Theme 15. Differential diagnosis of infectious diseases with exanthema syndrome

 

MEASLES

an acute communicable disease, is characterized by three stages: (1) an incubation stage of approximately 10–12 days with few, if any, signs or symptoms; (2) a prodromal stage with an enanthem (Koplik spots) on the buccal and pharyngeal mucosa, slight to moderate fever, mild conjunctivitis, coryza, and an increasingly severe cough; and (3) a final stage with a maculopapular rash erupting successively over the neck and face, body, arms, and legs and accompanied by high fever.

 

ETIOLOGY. Measles is an RNA virus of the family Paramyxoviridae, genus Morbillivirus. Only one antigenic type is known. During the prodromal period and for a short time after the rash appears, it is found iasopharyngeal secretions, blood, and urine. It can remain active for at least 34 hr at room temperature.

 

Measles virus may be isolated in cultures of human embryonic or rhesus monkey kidney tissue. Cytopathic changes, visible in 5–10 days, consist of multinucleated giant cells with intranuclear inclusions. Circulating antibody is detectable when the rash appears.

 

INFECTIVITY. Maximal dissemination of virus is by droplet spray during the prodromal period (catarrhal stage). Transmission to susceptible contacts often occurs prior to diagnosis of the original case. An infected person becomes contagious by the 9th–10th day after exposure (beginning of prodromal phase), in some instances as early as the 7th day. Isolation precautions, especially in hospitals or other institutions, should be maintained from the 7th day after exposure until 5 days after the rash has appeared.

 

EPIDEMIOLOGY. Measles is endemic over most of the world. In the past, epidemics tended to occur irregularly, appearing in the spring in large cities at 2- to 4-yr intervals as new groups of susceptible children were exposed. Measles is very contagious; approximately 90% of susceptible family contacts acquire the disease. It is rarely subclinical. Prior to the use of measles vaccine, the age of peak incidence was 5–10 yr; most adults were immune. At present in the United States, measles occurs most often in unimmunized preschool-aged children and in teenagers and young adults who have been immunized. Epidemics have occurred in high schools and colleges where immunization levels were high. These epidemics are thought to be due primarily to vaccine failure. Despite a resurgence of measles in the United States from 1989–1991, reported numbers of measles cases dropped to an all-time low in 1993, probably a result of widespread vaccination. Those older than 30 years are virtually all immune. Because measles is still a common disease in many countries, infective persons entering this country may infect United States citizens, and Americans traveling abroad risk exposure there.

 

The many similarities among the biologic features of measles and smallpox suggest the possibility that measles may be eradicable. These features are (1) a distinctive rash, (2) no animal reservoir, (3) no vector, (4) seasonal occurrence with disease-free periods, (5) no transmissible latent virus, (6) one serotype, and (7) an effective vaccine. A prevalence of more than 90% immunization of infants has been shown to produce disease-free zones. In 1980, three fourths of all counties in the United States did not report a single case of measles, but by 1988 the number of measles cases was increasing and the disease was more widespread.

 

Infants transplacentally acquire immunity from mothers who have had measles or measles immunization. This immunity is usually complete for the first 4–6 mo of life and disappears at a variable rate. Although maternal antibody levels are generally undetectable in the infant by the usual tests performed after 9 mo of age, some protection persists, which may interfere with immunization administered prior to 15 mo. Most women of child-bearing age in the United States now have measles immunity by means of immunization rather than disease. Some studies now suggest that infants of mothers with measles vaccine–induced immunity lose passive antibody at a younger age than infants of mothers who had measles infection. Infants of mothers susceptible to measles have no measles immunity and may contract the disease with the mother before or after delivery.

 

PATHOLOGY. The essential lesion of measles is found in the skin; in the mucous membranes of the nasopharynx, bronchi, and intestinal tract; and in the conjunctivae. Serous exudate and proliferation of mononuclear cells and a few polymorphonuclear cells occur around the capillaries. There is usually hyperplasia of lymphoid tissue, particularly in the appendix, where multinucleated giant cells of up to 100 mmin diameter (Warthin-Finkeldey reticuloendothelial giant cells) may be found. In the skin, the reaction is particularly notable about the sebaceous glands and hair follicles. Koplik spots consist of serous exudate and proliferation of endothelial cells similar to those in the skin lesions. A general inflammatory reaction of the buccal and pharyngeal mucosa extends into the lymphoid tissue and the tracheobronchial mucous membrane. Interstitial pneumonitis resulting from measles virus takes the form of Hecht giant cell pneumonia. Bronchopneumonia may be due to secondary bacterial infection.

 

In fatal cases of encephalomyelitis, perivascular demyelinization occurs in areas of the brain and spinal cord. In Dawson subacute sclerosing panencephalitis (SSPE), there may be degeneration of the cortex and white matter with intranuclear and intracytoplasmic inclusion bodies.

 

CLINICAL MANIFESTATIONS.

 

The incubation period is approximately 10–12 days if the first prodromal symptoms are selected as the time of onset, or approximately 14 days if the appearance of the rash is selected; rarely it may be as short as 6–10 days. A slight rise in temperature may occur 9–10 days from the date of infection and then subside for 24 hr or so.

 

The prodromal phase, which follows, usually lasts 3–5 days and is characterized by low-grade to moderate fever, a hacking cough, coryza, and conjunctivitis. These nearly always precede Koplik spots, the pathognomonic sign of measles, by 2–3 days. An enanthem or red mottling is usually present on the hard and soft palates. Koplik spots are grayish white dots, usually as small as grains of sand, with slight, reddish areolae; occasionally they are hemorrhagic. They tend to occur opposite the lower molars but may spread irregularly over the rest of the buccal mucosa. Rarely they are found within the midportion of the lower lip, on the palate, and on the lacrimal caruncle. They appear and disappear rapidly, usually within 12–18 hr. As they fade, red, spotty discolorations of the mucosa may remain. The conjunctival inflammation and photophobia may suggest measles before Koplik spots appear. In particular, a transverse line of conjunctival inflammation, sharply demarcated along the eyelid margin, may be of diagnostic assistance in the prodromal stage. As the entire conjunctiva becomes involved, the line disappears.

 

Conjunctivitis in measles

  

 

Koplik spots

 

Enanthema

 

Occasionally, the prodromal phase may be severe, being ushered in by sudden high fever, at times with convulsions and even pneumonia. Usually the coryza, fever, and cough are increasingly severe up to the time the rash has covered the body.

 

The temperature rises abruptly as the rash appears and often reaches 40–40.5º C (104–105º F). In uncomplicated cases, when the rash appears on the legs and feet, within about 2 days, the symptoms subside rapidly; the subsidence includes a usually abrupt temperature drop. Patients up to this point may appear desperately ill, but within 24 hr after the temperature drop, they appear essentially well.

 

The rash usually starts as faint macules on the upper lateral parts of the neck, behind the ears, along the hairline, and on the posterior parts of the cheek. The individual lesions become increasingly maculopapular as the rash spreads rapidly over the entire face, neck, upper arms, and upper part of the chest within approximately the first 24 hr

 

 

Fig. Maculopapular rash of measles, the first day of the eruption

 

Fig. Maculopapular rash of measles, the second day of the eruption

 

Fig. Maculopapular rash of measles, the third day of the eruption

 

Fig. Hemorrhagic rash of measles

 

The rash pigmentation

 

During the succeeding 24 hr it spreads over the back, abdomen, entire arms, and thighs. As it finally reaches the feet on the 2nd–3rd day, it begins to fade on the face. The fading of the rash proceeds downward in the same sequence in which it appeared. The severity of the disease is directly related to the extent and confluence of the rash. In mild measles the rash tends not to be confluent, and in very mild cases there are few, if any, lesions on the legs. In severe measles the rash is confluent, the skin being completely covered, including the palms and soles, and the face is swollen and disfigured.

 

The rash is often slightly hemorrhagic; in severe cases with a confluent rash, petechiae may be present in large numbers, and there may be extensive ecchymoses. Itching is generally slight. As the rash fades, branny desquamation and brownish discoloration occur and then disappear within 7–10 days.

 

The rash may vary markedly. Infrequently a slight urticarial, faint macular, or scarlatiniform rash may appear during the early prodromal stage and disappear in advance of the typical rash. Complete absence of rash is rare except in patients who have received human antibodies during the incubation period, in some patients with human immunodeficiency syndrome (HIV) infection, and possibly in infants younger than 8 mo who have appreciable levels of maternal antibody. In the hemorrhagic type of measles (black measles), bleeding may occur from the mouth, nose, or bowel. In mild cases the rash may be less macular and more nearly pinpoint, somewhat resembling that of scarlet fever or rubella.

 

Lymph nodes at the angle of the jaw and in the posterior cervical region are usually enlarged, and slight splenomegaly may be noted. Mesenteric lymphadenopathy may cause abdominal pain. Characteristic pathologic changes of measles in the mucosa of the appendix may cause obliteration of the lumen and symptoms of appendicitis. Changes of this type tend to subside with the disappearance of Koplik spots. Otitis media, bronchopneumonia, and gastrointestinal symptoms, such as diarrhea and vomiting, are more common in infants and small children (especially malnourished ones) than in older children.

 

The diagnosis of measles is frequently delayed in adults because practitioners providing health care for adults are not used to encountering the disease and rarely include it in the differential diagnosis. The clinical picture is similar to that seen in children. Liver involvement, with abdominal pain, mild to moderate elevation of aspartate aminotransferase (AST) levels, and occasionally jaundice, is common in adults. In developing countries and in recent outbreaks in the United States, measles frequently occurs in infants younger than 1 yr; possibly because malnutrition is concomitant there, the disease is very severe and has a high mortality.

 

DIAGNOSIS.

 

This is usually made from the typical clinical picture; laboratory confirmation is rarely needed. During the prodromal stage multinucleated giant cells can be demonstrated in smears of the nasal mucosa. Virus can be isolated in tissue culture, and diagnostic rises in antibody titer can be detected between acute and convalescent sera. The white blood cell count tends to be low with a relative lymphocytosis. Lumbar puncture in patients with measles encephalitis usually shows an increase in protein and a small increase in lymphocytes. The glucose level is normal.

 

DIFFERENTIAL DIAGNOSIS.

 

The rash of rubeola must be differentiated from exanthem subitum, rubella, infections resulting from echovirus, coxsackie virus, and adenovirus, infectious mononucleosis, toxoplasmosis, meningococcemia, scarlet fever, rickettsial diseases, serum sickness, Kawasaki disease, and drug rashes.

                            

Koplik spots are pathognomonic for rubeola, and the diagnosis of unmodified measles should not be made in the absence of cough.

 

Roseola infantum (exanthem subitum) is distinguished from measles in that the rash of the former appears as the fever disappears. The rashes of rubella and of enteroviral infections tend to be less striking than that of measles, as do the degree of fever and severity of illness. Although cough is present in many rickettsial infections, the rash usually spares the face, which is characteristically involved in measles. The absence of cough or the history of injection of serum or administration of a drug usually serves to identify serum sickness or drug rashes. Meningococcemia may be accompanied by a rash that is somewhat similar to that of measles, but cough and conjunctivitis are usually absent. In acute meningococcemia the rash is characteristically petechial purpuric. The diffuse, finely papular rash of scarlet fever with a “goose flesh” texture on an erythematous base is relatively easy to differentiate.

 

The milder rash and clinical picture of measles modified by gamma globulin or by partial immunity induced by measles vaccine, or in infants by maternal antibody, may be difficult to differentiate.

 

COMPLICATIONS.

 

The chief complications of measles are otitis media, pneumonia, and encephalitis. Noma of the cheeks may occur in rare instances. Gangrene elsewhere appears to be secondary to purpura fulminans or disseminated intravascular coagulation following measles.

 

Pneumonia (see Chapter 170) may be caused by the measles virus itself; the lesion is interstitial. Measles pneumonia in patients with HIV infection is often fatal and not always accompanied by rash. Bronchopneumonia is more frequent, however; it is due to secondarily invading bacteria, particularly the pneumococcus, streptococcus, staphylococcus, and Haemophilus influenzae. Laryngitis, tracheitis, and bronchitis are common and may be due to the virus alone.

 

One of the potential dangers of measles is exacerbation of an existing tuberculous process. There may also be a temporary loss of hypersensitivity to tuberculin.

 

Myocarditis is an infrequent serious complication; transient electrocardiographic changes are said to be relatively common.

 

Neurologic complications are more common in measles than in any of the other exanthems. The incidence of encephalomyelitis is estimated to be 1-2/1,000 reported cases of measles. There is no correlation between the severity of the measles and that of the neurologic involvement or between the severity of the initial encephalitic process and the prognosis. Rarely, encephalitis has been reported in association with measles modified by gamma globulin or by live attenuated measles virus vaccine. Infrequently, encephalitic involvement is manifest in the pre-eruptive period, but more often the onset occurs 2–5 days after the appearance of the rash. The cause of measles encephalitis remains controversial. It is suggested that when encephalitis occurs early in the course of the disease, viral invasion plays a large role, although measles virus has rarely been isolated from brain tissue; encephalitis that occurs later is predominantly demyelinating and may reflect an immunologic reaction. In this demyelinating type the symptoms and course do not differ from those of other parainfectious encephalitides. Fatal encephalitis has occurred in children receiving immunosuppressive treatment for malignancies. Other central nervous system complications, such as Guillain-Barré{acute-e} syndrome, hemiplegia, cerebral thrombophlebitis, and retrobulbar neuritis, are rare.

 

Subacute sclerosing panencephalitis  is due to measles virus.

 

PROGNOSIS.

 

Case fatality rates in the United States have decreased in recent years to low levels for all age groups, largely because of improved socioeconomic conditions but also because of effective antibacterial therapy for the treatment of secondary infections.

 

When measles is introduced into a highly susceptible population, the results may be disastrous. Such an occurrence in the Faroe Islands in 1846 resulted in the deaths of about one fourth, nearly 2,000, of the total population regardless of age. At Ungava Bay, Canada, where 99% of 900 persons had measles, the mortality rate was 7%.

 

PROPHYLAXIS.

 

Quarantine is of little value because of the contagiousness during its prodromal stage, when measles may not be suspected.

 

The initial measles immunization may be given at 12 to 15 mo but may be given earlier in areas where disease is occurring. Because the seroconversion rate following immunization is not 100% and there may be some waning of immunity with time, a second immunization against measles, usually given as measles-mumps-rubella (MMR), is indicated. This dose can be given when the child enters school or later on entry to middle school. Adolescents entering college should also have received a second measles immunization.

 

The response to live measles vaccine is unpredictable if immune globulin has been administered in the 3 mo preceding immunization. Anergy to tuberculin may develop and persist for 1 mo or longer after administration of live, attenuated measles vaccine. A child with active tuberculous infection should be receiving antituberculosis treatment when live measles vaccine is administered. A tuberculin test prior to or concurrent with active immunization against measles is desirable.

 

Use of live measles vaccine is not recommended for pregnant women or for children with untreated tuberculosis. Live vaccine is contraindicated in children with leukemia and in those receiving immunosuppressive drugs because of the risk of persistent, progressive infection such as giant cell pneumonia. After exposure of these susceptible children to measles, measles immune globulin (human) should be given intramuscularly in a dose of 0.25 mL/kg as soon as possible. A larger dose may be advisable in children with acute leukemia, even those in remission. Children with HIV infection should receive measles vaccine because mortality from measles is high in this group and they tolerate the vaccine well. Despite a history of having received measles immunization, these children should receive gamma globulin after exposure to measles in a dose of 0.5 mL/kg (maximum 15 mL). This is twice the usual recommended dose. Measles vaccine can be given following exposure to the disease. Reactions are not increased, and measles may be prevented.

 

The use of inactivated (killed) virus vaccine is not recommended.

 

Passive Immunization.

 

Passive immunization with pooled adult serum, pooled convalescent serum, placental globulin, or gamma globulin of pooled plasma is effective for prevention and attenuation of measles. Measles can be prevented by using immune serum globulin (gamma globulin) in a dose of 0.25 mL/kg given intramuscularly within 5 days after exposure but preferably as soon as possible. Complete protection is indicated for infants, for children with chronic illness, and for contacts in hospital wards and children’s institutions. Attenuation may be accomplished by the use of gamma globulin in a dosage of 0.05 mL/kg. Gamma globulin is approximately 25 times as potent in antibody titer as pooled adult serum, and it avoids the risk of hepatitis. Attenuation is variable, and the modified clinical patterns may vary from those with few or no symptoms to those with little or no modification. Encephalitis may follow measles modified by gamma globulin.

 

After the 7th–8th day of incubation the amounts of antibody administered must be increased greatly for any degree of protection. If the injection is delayed until the 9th, 10th, or 11th day, slight fever may already have started and only slight modification of the disease may be expected.

 

TREATMENT.

 

Sedatives, antipyretics for high fever, bed rest, and an adequate fluid intake may be indicated. Humidification of the room may be necessary for laryngitis or an excessively irritating cough, and it is best to keep the room comfortably warm rather than cool. The patient should be protected from being exposed to strong light during the period of photophobia. The complications of otitis media and pneumonia require appropriate antimicrobial therapy.

 

With complications such as encephalitis, subacute sclerosing panencephalitis, giant cell pneumonia, and disseminated intravascular coagulation, each case must be assessed individually. Good supportive care is essential. Gamma globulin, hyperimmune gamma globulin, and steroids are of limited value. Currently available antiviral compounds are not effective. Treatment with oral vitamin A (400,000 IU) reduces morbidity and mortality in children with severe measles in the developing world.

 

Short statement of the material

 

 

Measles is a viral infection that is passed by an air-droplet way, is characterized by cyclic course, syndromes of intoxication, catarrhal inflammation of respiratory tract, conjunctiva, and rashes on the skin.

 

Etiology: the measles virus is a member of the family Paramyxoviridae, genus

Morbillivirus.

 

Epidemiology:

1.      Source of infection – infected person during last 2 days of incubation period, catarrhal period, and 4 days period of eruption (in case of complications –10 days period of eruption).

2.      Infection is transmitted by inhalation of large and small airborne droplets.

3.      Susceptible organism – no immunized people, older than 6 month, which never had measles.

 

Pathogenesis:

• The primary site of infection is the respiratory epithelium and conjunctiva.

• Local replication of the virus is followed by viremia (primary).

• During this phase virus is spread by leukocytes to the reticuloendothelial systemwhere it replicates.

• Following necrosis of white blood cells, a secondary viremia occurs.

• Than:

– morphological changes in CNS, mucus membrains of the trachea, bronchi,

intestinum;

– inflammation, destruction, liberation of virus;

– secondary immune deficiency, and growth of the bacterial microflora;

– forming of complications.

• With the development of specific antibody and cell-mediated responses, viremia is terminated and the illness resolves.

 

Clinical presentation

1. The incubation period is 9-17 days, in those who has received specific immunoglobulin for prevention – it may be longer (up to 21 days).

4.      Prodromal period is the next, lasting 3 to 5 days. The classic three “C’s” (cough, corryza, conjunctivitis) make their appearance. The enanthema of measles occurs, Koplick’s spots (small, bluish-gray papules on a red base) localized on entire oral mucosa. They usually disappear by the second day of the exanthema. Temperature is usually high at first day.

5.      Exanthema period: Second increase of temperature. Initial lesions are noted behind the ears on the forehead and face. During 3-4 days they spread downward, involve the trunk and extremities. The rashes consist of an erythematosus maculopapular eruption. They are initially discrete but then became confluent on the areas of initial involvement.

6.      Pigmentation period progresses in the same fashion as the appearance of the rashes. As the rashes resolves, a brownish desquamation may occur.

 

Classification

By the form:

Typical, by the severity:

– mild;

– moderate;

– severe (without hemorrhagic syndrome, with hemorrhagic syndrome);

Atypical:

– abortive;

– mitigious;

– hyperreactive;

– subclinical;

            – asymptomatic;

– measles in vaccinated;

– measles in person who receive antibiotics and hormones.

By the course:

– smooth (uncomplicated);

– not smooth, uneven (complicated).

 

Complications:

By the etiology:

– primary (due to measles virus);

– secondary (bacterial).

By the time of development:

– early (in prodromal and rushes period);

– late (in pigmentation period).

By the localization:

– respiratory system (laryngitis, laryngotracheobronchitis, pneumonia);

– digestive system (enterocolitis, colitis);

– nervous system (encephalitis, serous meningitis, encephalomyelitis);

– eyes (keratitis);

– ears (otitis media);

– skin (staphylo- or streptodermia);

– urinary system (pyelonephritis).

Complications:

viral – laryngotracheitis (croup), bronchitis, encephalitis, Giant-cell pneumonia, and diarrhea is common in infants;

secondary bacterial – otitis media, pneumonia, gingivostomatitis, pyelonephritis, diarrhea, dermatitis.

 

Peculiarities of measles in infants

1. Atypical (mitigious) forms.

2. Reduction of the disease periods.

3. Unexpressed clinical signs (catarrhal phenomena, fever, small unabundant rashes with the shortened staging and pigmentation).

4. Complications are more frequent.

 

Laboratory work-up

• Common laboratory tests are non-specific, CBC – leucopenia, lymphocytosis, eosynophylia, and thrombocytopenia (may be).

• Cytoscopic examination of smears from the pharynx – presence of typical multinuclear giant cells.

• Viral isolation is technically difficult.

• Immune enzyme analysis (ELISA) – presence of Ig M antibodies in acute period.

• Serology (DHAR, PHAR) is confirmed when fourfold or greater rise in antibody titre or the presence of specific Ig M antibodies.

 

Diagnosis example:

• Measles, typical form, period of exanthema, moderate severity, uncomplicated.

• Measles, typical form, period of pigmentation, severe (with hemorrhagic

syndrome), complicated by the leftside polysegmental (S4–S6) pneumonia with

obstruction syndrome, Respiratory insufficiency 2nd degree.

Differential diagnose should be performed between scarlet fever, Epstein-Barr viral infection, meningococcal sepsis, pseudotuberculosis, Kawasaki syndrome, Stevens-Johnson syndrome, adenovirus, enterovirus infection, diaper rashes (photo 1), Rheumathoid arthritis systemic form (photo 2), and allergic rashes (photo 3-10).

During prodromal period – between other upper respiratory tract viral infections.

Heat rash

Rheumathoid arthritis systemic form

Drug allergy

Drug allergy

 

Drug allergy

 

Food allergy (urticaria)

Cool allergy

Differential diagnostics of infectious rashes (exanthemas)

 

Evidences for obligatory hospitalization of patients with infectious exanthema

1. The severe form of disease, when appears need in undertaking of intensive therapy; patients with moderate forms at age before 3 years.

2. Sick children from families with bad social-home conditions, especially in the event of impossibility of their isolation to prevent infections transmission.

3. Absence of conditions for examination and treatment at home.

4. Sick children from closed children institutions.

Advantages of the home treatment

1. Possibility of additional infection by hospital bacteria is completely excluded.

2. Realization of individual care principle for sick child is more full.

3. Avoiding stressful reactions, which could appear in case of hospital treatment.

Treatment in home conditions is possible

1. In conditions of isolated flat.

2. In case of satisfactory material position of the parents.

3. In case of parents desire to organize individual care and treatment at home.

Treatment

Noncomplicated mild, moderate measles and atypical forms do not need medicine.

1. Bed rest up to the normalization of body temperature.

2. Regular ventilation of the room.

3. Adequate rehydration with oral fluids (lemon tea, raspberry tea, warm alkalic

5. 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. Nasal drops (in infants before 6 mo – physiologic saline solutions as Salin; in elder children – naphtizin, rhinasolin, nasivin for children 1-2 drops 3 t.d. in the nostrils, not more than 3 days).

7. In case of dry cough – cough suppressors (such as dextramethorphan, synecod).

8. Mucolytics in case of the moist nonproductive cough (ambroxol, acetylcystein etc.).

9. Looking after oral cavity (gurgling with boiled water, antiseptic fluids).

10. Looking after conjunctiva (washing with boiled water, concentrated tea, sulfacyl Na in drops).

11. Vitamin A orally.

• In case of bacterial complication – antibacterial therapy should be used.

• In case of severe episodes – corticosteroids (1-2 mg/kg for 2-3 days).

• In case of croup: mist tent with 25-30 % oxygen inhalation, antianxiety medicines, steroids and mechanical ventilation in severe cases.

• In case of meningitis:

Base therapy:

1.      Bed regimen till body temperature normalization, disappearance of general cerebral and considerable improvement of focal neurological signs, not less than 14-16 days.

2.      A diet (before stable vital functions is due to adequate parenteral infusion therapy),

3.      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.

4.      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;

5.      Oral fluids intake corresponds to age norms (with including the IV fluids).

6.      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).

Etiologic therapy: specific therapy is absent.

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.

Prevention

1. Specific active immunization by MMR vaccine (measles, mumps, rubella) at age 12 months. Revaccination at 4 to 6 years or at 10 to 11 years (in Ukraine revaccination in 6 years).

2. Specific passive prophylaxis with immune serum globulin in a dose of 0.25 ml/kg as a postexposure prophylaxis.

3. Nonspecific: – isolation of ill person until 5th day of the exanthema period (if complicated by pneumonia, encephalitis – up to 10th day), isolation of contact person from 8 to 17 days (in case of the specific immunoglobulin prevention – up

to 21 day).

Key words and phrases: measles, Morbillivirus, prodromal period, exanthema period, enanthema, Koplick’s spots, maculopapular rashes, spread downward, cleaning (pigmentation) period, brownish desquamation, giant-cell pneumonia, specific and nonspecific prophylaxis.

Rubella

Rubella is a viral infection, that has the acquired form (with the air-droplet mechanism of transmission, mild clinical signs and benign completion) and innate (with the transplacental mechanism of transmission and development of severe fetal defects).

 

Etiology: an agent is a RNA-containing Rubivirus from the Togaviruses.

 

Rubivirus

 

Epidemiology:

– the source of infection is a patient or carrier;

– the mechanism of transmission is air-droplet, transplacental;

– receptivity is common, especially high in children 2-9 years.

 

Pathogenesis

Acquired Rubella:

1. An entrance gate is the mucus membranes of nasopharynx, where virus is replicating.

1. Hematogenous distribution (viremia).

2. Damage of organs and systems.

3. Immunological answer, recovery.

Innate Rubella:

1. Transplacental infection of the fetus.

4. Destruction of the cells by the virus, violation of the correct organs’ development.

5. Forming of the development defects.

 

Diagnostic criteria of the acquired Rubella:

• Latent period – 18-23 days.

• Prodromal period – 1-2 days:

– mild toxic syndrome;

– mild catarrhal syndrome (rhinitis, pharyngitis, catarrhal tonsillitis);

– increase of posterior cervical, occipital lymph nodes.

• Period of exanthema (rashes, erruption) – 3-4 days:

– rashes (maculous, pinky, on face, trunk, extensor surfaces of extremities, on the unchanged background, arises during one day) (photo 11);

– toxic syndrome (mild);

– increase of cervical, occipital lymph nodes (rarely – polyadenopathy).

 

Rubella, throat and skin changes

  

The rashes in acquired Rubella

 

Diagnostic criteria of the innate Rubella:

Classical Triad:

1. Cataract.

2. Congenital heart disease (open aortic channel, aortic valves defect, aortic stenosis, coarctation of the aorta, ventricular septal defect and pulmonary atery stenosis, atrial septal defect, large arteries transposition).

3. Deafness.

Exept enumerated:

• Microcephalus

• Microphthalmia

• Rhetinopathy

• Cornea clouding

• Glaucoma

• Clift palate

• Intersticial pneumonia

• Hepatitis

• Myocarditis

• Meningoencephalitis

• Damage of the vestibular organ

• Urinary tract and sexual organs defect

• Dermatitis

• Thrombocytopenia

• Hemolytic anemia

• Hypogammaglobulinemia

• Secondary immune deficit

• Low birth weight

  

The congenital Rubella rashes, cataract

 

Classification of the acquired Rubella:

By the type:

 – typical forms;

– atypical forms (effaced, asymptomatic).

By the severity:

– mild;

– moderate;

– severe;

By the course:

 – smooth (uncomplicated);

– uneven (complicated).

Specific complications: meningitis, encephalitis, synovitis.

 

Diagnosis example

Rubella, typical form, exanthema period, moderate severity, uncomplicated duration

 

Confirmation of the diagnosis:

1.      Complete blood test: leucopenia, lymphocytosis, plasmatic cells, normal ESR.

12. PCR – selection of virus from the nasopharyngeal smears, excrements, urine, blood, saliva and CSF.

13. Serologic – NR, PHAR (stable positive result in case of the innate rubella), CBR with 4 times or more increasing of the antibody tytre in dynamics.

14. Immune-enzyme analysis (ELISA test) with measuring of specific antibodies Ig M in the acute phase (and in the innate rubella) and Ig G after the recovery (in the blood or, if necessary, in CSF).

15. Express methods – phase-contrasting microscopy, micro agglutination reaction.

 

Differential diagnosis with measles, scarlet fever, allergic exanthema, infectious mononucleosis.

 

Treatment:

Base therapy:

• Bed regime in an acute period, then half-bed regime (3-7 days).

• Hygienic regime, often room ventilation.

 • Control of fever and myalgia (when the temperature is more than 38.5-39 °C); in chilren before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart deseases – 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.

In case of encephalitis, meningitis:

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 2-3nd 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).

Etiologic therapy: specific therapy is absent.

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.

 

Prognosis:

• Recovery;

• Invalaidization (in case of the innate Rubella).

 

Prophylaxis:

• Isolation of patients on 4 days from the disease beginning, new-born with innate Rubella – up to 1 year.

• An active immunization (vaccination) is done in 12-18 months by MMR vaccine (together with vaccination against measles, and mumps). Revaccination at 4 to 6 years or at 10 to 11 years, if not done before – vaccination by monovaccine in 12-14 years (girls), (in Ukraine vaccination in 12 month, revaccination in 6 years, if not done before – in 15 years by monovaccine in girls).

 

 

n  Passive prophylaxis to seronegative pregnant, (to children does not performed).

 

Key words and phrases: innate (inborn) rubella, acquired rubella, rubella virus, prodromal

period, exanthema period, enanthema, maculopapular rashes, giant-cell pneumonia,

meningoencephalitis, specific and nonspecific prophylaxis.

 

VARICELLA (Chickenpox)

 

Primary infection with varicella-zoster virus (VZV) causes varicella (chickenpox). The virus establishes latent infection in dorsal root ganglia; its reactivation causes herpes zoster (shingles).

 

ETIOLOGY.

VZV is a human herpesvirus; it is classified as an alpha herpesvirus because of its similarities to the prototype for this group, which is herpes simplex virus (HSV). VZV is an enveloped, double-stranded DNA virus; the viral genome encodes more than 70 proteins, including proteins that are targets of immunity and a viral thymidine kinase, which makes the virus sensitive to inhibition by acyclovir and related antiviral agents.

VZ-Virus

 

PATHOLOGY.

Varicella begins with mucosal inoculation of virus transferred in respiratory secretions or by direct contact with skin lesions of varicella or herpes zoster. Inoculation is followed by an incubation period of 10–21 days, during which subclinical viral spread occurs. Widespread cutaneous lesions result when the infection enters a viremic phase; peripheral blood mononuclear cells carry infectious virus, generating new crops of vesicles for 3–7 days. VZV is also transported back to respiratory mucosal sites during the late incubation period, permitting spread to susceptible contacts before the appearance of rash. The transmission of infectious virus by respiratory droplets distinguishes VZV from other human herpes viruses. Visceral dissemination of the virus follows the failure of host responses to terminate viremia, which results in infection of lungs, liver, brain, and other organs. VZV becomes latent in dorsal root ganglia cells in all individuals who experience primary infection. Its reactivation causes a localized vesicular rash that usually involves the dermatomal distribution of a single sensory nerve; necrotic changes are produced in the associated ganglia, sometimes extending into the posterior horn. The histopathology of varicella and herpes zoster lesions is identical; infectious VZV is present in herpes zoster lesions, as it is in varicella lesions, but is not released into respiratory secretions. Varicella elicits humoral and cell-mediated immunity that is highly protective against symptomatic reinfection. Suppression of cell-mediated immunity to VZV correlates with an increased risk of VZV reactivation as herpes zoster.

 

EPIDEMIOLOGY.

In the United States and other temperate climates, 90–95% of individuals acquire VZV in childhood. Annual varicella epidemics occur in winter and spring. Wild-type VZV strains that cause the annual epidemics of varicella do not exhibit changes in virulence as judged by the clinical severity of primary VZV infections from year to year. Household transmission rates are 80–90%; more casual contact, such as school classroom exposure, is associated with attack rates of 30% or less. Varicella is contagious from 24–48 hr before the rash appears and while uncrusted vesicles are present, which is usually 3–7 days. Susceptible children acquire varicella after close, direct contact with adults who have herpes zoster; this route of transmission maintains the circulation of the virus in the population. For unexplained reasons, varicella is much less common in tropical areas, so that susceptibility rates among adults are as high as 20–30%. Herpes zoster shows no seasonal variation in incidence because it is due to the reactivation of endogenous, latent virus. Despite anecdotal reports, epidemiologic studies demonstrate that exposure to varicella does not cause herpes zoster. Herpes zoster is very rare in children younger than 10 yr except among those given immunosuppressive therapy for malignancy or other diseases, those who have human immunodeficiency virus (HIV) infection, and those who have been infected in utero or during the first year of life. The risk of severe or life-threatening primary or recurrent VZV infection is related primarily to host factors rather than variations in the pathogenicity of VZV strains.

 

CLINICAL MANIFESTATIONS OF VARICELLA.

 

Although the incubation period of varicella ranges from 10–21 days, the illness usually begins from 14–16 days after exposure. Almost all exposed, susceptible children experience a rash, but it may be limited to fewer than 10 lesions. Prodromal symptoms are common, particularly in older children; fever, malaise, anorexia, headache, and occasionally mild abdominal pain occur 24–48 hr before the rash appears. Temperature elevation is usually moderate, ranging from 100–102º F but may be as high as 106º F; fever and other systemic symptoms persist during the first 2–4 days after the onset of the rash. Varicella lesions appear first on the scalp, face, or trunk. The initial exanthem consists of intensely pruritic erythematous macules that evolve to form clear, fluid-filled vesicles. Clouding and umbilication of the lesions begin in 24–48 hr. While the initial lesions are crusting, new crops form on the trunk and then the extremities; the simultaneous presence of lesions in various stages of evolution is characteristic of varicella.

 

  

Typical rash in varicella

 

 

Pustular rashes and hemorrhagic rashes

 

 

 Hemorrhagic form of varicella

 

Ulcerative lesions involving the oropharynx and vagina are common; many children have vesicular lesions on the eyelids and conjunctivae, but serious ocular disease is rare. The average number of varicella lesions is about 300, but healthy children may have from fewer than 10 to more than 1,500 lesions. In secondary household cases and cases involving older children, more days of new lesion formation and more lesions are likely. The exanthem is more extensive in children with skin disorders, such as eczema or recent sunburn. Hypopigmentation of lesion sites persists for days to weeks in some children, but scarring is unusual.

 

 An element on the palate

 

Varicella Convalescent

 

The differential diagnosis of varicella includes vesicular rashes caused by other infectious agents, such as enterovirus or Staphylococcus aureus, drug reactions, contact dermatitis, and insect bites.

 

COMPLICATIONS OF VARICELLA.

 

Secondary bacterial infections, usually resulting from S. aureus or Streptococcus pyogenes (group A b{beta}-hemolytic streptococcus), are the most common complication of varicella. Cellulitis, lymphadenitis, and subcutaneous abscesses also occur. Varicella gangrenosa, usually resulting from S. pyogenes, is a rare but potentially life-threatening consequence of secondary infection. Acute bacterial sepsis is uncommon, but transient bacteremia may cause focal infections, including staphylococcal or streptococcal pneumonia, arthritis, or osteomyelitis. Encephalitis and cerebellar ataxia are well-described neurologic complications of varicella; the incidence of central nervous system morbidity is highest among patients younger than 5 yr and older than 20 yr. Meningoencephalitis is characterized by seizures, altered consciousness, and nuchal rigidity; patients with cerebellar ataxia have a more gradual onset of gait disturbance, nystagmus, and slurred speech. Neurologic symptoms usually begin from 2–6 days after the onset of the rash but may occur during the incubation period or after resolution of the rash. VZV-related encephalitis and cerebellar ataxia may be immune mediated; the severe hemorrhagic encephalitis caused by HSV is very rare in children with varicella. Clinical recovery is typically rapid, occurring within 24–72 hr, and is usually complete. Before the association of salicylates was documented, some children with varicella had neurologic symptoms caused by the encephalopathy associated with Reye syndrome. Varicella hepatitis is relatively common and is usually subclinical, but some children have severe vomiting, which must be differentiated from that associated with Reye syndrome. Acute thrombocytopenia, accompanied by petechiae, purpura, hemorrhagic vesicles, hematuria, and gastrointestinal bleeding, is a rare complication that is usually self-limited. Other rare complications of varicella include nephritis, nephrotic syndrome, hemolytic-uremic syndrome, arthritis, myocarditis, pericarditis, pancreatitis, and orchitis.

 

Progressive disease caused by primary VZV infection occurs in otherwise healthy adolescents and adults, immunocompromised children, pregnant women, and newborn infants. Varicella pneumonia is very rare in children, but this complication accounts for most of the increased morbidity and mortality in high-risk populations. Respiratory symptoms, which may include cough, dyspnea, cyanosis, pleuritic chest pain, and hemoptysis, usually begin within 1–6 days (average, 3 days) after the onset of the rash. Hypoxemia is often much more severe than is suggested by the physical findings; the chest radiograph may be normal or may show diffuse bilateral infiltrates. Varicella pneumonia is often transient, resolving completely within 24–72 hr, but in severe cases, the interstitial pneumonitis progresses rapidly to cause respiratory failure. Hemorrhage into the cutaneous lesions is a sign of severe varicella in high-risk patients, as is severe abdominal or back pain, although its pathogenesis is uncertain.

 

The risk of progressive varicella is highest in children with malignancy if chemotherapy was given during the incubation period and the absolute lymphocyte count is less than 500 cells. In one large series, the mortality rate without antiviral therapy was 7%, and all varicella-related deaths occurred within 3 days after the diagnosis of varicella pneumonia. Hepatitis, encephalitis, and disseminated intravascular coagulopathy are other frequent complications. The syndrome of inappropriate antidiuretic hormone secretion may accompany disseminated varicella with or without clinical encephalitis. Children who acquire varicella after organ transplantation are also at risk for progressive VZV infection. Children on long-term, low-dose steroid therapy usually have no complications, but fatal varicella has occurred in patients receiving high-dose steroids. Untreated varicella is severe or fatal in children with congenital immunodeficiency disorders, especially involving cell-mediated immunity. Unusual clinical findings of varicella, including lesions that develop a unique hyperkeratotic appearance and chronic new lesion formation for weeks or months, have been described in children with HIV infection.

 

In rare instances, maternal varicella results in the congenital varicella syndrome, associated with unusual cutaneous defects, atrophy of an extremity, microcephaly, ocular defects, and damage to the autonomic nervous system. Infants who are born within 4 days after or 2 days before the onset of maternal varicella may acquire progressive varicella.

 

CLINICAL MANIFESTATIONS OF HERPES ZOSTER.

 

VZV reactivation is rare in childhood. When it occurs, it causes vesicular lesions clustered unilaterally in the dermatomal distribution of one or more adjacent sensory nerves, which are preceded or accompanied by localized pain, hyperesthesias, pruritus, and low-grade fever.

 

The rash is mild, with new lesions appearing for a few days, symptoms of acute neuritis are minimal, and complete resolution usually occurs within 1–2 wk. Immunocompromised children have more severe dermatomal disease and may experience viremia, causing pneumonia, hepatitis, encephalitis, and disseminated intravascular coagulopathy. Severely immunocompromised children, particularly those with HIV infection, may have unusual, chronic, or relapsing cutaneous disease, retinitis, or central nervous system disease without rash. Transverse myelitis with transient paralysis is a rare complication of herpes zoster. In contrast to adults, postherpetic neuralgia is very unusual in children.

  

 

 

The rash in herpes Zoster

 

LABORATORY FINDINGS AND DIAGNOSIS.

 

Laboratory evaluation is not necessary for appropriate management of healthy children with varicella or herpes zoster. Abnormal laboratory values are common during varicella. Leukopenia is typical during the first 72 hr; it is followed by a relative and absolute lymphocytosis. Liver function tests are also often moderately elevated. Patients with neurologic complications of varicella or uncomplicated herpes zoster have a mild lymphocytic pleocytosis and a slight to moderate increase in protein; the cerebrospinal fluid glucose is usually normal. Rapid laboratory diagnosis of VZV is often important in high-risk patients and can be accomplished by direct immunohistochemical staining of cells from cutaneous lesions. Multinucleated giant cells can be detected with nonspecific stains, but false-negative results are common, and these methods do not differentiate VZV and HSV infections. The definitive diagnosis of VZV infection requires the recovery of infectious virus using tissue culture. VZV immunoglobulin G (IgG) antibodies can be detected by several methods, but serologic diagnosis is retrospective; testing for VZV IgM antibodies is not useful for clinical diagnosis because commercially available methods are unreliable. VZV IgG antibody tests are valuable to determine the immune status of individuals whose clinical history of varicella is unknown or equivocal.

 

TREATMENT.

 

Acyclovir—9-[(2-hydroxyethoxy) methyl] guanine—is the drug of choice for varicella and herpes zoster when specific therapy is indicated. Any patient who has signs of disseminated VZV including pneumonia, hepatitis, thrombocytopenia, or encephalitis should receive immediate treatment with intravenous acyclovir. Acyclovir therapy given within 72 hr prevents progressive varicella and visceral dissemination in high-risk patients; the dosage is 500 mg/m2 every 8 hr, administered intravenously for 7 days or until no new lesions have appeared for 48 hr. Delaying antiviral treatment until prolonged new lesion formation is evident is not an option because visceral dissemination occurs during the same time period. Recent large, placebo-controlled clinical studies have shown that oral acyclovir diminishes the clinical symptoms of varicella in otherwise healthy children, adolescents, and adults when it is administered within 24 hr after the appearance of the initial cutaneous lesions. Drug efficacy was established for all groups, but the clinical benefit may be considered more significant in older children and in secondary household cases. Acyclovir therapy does not interfere with the induction of VZV immunity.

 

Acyclovir is also effective for treatment of herpes zoster in healthy and immunocompromised patients. Patients at high risk for disseminated disease should receive 500 mg/m2 or 10 mg/kg every 8 hr intravenously. Onset of VZV reactivation reduces the duration of new lesion formation to only about 3 days. Oral acyclovir is an option for immunocompromised patients who are considered at low risk for visceral dissemination. Antiviral drug resistance is rare but has occurred in children with HIV infection; foscarnet is the only drug now available for the treatment of acyclovir-resistant VZV infections.

 

PREVENTION.

 

VZV transmission is difficult to prevent because the infection is contagious for 24–48 hr before the rash appears. Infection control practices, including caring for infected patients in isolation rooms with filtered air systems, are essential in hospitals that treat immunocompromised children. Susceptible health care workers who have had a close exposure to varicella should not care for high-risk patients during the incubation period.

 

Varicella-zoster immune globulin (VZIG) prophylaxis is recommended for immunocompromised children, pregnant women, and newborn infants exposed to maternal varicella. VZIG is distributed by the American Red Cross Blood Services; the dosage is one vial per 10 kg intramuscularly given within 96 hr or, if possible, within 48 hr after exposure. Adults should be tested for VZV IgG antibodies before VZIG administration because many adults with no clinical history of varicella are immune. Because VZIG prophylaxis does not eliminate the possibility of progressive disease, patients should be monitored and treated with acyclovir if necessary. Immunocompromised patients who have received high-dose intravenous immune globulin (100–400 mg/kg) for other indications within 2–3 wk before the exposure can be expected to have serum antibodies to VZV. Close contact between a susceptible high-risk patient and a patient with herpes zoster is also an indication for VZIG prophylaxis. Passive antibody prophylaxis does not reduce the risk of herpes zoster or alter the clinical course of varicella or herpes zoster when given after the onset of symptoms.

 

Acyclovir should not be given as prophylaxis against varicella. Acyclovir prophylaxis for herpes zoster is not essential because the prompt initiation of acyclovir for the treatment of recurrent VZV infections is very effective in reducing morbidity and mortality among immunocompromised patients. Prolonged low-dose administration of acyclovir should be avoided to minimize the emergence of drug-resistant VZV.

 

The live, attenuated varicella vaccine, made from the Oka strain, is the first human herpesvirus vaccine. The live, attenuated varicella vaccine (Oka-Merck strain) has been given to more than 8,500 healthy children and adults in clinical trials in the United States. The vaccine induced seroconversion rates of more than 95%, with complete protection against disease in 85–95% of exposures. Persistence of humoral and cell-mediated immunity has been documented in 94–100% of vaccine recipients monitored for 1–6 yr. The Oka-Merck varicella vaccine can be given to children with acute leukemia in remission, with careful attention to the status of their underlying disease and immunosuppressive therapy regimens.

 

 

Short statement of the material

Chicken pox is an acute viral disease caused by the virus from herpes virus family, is

characterized by the moderate fever, appearance on a skin, mucus membranes small vesicles

with transparent content.

 

Etiology: DNA containing Varicella-Zoster virus.

 

Epidemiology:

• Source of infection – ill person with chicken pox, (rare – herpes zoster).

• Chickenpoxis is transmitted from person to person by respiratory route or by the direct contact.

• Susceptible organism – everyone, who didn’t ill before.

• Infection confers lifetime immunity – in 3 % of patients it may develop for the 2nd

time.

 

Pathogenesis:

1. Inoculation of virus and it’s replication in epithelial cells of upper respiratory tract.

2. With lymph it enters to the blood and viremia develops.

3. Damage of the skin epithelium and mucosa epithelium.

4. Damage of the nervous system – (intravertebral ganglia, brain and cerebellum cortex, subcortical region).

5. Generalization of the infection (damage of liver, kidneys, lungs) in immunosupressed people.

 

Clinical presentation

• The incubation period ranges from 11 to 21 days (most cases 14-17 days).

• The contagious period extends from 1 to 2 days before the rashes erupt until all of the lesions have crusted (5 days after the last rashes have appeared).

• The prodrome consists of 1 to 2 days of fever, headache, malaise, and anorexia.

• The rashes, often pruritic, begin as a maculae and progresses rapidly through the stages of papule, vesicle (photo 12), and crusted lesion (photo 13). The spots first appear on the face or trunk, obvious on the scalp (photo 14) and, at the height of the illness, are more numerous centrally than distally (photo 15). In severe cases may be present on palms and soles (as spots and papules) (photo 16). The lesions erupt in crops for 3 to 4 days (sometimes to 7 days) and it is characteristic of the rashes that lesions in different stages of development may be found on one area (false polymorphism) (photo 17). The vesicle is a 2 to 3 mm oval filled with clear fluid surrounded by an erythematous base. The fluid clouds and a crust forms appear within 1 day. Lesions occurring on the mucous membranes do not crust but form a shallow ulcer (photo 18, 19). Posterior cervical lymph nodes usually are enlarged (photo 20).

 

 

stages of papule, vesicle

 

crusted lesion

 

crusted lesion on the scalp

 

Lesions are more numerous centrally than distally

 

spots and papules on soles

 

Rashes polymorphism

 

Rashes on the oral mucosa

 

Posterior neck lymphadenitis

 

The congenital varicella syndrome in case of infection in the 1st trimester of pregnancy by VZ-virus – may occur embryopathies. Maternal varicella 5-10 days before delivery result in mild chickenpox iewborn from the first days of his life. Maternal varicella 4 days or less before delivery may result in severe disseminated or total chickenpox in the newborn.

 

Clinical classification

Type

• Typical forms

• Atypical forms:

– Effaced (rudimentary): in children with passive immunity received transplacentally,

or due to immune globulin or plasma injection in the latent period (not numerous rashes as papules with several vesicles appear, body temperature is normal).

– Bullous: together with typical rashes appear large vesicles up to 2-3 cm with cloudy content, after them erosion and pigmentation develop.

– Hemorrhagic: develops in immune compromised children, vesicles content become hemorrhagic, crusts are black. Other signs of hemorrhagic syndrome are present (petechia, ecchymoses, nasal bleeding, hemorrhages into the inner organs).

– Gangrenous: develops in immune compromised children in case of bad care. Vesicles content become hemorrhagic with infiltration around them, crusts are black, ulceration is typical.

– Generalized (visceral) is typical for the newborns and in case of the immune deficit.

 

Severity	Severity criterions	Duration
Mild	vesicles rashes are not numerous on the skin,  body t° 37,5-38 °С	1.  Smooth, without complications 2.  Complicated by encephalitis, neuritis, polyradiculoneuritis Complicated by secondary bacterial infection as lymphadenitis, pyodermia (staphylo– and streptodermia), erysipelas, phlegmon, abscess, sepsis.
Moderate	Considerable presence of the vesicles rashes on a skin, single on mucus membranes of the oral cavity, body t°  38-39 °С
Severe	numerous rashes, hardening on the stage of vesicles on a skin and mucus membranes, body t° is up to 40 °С and higher
Generalized  (visceral)	neurotoxicosis with a convulsive syndrome and meningoencephalitic reactions, hyperthermia, multiple rashes as vesicles quite often with the hemorrhagic impregnation, damage of the internal organs
Effaced  (rudimentary)	rashes on the skin does not achieve the stage of vesicles (only macula-papules), body t° is normal

 

Complications:

– Secondary bacterial – infection of lesions (with staphylococci as pustulosis (photo 21) or b-hemolytic group A streptococci as erysipelas, phlegmona (photo 22) are the most common complications; also may be otitis, pneumonia, lymphadenitis, stomatitis, purulent conjunctivitis and keratitis, sepsis, osteomyelitis.

 

Pustulosis

 

Phlegmona

 

– Viral: Primary varicella pneumonia affects immunocompromised patients and up to 35 % of normal adults; croup; Encephalitis follows varicella in fewer than 1:1000 cases (involvement of the cerebellum, or cerebrum), meningoencephalitis, encephalomyelitis, less common – Guillain-Barre syndrome, transverse myelitis, optic neuritis, and facial nerve palsy.

– Rare complications: idiopathic thrombocytopenic purpura, nephritis, myocarditis, arthritis, acute adrenal insufficiency because of adrenal hemorrhages.

 

Work-up. Laboratory tests are rarely needed. In CBC: leucopenia, relative lymphocytosis, normal ESR. Vesicle scrapings contain multinucleated giant cells, and vesicle fluid contains virus in the first days of illness. It could be detected by the:

• Immune Fluorescent method;

• Serological reactions: CBR, Immune-enzyme reaction, IHAR to find antibodies

against viruses with fourfold increasing of antibodies title in 10-14 days may be

used;

• CSF investigation (signs of serous meningitis) – in case of meningoencephalitis;

• Virological separation of the VZ-virus on embryonic cells.

 

Diagnosis example: Chickenpox, typical form, moderate severity, complicated by

the bilateral medial otitis.

 

Differential diagnosis should be performed among early impetigo, insect bites, scabies,

and urticarial lesions.

 

Features of chicken pox in infants

·Beginning from a general infectious signs (malaise, anxiety, absence of appetite), dyspepsia phenomena.

·Body t° is normal or subfebrile, grows when rashes appear.

·Rashes appear on 2nd-5th day, massive, sometimes remain in one phase of development (gradual development of illness).

·Neurotoxicosis (cramps, meningeal symptoms).

· Possible visceral signs.

· Frequent is secondary bacterial infection.

 

Evidences for obligatory hospitalization of patients with infectious exanthema

• The severe form of disease, when appears need in undertaking of intensive therapy; patients with moderate forms at age before 3 years.

7.      Sick children from families with bad social-home conditions, especially in the event of impossibility of their isolation to prevent infections transmission.

8.      Absence of conditions for examination and treatment at home.

9.      Sick children from closed children institutions.

 

Advantages of the home treatment

1. Possibility of additional infection by hospital bacteria is completely excluded.

2. Realization of individual care principle for sick child is more full.

3. Avoiding stressful reactions, which could appear in case of hospital treatment.

 

Treatment in home conditions is possible

1. In conditions of isolated flat.

2. In case of satisfactory material position of the parents.

3. In case of parents desire to organize individual care and treatment at home.

 

Treatment

In most cases only symptomatic (Basic therapy) up to disappear of clinical signs

• Antiseptic fluids for skin lesions to prevent secondary bacterial infection (1 % brilliant green, 1-2 % KMnO4);

• Gurgling with oral antiseptic fluids after the food intake;

• Antihistamines for itching;

• Acetaminophen for fever control.

Etiological therapy by Acyclovir (IV 10 mg/kg 3 t.d. for 7 days or up to 48 hours the last elements appear) – for immunocompromised children:

n Patients with oncohematologic diseases;

n Patients after bone marrow or inner organs transplantation;

n Patients who achieve corticosteroids;

n Patients with the primary immune deficit;

n Patients with HIV-infection;

n Inborn Chicken pox;

n Chicken pox complicated by the damage of CNS, hepatitis, thrombocytopenia, pneumonia;

n  And Severe forms of Chicken pox (Acyclovir orally 80 mg/kg/day 4 t.d. for children elder than 2 years and teenagers).

Also for severe cases ieonates – Varicella-Zoster immune globulin (0.2 ml/kg).

 

In case of encephalitis:

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 2-3th 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).

Etiologic therapy:

• In encephalitis without the expressed general cerebral symptoms – IV acyclovir 10 mg/kg 3 times per day during 7-10 days; in the case of encephalitis with the expressed general cerebral symptoms (violation of consciousness, cramps) –15-30 mg/kg 3 times per day during 10-14 days, then continue 200-400 mg 5 times per day PO during 14 days;

• In meningitis IV acyclovir 10-15 mg/kg 3 times per day during 5-7 days.

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.

 

Prevention:

1. To isolate ill person until the 5 day after the last vesicles has appeared.

2. To isolate contacts from 11 till 21 day after exposure.

3. VZ immune globulin in immunocompromised children (not later than 72 hours

after exposure).

 

Key words and phrases: Varicella-Zoster, chickenpox, polymorphism, congenital

varicella syndrome, bullous varicella, multinuclear giant cells, acyclovir, Varicella-Zoster

immune globulin, immunocompromised children.

 

HERPES VIRUS INFECTION

 

The Herpetic infection is caused by the Herpes virus family, which are incorporated by the property to persist in the human organism during all his life and by the ability to cause the various clinical forms in case of immune deficit development.

 

Herpes simplex is the viral disease caused by Herpes simplex viruses (HSV 1 and HSV 2), that is characterized by the prolonged latent duration with the periodic relapses which are accompanied by appearance of vesicles on a skin and mucus membranes, the CNS and internal organs damage.

 

Herpes zoster is the viral disease, that is caused by the Varicella-Zoster virus, is characterized by inflammation of intravertebral or cranial nerves nodes and is shown up by a vesicles rash on a skin along the nerves and symptoms of intoxication.

 

Etiology: DNA-containing virus of HSV 1 and 2 types, the Varicella-Zoster virus, EBV (Epstain Barr virus), CMV (cytomegalovirus), HHV 6, HHV 7, 8 (Human Herpes virus).

 

Epidemiology:

• The source are patients and virus carriers;

• The way of transmitting is air-droplet, contact (HSV 1), sexual (contact) – HSV 2, transplacental, intranatal (HSV 1), air-droplet (Varicella-Zoster);

• Susceptibility is high on a background of immune deficit, URT viral infections;

• Seasonality: infection more often occurs in winter as sporadic diseases.

Pathogenesis:

• An entrance gate are the injured mucus membranes and skin.

• Reproduction of virus.

• Local changes.

• Virus by the lymph gets into regional lymph nodes (rarely).

• Viremia.

• Organs and systems damage (liver, spleen, lungs, localization in intravertebral ganglia, ganglia of cerebrum).

• Chronic carrying of the virus (in case of immune deficit).

• Relapses (on a background of URT viral infections, ultraviolet irradiation, cooling).

 

Herpes Simplex diagnostic criteria

• Latent period is 2-14 days.

• Acute beginning, toxic signs.

• Mucosa membranes damage (gingivitis, stomatitis (photo 23, 24, 25), tonsillitis) as vesicles, that ruin, forming erosions, are accompanied by the pain.

• Eye damage (conjunctivitis, blepharoconjunctivitis, keratitis, keratoiridocyclitis, choreoretinitis, uveitis, retinal perivasculitis, optic nerve neuritis).

• Skin damage (lips (photo 26), nose (photo 27), eyelids, face, hands, other localization) – painful papules on the red base, than their evolution to small vesicles with the transparent content, they may be connected, clouding of the content, erosions, crusts formation.

• Genital herpes (damage of penis, vulva, vagina, cervical channel, perineum, urethra, endometrium).

• CNS damage (encephalitis, meningoencephalitis, meningitis), peripheral NS damage (neuritis).

• Visceral forms (hepatitis, pneumonia, nephritis and other).

• Relapsed course.

 

stomatitis

 

Stomatitis

 

 

Skin damage

 

 

Skin damage

 

 

 

Herpetic whitlow

→→→→

 

Herpes Zoster diagnostic criteria

• Latent period is 7-21 days, sometimes several months or years (after the chickenpox).

• Acute beginning from high body temperature, toxic signs.

• Burning, itching, pain along the damaged sensory nerve.

• Than skin hyperemia, infiltration in the zone of innervation.

• Firmly grouped papules (in the end of the 1st, on the 2nd day) on the red base, than their evolution to small vesicles with the transparent content, they may be connected, clouding of the content, crusts formation (photo 28), than hyperemied base pales, epithelization ® slight hyperpigmentation (in a week).

 

 

Additional investigations

• Virology research of vesicular content, nasopharyngeal smears.

• IF method, PCR.

• Serology: CBR, IEА, PHAR, NR with paired sera (growth of antibodies title in the dynamics).

• CSF investigation (in case of meningoencephalitis signs).

 

Diagnosis example: Herpes Simplex 1st type local form: stomatitis, severe degree.

 

Differential diagnostics with herpangina, enterovirus encephalitis, adenoviral keratoconjunctivitis, chicken pox, streptococcus impetigo, erysipelas, eczema, mumps

encephalitis.

 

Prognosis: The virus of herpes simplex remains in an organism for all the life, severity of relapses is related to the state of the immune system. Lethality makes 80-85 % in case of herpetic encephalitis, in case of recovery severe phenomena remains with the abscense of cork centers function. The defeat of pregnant by the herpes virus results in forming of the inborn defects.

 

Treatment:

Local damage of the skin and mucous membranes:

• antiviral ointments and creams locally (herpevir, acyclovir, oxolin, tebrophen, bonaphton, cytozar);

• antiseptic fluids (solution of diamond green, methylen blue, peroxide of hydrogen);

• local anesthetics, novocain blockades (in case of Herpes Zoster);

• NSAIDs (paracethamol 10-15 mg/kg or ibuprophen 10mg/kg);

• ultraviolet irradiation.

Keratitis:

• locally 5-iodine-2-desoxyuridin, adenine arabinosid.

 

In severe forms (encephalitis):

Etiologic therapy:

• Acyclovir 10-20 mg/kg 3 times per day during 14-21 days IV.

Pathogenetic therapy:

• In case of brain edema – dehydration by 25 % MgSO4 IM, lasix 1-3 mg/kg IV or IM, acethazolamid orally;

• Detoxication in moderate case – orally (oral fluids intake corresponds to age norms with including the IV fluids);

• Detoxication in severe cases – IV not more than 1/2 of physiologic age norms during the 1st day, total fluids intake (IV and PO) not more than 2/3 of physiologic age norms in case of normal urination and absense of dehydration.from the 2^nd week correct fluids intake (daily amount of urine not less than 2/3 of all fluids intake;

• 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;

• Glucocrticoids 3-5 mg/kg (by prednisolon), course not more than 10 days.

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 – 3th 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.

Antibacterial therapy: in case of possible concomitant bacterial infection (by the broadspectrum antibiotic in average therapeutic doses, as cephalosporines 3rd generation or aminoglycosides 3rd generation).

In rehabilitation period:

• Vascular medicine (penthoxyphyllin, nicergolin and others like that);

• In posthypoxia period – nootrops, vitamins group B.

 

In case of relapsed course:

· adaptogens (eleutherocock, pyrogenal and other);

· vitamins of group B (B1, B2, B12);

· specific antiherpetic immune globulin (in an early period of relapse) 1.5-3 ml IM,

daily during 5-10 days;

·antiherpetic vaccine 0.1-0.2 ml IC in 2-3 days 5 times, twice per year.

At secondary bacterial infection: (penicillins, cefalosporins, aminoglycosides).

 

Prophylaxis:

•Isolation of patient up to 5 days since the last rashes appear (in case of Herpes Zoster), hospitalization in case of severe and complicated course.

• Contact person younger than 3 years, which have not Herpes Zoster before, are isolated from 11 till 21 day since the contact, for the newborns 0.2 ml/kg normal immunoglobulin IM.

• Carrying of masks by mothers who are breast feeding in case of Herpes simplex 1, observance of hygienic norms.

• To infected pregnant – immunoglobulin IM 0.2 ml/kg.

• Delivery by the caesarean section at Herpes simplex 2 infection.

• Supervision after new-born, whose mothers has herpetic infection, till 2 months.

• Ventilation and moist cleaning up.

Passive immunization (Varicella-Zoster): donor Varicella-Zoster immunoglobulin 0.2-0.5 ml/kg in the first 2 days after the contact (an effect lasts till 21 day), at the secondary contact – immunize again.

 

Key words and phrases: Varicella-Zoster, Herpes simplex, polymorphism, congenital herpes syndrome, multinuclear giant cells, acyclovir, Varicella-Zoster immune globulin, immunocompromised children.

 

 

Scarlet Fever.

 

This disease is the result of infection by streptococci that elaborate one of three pyrogenic (erythrogenic) exotoxins.

Β-hemolytic streptococcus group A

 

The incubation period ranges from 1–7 days, with an average of 3 days. The onset is acute and is characterized by fever, vomiting, headache, toxicity, pharyngitis, and chills. Abdominal pain may be present; when this is associated with vomiting prior to the appearance of the rash, an abdominal surgical condition may be suggested. Within 12–48 hr the typical rash appears.

 

Generally, temperature increases abruptly and may peak at 39.6–40º C (103–104º F) on the 2nd day and gradually returns to normal within 5–7 days in the untreated patient; it is usually normal within 12–24 hr after initiation of penicillin therapy. The tonsils are hyperemic and edematous and may be covered with a gray-white exudate.

 

 

Group A streptococcal pharyngitis with inflammation of the tonsils and uvula.

 

The pharynx is inflamed and covered by a membrane in severe cases. The tongue may be edematous and reddened. During the early days of illness the dorsum of the tongue has a white coat through which the red and edematous papillae project (i.e., white strawberry tongue). After several days the white coat desquamates; the red tongue studded with prominent papillae persists (i.e., red strawberry tongue, raspberry tongue). The palate and uvula may be edematous, reddened, and covered with petechiae.

 

 

 

Note inflammation of the oropharynx with petechiae on the soft palate, small red spots caused by group A streptococcal pharyngitis.

 

  

 

 

The exanthem is red, is punctate or finely papular, and blanches on pressure. In some individuals, it may be palpated more readily than it is seen, having the texture of gooseflesh or coarse sandpaper. The rash appears initially in the axillae, groin, and neck but within 24 hr becomes generalized. Punctate lesions generally are not present on the face. The forehead and cheeks appear flushed, and the area around the mouth is pale (i.e., circumoral pallor). The rash is most intense in the axillae and groin and at pressure sites. Petechiae may occur owing to capillary fragility. Areas of hyperpigmentation that do not blanch with pressure may appear in the deep creases, particularly in the antecubital fossae (i.e., pastia lines). In severe disease, small vesicular lesions (miliary sudamina) may appear over the abdomen, hands, and feet.

 

 

 

 

Typical rashes in scarlet fever

 

   

Flushed face, circumoral pallor (Filatov’s sign), Pastia lines in skin folds

 

  

Miliary sudamina and “sand paper” or goose skin (shagreen) sign

 

Desquamation begins on the face in fine flakes toward the end of the 1st wk and proceeds over the trunk and finally to the hands and feet. The duration and extent of desquamation vary with the intensity of the rash; it may continue for as long as 6 wk.

 

Desquamation on the skin (fine flakes)

 

  

 

Desquamation on the palms and soles (macrolamellar)

 

 

Scarlet fever may follow infection of wounds (i.e., surgical scarlet fever), burns, or streptococcal skin infection. Clinical manifestations are similar to those just described, but the tonsils and pharynx generally are not involved. A similar picture may be observed with certain strains of staphylococci that produce an exfoliative toxin.

 

Scarlet fever must be differentiated from other exanthematous diseases, including measles (characterized by its prodrome of conjunctivitis, photophobia, dry cough, and Koplik spots), rubella (disease is mild, postauricular lymphadenopathy usually is present, and throat culture is negative), and other viral exanthems. Patients with infectious mononucleosis, have pharyngitis, rash, lymphadenopathy, and splenomegaly as well as atypical lymphocytes. The exanthems produced by several enteroviruses can be confused with scarlet fever, but differentiation can be established by the course of the disease, the associated symptoms, and the results of culture. Roseola is characterized by the cessation of fever with the onset of rash and the transient nature of the exanthem. Kawasaki disease, drug eruption, and toxic shock syndrome must also be considered.

 

Septic or severe scarlet fever associated with bacteremia or toxemia may manifest high fever and may be complicated by arthritis, jaundice, and hydrops of the gallbladder. Scarlet fever may be differentiated from Kawasaki disease by an older age at onset, absence of conjunctival involvement, and recovery of group A streptococci. Streptococcal toxic shock–like syndrome, associated with the pyrogenic toxins, produces toxicity, fever, shock, tissue injury (necrotizing fasciitis, myositis), pneumonia, rash (local or diffuse erythema, maculopapular, petechial, desquamation), and multiorgan dysfunction (kidney, lung, central nervous system). The shock, local tissue injury, older age, and nonscarlatiniform rash differentiate this syndrome from scarlet fever. Arcanobacterium haemolyticum (formerly Corynebacterium haemolyticum) also produces tonsillitis, pharyngitis, and a scarlatiniform rash in adolescents and young adults. Severe sunburn can also be confused with scarlet fever.

 

DIAGNOSIS. Although 30% of children with sore throat have a positive throat culture for group A streptococci, only 50% of these have a positive antibody response indicative of active infection rather than colonization. Streptococcal pharyngitis is suggested by age greater than 5 yr, high fever, exudates, tender anterior cervical lymphadenopathy, scarlatiniform rash, and a history of exposure. However, only 15% of children with pharyngitis and 25% of those with exudates have streptococcal infection; 50% of those with streptococcal pharyngitis do not have tonsillar exudates. Clinical judgment does not predict which children may have streptococcal infection, which must be diagnosed by throat culture or antigen detection.

 

Throat culture is the most useful laboratory aid in reaching a diagnosis in patients with acute tonsillitis or pharyngitis. Selective media give a higher yield than sheep blood agar plates. A positive result for a throat culture may indicate streptococcal pharyngitis, but hemolytic streptococci are common inhabitants of the nasopharynx in well children. Isolation of a group A streptococcus from the pharynx of a child with pharyngeal infection does not necessarily indicate that the disease is caused by this organism. When streptococci are isolated from children with moderate or severe exudative pharyngitis who have petechiae on the palate and cervical adenitis, the diagnosis is more secure. Rapid antigen detection tests are not sufficiently sensitive to be used without a back-up culture. Treatment is, however, recommended for all children with pharyngitis and a positive throat culture or rapid antigen test for group A streptococci, even though in some cases the streptococci represent colonization.

 

The immunologic response of the host after exposure to streptococcal antigen can be assessed by measuring antistreptolysin O (ASO) titers. An increase in ASO titer to greater than 166 Todd units occurs in more than 80% of untreated children with streptococcal pharyngitis within the first 3–6 wk following infection. This response may be modified or abolished by early and effective antibiotic therapy. ASO titers may be very high in patients with rheumatic fever; in contrast, they are weakly positive or not elevated at all in patients with streptococcal pyoderma; responses in patients with glomerulonephritis are variable. Group A b-hemolytic streptococci also may be recovered from the pharynx of asymptomatic individuals who develop an antibody response to this organism, indicating that subclinical infection has occurred.

 

Individuals with impetigo may react strongly to stimulation by other streptococcal extracellular products. Anti-DNase (deoxyribonuclease) B provides the best serologic test for streptococcal pyoderma; it begins to rise 6–8 wk after infection. Most patients with streptococcal pharyngitis also develop elevated titers to this enzyme. Patients with pyoderma and pharyngitis also may develop antibody responses to hyaluronidase, but antihyaluronidase (AH) titers are elevated with less regularity than are ASO titers.

 

A 2-min, inexpensive Streptozyme slide test (Wampole Laboratories, Cranbury, NJ) is designed to detect antibodies against multiple streptococcal extracellular antigens. This test detects more patients with increased antibody titers than any other single test presently available. Nonspecific (false-positive) reactions have been limited iumber, and the test is capable of detecting antibody responses within 7–10 days of infection. However, the strength of the Streptozyme reagent varies from lot to lot, and it may not be specific for antibodies to extracellular products of group A streptococci.

 

The white blood cell count may or may not be elevated. Because leukocytosis may occur in many bacterial and viral diseases, this finding is nonspecific. Similarly, elevations in the erythrocyte sedimentation rate and C-reactive protein do not help to establish a specific diagnosis.

 

DIFFERENTIAL DIAGNOSIS.

 

Acute pharyngitis that is indistinguishable clinically from that caused by group A b-hemolytic streptococci may be caused by many viruses, including Epstein-Barr virus (infectious mononucleosis). A viral cause may be suggested by failure to isolate streptococci and can be identified specifically by viral culture and serologic studies. Infectious mononucleosis may be suggested by the clinical manifestations, the presence of atypical lymphocytes in the peripheral blood, and a rise in heterophil and Epstein-Barr viral antibody titers. Acute pharyngitis similar to that caused by b-hemolytic streptococci may occur in patients with diphtheria, tularemia, toxoplasmosis, infection with Mycoplasma or A. haemolyticum, and, rarely, in individuals with tonsillar tuberculosis, salmonellosis, and brucellosis or infections caused by Neisseria gonorrhoeae, Neisseria meningitidis, and Yersinia enterocolitica. These diseases can be differentiated by appropriate cultures and serologic tests.

 

 Streptococcal pyoderma must be differentiated from staphylococcal skin disease. Often these bacterial species coexist. The lesions produced are clinically indistinguishable; distinction is made only by culture.

 

Streptococcal septicemia, meningitis, septic arthritis, and pneumonia present signs and symptoms similar to those produced by other bacterial organisms. The offending pathogen can be established only by culture.

Vinsent’s angina need to be differentiated from streptococcal angina in Scarlet fever

 

COMPLICATIONS. Complications generally reflect extension of streptococcal infection from the nasopharynx. This may result in sinusitis, otitis media, mastoiditis, cervical adenitis, retropharyngeal or parapharyngeal abscess, or bronchopneumonia. Hematogenous dissemination of streptococci may cause meningitis, osteomyelitis, or septic arthritis. Nonsuppurative late complications include rheumatic fever and glomerulonephritis.

 

PREVENTION. Administration of penicillin will prevent most cases of streptococcal disease if the drug is provided prior to the onset of symptoms. Except for rheumatic fever (see Chapter 175), indications for prophylaxis are not clear. Oral penicillin G or V (400,000 U/dose) is provided four times each day for 10 days. Alternatively, 600,000 U of benzathine penicillin in combination with 600,000 U of aqueous procaine penicillin may be given as a single intramuscular injection. This approach should be used for institutional epidemics. Children exposed to an individual case at school may be observed carefully.

 

Management of carriers of group A b{beta}-hemolytic streptococci is controversial. It has been suggested that treatment of the carrier precludes the development of type-specific immunity, thereby leaving the individual susceptible to reinfection later in life. It is probably unnecessary to re-treat asymptomatic convalescent patients with persistently positive throat cultures for group A streptococci, since they are generally carriers who do not have persistent or recurrent streptococcal infections. Children thought to have recurrent streptococcal infections may be carriers who have frequent viral respiratory infections masquerading as streptococcal infections. Parental anxiety may be high after several such episodes. Treatment with a non-penicillin antibiotic (e.g., cephalosporin, erythromycin, clindamycin) may be useful in eradicating the carrier state but should be reserved for the rare problem case.

 

No streptococcal vaccines are available for clinical use.

 

TREATMENT. The goals of therapy are to decrease symptoms and prevent septic, suppurative, and nonsuppurative complications. Penicillin is the drug of choice for the treatment of streptococcal infections. All strains of group A b{beta}-hemolytic streptococci isolated to date have been sensitive to concentrations of penicillin achievable in vivo.

 

Blood and tissue levels of penicillin sufficient to kill streptococci should be maintained for at least 10 days. Children with streptococcal pharyngitis should be treated with penicillin (125–250 mg/dose three times a day) for 10 days. Penicillin G or penicillin V may be employed; the latter is preferable because satisfactory blood levels are achieved even when the stomach is not empty. A single intramuscular injection of a long-acting benzathine penicillin G (600,000 U for children <60 lb and 1,200,000 U for children >60 lb) may be more effective for treatment or prevention of relapse and is indicated for all noncompliant patients or those having nausea, vomiting, or diarrhea.

 

Erythromycin (40 mg/kg/24 hr), clindamycin (30 mg/kg/24 hr), or cefadroxil monohydrate (15 mg/kg/24 hr) may be used for treating streptococcal pharyngitis in patients who are allergic to penicillin. Generally, relapse rates are lower with regimens other than penicillin. Tetracyclines and sulfonamides should not be used for treatment, although sulfonamides may be used for prophylaxis of rheumatic fever.

 

Treatment failure, defined as persistence of streptococci after a complete course of penicillin, occurs in 5–20% of children and is more common with oral than with intramuscular therapy. It may be due to poor compliance, reinfection, the presence of b{beta}-lactamase–producing oral flora, tolerant streptococci, or presence of a carrier state. Persistent carriage of streptococci predisposes a small number of patients to symptomatic relapse. Repeating the throat culture after a course of penicillin therapy is indicated only in high-risk situations, such as in patients with a history of previous rheumatic fever. If the throat culture is again positive for group A streptococci, some clinicians recommend a second course of treatment. Persistence after a second course of antibiotics probably indicates a carrier state, which has a low risk for the development of rheumatic fever and does not require further therapy.

 

Patients with severe scarlet fever, streptococcal bacteremia, pneumonia, meningitis, deep soft tissue infections, erysipelas, streptococcal toxic shock syndrome, or complications of streptococcal pharyngitis should be treated parenterally with penicillin, preferably intravenously. The dose and duration of therapy must be tailored to the nature of the disease process, with daily doses as high as 400,000 U/kg/24 hr required in the most severe infections. Severe, necrotizing infections may require the addition of a second antibiotic (e.g., clindamycin) to ensure complete bacterial killing.

 

PROGNOSIS. The prognosis for adequately treated streptococcal infections is excellent; most suppurative complications are prevented or readily treated. When therapy is provided promptly, nonsuppurative complications are prevented and complete recovery is the rule. In rare instances, particularly ieonates or in children whose response to infection is compromised, fulminant pneumonia, septicemia, and death may occur despite usually adequate therapy.

 

Short statement of the material

Scarlet fever is an acute infectious disease, that is caused by group A b-hemolytic streptococcus, transmitted by an air-droplet way, characterized by intoxication, rashes on a

skin, tonsillitis, regional lymphadenitis, and strawberry tongue.

 

Etiology: group A b-hemolytic streptococcus (GABHS).

 

Epidemiology:

– source of infection – ill persoot only with scarlet fever, but other forms of  GABHS infections (sore throat, erysipelas, streptodermia).

– infection is transmitted by inhalation of infected airborne droplets, rare with food and direct contact.

– susceptible organism – children 2-9 years old.

 

Pathogenesis An entrance gate is the mucus membrane of the throat, seldom damaged skin, and maternity ways (at delivery).

 

Pathogenesis has three lines:

• Toxic (toxically damage of cardiovascular, central nervous, endocrine systems).

• Septic – primary inflammation in the place of infection (tonsillitis, secondary bacterial complication).

• Allergic – sensibilization by GABHS proteins (depression of immunity leads to allergic complications – nephritis, arthritis, myocarditis, rheumatism).

 

Clinical presentation: Onset is usually acute and is characterized by a sore throat (often with dysphagia), fever (often above 39 °C), pharyngeal and purulent tonsilar exudates. Anterior cervical lymph nodes, particularly the jugular-digastric nodes just beneath the angle of the mandible, are tender and enlarged. Erythema of the soft palate is common, and an enanthema of “doughnut” lesions on the soft palate. Strawberry tongue. Other features are nausea and vomiting, headache, abdominal discomfort. One to two days later the rashes like “sandpaper” appears, first on the neck and then on the trunk and extremities till the end of the day.

The eruption is characterized by dusky red, blanching tiny papules that have a rough texture. Papules are usually absent on the face, palms, and soles, but the face characteristically shows flushing with circumoral pallor. On the body, the rashes are intensified in skin folds and at sites of pressure. In the antecubital and axillary fosses, linear petechias are seen with accentuation of the erythema (Pastia’s lines).

The exanthema usually lasts 4 to 5 days and then begins to desquamate, first on the face last on the palms and soles. Pharyngitis usually resolves in 5 to 7 days.

 

Clinical diagnostic criteria:

1. Latent period: a few hours – 7 days.

2. Initial or prodromal period (from the first signs of illness to rashes appearance):

up to 1-2 days

• acute beginning;

• toxic syndrome, hyperthermia;

• in the throat: pain, bright hyperemia, pin-point enanthema,

• catarrhal regional lymphadenitis (photo).

 

 

3.   Period of exanthema (rashes):

а) Phase of height (1 – 2 days)

• maximal intoxication, fever up to 39-40 °C;

• tonsillitis: bright hyperemia of the throat marked off a hard palate (photo 31), pinpoint enanthema, hypertrophied tonsils, catarrhal, lacunar (photo 32, 33), follicle (photo 34, 35) or necrotizing (photo 36) tonsillitis;

• regional lymphadenitis;

• pin-point rashes for a few hours spread all over the body, intensified on the front and lateral surface of neck, lateral surfaces of trunk (photo 37), abdomen (photo 38, 39), lumbar region (photo 40, 41), in natural skin folds (photo 42), on the red background of skin, typical intensified in skin folds with hemorrhagic elements (Pastia’s lines) (photo 43), a skin is rough (“sand paper” sign), pale perioral triangle (Filatov’s sign) (photo 44, 45);

• white dermatographia;

• coated tongue (photo 46) within 2-3 days clears up (photo 47, 48), on 4th – 5th day becomes “strawberry” (photo 49, 50);

• sympatic phase of “scarlet fever” heart (tones are loud, tachycardia, BP is elevated).

 

 

bright hyperemia of the throat marked off  a hard palate

 

pin-point enanthema

 

Follicular tonsillitis

 

 

Lacunar tonsillitis

 

Necrotizing tonsillitis

 

Typical rashes localization

 

pin-point rashes

 

Typical rashes localization

 

Typical rashes localization in skin folds

 

Typical rashes localization in skin folds

 

Pale perioral triangle

 

Coated tongue

 

 

Tongue begin to clear up

 

 Strawberry tongue

 

b) Fading phase:

• normalization of body temperature till 3rd – 4th day of the disease, decrease of the toxic syndrome;

• rashes and redness of the skin from 2nd – 3rd up to 6th day turns pale;

• throat: enanthema disappears from 2nd – 3rd day, hyperemia turns pale till 6-7 day;

• the sizes of lymphnodes normalized till 4th – 5th day;

• vagus-phase of scarlet fever heart (bradycardia, dilation of the cardiac dullness borders, systolic murmur on the apex, low BP);

• a tongue turns pale till 10th – 12th day, with enlarged follicles.

 

4. Period of recovery: from 2nd week (for 10-14 days)

• changes on the skin: flakes-like desquamation all over the body except palms and soles (where it is larger) (photo 51);

• tongue with enlarged follicles;

• the vagus-phase of scarlet fever heart continue for 2-4 weeks;

• rise sensitivity to the streptococcus infection, possibility of complications.

Classification

1. Form:

a) typical;

b) atypical:

• without rashes;

• effaced;

• extra pharyngeal (burns, wounds, post-natal, after operations, delivery);

• with aggravated symptoms (hypertoxic, hemorrhagic).

2. Severity:

a) mild;

b) moderate;

c) severe: toxic, septic, toxic-septic.

3. Course:

a) smooth;

b) uneven (relapses, complications).

 

Complications

By the character:

• are infectious (streptodermia (photo 50, 52), necrotizing tonsillitis (photo 36), secondary tonsillitis (photo 54), peritonsilitis (photo 53) peritonsilar abscess (photo 55), otitis, purulent lymphadenitis, sepsis);

• and allergic (rheumatism, myocarditis, arthritis, glomerulonephritis).

By the time of development:

• early (first week of the disease);

• late (2nd – 3rd week).

By the etiology:

• specific or primary (caused by the same streptococcus);

• secondary (caused by the other bacteria).

 

 

Streptodermia

 

Peritonsillitis

 

  

Peritonsilar abscess

 

Laboratory tests

1. The diagnose is confirmed by throat culture with group A b-hemolytic streptococcus.

2. Serology (antistreptolysin O, antidesoxyribonuclease B) with their grows in 2 weeks may be useful for documenting recent GABHS infection.

3. The complete blood cell count is helpful: usually white blood cell count higher 12500 cells/mm3, neutrophyllosis, left shift, eosynophylia, elevated ESR ECG, CBC and urinanalysis on the 10th day after the disease began, and on 21th day for possible late complications diagnostic (nephritis, myocarditis).

Diagnosis example:

• Scarlet fever, typical form, exanthema period, severe (toxic) degree, complicated by the right side peritonsilar abscess.

• Scarlet fever, typical form, recovery period, moderate degree, complicated by the myocarditis.

 

Differential diagnosis: tonsillitis may be seen with diphtheria, mononucleosis, adenovirus, and micoplasm; rashes may be seen with measles, rubella, and pseudotuberculosis.

 

Evidences for obligatory hospitalization of patients with infectious exanthema

–          The severe form of disease, when appears need in undertaking of intensive therapy; patients with moderate forms at age before 3 years.

–          Sick children from families with bad social-home conditions, especially in the event of impossibility of their isolation to prevent infections transmission.

–          Absence of conditions for examination and treatment at home.

–          Sick children from closed children institutions.

Advantages of the home treatment

1.      Possibility of additional infection by hospital bacteria is completely excluded.

2.      Realization of individual care principle for sick child is more full.

3.      Avoiding stressful reactions, which could appear in case of hospital treatment.

Treatment in home conditions is possible

1.      In conditions of isolated flat.

2.      In case of satisfactory material position of the parents.

3.      In case of parents desire to organize individual care and treatment at home.

Treatment

1. Bed regime during an acute period.

2. Etiological treatment for scarlet fever is:

a. In the mild case penicillin orally (penicillin V) for 10 days 50,000-100,000 EU/kg/day divided in 3-4 doses. Erythromycin (or another macrolides) is alternative antibiotic (30-50 mg/kg/day). The course of treatment is 10 days.

b. In the moderate case penicillin intramuscularly (penicillin G), the same dose as in the mild case. The course of treatment is 10-14 days.

c. In the severe case: cefalosporins of the 1st-2nd generation, klindamycin, vancomycin intravenously for 10-14 days.

3. Detoxication therapy:

a. In the mild case large amount of oral fluids.

b. In the moderate and severe cases – Glucose and saline solutions IV.

4. Antihistamines (in average doses) – pipolphen, suprastin, claritin, cetirizin.

5. Medicine which strengthens vascular wall (vit. C and PP: ascorutin, galascorbin)

6. 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.

7. Local treatment with antiseptic fluids (gurgling), UV-insolation. Patient may go home from infection department not earlier the 10th day of the illness, in 10 days blood analysis, urinalyses, ECG must be done.

 

Prevention: isolation of the patient on the 10 days, but he mustn’t visit school until 22 day of the disease. Contact person (children before 8 years) must be isolated for 7 days (period of incubation).

Key words and phrases: scarlet fever, three lines of pathogenesis, Group A b-hemolytic streptococcus(GABHS), ”doughnut” lesions on the soft palate, rashes “sandpaper”, dusky red, blanching tiny papules, circumoral pallor. Pastia‘s lines, desquamate, purulent and allergic complications.

 

YERSINIA PSEUDOTUBERCULOSIS

 

Infection due to Y. pseudotuberculosis is most often seen as a pseudoappendicitis syndrome without diarrhea.

 

ETIOLOGY. Y. pseudotuberculosis is differentiated biochemically from Y. enterocolitica on the basis of ornithine decarboxylase activity, fermentation of sucrose, sorbitol, cellobiose, and other tests, although some overlap between species may be seen. Antisera to somatic O antigens and sensitivity to yersinial phages may also be used to differentiate the two species. Subspecies-specific DNA sequences have been isolated that allow direct probe- and primer-specific differentiation of Y. pestis, Y. pseudotuberculosis, and Y. enterocolitica.

 

EPIDEMIOLOGY. Less is known of the epidemiology of Y. pseudotuberculosis infections than for Y. enterocolitica or Y. pestis. The seasonal incidence in humans parallels that in wild and domestic animals. Transmission from cats and cat-contaminated substances is established. There is a low reported incidence in the 5–12-yr age range.

 

PATHOLOGY AND PATHOGENESIS. The pathology is similar to that described for Y. enterocolitica, with ileal and colonic mucosal ulceration and mesenteric adenitis. Necrotizing, epithelioid granulomas are seen in the mesenteric nodes. The appendix is frequently grossly and microscopically normal. Mesenteric nodes are frequently the only source of positive cultures. Y. pseudotuberculosis antigens bind directly to HLA class II molecules and function as superantigens, which may partly explain the clinical syndromes resembling Kawasaki syndrome caused by this organism.

 

CLINICAL MANIFESTATIONS. Children usually present with fever and abdominal pain that is diffuse or localized to the right lower quadrant. Frequently, there is tenderness over the McBurney point and strong clinical suspicion of appendicitis. At surgery, the terminal ileum is thickened and shiny with enlarged mesenteric nodes, which may appear necrotic. The appendix is normal or only mildy inflammed.

 

Presentations resembling scarlet fever or Kawasaki syndrome are reported.

 

DIAGNOSIS. Mesenteric adenitis should be suspected in children with unexplained fever and abdominal pain. A characteristic picture of enlarged mesenteric lymph nodes, thickening of the terminal ileum, and no image of the appendix may appear on ultrasound. Y. pseudotuberculosis is rarely isolated. It is almost never isolated from stools, and the best source is an involved mesenteric node. Culture conditions are the same as for Y. enterocolitica.

 

Serologic tests have been described, but commercially available tests or standardized antigens are not available.

 

DIFFERENTIAL DIAGNOSIS. Appendicitis is the most common diagnosis. Inflammatory bowel disease and nonspecific intra-abdominal infections are also considered.

 

PREVENTION. Specific preventive measures other than avoiding exposure to potentially infected animals and careful food-handling practices are not apparent. Vaccines for prevention of Y. pseudotuberculosis have not been developed.

 

TREATMENT. Uncomplicated mesenteric adenitis due to Y. pseudotuberculosis is a self-limited disease, and antimicrobial therapy is not required. Culture-confirmed bacteremia should be treated with an aminoglycoside in combination with another agent, as for infections due to Y. enterocolitica.

 

Short statement of the material

Pseudotuberculosis is an acute infectious disease that is characterized by the expressed polymorphism of clinical symptoms with predominance of toxic-allergic syndrome, rashes like in scarlet fever, the damage of gastro-intestinal tract, liver; quite often has relapsed motion.

 

Etiology: Yersinia pseudotuberculosis, gram-negative bacillus

 

Epidemiology:

• Source of infection-wild and home animals (rats, dogs, foxes, cats and other);

• Way of transmitting – alimentary;

• Susceptible organism – children (not infants), adults.

 

Pathogenesis:

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

2. Enteral phase: invasion of bacteria in enterocytes, development of local inflammation, diarrhea, enterotoxin secretion.

3. Regional lymphadenitis (regional infection).

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

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

6. Immunological response, recovering from disease.

7. May be secondary bacteriemia (exacerbations and relapses), because of possible persistency in lymph nodes.

 

Clinical criteria

Incubation period is 3-18 days. Beginning is acute with high temperature, intoxication.

• Polymorphism of complaints: malaise, fatigue, headache, sleepless, anorexia, arthralgias, muscle pain, sore throat, nausea, abdominal pain, dyspepsia.

• Rashes: maculopapulous (like in scarlet fever), may be erythematosus or even erythema nodosum may developed (photo 56a, 56b);

– The eruption is characterized by dusky red, tiny papules;

– The rashes are present on face, intensified periorbitally, on the neck (“glasses” symptom, “hood” symptom (photo 56));

– On the body the rashes are intensified in skin folds (photo 57), at the sites of pressure (red dermographysm), on the hands, feet, (“gloves”,”socks” symptom), round the joints;

– The exanthema usually lasts 4 to 5 days and then begins to desquamate, first on the face, other parts of the body (photo 58) and last on the palms and soles (photo 59, 60).

• Pharyngeal and tonsilar erythema without the exudates, erythema of the soft palate, conjunctivitis, corryza demonstrate catarrhal syndrome.

• “Strawberry” tongue also simulates the scarlet fever (photo 61).

• Abdominal syndrome; tenderness during the palpation of abdomen, may be acute appendicitis.

• Dyspepsia: nausea, vomiting, liquid feces.

• Hepatomegaly, rare – splenomegaly, lymphadenopathy.

• Arthritis of knees (photo 62), elbows, foot and hand small joints or arthralgia.

• Hepatitis with or without the jaundice.

• Toxic myocarditis.

• Toxic nephritis, pyelonephritis.

• Bronchitis or pneumonia may also develop.

 

”hood” symptom

 

Rashes are intensified in skin folds (Pastia lines)

 

“socks” symptom

 

Skin desquamation

 

Desquamation on palms

 

Desquamation on palms

 

Strawberry tongue

 

Arthritis

 

Nodular erythema in case of relapsed course

 

Clinical forms classification

 

Type	Severity	Course
Typical forms Like Scarlet fever Abdominal Arthralgic Icteric (jaundice) Combined Generalized (septic)   Atypical  forms Catarrhal Effaced Subclinical	Mild Moderate Severe   Indexes of severity: Meningoencephalitic  syndrome Hemorrhagic syndrome Considerable damage of liver Abdominal syndrome Damage of joints Signs of process generalization	Smooth    Uneven with exacerbations and relapses   Uneven with complications

 

Diagnosis example:

Pseudotuberculosis, typical combined (Scarlet fever like + arthralgic) form, moderate severity, uneven prolonged duration with exacerbation.

 

Features of pseudotuberculosis at the children of early age

• high and prolong fever;

• expressed hepatolienal syndrome;

• systemic increase of lymphnodes;

• dyspeptic syndrome;

• damage of respiratory tract, development of pneumonia (very often);

• rarely: scarlatina rashes, damage of joints;

• prolong, undulating duration with exacerbation and relapses;

• frequent complications.

 

Laboratory findings

·         Complete blood analyses: leucocytosis, neutrophilia with left shift, eosynophilia, ERS is enlarged.

·         Bacteriological: Yersinia Pseudotuberculosis may be found in feces, urine, blood and mucus.

·         Serologically: increasing of special antibodies 4 times and more in paired sera (AR, IHAR with diagnostic titles 1:200 and more).

·         Immune-enzyme analysis (ELISA test): Specific antibodies Ig M are positive in an acute phase of the disease.

 

Differential diagnosis should be performed among scarlet fever, measles, viral hepatitis, typhoid fever, paratyphoid fever, sepsis, enterovirus infection, bacterial diarrhea.

 

 

 

 

INFECTIOUS MONONUCLEOSIS (EPSTAIN – BARR VIRUS

INFECTION)

 

Infectious mononucleosis is the best-known clinical syndrome caused by Epstein-Barr virus (EBV). It is characterized by systemic somatic complaints consisting primarily of fatigue, malaise, fever, sore throat, and generalized lymphadenopathy. Originally described as glandular fever, it derives its name from the mononuclear lymphocytosis with atypical-appearing lymphocytes that accompany the illness. Other less common infections may cause infectious mononucleosis–like illnesses.

 

 

 

EBV, a member of the Herpesviridae, causes more than 90% of infectious mononucleosis cases. Approximately 5–10% of infectious mononucleosis–like illnesses are caused by primary infection with cytomegalovirus, Toxoplasma gondii, adenovirus, viral hepatitis, human immunodeficiency virus (HIV), and possibly rubella virus. In the majority of EBV-negative infectious mononucleosis–like illnesses, the exact cause remains unknown.

 

EPIDEMIOLOGY.

 

The epidemiology of infectious mononucleosis is related to the epidemiology and age of acquisition of EBV infection. EBV infects up to 95% of the world’s population. It is transmitted in oral secretions by close contact such as kissing or exchange of saliva from child to child, such as occurs between children in out-of-home child care. Nonintimate contact, environmental sources, or fomites do not contribute to spread of EBV.

 

EBV is shed in oral secretions for 6 mo or longer after acute infection and then intermittently for life. Healthy individuals with serologic evidence of past EBV infection excrete virus 10–20% of the time. Immunosuppression may permit reactivation of latent EBV; approximately 60% of seropositive, immunosuppressed patients shed the virus. EBV is also found in the genital tract of women and may possibly be spread by sexual contact.

 

Infection with EBV in developing countries and among socioeconomically disadvantaged populations of developed countries usually occurs during infancy and early childhood. In central Africa, almost all children are infected by 3 yr of age. Primary infection with EBV during childhood is usually inapparent or indistinguishable from other childhood infections; the clinical syndrome of infectious mononucleosis is practically unknown in undeveloped regions of the world. Among more affluent populations in industrialized countries, infection during childhood is still most common, but approximately one third of cases occur during adolescence and young adulthood. Primary EBV infection in adolescents and adults is manifest in 50% or more of cases by the classic triad of fatigue, pharyngitis, and generalized lymphadenopathy, which constitute the major clinical manifestations of infectious mononucleosis. This syndrome may be seen at all ages but is rarely apparent in children younger than 4 yr, when most EBV infections are asymptomatic, or in adults older than 40 yr, when most individuals have already been infected by EBV. The true incidence of the syndrome of infectious mononucleosis is unknown but is estimated to occur in 20–70 of 100,000 persons per year; in young adults the incidence rises to about 1 in 1,000 persons per year. The prevalence of serologic evidence of past EBV infection increases with age; almost all adults in the United States are seropositive.

 

PATHOGENESIS.

 

After acquisition in the oral cavity, EBV initially infects oral epithelial cells; this may contribute to the symptoms of pharyngitis. After intracellular viral replication and cell lysis with release of new virions, virus spreads to contiguous structures such as the salivary glands with eventual viremia and infection of B lymphocytes in the peripheral blood and the entire lymphoreticular system including the liver and spleen. The atypical lymphocytes that are characteristic of infectious mononucleosis are CD8+{plus} T lymphocytes, which exhibit both suppressor and cytotoxic functions that develop in response to the infected B lymphocytes. This relative as well as absolute increase in CD8+{plus} lymphocytes results in a transient reversal of the normal 2:1 CD4+{plus}/CD8+{plus} (helper-suppressor) T-lymphocyte ratio. Many of the clinical manifestations of infectious mononucleosis may result, at least in part, from the host immune response, which is effective in reducing the number of EBV-infected B lymphocytes to less than one per 106 of circulating B lymphocytes.

 

Epithelial cells of the uterine cervix may become infected by sexual transmission of the virus, although neither local symptoms nor infectious mononucleosis have been described following sexual transmission.

 

EBV, like the other herpesviruses, establishes lifelong latent infection after the primary illness. The latent virus is carried in oropharyngeal epithelial cells and systemic B lymphocytes as multiple episomes in the nucleus. The viral episomes replicate with cell division and are distributed to both daughter cells. Viral integration into the cell genome is not typical. Only a few viral proteins, including the EBV-determined nuclear antigens (EBNA), are produced during latency. These proteins are important in maintaining the viral episome during the latent state. Progression to viral replication begins with production of EBV early antigens (EA), proceeds to viral DNA replication, followed by production of viral capsid antigen (VCA), and culminates in cell death and release of mature virions. Reactivation with viral replication occurs at a low rate in populations of latently infected cells and is responsible for intermittent viral shedding in oropharyngeal secretions of infected individuals. Reactivation is apparently asymptomatic and not recognized to be accompanied by distinctive clinical symptoms.

 

Oncogenesis. EBV was the first human virus to be associated with malignancy and, therefore, was the first virus to be identified as a human tumor virus. EBV infection may result in a spectrum of proliferative disorders ranging from self-limited, usually benign disease such as infectious mononucleosis to aggressive, nonmalignant proliferations such as the virus-associated hemophagocytic syndrome to lymphoid and epithelial cell malignancies. Benign EBV-associated proliferations include oral, hairy leukoplakia, primarily in adults with the acquired immunodeficiency syndrome (AIDS), and lymphoid interstitial pneumonitis, primarily in children with AIDS. Malignant EBV-associated proliferations include nasopharyngeal carcinoma, Burkitt lymphoma, Hodgkin disease, and lymphoproliferative disorders and leiomyosarcoma in immunodeficient states including AIDS.

 

Nasopharyngeal carcinoma occurs worldwide but is 10 times more common in persons in southern China, where it is the most common malignant tumor among adult men. It is also common among whites in North Africa and Inuits in North America. All malignant cells of undifferentiated nasopharyngeal carcinoma contain a high copy number of EBV episomes. Undifferentiated and partially differentiated, nonkeratinizing nasopharyngeal carcinomas have diagnostic and prognostic antibodies to EBV antigens. High levels of immunoglobulin (Ig) A antibody to EA and VCA may be detected in asymptomatic individuals and can be used to follow response to tumor therapy (Table 215–1 Table 215–1). Cells of well-differentiated, keratinizing nasopharyngeal carcinoma contain a low or zero copy number of EBV genomes and have EBV serologic patterns similar to those of the general population.

 

Endemic (African) Burkitt lymphoma, often found in the jaw, is the most common childhood cancer in equatorial East Africa and New Guinea. The median age of onset is 5 yr. These regions are holoendemic for Plasmodium falciparum malaria and have a high rate of EBV infection early in life. The constant malarial exposure acts as a B-lymphocyte mitogen that contributes to the polyclonal B-lymphocyte proliferation with EBV infection. It also impairs the T-lymphocyte control of EBV-infected B lymphocytes. Approximately 98% of cases of endemic Burkitt lymphoma contain the EBV genome compared with only 20% of nonendemic (sporadic or American) Burkitt lymphoma cases. Individuals with Burkitt lymphoma have unusually and characteristically high levels of antibody to VCA and EA that correlate with the risk of developing tumor.

 

All cases of Burkitt lymphoma, including those that are EBV negative, are monoclonal and demonstrate chromosomal translocation of the c-myc proto-oncogene to the constant region of the immunoglobulin heavy-chain locus, t(8;14), to the kappa constant light-chain locus, t(2;8), or to the lambda constant light-chain locus, t(8;22). This results in the deregulation and constitutive transcription of the c-myc gene with overproduction of a normal c-myc product that autosuppresses c-myc production on the untranslocated chromosome.

 

The incidence of Hodgkin disease peaks in childhood in developing countries and in young adulthood in developed countries. Levels of EBV antibodies are consistently elevated preceding development of Hodgkin disease; only a small minority of patients are seronegative for EBV. Infection with EBV appears to increase the risk of Hodgkin disease by a factor of two to four. EBV is associated with more than one half of cases of mixed-cellularity Hodgkin disease and approximately one quarter of cases of the nodular sclerosing subtype and is rarely associated with lymphocyte-predominant Hodgkin disease. Immunohistochemical studies have localized EBV to the Reed-Sternberg cells and their variants, the pathognomonic malignant cells of Hodgkin disease.

 

Failure to control EBV infection may result from host immunologic deficits. The prototype is the X-linked lymphoproliferative syndrome (Duncan syndrome), an X chromosome–linked recessive disorder of the immune system associated with severe, persistent, and sometimes fatal EBV infection. Approximately two thirds of these male patients die of disseminated and fulminating lymphoproliferation involving multiple organs at the time of primary EBV infection. Surviving patients acquire hypogammaglobulinemia, B-cell lymphoma, or both. Most patients die by 10 yr.

 

A number of other congenital and acquired immunodeficiency syndromes are associated with an increased incidence of EBV-associated B-lymphocyte lymphoma, particularly central nervous system lymphoma. The incidence of lymphoproliferative syndromes parallels the degree of immunosuppression. A decline in T-cell function evidently permits EBV to escape from immune surveillance. Congenital immunodeficiencies predisposing to EBV-associated lymphoproliferations include the X-linked lymphoproliferative syndrome, common-variable immunodeficiency, ataxia-telangiectasia, Wiskott-Aldrich syndrome, and Ché-iak-Higashi syndrome. Individuals with acquired immunodeficiencies resulting from anticancer chemotherapy, immunosuppression after solid organ or bone marrow transplantation, or HIV infection have a significantly increased risk of EBV-associated lymphoproliferations. The lymphomas may be focal or diffuse, and they are usually histologically polyclonal but may become monoclonal. Their growth is not reversed on cessation of immunosuppression.

 

EBV has been linked with a multitude of other tumors; the strongest association of EBV is to primary central nervous system lymphoma and carcinoma of the salivary glands. Other tumors include T-lymphocyte lymphoma, lethal midline granuloma (a T-cell lymphoma), angioimmunoblastic lymphadenopathy–like lymphoma, thymomas and thymic carcinomas derived from thymic epithelial cells, supraglottic laryngeal carcinomas, lymphoepithelial tumors of the respiratory tract and gastrointestinal tract, leiomyosarcoma, and gastric adenocarcinoma. The precise contribution of EBV to these various malignancies is not well defined.

 

CLINICAL MANIFESTATIONS.

 

The incubation period of infectious mononucleosis in adolescents is 30–50 days. In children it may be shorter. The majority of cases of primary EBV infection in infants and young children are clinically silent. In older patients, the onset of illness is usually insidious and vague. Patients may complain of malaise, fatigue, fever, headache, sore throat, nausea, abdominal pain, and myalgia. This prodromal period may last 1–2 wk. The complaints of sore throat and fever gradually increase until patients seek medical care. Splenic enlargement may be rapid enough to cause left upper quadrant abdominal discomfort and tenderness, which may be the presenting complaint.

 

The physical examination is characterized by generalized lymphadenopathy (90% of cases), splenomegaly (50% of cases), and hepatomegaly (10% of cases). Lymphadenopathy occurs most commonly in the anterior and posterior cervical nodes, and submandibular lymph nodes and less commonly in the axillary and inguinal lymph nodes. Epitrochlear lymphadenopathy is particularly suggestive of infectious mononucleosis. Symptomatic hepatitis or jaundice is uncommon. Splenomegaly to 2–3 cm below the costal margin is typical; massive enlargement is uncommon.

 

The sore throat is often accompanied by moderate to severe pharyngitis with marked tonsillar enlargement, occasionally with exudates.

 

chiae at the junction of the hard and soft palate are frequently seen. The pharyngitis resembles that caused by streptococcal infection. Other clinical findings may include rashes and edema of the eyelids. Rashes are usually maculopapular and have been reported in 3–15% of patients. Eighty per cent of patients with infectious mononucleosis will experience a rash if treated with ampicillin or amoxicillin; the reason for this phenomenon is unknown.

 

COMPLICATIONS.

 

Very few patients with infectious mononucleosis experience complications. The most feared complication is splenic rupture, which occurs most frequently during the 2nd week of the disease. A 0.2% rate has been reported in adults; the rate in children is unknown but is probably much lower. Rupture is commonly related to trauma, which often may be mild. Swelling of the tonsils and oropharyngeal lymphoid tissue may be substantial and cause airway impairment manifest by stridor and interference with breathing. Airway impairment may be treated by administration of corticosteroids; respiratory distress with incipient or actual airway occlusion should be managed by maintaining the airway with intubation in an intensive care setting.

 

Many uncommon and unusual conditions have been reported to be associated with EBV infectious mononucleosis. Neurologic involvement may be serious with ataxia and seizures. Perceptual distortions of space and size, referred to as the Alice in Wonderland syndrome, may be a presenting symptom. There may be meningitis with nuchal rigidity and mononuclear cells in the cerebrospinal fluid, facial nerve palsy, transverse myelitis, and encephalitis. Guillain-Barré syndrome or Reye syndrome may follow acute illness. Hemolytic anemia, often with a positive Coombs test and with cold agglutinins specific for red cell antigen i, may occur late in the illness. Aplastic anemia is a rare complication that usually presents 1 mo after the onset of illness. The prognosis for eventual recovery is good, although substantial supportive treatment is necessary during the acute stages. Myocarditis or interstitial pneumonia may occur, both resolving in 3–4 wk. Other rare complications include pancreatitis, parotitis, and orchitis.

 

DIAGNOSIS.

 

The diagnosis of infectious mononucleosis implies primary EBV infection. A presumptive diagnosis may be made by the presence of typical clinical symptoms with atypical lymphocytosis in the peripheral blood. The diagnosis is confirmed by serologic testing.

 

 

Differential Diagnosis.

 

Infectious mononucleosis–like illnesses may be caused by primary infection with cytomegalovirus, T. gondii, adenovirus, viral hepatitis, HIV, or possibly rubella virus. Cytomegalovirus infection is a particularly common cause in adults. Streptococcal pharyngitis may cause sore throat and cervical lymphadenopathy indistinguishable from that of infectious mononucleosis but is not associated with hepatosplenomegaly. Approximately 5% of cases of EBV-associated infectious mononucleosis have positive throat cultures for group A b-hemolytic streptococci; this represents pharyngeal streptococcal carriage. Failure of a patient with streptococcal pharyngitis to improve within 48–72 hr should evoke suspicion of infectious mononucleosis. The most serious problem in the diagnosis of acute illness arises in the occasional patients with low white cell counts, moderate thrombocytopenia, and even hemolytic anemia. In these patients, bone marrow examination and hematologic consultation are warranted to exclude the possibility of leukemia.

 

Routine Laboratory Tests. In more than 90% of cases, there is leukocytosis of 10,000–20,000 cells/mm3, of which at least two thirds are lymphocytes; atypical lymphocytes usually account for 20–40% of the total number. The atypical cells are mature T lymphocytes that have been antigenically activated. Compared with regular lymphocytes microscopically, atypical lymphocytes are larger overall, with larger, eccentrically placed indented and folded nuclei with a lower nuclear-cytoplasm ratio. Although atypical lymphocytosis may be seen with many of the infections usually causing lymphocytosis, the highest degree of atypical lymphocytes is classically seen with EBV infection. Other syndromes associated with atypical lymphocytosis include acquired cytomegalovirus infection (as contrasted to congenital cytomegalovirus infection), toxoplasmosis, viral hepatitis, rubella, roseola, mumps, tuberculosis, typhoid, mycoplasma infection, malaria, as well as some drug reactions. Mild thrombocytopenia to 50,000–200,000 platelets/mm3 occurs in more than 50% of patients, but only rarely are values low enough to cause purpura. Mild elevation of hepatic transaminases occurs in approximately 50% of uncomplicated cases but is usually asymptomatic without jaundice.

 

Heterophile Antibody Test. Heterophile antibodies agglutinate cells from species different from those in the source serum. The transient heterophile antibodies seen in infectious mononucleosis, also known as Paul-Bunnell antibodies, are IgM antibodies detected by the Paul-Bunnell–Davidsohn test for sheep red cell agglutination. The heterophile antibodies of infectious mononucleosis agglutinate sheep or, for greater sensitivity, horse red cells but not guinea pig kidney cells. This adsorption property differentiates this response from the heterophile response found in patients with serum sickness, rheumatic diseases, and some normal individuals. Titers greater than 1:28 or 1:40 (depending on the dilution system used) after absorption with guinea pig cells are considered positive.

 

The sheep red cell agglutination test is likely to be positive for several months after infectious mononucleosis; the horse red cell agglutination test may be positive for as long as 2 yr. The most widely used method is the qualitative, rapid slide test using horse erythrocytes. It detects heterophile antibody in 90% of cases of EBV-associated infectious mononucleosis in older children and adults but in only up to 50% of cases in children younger than 4 yr because they typically develop a lower titer. Approximately 5–10% of cases of infectious mononucleosis are not caused by EBV and are not uniformly associated with a heterophile antibody response. The false-positive rate is less than 10%, usually resulting from erroneous interpretation. If the heterophile test is negative and an EBV infection is suspected, EBV-specific antibody testing is indicated.

 

Specific EBV Antibodies. EBV-specific antibody testing is useful to confirm acute EBV infection, especially in heterophile-negative cases, or to confirm past infection and determine susceptibility to future infection. Several distinct EBV antigen systems have been characterized for diagnostic purposes.

 

 The EBNA, EA, and VCA antigen systems are most useful for diagnostic purposes. The acute phase of infectious mononucleosis is characterized by rapid IgM and IgG antibody responses to VCA in all cases and an IgG response to EA in most cases. The IgM response to VCA is transient but can be detected for at least 4 wk and occasionally up to 3 mo. The laboratory must take steps to remove rheumatoid factor, which may cause a false-positive IgM VCA result. The IgG response to VCA usually peaks late in the acute phase, declines slightly over the next several weeks to months, and then persists at a relatively stable level for life.

 

Anti-EA antibodies are usually detectable for several months but may persist or be detected intermittently at low levels for many years. Antibodies to the diffuse-staining component of EA, EA-D, are found transiently in 80% of patients during the acute phase of infectious mononucleosis and reach high titers in patients with nasopharyngeal carcinoma. Antibodies to the cytoplasmic-restricted component of EA, EA-R, emerge transiently in the convalescence from infectious mononucleosis and often attain high titers in patients with EBV-associated Burkitt lymphoma, which in the terminal stage of the disease may be exceeded by antibodies to EA-D. High levels of antibodies to EA-D or EA-R may be found also in immunocompromised patients with persistent EBV infections and active EBV replication. Anti-EBNA antibodies are the last to develop in infectious mononucleosis and gradually appear 3–4 mo after the onset of illness and remain at low levels for life. Absence of anti-EBNA when other antibodies are present implies recent infection, while the presence of anti-EBNA implies infection occurring more than 3–4 mo previously. The wide range of individual antibody responses and the various laboratory methods used can occasionally make interpretation of an antibody profile difficult. The detection of IgM antibody to VCA is the most valuable and specific serologic test for the diagnosis of acute EBV infection and is generally sufficient to confirm the diagnosis.

 

TREATMENT.

 

There is no specific treatment for infectious mononucleosis. Therapy with high doses of intravenous acyclovir decreases viral replication and oropharyngeal shedding during the period of administration but does not affect the severity of symptoms or the eventual clinical course. Rest and symptomatic therapy are the mainstays of management. Bed rest is necessary only when the patient has debilitating fatigue. As soon as there is definite symptomatic improvement, the patient should be allowed to begin resuming normal activities. Because blunt abdominal trauma may predispose patients to splenic rupture, it is customary and prudent to advise withdrawal from contact sports and strenuous athletic activities during the first 2–3 wk of illness or while splenomegaly is present.

 

Short courses of corticosteroids (less than 2 wk) may be helpful for complications of infectious mononucleosis, but their use has not been evaluated critically. Some appropriate indications include incipient airway obstruction, thrombocytopenia with hemorrhaging, autoimmune hemolytic anemia, and seizures and meningitis. A recommended dosage is prednisone 1 mg/kg/24 hr (maximum 60 mg/24 hr) or equivalent for 7 days and tapered over another 7 days. There are no controlled data to show efficacy of corticosteroids in any of these conditions. In view of the potential and unknown hazards of immunosuppression for a virus infection with oncogenic complications, corticosteroids should not be used in usual cases of infectious mononucleosis.

 

PROGNOSIS. The prognosis for complete recovery is excellent if no complications ensue during the acute illness. The major symptoms typically last 2–4 wk followed by gradual recovery. Second attacks of infectious mononucleosis caused by EBV have not been documented. Fatigue, malaise, and some disability that may wax and wane for several weeks to a few months are common complaints even in otherwise unremarkable cases. Occasional persistence of fatigue for a few years after infectious mononucleosis is well recognized. At present, there is no specific evidence linking EBV infection to chronic fatigue syndrome (see Chapter 661).

 

 

Short statement of the material

 

Infectious mononucleosis is an acute infectious disease that is caused by the Epstein-Barr virus is characterized by the fever, tonsillitis, increase of lymphatic nodes, hepato- and splenomegaly, by presence of atypical mononuclear cells in a peripheral blood and heterophyl antibodies.

 

Etiology: an EBV, belong to Herpes viruses, type IV

 

Epidemiology:

Source of infection are patients with symptomatic and asymptomatic forms, EBV-carriers

Mechanism of transmission is droplet, rarer is contact. The virus is transmitted primarily through saliva during speaking, breathing, coughing, especially during kisses, hand-to-hand contacts.

The transmission of EBV through blood product transfusions has been well documented.

Susceptibility – any age, disease is low contagious, more frequent up to 15 years, in boys

 

Pathogenesis:

Inoculation of the virus into upper respiratory tract mucous membranes.

Diffusion by lymph to the lymph nodes, spleen, liver.

Lymphoprolipherative syndrome.

Bacterial complications.

Persistence of the virus (even 16 months or more).

 

Clinical criteria

Incubation period is 10-15 days (may be longer-2 month).

Beginning is acute from fever, intoxication (headache, myalgia, arthralgias, malaise).

Fever usually febrile from 3 days till 3 weeks

Tonsilopharyngitis, which may be exudative (follicular, lacunar) in case of secondary bacterial infection (photo), lymphoid follicles hyperplasia (on the back pharyngeal wall).

Adenoiditis, posterior rhinitis (appearance of the patient is typical – breathing with open mouth, absence of nasal discharge, usually snore is present).

Generalized lymphadenopathy with previous enlargement of cervical and occipital lymph nodes (photo).

Hepatosplenomegaly is the sign of lymphoproliferative syndrome (photo).

Maculopapular rashes (photo), wich may confluence with erythema development (photo), sometimes hemorrhagic elements with later skin pigmentation (photo) may occur as a sign of hypersensitivity in case of amoxicillin, ampicillin treatment (in 70-80%).  In the young childhood patient in 25% of cases “spontaneous” rashes can develop.

Other signs: hepatitis (jaundice form of infectious mononucleosis);

toxic myocarditis

diarrhea.

 

Tonsilopharyngitis

 

Tonsilopharyngitis

 

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

 

Generalized lymphadenopathy with previous enlargement of cervical lymph nodes

 

 

Hepatosplenomegaly

 

Maculopapular rashes

 

Maculopapular rashes wich confluence

 

Maculopapular rashes wich confluence

 

Toxic erythema (next day)

 

Pigmentation in few days

 

Classification            

            Form: – typical                                                         

                                   – atypical:        – effaced (mild)              

                                                           – asymptomatic (subclinical) mild

                                                           – visceral – severe (heart, kidneys, adrenal glands, CNS damage)

            Severity (for typical forms):   – mild

                                                           – moderate

                                                           – severe

            Duration         –    smooth (uncomplicated)

complicated

prolonged

 

Infectious mononucleosis Severity Criteria

 

Sign	Mild	Moderate	Severe
Toxic syndrome	absent, mild	Moderate	Expressed
Body t°	Up to 38 °С	38,5-39 °С	More than 40 °С
Lymph nodes damage	mild, cervical predominantly	marked, cervical especially, visible	conglomerates, neck disfiguration, neck subcutaneous tissue swelling
Nasal breathing	Some labored	Labored, “snoring” in sleep	Absent, snoring, opened mouth, puffy face
Throat damage	Catarrhal tonsillitis	tonsils hyperplasia  1st-2nd degree, considerable exudates	tonsils hyperplasia  3rd  degree, large membranous exudates
Hepato–  splenomegaly (outcome from the rib arch)	Up to 2-3 сm	3-4 сm	4-5 сm and more, jaundice
Atypical mononuclear cells number	Up to 30 %	20-50 %	More than 50 %
Cough	Rare	Often	Often
Rashes	Rare	Often	Hemorrhagic in 1/3, nasal bleeding
Dyspepsia	Rare	Present abdominal pain, vomiting	abdominal pain, several vomiting
Heart changes “toxic-infectious heart”	Not typical	Rare	Often

 

Peculiarities of infectious mononucleosis in infants:

often catarrhal syndrome is present (cough, sneezing, corryza);

expressed polyadenia, snore, edematous face from the first day of the disease;

early development of bacterial tonsillitis (on the third day);

rashes are more often;

dyspepsia;

in the peripheral blood – neutrophyllosis with left shift;

favorable duration.

 

Complications, which may occur (rare):  

Respiratory tract – pneumonia, airway obstructions.

Neurological – seizures, meningitis, encephalitis, peripheral facial nerve paralysis, Gillian – Barrette syndrome. 

Hematological – thrombocytopenia, hemolytic anemia.

Infectious – recurrent tonsilopharyngitis.

Renal – glomerulonephritis.

Genital – orchitis.

Spleen rupture (is lethal).

 

Laboratory findings

Blood analyses: leucocytosis, even 15-30,000/mm3, lymphocytosis, monocytosis, appearing of atypical mononuclear cells (virocytes) more than 10%, ESR enlarges to 20-30mm/hour.

Heterophil agglutination test (is positive in 25-95% of preschool children, 53-94 young school children, and nearly 100% of older children).

Immune-enzyme method – VCA Ig M, EA Ig M presence in the blood.

PCR (measuring of EBV nucleinic acid in the blood, saliva, lymphatic tissues).

 

atypical mononuclear cells

 

Diagnosis example:

Infectious mononucleosis, typical form, moderate severity, complicated by the bilateral  bronchopneumonia  

 

Differential diagnosis should be performed with ‘mononucleosis like’ syndrome caused of AIDS. Another disease, which has similar features: diphtheria, adenoviral infection, acute leukemia, lymphogranulomathosis, viral hepatitis etc.

 

 

Differential diagnostic of tonsillitis different etiology

 

 

Treatment

Reduction of activity and bed rest.

special diet (diet N 5),

Exclude heavy fats (like pork), spices, fried foods, “fast food””; avoid stimulators of gastrointestinal secretions, the diet must be rich by metionine, lecithin, and choline to stimulate synthesis of proteins and enzymes in the liver. Diet with normal value of proteins and vitamins, with restriction of fats and carbohydrates is administered, also restrict salt.

Foods boiled, steamed and baked are recommended; food taking 5 times daily

Control of fever and myalgia (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. Aspirin is contraindicated for children before 12 years.

Antihistamines (in average doses) – pipolphen, suprastin, claritin, cetirizin.

Corticosteroids – in severe cases 1-2 mg/kg/day prednisone for 3-5 days.

In case of secondary bacterial complications macrolides (erythromycin 30-50 mg/kg/day, azythromycin 10 mg/kg/day, clarythromycin) or cefalosporins (cefalexin 50 mg/kg/day, cefuroxim 50 mg/kg/day, cephasolin 100 mg/kg/day), Ampicillin and other semisynthetic penicillins are contraindicated!

The administration of oral acyclovir does not significantly alter the course of clinical illness from placebo.

 

Prophylaxis: is nonspecific, includes disinfecting;

Isolation of the patient, hospitalization of children younger 1 year, in case of severe forms.

A quarantine is not imposed.

Key words and phrases: infectious mononucleosis, EBV-infection, lymphoprolipherative syndrome, atypical mononuclear cells, heterophyl  agglutination test, and “mononucleosis” syndrome.

 

 

MUMPS (INFECTIOUS PAROTITIS).

 

 Mumps is an acute, generalized viral disease in which painful enlargement of the salivary glands, chiefly the parotids, is the usual presenting sign.

 

ETIOLOGY.

 

The virus is a member of the paramyxovirus group, which also includes the parainfluenza, measles, and Newcastle disease viruses. Only one serotype is known. Primary cultures of human or monkey kidney cells are used for viral isolation. Cytopathic effect is occasionally observed, but hemadsorption is the most sensitive indicator of infection. Virus has been isolated from saliva, cerebrospinal fluid, blood, urine, brain, and other infected tissues.

 

EPIDEMIOLOGY.

 

Mumps is endemic in most urban populations; the virus is spread from a human reservoir by direct contact, airborne droplets, fomites contaminated by saliva, and possibly by urine. It is distributed worldwide and affects both sexes equally; 85% of infections occurred in children younger than 15 yr prior to widespread immunization. Now disease often occurs in young adults, producing epidemics in colleges or in the work place. Epidemics appear to be primarily related to lack of immunization rather than to waning of immunity. Epidemics occur at all seasons but are slightly more frequent in late winter and spring. Sources of infection may be difficult to trace because 30–40% of infections are subclinical. There has been a decrease in the incidence since the introduction of mumps vaccine in 1968.

 

Virus has been isolated from saliva as long as 6 days before and up to 9 days after appearance of salivary gland swelling. Transmission does not seem to occur longer than 24 hr before appearance of the swelling or later than 3 days after it has subsided. Virus has been isolated from urine from the 1st–14th day after the onset of salivary gland swelling.

 

Lifelong immunity usually follows clinical or subclinical infection, although second infections have been documented. Transplacental antibodies seem to be effective in protecting infants during their first 6–8 mo. Infants born to mothers who have mumps in the week prior to delivery may have clinically apparent mumps at birth or experience illness in the neonatal period. Severity ranges from mild parotitis to severe pancreatitis. The serum neutralization test is the most reliable method for determining immunity but is cumbersome and expensive. A complement-fixing antibody test is available (see Diagnosis). The presence of V antibodies alone suggests previous mumps infection.

 

PATHOGENESIS.

 

After entry and initial multiplication in the cells of the respiratory tract, the virus is blood-borne to many tissues, among which the salivary and other glands are the most susceptible.

 

CLINICAL MANIFESTATIONS.

 

The incubation period ranges from 14–24 days, with a peak at 17–18 days. In children, prodromal manifestations are rare but may be manifest by fever, muscular pain (especially in the neck), headache, and malaise. The onset is usually characterized by pain and swelling in one or both parotid glands. The parotid swells characteristically; it first fills the space between the posterior border of the mandible and the mastoid and then extends in a series of crescents downward and forward, being limited above by the zygoma. Edema of the skin and soft tissues usually extends further and obscures the limit of the glandular swelling, so that the swelling is more readily appreciated by sight than by palpation. Swelling may proceed extremely rapidly, reaching a maximum within a few hours, although it usually peaks in 1–3 days. The swollen tissues push the ear lobe upward and outward, and the angle of the mandible is no longer visible. Swelling slowly subsides within 3–7 days but occasionally lasts longer. One parotid gland usually swells a day or two before the other, but swelling limited to one gland is common. The swollen area is tender and painful, pain being elicited especially by tasting sour liquids such as lemon juice or vinegar. Redness and swelling about the opening of the Stensen duct are common. Edema of the homolateral pharynx and soft palate accompanies the parotid swelling and displaces the tonsil medially; acute edema of the larynx has also been described. Edema over the manubrium and upper chest wall may occur probably because of lymphatic obstruction. The parotid swelling is usually accompanied by moderate fever; normal temperatures are common (20%), but temperatures of 40º C (104º F) or more are rare.

 

Although the parotid glands alone are affected in the majority of patients, swelling of the submandibular glands occurs frequently and usually accompanies or closely follows that of the parotid glands. In 10–15% of patients only the submandibular gland(s) may be swollen. Little pain is associated with the submandibular infection, but the swelling subsides more slowly than that of the parotids. Redness and swelling at the orifice of the Wharton duct frequently accompany swelling of the gland.

 

Least commonly the sublingual glands are infected, usually bilaterally; the swelling is evident in the submental region and in the floor of the mouth.

 

A maculopapular erythematous rash, most prominent on the trunk, occurs infrequently; rarely it is urticarial.

 

OTHER ORGANS DAMAGE

Meningoencephalomyelitis. This is the most frequent complication in childhood. The true incidence is hard to estimate because subclinical infection of the central nervous system, as evidenced by cerebrospinal fluid pleocytosis, has been reported in more than 65% of patients with parotitis. Clinical manifestations occur in over 10% of patients. The incidence of mumps meningoencephalitis is approximately 250/100,000 cases; 10% of these cases occurred in patients older than 20 yr. The mortality rate is about 2%. Males are affected three to five times as frequently as females. Mumps is one of the most common causes of aseptic meningitis

 

The pathogenesis of mumps meningoencephalitis has been described as (1) a primary infection of neurons and (2) a postinfectious encephalitis with demyelination. In the first type, parotitis frequently appears at the same time or following the onset of encephalitis. In the latter type, encephalitis follows parotitis by an average of 10 days. Parotitis may in some cases be absent. Aqueductal stenosis and hydrocephalus have been associated with mumps infection. Injecting mumps virus into suckling hamsters has produced similar lesions.

 

Mumps meningoencephalitis is clinically indistinguishable from meningoencephalitis of other origins. Moderate stiffness of the neck is seen, but the remainder of the neurologic examination is usually normal. The cerebrospinal fluid (CSF) usually contains fewer than 500 cells/mm3, although occasionally the count may exceed 2,000. The cells are almost exclusively lymphocytes, in contrast to enteroviral aseptic meningitis, in which polymorphonuclear leukocytes often predominate early in the disease. Mumps virus can be isolated from cerebrospinal fluid early in the illness.

 

Orchitis, Epididymitis. These complications rarely occur in prepubescent boys but are common (14–35%) in adolescents and adults. The testis is most often infected with or without epididymitis; epididymitis may also occur alone. Rarely, there is a hydrocele. The orchitis usually follows parotitis within 8 days or so; it may also occur without evidence of salivary gland infection. In about 30% of patients both testes are affected. The onset is usually abrupt, with a rise in temperature, chills, headache, nausea, and lower abdominal pain; when the right testis is implicated, appendicitis may be suggested as a diagnostic possibility. The affected testis becomes tender and swollen, and the adjacent skin is edematous and red. The average duration is 4 days. Approximately 30–40% of affected testes atrophy. Impairment of fertility is estimated to be about 13%, but absolute infertility is probably rare.

 

Oophoritis. Pelvic pain and tenderness are noted in about 7% of postpubertal female patients. There is no evidence of impairment of fertility.

 

Pancreatitis. Severe involvement of the pancreas is rare, but mild or subclinical infection may be more common than is recognized. It may be unassociated with salivary gland manifestations and be misdiagnosed as gastroenteritis. Epigastric pain and tenderness, which are suggestive, may be accompanied by fever, chills, vomiting, and prostration. An elevated serum amylase value is characteristically present with mumps, with or without clinical manifestations of pancreatitis.

 

Nephritis. Viruria has been reported frequently. In one study of adults, abnormal renal function occurred at some time in every patient, and viruria was detected in 75%. The frequency of renal involvement in children is unknown. Fatal nephritis, occurring 10–14 days after parotitis, has been reported.

 

Thyroiditis. Although uncommon in children, a diffuse, tender swelling of the thyroid may occur about 1 wk after the onset of parotitis with subsequent development of antithyroid antibodies.

 

Myocarditis. Serious cardiac manifestations are extremely rare, but mild infection of the myocardium may be more common than is recognized. Electrocardiographic tracings revealed changes, mostly depression of the ST segment, in 13% of adults in one series. Such involvement may explain the precordial pain, bradycardia, and fatigue sometimes noted among adolescents and adults with mumps.

 

Mastitis. This is uncommon in each sex.

 

COMPLICATIONS.

Deafness. Unilateral, rarely bilateral, nerve deafness may occur; although the incidence is low (1:15,000), mumps is a leading cause of unilateral nerve deafness. The hearing loss may be transient or permanent.

 

Ocular Complications. These include dacryoadenitis, painful swelling, usually bilateral, of the lacrimal glands; optic neuritis (papillitis) with symptoms varying from loss of vision to mild blurring with recovery in 10–20 days; uveokeratitis, usually unilateral, with photophobia, tearing, rapid loss of vision, and recovery within 20 days; scleritis; tenonitis, with resultant exophthalmos; and central vein thrombosis.

 

Arthritis. Arthralgia associated with swelling and redness of the joints is an infrequent complication; complete recovery is the rule.

 

Thrombocytopenic Purpura. This sign is infrequent.

 

Mumps Embryopathy. There is no firm evidence that maternal infection is damaging to the fetus; a possible relationship to endocardial fibroelastosis has not been established. Mumps in early pregnancy does increase the chance of abortion.

 

DIAGNOSIS.

 

The diagnosis of mumps parotitis is usually apparent from the symptoms and physical examination. When the clinical manifestations are limited to those of one of the less common lesions, the diagnosis is not so clear but may be suspected, especially during an epidemic. The routine laboratory tests are nonspecific; there is usually leukopenia with relative lymphocytosis, but complications often result in polymorphonuclear leukocytosis of moderate degree. An elevation of serum amylase is common; the rise tends to parallel the parotid swelling and then to return to normal within 2 wk or so. The etiologic diagnosis depends on isolation of the virus from the saliva, urine, spinal fluid, or blood or the demonstration of a significant rise in circulating complement fixation antibodies during convalescence. Serum antibodies to the S antigen reach their peak early in about 75% of patients and are detectable at the time of the presenting symptoms. They gradually disappear within 6–12 mo; antibodies against the V or viral antigen usually reach a peak titer in about 1 mo, remain stationary for about 6 mo, and then slowly decline during the ensuing 2 yr to a low level, at which they persist. The presence of a high anti-S titer and a low anti-V titer during the acute stage of an otherwise undiagnosed meningoencephalitis, for example, strongly suggests a mumps infection, which would be confirmed if a convalescent serum (taken 14–21 days later) revealed a fourfold rise of anti-V antibodies accompanied by little change in the titer of anti-S antibodies.

 

DIFFERENTIAL DIAGNOSIS.

 

This includes parotitis of other origin, as in viral infections including human immunodeficiency virus (HIV) infection, influenza, parainfluenza 1 and 3, cytomegalovirus, or the rare instances of coxsackievirus A and lymphocytic choriomeningitis infections. These infections can be distinguished by specific laboratory tests; suppurative parotitis, in which pus can often be expressed from the duct; recurrent parotitis, a condition of unknown origin, but possibly allergic iature, which has frequent recurrences and a characteristic sialogram; salivary calculus, obstructing either a parotid or, more commonly, a submandibular duct, in which the swelling is intermittent; preauricular or anterior cervical lymphadenitis from any cause; lymphosarcoma or other rare tumors of the parotid; orchitis resulting from infections other than mumps, for example, the rare infections by coxsackievirus A or lymphocytic choriomeningitis viruses; and parotitis caused by cytomegalovirus in immunocompromised children.

 

TREATMENT.

 

Treatment of parotitis is entirely symptomatic. Bed rest should be guided by the patient’s needs, but no statistical evidence indicates that it prevents complications. The diet should be adjusted to the patient’s ability to chew. Orchitis should be treated with local support and bed rest. Mumps arthritis may respond to a 2-wk course of corticosteroids or a nonsteroidal anti-inflammatory agent. Salicylates do not appear to be effective.

 

PROPHYLAXIS

 

Passive. Hyperimmune mumps gamma globulin is not effective in preventing mumps or decreasing complications.

 

Active. The routine administration of live, attenuated mumps vaccine is discussed in Chapter 247. Vaccinated children usually do not experience fever or other detectable clinical reactions, do not excrete virus, and are not contagious to susceptible contacts. Rarely, parotitis can develop 7–10 days after vaccination. The vaccine induces antibody in about 96% of seronegative recipients and has a protective efficacy of about 97% against natural mumps infection. The protection appears to be long lasting. In one outbreak of mumps, several children who had been immunized with mumps vaccine in the past experienced an illness characterized by fever, malaise, nausea, and a red papular rash involving the trunk and extremities but sparing the palms and soles. The rash lasted about 24 hr. No virus was isolated from these children, but increases in the titer of mumps antibody were demonstrated

 

 

References:

1. Ambulatory pediatric care/ edited by Robert A.Derchewitz; – 2^nd ed. Lippincot – Raven,1992.- p.58-59;151-153, 193-195; 254, 265; 315-319; 329-330; 742-751.

2. Current therapy in pediatric infections disease-2/edited by John D. Nelson, M.D.- B. C. Decker inc. Toronto. Philadelphia,1988.- p.29-34; 46-49; 247-251.

3. Feigin RD, Cherry JD, eds. Textbook of Pediatric Infectious Diseases. Vol 2. 4th ed. WB Saunders Co; 1998:1922-1949.

4. Principles and Practice of Pediatric Infectious Diseases. / Edited by Saran S. Long, Larry K. Pickering, Charles G. Prober, Philadelphia, Pa: Churchill Livingstone; 1997. – 1921 p.

Additional:

1. Textbook of Pediatric Nursing.  Dorothy R. Marlow; R. N., Ed. D. –London, 1989.-661p.

2. Pediatrics ( 2^nd edition, editor – Paul H.Dworkin, M.D.) – 1992. – 550 pp.