Lesson 1

Theme 1. Measles. Rubella. Chicken pox. Herpes Zoster

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 in neonates – 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.

 

References:

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

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

3.           Illustrated Textbook of Paediatrics, 4th Edition.  Published by  Lissauer & Clayden, 2012, p. 552 ISBN: 978-072-343-566-2.

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

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

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