesicles, crusts) |
|
Sizes of elements |
Small, middle, large |
from small to significant |
middle |
|
Localization |
“hood”, “mitten”, “socks” signs, in skin folds, bends, around joints |
buttocks, lower limbs, less – on trunk, hands, face |
On whole body, on hair part of the head, seldom – on palms and soles |
|
Brightness and color of elements |
bright |
hemorrhagic, bright, sometimes cyanotic |
Papules are pink, vesicles – on hyperemied base |
|
Further rashes’ development |
gradually disappear for 2-5 days, small, lamellar shelling |
Small, disappear gradually, significant, leave “dry” necrosis |
After desquamation of the crusts – a slight pigmentation |
|
Catarrhal phenomena |
Not typical |
are absent, in 30-40% on previous 2-3 days – nasopharyngitis |
Moderate, |
|
Oral mucous membranes |
Possible hyperemia of the pharynx, tonsils, |
hyperemia and groiness of back pharyngeal wall, hypertrophy of follicles |
On pink background – polymorphic elements |
|
Intoxication |
expressed, long-lasting (2-3 weeks) |
sharply expressed |
Small or moderate |
|
Other symptoms |
arthritis, myocarditis, diarrhea, hepatitis, abdominal syndrome, lymphoproliferative symptom, kidneys, nervous system damage, pneumonia |
meningitis, encephalitis, arthritis, iridocyclitis, endocarditis, aortitis, pneumonia, pleurisy |
Seldom: generalized visceral forms, meningoencephalitis |
|
Laboratory criteria |
leucocytosis, shift to the left, high ESR, Indirect hemagglutination reaction with special diagnosticum (+), separation of Y. pseudotuberculosis from excrements |
leucocytosis, shift to the left, neutrophyllosis, high ESR, iasopharyngeal swab, thick drop of blood – meningococci |
Leucopenia, lymphocytosis, serological: binding complement reaction with Chickenpox antigen (+) |
Treatment of nasopharyngitis includes:
1. Antibacterial therapy with rifampicin 10 mg/kg/daily for 3-5 days or macrolides (erythromycin 30-50 mg/kg/daily, spiramycin, azythromycin 10 mg/kg/daily) or chloramphenicol 30-50 mg/kg/daily;
2. Bed rest up to the normalization of body temperature,
3. Adequate rehydration with oral fluids (lemon tea, raspberry tea, warm alkalic drinks
4. Vitaminized milk-vegetable food;
5. Control of fever (when the temperature is more than 38.5-39˚C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours.;
6. Antiseptic fluids locally (gurgling), ultraviolet insolation of the pharynx.
Generalized forms before transporting (prehospital treatment):
1. Oxygen therapy by water-wet oxygen;
2. To perform the peripheral venous puncture;
3. Infusion therapy by isotonic salt solutions (0.9 % sodium chloride solution or sodium chloride solution + potassium chloride + calcium chloride dihydrate + sodium lactate) in a volume 20 ml/kg body weight for 20 minutes;
4. Antibacterial therapy – cefotaxim for one occasion dose 75 mg/kg (when on the hospital stage application of solutions which contain in the composition a calcium (Ringer’s solution and others like that) or ceftriaxon for one occasion dose 50 mg/kg (when infusion of preparations of calcium at subsequent therapy is not needed) intravenously droplet. Possibly application of chloramphenicol for one occasion dose 25 mg/kg intravenously stream;
5. Glucocorticoids only intravenously (prednisolon, hydrocortisone) in a dose 10 mg/kg (by prednisolon);
6. Antipyretic therapy (in the case of necessity) – (paracethamol 10-15 mg/kg, Ibuprofen 5-10 mg/kg through a mouth, methamisol sodium 50 % IV 0,1 ml/yrs of life;
7. Anticonvulsant therapy (in the case of necessity) – diazepam in a single dose 0.3-0.5 mg/kg (not more than 10 mg on one injection);
8. Transporting of patients with the severe forms of meningococcemia is carried out by the reanimation brigades of first-aid.
An algorithm of meningococcemia intensive care in the specialized hospital:
1. Providing of communicating of respiratory tracts and adequate breathing
2. Providing of venous access. At fulminant forms MI must be provided 2 venous accesses simultaneously.
3. At presence of refractive shock, progressive increase of intracranial pressure, cramps – intubation of trachea and acquired pulmonary ventilation.
4. Infusion therapy by salt solutions, by colloid solutions for blood circulation stabilizing.
5. Correction of hypo- and hyperglycemias
6. Antibacterial therapy
7. support of hemodynamics in case of refractive shock (dopamine, Dobutaminum, epinephrinum, norepinephrinum).
8. Purposeful correction of acid-basic balance and water-electrolyte disorders.
9. At presence of signs of adrenal insufficiency and/or refractive to adequate doses of sympathomimetics – Glucocorticoids intravenously. Preparation of choice is hydrocortisone as daily infusion or every 6 hours.
10. Treatment of hyperthermia (paracethamol, Ibuprofen, methamisol sodium, physical methods of cooling).
11. Anticonvulsant therapy (diazepam, sodium oxybutiratis, barbiturates, phenitoin).
12. Treatment of DIC-syndrome.
13. At growth of intracranial hypertension, head cerebral edema:
• location of bed with elevated head end on 30 °;
• acquired pulmonary ventilation;
• control of plasma osmolarity (within the limits of 300-310 mosmol/l);
• glycemia control;
• control of hyperthermia and cramps;
• effective cardiac output or insignificant increase of arterial pressure;
• at the terms of stable hemodynamics manitol and furosemid injection.
Glasgow coma scale
|
Indexes |
Points |
|
Systolic pressure (< Systolic pressure (< Dermal-rectal temperature gradient > 3°С Estimation of comma by Glasgow scale – less than 8 points or worsening on 3 and more points in a hour Worsening of the state during last hour Absence of meningism Widespread purpura, large ecchymoses A deficit of bases is in arterial or capillary blood > 8,0
|
3
3
3 2 2 1 1
|
|
Maximal estimation |
15 points
|
At estimation by the Glasgow scale more than 8 points – the lethality forecast is 73 %. At estimation by the Glasgow scale more than 10 points – lethality forecast – 87.5 %.
An algorithm of meningococcemia intensive care in the specialized hospital:
1. Providing of communicating of respiratory tracts and adequate breathing
2. Providing of venous access. At fulminant forms MI must be provided 2 venous accesses simultaneously.
3. At presence of refractive shock, progressive increase of intracranial pressure, cramps – intubation of trachea and acquired pulmonary ventilation.
4. Infusion therapy by salt solutions, by colloid solutions for blood circulation stabilizing.
5. Correction of hypo- and hyperglycemias
6. Antibacterial therapy
7. support of hemodynamics in case of refractive shock (dopamine, dobutaminum, epinephrinum, norepinephrinum).
8. Purposeful correction of acid-basic balance and water-electrolyte disorders.
9. At presence of signs of adrenal insufficiency and/or refractive to adequate doses of sympathomimetics – Glucocorticoids intravenously. Preparation of choice is hydrocortisone as daily infusion or every 6 hours.
10. Treatment of hyperthermia (paracethamol, Ibuprofen, methamisol sodium, physical methods of cooling).
11. Anticonvulsant therapy (diazepam, sodium oxybutiratis, barbiturates, phenitoin).
12. Treatment of DIC-syndrome.
13. At growth of intracranial hypertension, head cerebral edema:
• location of bed with elevated head end on 30 °;
• acquired pulmonary ventilation;
• control of plasma osmolarity (within the limits of 300-310 mosmol/l);
• glycemia control;
• control of hyperthermia and cramps;
• effective cardiac output or insignificant increase of arterial pressure;
• at the terms of stable hemodynamics manitol and furosemid injection.
Antibacterial therapy
Intravenous infusion of cefotaxim or ceftriaxon. At mild and moderate forms of meningococcemia benzylpenicillin is possible (reserve antibiotics are ampicillin, ceftriaxon, cefotaxim or chloramphenicol), in case oh hypersensitivity to beta-lactams chloramphenicol is used. For protecting from a nosocomeal infection (if necessary) the second antibiotic should be given (amikacin 15 mg/kg/day, nethylmicin – to the children before 1 year 7.5-9 mg/kg, to the elder children – 6-7.5 mg/kg).
|
Antibiotic |
Optimum way of injection |
Day’s dose |
Amount of injection |
|
Ceftriaxon |
Bolus, slow IV infusion |
100 mg/kg |
2 |
|
Benzylpenicillin |
Bolus IV |
300-500 thousands of IU/kg |
6-8 |
|
Сhloramphenicol |
Bolus IV |
100 mg/kg |
2-4 |
|
Cefotaxim |
Bolus, slow IV infusion |
150 mg/kg |
2-4 |
|
Ampicillin |
Bolus IV injection |
injection |
300 mg/kg |
Duration of antibacterial therapy at MI is 7-10 days.
Infusion therapy is performed in the hyperhydratation regime
• Solutions are entered intravenously, stream.
• Isotonic crystalloid solutions (sodium chloride, Ringer’s solution, sodium chloride + potassium chloride + calcium chloride dehydrate + sodium lactate) are entered in a dose 20-30 ml/kg during the first 20 minutes.
• Colloid solutions (derivates of hydroxethylen starch of ІІІ generation) are entered with the speed of 20-40 ml/kg/hour.
• In case of ITSH immediate infusion of crystalloid solutions 20 ml/kg during the first 20 minutes with subsequent infusion of colloid solution in a dose 10-20 ml/kg iext 20 minutes.
• In case of fulminant forms of MI it is expedient to connect crystalloid and colloid solutions in correlation 2:1.
• If infusion 60-90 ml/kg of salt solution or 20-40 ml/kg of colloids during the first hour of treatment appeared uneffective, then in such cases there is a necessity for application of sympathomimetics and respirator support.
• Stimulation of urination by saluretics in case of oliguria, anuria – (furosemide 1-2 mg/kg) expedient only in case of hemodynamics stabilizing (satisfactory perfusion, arterial pressure, central venous pressure).
• Application of glucose solutions, especially water is impermissible in case of ITSH, metabolic acidosis and cerebral edema. They do not stay too long in the vessels, strengthen the edema of cells, brain edema. Water solutions of glucose can be appointed only after stabilizing of hemodynamics, normalization of perfusion and liquidation of acidosis. By the unique testimony for infusion of glucose for patients with shock and head cerebral edema there can be hypoglycemia. The level of glucose must be supported within the limits of 3.5-8.3 mmol/l. At the level of glucose less than 3.5 mmol/l the correction by 20-40 % glucose solution is used, at the level over 10-11 mmol/l – insulin.
• Metabolic acidosis is corrected by intravenous infusion of sodium bicarbonate at blood pH below 7.1-7.2.
• Infusion therapy must remove electrolyte disorders also (hypocalcaemia, hyperkalimia, hypokalimia).
• Meningitis is not an in indication for IV therapy limitation in case of effective hemodynamics maintenance.
• After shock liquidation protracted infusion therapy is need.
• The calculation of volumes for infusion therapy is done on the basis of physiologic necessity, correction of deficits of water and electrolytes, taking into account pathological losses, level of glucose, general albumen, state of alimentary canal, and degree of cerebral edema.
• One of aspects of infusion therapy there is a necessity of partial parenterally feed in after shock period. Its basis is infusion of 10-20 % glucose solutions with insulin and amino acids solutions.
Sympathomimetic and inothrope support of hemodynamics.
• Application of inothrope preparations for children with refractive to infusion therapy shock – dopamine as permanent intravenous infusion 10 мcg/kg/min, if ineffective – increase the dose to 20-30 мcg/kg/min. At decreased cardiac output Dobutaminum is appointed in the same doses, as dopamine.
• If, without regard of dopamine administration in the dose of 20-30 мcg/kg/min, hypotension is saved, expedient is application of norepinephrinum or epinephrinum from 0.05 to 3 мcg/kg/min. If dopamine is ineffective quite often it is succeeded to obtain the substantial improvement of hemodynamics by the combined application of Dobutaminum and norepinephrinum.
Glucocorticoids
• Glucocorticoids are appointed at presence or suspicion on acute adrenal insufficiency and/or refractivity to the sympathomimetics.
• Hydrocortisone is a medicine of choice. Possible is prednisolone application.
• Preparations are entered every 6 hours.
• The calculation of dose is done by prednisolone 10 mg/kg. Glucocorticoids are appointed as adjuvant therapy of purulent meningitis. Dexamethazonum is a medicine of choice 0.15 mg/kg х 4-6 times per day during 2-4 days.
Treatment of DIC-syndrome
• Therapy of DIC-syndrome assumes administration of heparin in a dose 50-200 EU/kg per day, under control of coagulogram indexes.
• At presence of hypercoagulability a dosage is applied to 150-200 EU/kg, that in combination with infusion, antibacterial and antiagregant therapy lead to the rapid normalization of coagulogram indexes.
• The criterion of efficiency of heparin therapy is lengthening of coagulation time in 2-3 times from an initial index.
• In transitional and hypocoagulation phases of DIC-syndrome fresh-frozen plasma in a dose 10-20 ml/kg as a fast, stream infusion in combination with heparin in a dose 25-50 EU/kg is applied. If necessary plasma is entered again.
• The criterion of such therapy efficiency is an increase of fibrinogen level to 1.5-2 gs/l, prothrombine index increase over 60 %, stopping of mucosal bleeding, and bleeding from the places of injections.
• In phase of incoagulability and fibrinolysis the inhibitors of proteases are given: contrical in a dose of 1000 EU/kg, and other in equivalent doses.
A diet in case of intensive therapy
• For warning of translocation of intestinal microflora at the severe forms of meningococcemia early tube enteroalimentation have to begin at once after stabilizing of hemodynamics, in absence of enteroplegia displays.
• In the beginning of infants feeding optimal is application of lactose-free formulas which also contain prebiotics.
• Formulas can be entered through a nasogastric tube.
• Infants who have breastfeeding will achieve pasteurized breast milk.
Care of skin, prophylaxis and treatment of skiecroses
• At meningococcemia is needed a careful care of skin, prophylaxis of bedsores, treatment of skin by antiseptic fluids.
• At presence of deep skin and soft tissues defects there can be necessary a necrectomy and plastic closing of a skin defect or amputation of distal segments of extremities.
• Expedient treatment of necrotizing surfaces by antiseptic aerosols, creams which contain silver sulphodiasinum.
• Carotinoids applications speed up cicatrisation of necroses.
• Not deep necroses heal over independently and do not need treatment.
• At arthritis – NSAIDs, warm on joints, massage, gymnastics.
• At iridocyclitis – nicotine acid, nitrate of sodium in a temporal area.
• At pneumonia – combination of antibiotics, oxygenation, physiotherapy.
• At carditis – bed rest, cardiac glycosides, cardiothrope medicine.
• At hypertensive syndrome – diacarb (acethasolamid) + asparkam according the
syndrome severity.
Discharge the patient:
• clinically healthy, with normal CSF analyses;
• with one documented negative nasopharyngeal culture which is performed in 3 days after antibiotic therapy.
Dispensarization for 2 years by paediatrician, in case of meningitis, meningoencephalitis – also neurologist.
Prophylaxis:
1. Sanation of carriers by erythromycin, chloramphenicol, ciprofloxacin or rifampin for 3-5 days;
2. Quarantine for 10 days, contacts inspection with one bacteriological test of nasopharyngeal culture;
3. Disinfection.
Vaccination is done by epidemic evidences
Poliomyelitis
Poliomyelitis is an acute infectious disease that is caused by one of three types of poliovirus and is characterized by the large range of clinical forms (from abortive to paralytic one).
Etiology: an agent is the poliovirus from the Picornaviridae family, sort of enterovirus.
Epidemiology:
· the source of infection are patients, viral carriers;
· the mechanism of transmission is droplet, fecal-oral
· receptivity is high, especially at the children up to 3 years.
Pathogenesis
1. Inoculation and reproduction of virus in the intestinal or upper respiratory tract epithelium.
2. lymphogenic distribution of virus.
3. Reproduction in organs and tissues.
4. Fixation iervous tissues, damage of motoneurons.
Classification
Forms of poliomyelitis without the CNS damage:
I. Innaparant (virus carrying).
ІІ. Abortive (small illness).
Forms of poliomyelitis with the CNS damage:
І. nonparalytic or meningeal.
ІІ. Paralytic:
1. Spinal (neck, pectoral, lumbar, limited or widespread).
2. pontinus.
3. Bulbar.
4. Pontospinal.
5. Bulbospinal.
6. Bulbopontospinal.
Diagnostic criteria of several poliomyelitis forms
Meningeal:
· latent period is 5-35 days;
· severe toxicsyndrome;
· meningeal syndrome;
· CSF changes, as at serous meningitis (on 4-5 day);
· pain in extremities, neck, back;
· horizontal nistagmus (in half of patients);
· complete recovery in 3-4 weeks.
Paralytic:
Preparalytic period (lasts for 2-3 days):
· high fever, intoxication;
· insignificant catarrhal phenomena;
· dyspepsia syndrome;
· pain in a neck, back, extremities;
· hyperesthesia;
· positive tension symptoms;
· typical «trypod» position of a patient
· CSF changes (as at serous meningitis).
Paralytic period (1 day – 2 weeks):
· development of languid (peripheral) paralyses and paresis.
· someximes secondary increasment of the temperature
· damage of lower limbs (80%), or upper limbs, trunk or neck muscles
· muscular tonus is decreased
· tendon rephlexes are absent
Period of rehabilitation (to 1 year):
· renewal of least staggered motoneurons function.
Residual period
· Increasing muscular atrophies, contractures, osteoporosis, bone deformations.
Spinal form of poliomyelitis
Pontinus form of poliomyelitis
Specific confirmation of diagnosis:
· virology research of excrements, pharyngeal mucus, CSF;
· serologic research (NR, CBR) of paired sera.
Diagnosis example: Poliomyelitis, paralytic pontospinal form, period of rehabilitation
Differential diagnosis
1. The Spinal form is differentiated with orthopedic pathology, myelitis, poliradiculoneuritis.
2. Pontinus form – with neuritis of facial nerve.
3. Meningeal form – with serous meningitis of tubercular, meningeal, measles, varicella, measles, enterovirus origin.
Poliomyelitis need to be differentiated from neurologic diseases as polyradiculoneuritis, myelitis, congenital myotonia, facial neuritis of other etiology. Meningeal form need to be differentiated with serous meningitis caused by Coxacie or ECHO-viruses.
Differential diagnostics of poliomyelitis with similar forms of enterovirus infection
Signs |
poliomyelitis |
poliomyelitis like forms of enterovirus infection |
|
Latent period |
5-35 days |
2-10 days |
|
Toxic syndrome |
severe |
Mild or moderate |
|
fever |
high |
moderate |
|
Catarrhal signs |
mild |
typical (herpangina) |
|
Preparalytic period duration |
2-3 days |
5-7 days |
|
Skin rashes |
absent |
Often present |
|
paralysis |
peripheral paralysis, stable |
peripheral paresis, usually disappears |
|
the tendon reflexes |
absent |
Decreased or normal |
|
Muscular atrophy |
typical |
Rare, some muscles |
|
Renewal of function |
Less damaged motoneurons in a year |
Practically complete in 3-4 wks |
|
CSF changes |
As in serous meningitis |
Not typical |
|
Virological studies |
Poliovirus |
Coxackie A, ЕСНО |
Treatment:
In acute period
· Obligatory hospitalization.
· Physical and psychical rest.
· Analgetics (analgin 50% 0,1 ml/year of life, bromides).
· Thermal procedures (hot wrappings, ozocerite, paraffin appliques).
· dehydration (lasix 1-3 mg/kg, mannit, manitol 1-1.5 g/kg).
· glucocorticoids (in severe cases) 1-3 mg/kg (by prednisolon).
· Human immuneglobulin 0.5 m/kg 2-3 days.
In the early period of rehabilitation
· Proserin 1 mg/year of life, galantamin, dibasol 1-5 mg per day for 20-30 days.
· physical exercises, physiotherapy, ozocerite, paraffin appliques, diathermy, massage.
· Vitamins (В6, В12), ATPh.
· anabolic steroids (2-3 courses per year).
An orthopaedic correction in residual period.
Prophylaxis
· Isolation on 21 day from the disease beginning, hospitalization of patient.
· Supervision after contact for 3 weeks.
· Specific active: vaccination by an inactivated (once) than an oral (twice)polo vaccine (IPV, OPV) from a 3 mo age, with a 30 days interval, OPV revaccinatiion in 18 months, 6, 14 years.
Poliovaccine (inactivated)
Combined Poliovaccine (inactivated)
Oral Poliovaccine
Vaccination by Oral Poliovaccine
Vaccine associated poliomyelitis (diagnostic criteria)
· Beginning of illness not early than 4 days and not later than 30 days after the reception of vaccine, for those, who contacted with vaccinated children – up to 60 days.
· Development of languid paresis or paralyses without violation of sensitiveness with the proof (after 2 mo) remaining phenomena.
· Absence of the disease progress.
· Selection of identical virus with the vaccinal culture of virus (by the antigen properties), 4-times growth of specific antibodies.
ENTEROVIRUS INFECTION
Enterovirus infections (ECНO and Coxsackie’s infections) a group of an acute diseases caused by ECНO and Coxsackie’s enteroviruses, that are characterized by the variety of clinical displays from the mild fever and simple carrying of virus to protracted meningoencephalitis, myocarditis, myalgia and other.
Etiology: ECНO and Coxsackie’s enteroviruses.
Enteroviruses
Epidemiology:
§ the source of infection is patients and viral carriers;
§ the mechanism of transmission is droplet, fecal-oral, transpacental;
§ receptivity is high, especially in age 3-10 years.
Pathogenesis
1. Inoculation and replication of virus in an epithelium and lymphoid formations of the intestine and upper respiratory tract.
2. Viremia.
3. Damage of organs and systems.
Classification
A form: –1. typical forms:
Isolated forms:
· serous meningitis;
· epidemic myalgia;
· herpangina;
· paralytic form;
· ECНO and Coxsackie’s fever;
· ECНO and Coxsackie’s exanthema;
· gastroenteritis;
· myocarditis;
· encephalomyocarditis of the new-borns;
· enteroviral uveitis;
· orchitis, epididimitis.
· Combined forms;
2. atypical (effaced, subclinical).
Severity:
· mild degree;
· moderate degree;
· severe degree.
Course:
· smooth;
· uneven.
Diagnostic criteria, common for all forms of Enterovirus infection
• Latent period lasts 2-10 days.
• Acute beginning from toxic syndrome (high body temperature 39-
• Hyperemia of overhead half of trunk skin, neck, and face.
• Injection of sclera vessels.
• Hyperemia, graininess of soft palate, and back pharyngeal wall.
• Neck catarrhal lymphadenitis, or polyadenitis, may be hepato-splenomegaly.
Serous meningitis – one of the most often forms
• Often in children of 5-9 years.
• Sporadic or flashes in children collectives.
• High temperature (39-
• Intensive headache, nausea, vomiting, seizures and hallucinations.
• Loss of appetite, abdominal pain.
• Positive meningeal signs from the desease beginning (nuchal rigidity, Brudzinski’s and Kernig’s signs, anterior fontanel bulging, decreased abdominal skin rephlexes).
• All this signs are instabile, disappear when temperature becomes normal.
• CSF: moderate polymorphonuclear-lymphocyte cytosis in the beginning, later – lymphocyte cytosis, protein is normal (Pandy’s test is negative), shugar is normal or slightly decreased.
• CSF normalization in 3-4 weeks.
• Possible relapses (on 15-30 days) – fever, headache, vomiting.
• In recovery period – asthenia, CSF hypertension.
Epidemic myalgia
• Acute muscular pain in the chest, upper part of abdomen, back, limbs.
• Painful superficial breathing.
• Orthopnoe position of the patient (in case of pain attack).
• Duration is 3-14 days.
• May be relapses.
• May be combination with other forms.
Paralytic form
• More often in children of 4-8 years.
• Normal temperature.
• Languid monoparesis of limbs (muscular weakness of buttocks, thighs, mimic
muscles, impaired gait).
• Decresed muscular tonus and tendon rephlexes.
• Rapid normalization of impaired muscles function.
• CSF is normal.
Herpangina (vericulous pharyngitis)
• Exept common criteria – pharyngeal hyperemia with small papules (1-
• Submandibular lymphnodes enlargement
• Recovery in 4-7 days
Enteroviral fever (“small disease”)
• The most often form in preschoolers.
• Three days fever.
• Mild headache.
• Sometimes nausea, vomiting and abdominal pain.
• Conjunctives and pharynx are hyperemied.
• Lymphadenopathy, mild hepato-, splenomegaly.
• Duration is 2-3 weeks.
Epidemic exanthema
• Is often in schoolchildren.
• Typical common toxic and catarrhal signs.
• Rashes appear in 1-2 days simultaneously on the face, chest and limbs (pinkish maculous-papulous or erythematous, descreate).
• Maculous enanthema on the soft palate.
• Rashes disappear in 2-4 days, sometimes with pigmentation, without desquamation.
Enteroviral diarrhea
• Is often in infants and toddlers.
• Moderate fever (39-
• Abdominal pain, vomiting.
• Stools are watery, sometimes with mucus, green admixtures.
• Metheorism may be present.
Respiratory-catarrhal form (“summer flu”)
• Is characterized by common signs, typical for enteroviral infection
• Short (for 1-5 days) course, mild severity, without complications
• Dry cough and rhinitis
Encephalomyocarditis and myocarditis iewborns
• Is caused by Coxsackie B viruses.
• Is transmitted enterally or trasplacentary.
• Typical acute beginning from fever (39-
• Dyspepsia (vomiting, diarrhea).
• Intoxication (malaise, decreased appetite, sleepiness).
• Dilation of cardiac borders, systolic murmur, tachycardia.
• Rapid development of cardiac insufficiency (dyspnea, hepatomegaly).
• Encephalitis with tonic-clonic seizures, consciousness violation.
• In CSF: lymphocyte pleocytosis, protein is elevated.
• On ECG – changes, typical for myocarditis (low voltage, negative T-vave, QRSdilation,
ST-interval depression, hypoxic P-vave).
• Letal exit in 1-2 days.
Rash in Enterovirus infection
Enterovirus herpangina
Laboratory diagnostics
• Virological investigation of nasopharyngeal smears, feces, CSF.
• Serological investigations (CBR with paired sera), titre enlargement 4 times and more.
• CBC: leucopenia, with neutrophylosis, lymphopenia, eosynophylia, elevated ESR.
• CSF: moderate neuthrophyl-lymphocyte, than lymphocyte pleocytosis, normal or slight elevated protein, Pandy’s test is negative, sugar and chlorides are normal or slight decreased.
Diagnosis example: Enterovirus infection, typical, isolated form (epidemic myalgia), moderate degree, smooth course
Differential diagnostics with: URT viral infections, typhoid, paratyphoid, tubercular meningitis, acute appendicitis, cholecystitis, pancreatitis, rubella, yersiniosis, medicinal rashes, herpetic infection, acute intestinal infections.
Differential diagnostics of poliomyelitis with similar forms of enteroviral infection
Signs |
Poliomyelitis |
Poliomyelitis like forms of enteroviral infection |
|
Latent period |
5-35 days |
2-10 days |
|
Toxic syndrome |
severe |
Mild or moderate |
|
fever |
high |
moderate |
|
Catarrhal signs |
mild |
typical (herpangina) |
|
Preparalytic period duration |
2-3 days |
5-7 days |
|
Skin rashes |
absent |
Often present |
|
paralysis |
peripheral paralysis, stable |
peripheral paresis, usually disappears |
|
the tendon reflexes |
absent |
Decreased or normal |
|
Muscular atrophy |
typical |
Rare, some muscles |
|
Renewal of function |
Less damaged motoneurons in a year |
Practically complete in 3-4 wks |
|
CSFchanges |
As in serous meningitis |
Not typical |
|
Virological studies |
Poliovirus |
Coxackie A, ЕСНО |
Treatment:
• Bed regimen in acute period.
• Etiologic therapy: specific therapy is absent.
• Control of fever.
• NSAIDs for pain relieve.
• Physiotherapy (in case of epidemic myalgia or paralytic form).
Meningitis treatment
Base therapy:
• Bed regimen till body temperature normalization, disappearance of general cerebral and considerable improvement of focal neurological signs, not less than 14-16 days;
• A diet (before stable vital functions is due to adequate parenteral infusion therapy);
• Brest feeding or bottle feeding by adopted formulas for infants, in the first day 1/2-1/3 of average volume with a next increase to the complete volume during 2 -3rd days;
• A milk vegetable diet (№5) is appointed for preschoolers or school children, 5-6 times per day with the next passing to the diet №2 whether №15 (depending the age) in the recovery period;
• Oral fluids intake corresponds to age norms (with including the IV fluids);
• Antibacterial therapy: for infants at presence of concomitant bacterial infection, chronic infection, inflammatory changes in the CBC (by the broadspectrum antibiotic in average therapeutic doses, a short course).
Pathogenetic therapy:
• Glucocrticoids 3-5 mg/kg (by prednisolon), course not more than 10 days;
• Vascular medicine (penthoxyphyllin, nicergolin and others like that);
• In posthypoxia period – nootrops, vitamins group B;
• In case of CSF hypertension – dehydration by 25 % MgSO4 IM, lasix 1-3 mg/kg IV or IM, acethazolamid orally
• In case of seizures – Anticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) 0.3-0.5 mg/kg IV, if they are ineffective – 1 % hexenalum or thiopenthalum sodii in 3-5 mg/kg IV. Dehydration therapy: lasix 2-3 mg/kg IM or IV.
Encephalomyocarditis treatment:
· dehydration (lasix 1-3 mg/kg, mannit, mannitol 1-1.5 g/kg); in case of seizures (seduxen 0.3 mg/kg, droperidol 0.25% 0.05-0.1 ml/kg);
· detoxication (rheosorbilact, albumen 5-15 ml/kg, 5% glucose);
· glucocorticoids (prednisolone 1-3 mg/kg,);
· trental 0.2-0.5 ml/kg;
· noothrope facilities (noothropil 50 mg/kg, stugeron, cavinton, aminalon);
· cardiac glycosides (strophantyn, corglycon up to 6 month 0.05 ml, 6-12 months 0.1 ml, farther 0.012 ml/kg);
· cardiotonic medicine (mildronat, ryboxin)
Bacterial complications: antibiotics (penicillins, cefalosporins).
Prophylaxis:
1. Early exposure and isolation of patients up to 10 days, patients with serous meningitisare discharged from hospital not early than 21 days, clinicaly healthy and after normalizationof CSF.
2. Interferon (iostrils) 5 drops 3-4 times per day, for 10-15 days.
3. Human immune globulin 0.2 ml/kg IM.
4. Quaranteen to contacts for 14 days.
5. Current disinfection, hygienic regimen, respiratory mask wearing.
6. Ultraviolet insolation.
Enteroviruses are small viruses that are made of ribonucleic acid (RNA) and protein. This group or family of viruses includes the polioviruses, coxsackieviruses, and echoviruses. In addition to the three different poliovirus strains, there are 61 non-polio enteroviruses that can cause disease in humans: 23 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, and 4 other enteroviruses that are designated by numbers. All three types of polioviruses have been virtually eliminated from the Western Hemisphere by the widespread use of vaccines. Only the non-polio enteroviruses are known to cause disease in the US. Non-polio enteroviruses are second only to the “common cold” viruses (the rhinoviruses), as the most common viral infectious agents in humans. It is interesting that rhinoviruses and enteroviruses are very similar. Enterovirus infections are among the most common reasons a pediatric patient will visit a pediatrician. The enteroviruses cause an estimated 10-15 million or more symptomatic infections a year in the United States.
What illnesses or symptoms do these viruses cause?
Enteroviruses cause many different symptoms in infected individuals. Most enterovirus infections are not serious at all and resolve on their own without treatment. Typically, the younger the infected person, the more severe the disease. Some very young infants infected with an enterovirus may have the appearance of sepsis (a severe bacterial infection of the blood) with high fever and lethargy, requiring tests to investigate what is causing the illness. Newborns who become infected with an enterovirus may rarely develop an overwhelming infection of many organs, including liver and heart, and die from the infection. Thankfully this is very rare. Because most adults have quite a bit of immunity to enteroviral infections, breastfeeding is a very good way to prevent this possibility by passing on maternal immunity to the child through breast milk.
Thankfully, older children who become ill with enterovirus, usually develop much milder symptoms. This may include upper respiratory symptoms much like a “cold” with a runny nose, sore throat and cough. Headache is common with an enterovirus infection. Other children may develop a flu-like illness with fever and muscle aches. Many enteroviral infections may cause a rash. Typically the rash is characterized by many very small, flat red dots on the skin of the chest and back with individual lesions having the size of a pin head (1/8th of an inch). Another, prominent feature of enterovirus infection is the development of vomiting and diarrhea sometimes associated with abdominal pain. Mouth ulcers are also possible. An individual child may have one or all of the above mentioned symptoms with any particular infection.
It is a very common scenario for a child with enterovirus infection to develop fever and vomit a few times on the first day of the illness. Then shortly later develop mild abdominal pain and mild diarrhea followed by symptoms of runny nose, cough and a mild sore throat. As the illness goes away by day 5 to 7, a fleeting rash as described above, lasts for 1 to 3 days and then fades. The child completely recovers.
Another common peculiar enterovirus infection syndrome is known as hand, foot and mouth disease, in which the child develops ulcers and blisters on the hands, feet and in the mouth. Sometimes a child with hand foot and mouth disease may also have blisters on the buttocks. The most common cause of hand, foot and mouth disease is coxsackievirus A16, although sometimes, the infection is caused by enterovirus 71 or other enteroviruses. Like other enterovirus infections, this is typically a minor illness that resolves on its own.
Rarely, some persons with enteroviral infections may have aseptic or viral meningitis. Usually, there are no long-term complications from aseptic meningitis. Eye infections can also occur. Recovery is the rule. Very rarely, a person may develop an illness that affects the heart (myocarditis) or the brain (encephalitis) or even have an infection that causes paralysis. Thankfully severe infections like this are very very rare. Enterovirus infections are suspected to play a role in the development of juvenile-onset diabetes mellitus (sugar diabetes). Most adults who are infected with an enterovirus actually have no disease at all.
How does someone become infected with one of these viruses?
Enteroviruses can be found in the respiratory secretions (e.g., saliva, sputum, or nasal mucus) and stool of an infected person. Other persons may become infected by direct contact with secretions from an infected person or by contact with contaminated surfaces or objects, such as a drinking glass or telephone. Parents, teachers, and child care center workers may also become infected by contamination of the hands with stool from an infected infant or toddler during diaper changes.
On average, enteroviruses cause about four infections per child per year during the first several years of a child’s life. Once a child has had an infection with a specific enterovirus, the child is typically immune to that particular virus for life. Doing the math, 61 possible infections at 4 infections per year means that a typical child is immune to most enteroviruses by the time they are an adult. So, these are truly “pediatric viruses” primarily affecting children. This is why a child may become ill with a certain enterovirus and the parent usually will not become ill with that virus. However, everyone is potentially at risk. Infants, children, and adolescents are more likely to be susceptible to infection and illness from these viruses, but adults can also become infected and ill if they do not have immunity to a specific enterovirus. In the United States, infections caused by the enteroviruses are most likely to occur during the summer and fall. No vaccine is currently available for prevention of infection with the non-polio enteroviruses.
Treatment:
1. The treatment of an enterovirus infection is supportive and determined by the symptoms present. Because it is a virus, there is no definitive treatment to stop this infection.
2. Cold symptoms are treated according to our “common cold” guidelines.
3. Painful mouth ulcers of Hand, Foot and Mouth disease are treated with an equal mixture of Benadryl and Maalox liquid. The dose is one teaspoon of Benadryl and one teaspoon of Maalox mixed together per 22 pounds. The child should swish this mixture around in her mouth to help ease the discomfort. You may repeat this treatment every four hours.
4. Vomiting and diarrhea are treated according to “vomiting and diarrhea” guidelines of this website. Give plenty of fluids to prevent dehydration. Sometimes promethazine or Zofran can be prescribed to control nausea and vomiting at an office visit if the vomiting is bothersome.
5. Fever is treated according to our “fever” guidelines on this website. We generally discourage the treatment of fever with enterovirus infections unless your child has a history of seizures, so that your body can fight off this infection more effectively.
6. The rash of enterovirus is treated with Benadryl. See our dosing guidelines for Benadryl.
7. More serious symptoms such as meningitis or encephalitis (severe headache and stiff neck), and myocarditis (chest pain and extreme fatigue) require the immediate attention of one of our physicians. These complications are very rare.
8. Newborns with enterovirus infections require our immediate attention.
References:
1. Manual of children’s infectious diseases / O. Ye. Fedortsiv, I. L. Horishna, I. M. Horishniy. – TERNOPІL : UKRMEDKNYHA, 2010. – 382 p. – ISBN 978-966-673-145-9
2. Manual of Childhood Infections: The Blue Book (Oxford Specialist Handbooks in Paediatrics) by Mike Sharland, Andrew Cant and al. Published by Oxford University Press Inc., New York, 2011 , p. 881 ISBN: 978-019-957-358-5.
3. Illustrated Textbook of Paediatrics, 4th Edition. Published by Lissauer & Clayden, 2012, p. 552 ISBN: 978-072-343-566-2.
4. Nelson Textbook of Pediatrics, 19th Edition Kliegman, Behrman. Published by Jenson & Stanton, 2011, 2608. ISBN: 978-080-892-420-3.
5. Oxford Textbook of Medicine: Infection by David Warrell, Timothy M. Cox, John Firth and Mili Estee Torok , Published by Wiley-Blackwell, 2012
6. http://www.merckmanuals.com/professional/index.html
