Lesson 1

Theme. Measles. Rubella. nChicken pox. Herpes Zoster

MEASLES

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

 

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

 

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

 

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

 

EPIDEMIOLOGY. Measles is endemic nover most of the world. In the past, epidemics tended to occur irregularly, nappearing in the spring in large cities at 2- to 4-yr intervals as new groups nof susceptible children were exposed. Measles is very contagious; approximately n90% of susceptible family contacts acquire the disease. It is rarely subclinical. nPrior to the use of measles vaccine, the age of peak incidence was 5–10 yr; nmost adults were immune. At present in the United States, measles occurs most noften in unimmunized preschool-aged children and in teenagers and young adults nwho have been immunized. Epidemics have occurred in high schools and colleges nwhere immunization levels were high. These epidemics are thought to be due nprimarily to vaccine failure. Despite a resurgence of measles in the United nStates from 1989–1991, reported numbers of measles cases dropped to an all-time nlow in 1993, probably a result of widespread vaccination. Those older than 30 nyears are virtually all immune. Because measles is still a common disease imany countries, infective persons entering this country may infect United nStates citizens, and Americans traveling abroad risk exposure there.

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

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

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

In fatal cases of encephalomyelitis, perivascular ndemyelinization occurs in areas of the brain and spinal cord. In Dawsosubacute sclerosing panencephalitis (SSPE), there may be degeneration of the ncortex and white matter with intranuclear and intracytoplasmic inclusiobodies.

 

CLINICAL MANIFESTATIONS.

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

 

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

 

Conjunctivitis nin measles

  

 

Koplik nspots

 

Enanthema

 

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

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

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

 

 

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

 

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

 

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

 

Fig. Hemorrhagic rash of measles

 

The rash pigmentation

 

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

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

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

 

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

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

 

DIAGNOSIS.

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

 

DIFFERENTIAL DIAGNOSIS.

The rash of rubeola must be differentiated from nexanthem subitum, rubella, infections resulting from echovirus, coxsackie nvirus, and adenovirus, infectious mononucleosis, toxoplasmosis, nmeningococcemia, scarlet fever, rickettsial diseases, serum sickness, Kawasaki ndisease, and drug rashes.

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

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

The milder rash and clinical picture of measles nmodified by gamma globulin or by partial immunity induced by measles vaccine, nor in infants by maternal antibody, may be difficult to differentiate.

 

COMPLICATIONS.

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

Pneumonia may be caused by the measles virus itself; the lesiois interstitial. Measles pneumonia in patients with HIV infection is oftefatal and not always accompanied by rash. Bronchopneumonia is more frequent, nhowever; it is due to secondarily invading bacteria, particularly the npneumococcus, streptococcus, staphylococcus, and Haemophilus influenzae. nLaryngitis, tracheitis, and bronchitis are common and may be due to the virus nalone.

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

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

Neurologic complications are more common in measles nthan in any of the other exanthems. The incidence of encephalomyelitis is nestimated to be 1-2/1,000 reported cases of measles. There is no correlatiobetween the severity of the measles and that of the neurologic involvement or nbetween the severity of the initial encephalitic process and the prognosis. nRarely, encephalitis has been reported in association with measles modified by ngamma globulin or by live attenuated measles virus vaccine. Infrequently, nencephalitic involvement is manifest in the pre-eruptive period, but more oftethe onset occurs 2–5 days after the appearance of the rash. The cause of nmeasles encephalitis remains controversial. It is suggested that wheencephalitis occurs early in the course of the disease, viral invasion plays a nlarge role, although measles virus has rarely been isolated from brain tissue; nencephalitis that occurs later is predominantly demyelinating and may reflect nan immunologic reaction. In this demyelinating type the symptoms and course do nnot differ from those of other parainfectious encephalitides. Fatal nencephalitis has occurred in children receiving immunosuppressive treatment for nmalignancies. Other central nervous system complications, such as nGuillain-Barré{acute-e} syndrome, hemiplegia, cerebral thrombophlebitis, nand retrobulbar neuritis, are rare.

 

Subacute sclerosing panencephalitis  is due to measles virus.

 

PROGNOSIS.

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

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

 

PROPHYLAXIS.

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

The initial measles immunization may be given at 12 to n15 mo but may be given earlier in areas where disease is occurring. Because the nseroconversion rate following immunization is not 100% and there may be some nwaning of immunity with time, a second immunization against measles, usually ngiven as measles-mumps-rubella (MMR), is indicated. This dose can be given whethe child enters school or later on entry to middle school. Adolescents nentering college should also have received a second measles immunization.

 

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

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

 

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

 

Passive Immunization.

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

 

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

 

TREATMENT.

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

 

With complications such as encephalitis, subacute nsclerosing panencephalitis, giant cell pneumonia, and disseminated nintravascular coagulation, each case must be assessed individually. Good nsupportive care is essential. Gamma globulin, hyperimmune gamma globulin, and nsteroids are of limited value. Currently available antiviral compounds are not neffective. Treatment with oral vitamin A (400,000 IU) reduces morbidity and nmortality 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 nby cyclic course, syndromes of intoxication, catarrhal inflammation of nrespiratory tract, conjunctiva, and rashes on the skin.

 

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

Morbillivirus.

 

Epidemiology:

1.                     nSource of ninfection – infected person during last n2 days of incubation period, catarrhal period, and 4 days period of eruptio(in case of complications –10 days period of eruption).

2.                     nInfection is ntransmitted by inhalation of large and nsmall airborne droplets.

3.                     nSusceptible norganism – no immunized people, older nthan 6 month, which never had measles.

 

Pathogenesis:

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

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

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

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

• Than:

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

intestinum;

– inflammation, ndestruction, liberation of virus;

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

– forming of ncomplications.

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

 

Clinical npresentation

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

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

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

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

 

Classification

By the form:

Typical, by the severity:

– mild;

– moderate;

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

Atypical:

– abortive;

– mitigious;

– hyperreactive;

– subclinical;

  – nasymptomatic;

– measles in vaccinated;

– measles in person who nreceive antibiotics and hormones.

By the ncourse:

– smooth (uncomplicated);

– not smooth, uneve(complicated).

 

Complications:

By the netiology:

– primary (due to measles nvirus);

– secondary (bacterial).

By the time nof development:

– early (in prodromal and nrushes period);

– late (in pigmentatioperiod).

By the nlocalization:

– respiratory system n(laryngitis, laryngotracheobronchitis, pneumonia);

– digestive system n(enterocolitis, colitis);

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

– eyes (keratitis);

– ears (otitis media);

– skin (staphylo- or nstreptodermia);

– urinary system n(pyelonephritis).

Complications: n

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

secondary nbacterial – otitis media, pneumonia, ngingivostomatitis, pyelonephritis, diarrhea, dermatitis.

 

Peculiarities nof measles in infants

1.                     nAtypical n(mitigious) forms.

2.                     nReduction of nthe disease periods.

3.                     nUnexpressed clinical nsigns (catarrhal phenomena, fever, small unabundant rashes with the shortened nstaging and pigmentation).

4.                     nComplications nare more frequent.

 

Laboratory nwork-up

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

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

• Viral isolation is ntechnically difficult.

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

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

Diagnosis example:

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

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

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

obstruction syndrome, Respiratory insufficiency n2nd degree.

Differential ndiagnose should be performed betweescarlet fever, Epstein-Barr viral infection, meningococcal sepsis, npseudotuberculosis, Kawasaki syndrome, Stevens-Johnson syndrome, adenovirus, nenterovirus infection, diaper rashes (photo 1), Rheumathoid arthritis systemic nform (photo 2), and allergic rashes (photo 3-10).

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

Heat nrash

Rheumathoid narthritis systemic form

Drug allergy

Drug nallergy

 

Drug nallergy

 

Food nallergy (urticaria)

Cool allergy

Differential diagnostics of infectious rashes (exanthemas)

 

Evidences for obligatory hospitalization of patients with infectious nexanthema

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

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

3.                     nAbsence of nconditions for examination and treatment at home.

4.                     nSick nchildren from closed children institutions.

Advantages of the home treatment

1.                     nPossibility nof additional infection by hospital bacteria is completely excluded.

2.                     nRealizatioof individual care principle for sick child is more full.

3.                     nAvoiding nstressful reactions, which could appear in case of hospital treatment.

Treatment in home conditions is possible

1.                     nIconditions of isolated flat.

2.                     nIn case of nsatisfactory material position of the parents.

3.                     nIn case of nparents desire to organize individual care and treatment at home.

Treatment

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

1.                     nBed rest up nto the normalization of body temperature.

2.                     nRegular ventilatioof the room.

5.                     nAdequate nrehydration with oral fluids (lemon tea, raspberry tea, warm alkali drinks).

3.                     nVitaminized nmilk-vegetable food.

4.                     nControl of nfever (when the temperature is more than 38.5-39 °C); in childrebefore 2 mo and in case of perinatal CNS damage, seizures in the history, nsevere heart diseases – when the temperature is up to 38 °C with acetaminophe(paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 ntimes per day) or ibuprophen 10 mg/kg per dose, not often than every 6 nhours.

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

6.                     nIn case of dry ncough – cough suppressors (such as dextramethorphan, synecod).

7.                     nMucolytics nin case of the moist nonproductive cough (ambroxol, acetylcystein etc.).

8.                     nLooking nafter oral cavity (gurgling with boiled water, antiseptic fluids).

9.                     nLooking nafter conjunctiva (washing with boiled water, concentrated tea, sulfacyl Na idrops).

10.                nVitamin A norally.

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

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

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

• In case of meningitis:

Base ntherapy:

1.                     nBed regimetill body temperature normalization, disappearance of general cerebral and nconsiderable improvement of focal neurological signs, not less than 14-16 days.

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

3.                     nBrest nfeeding or bottle feeding by adopted formulas for infants, in the first day n1/2-1/3 of average volume with a next increase to the complete volume during n2-3rd days.

4.                     nA milk nvegetable diet (№5) is appointed for preschoolers or school children, 5-6 times nper day with the next passing to the diet №2 whether №15 (depending the age) ithe recovery period;

5.                     nOral fluids nintake corresponds to age norms (with including the IV fluids).

6.                     nAntibacterial ntherapy: for infants at presence of concomitant bacterial infection, chronic ninfection, inflammatory changes in the CBC (by the broadspectrum antibiotic iaverage therapeutic doses, a short course).

Etiologic ntherapy: specific therapy is absent.

Pathogenetic ntherapy:

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

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

• In posthypoxia period – nnootrops, vitamins group B.

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

• In case of seizures – nAnticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) 0.3-0.5 mg/kg IV, nif they are ineffective – 1 % hexenalum or thiopenthalum sodii in 3-5 mg/kg IV. nDehydration therapy: lasix 2-3 mg/kg IM or IV.

Prevention

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

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

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

to 21 day).

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

Rubella

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

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

 

Rubivirus n

 

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.                     nAn entrance ngate is the mucus membranes of nasopharynx, where virus is replicating.

1.                     nHematogenous ndistribution (viremia).

2.                     nDamage of norgans and systems.

3.                     nImmunological nanswer, recovery.

Innate Rubella:

1.                     nTransplacental ninfection of the fetus.

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

5.                     nForming of nthe development defects.

 

Diagnostic criteria of the nacquired Rubella:

• Latent period – 18-23 days.

• Prodromal period – 1-2 days:

– mild toxic syndrome;

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

– increase of posterior ncervical, occipital lymph nodes.

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

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

– toxic syndrome (mild);

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

Rubella, throat and skin changes

  

The rashes in acquired Rubella

 

Diagnostic criteria of the innate Rubella:

Classical Triad:

1.                     nCataract.

2.                     nCongenital nheart disease (open aortic channel, aortic valves defect, aortic stenosis, ncoarctation of the aorta, ventricular septal defect and pulmonary atery stenosis, natrial septal defect, large arteries transposition).

3.                     nDeafness.

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

 

Classificatioof the acquired Rubella:

By the type:

 – typical nforms;

– atypical forms (effaced, nasymptomatic).

By the nseverity:

– mild;

– moderate;

– severe;

By the ncourse:

 – smooth (uncomplicated);

– uneven (complicated).

Specific ncomplications: meningitis, encephalitis, nsynovitis.

 

Diagnosis nexample

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

 

Confirmatioof the diagnosis:

1.                     nComplete nblood test: leucopenia, lymphocytosis, plasmatic cells, normal ESR.

11.                nPCR – selectioof virus from the nasopharyngeal smears, excrements, urine, blood, saliva and nCSF.

12.                nSerologic – nNR, PHAR (stable positive result in case of the innate rubella), CBR with 4 ntimes or more increasing of the antibody tytre in dynamics.

13.                nImmune-enzyme nanalysis (ELISA test) with measuring of specific antibodies Ig M in the acute nphase (and in the innate rubella) and Ig G after the recovery (in the blood or, nif necessary, in CSF).

14.                nExpress nmethods – phase-contrasting microscopy, micro agglutination reaction.

 

Differential ndiagnosis with measles, scarlet fever, nallergic exanthema, infectious mononucleosis.

 

Treatment:

Base therapy:

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

• Hygienic regime, often room nventilation.

 • Control of fever and myalgia (when the temperature is more than 38.5-39 °C); in chilrebefore 2 mo and in case of perinatal CNS damage, seizures in the history, nsevere heart deseases – when the temperature is up to 38 °C with acetaminophe(paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 ntimes per day) or ibuprophen 10 mg/kg per dose, not often than every 6 nhours.

In case of nencephalitis, meningitis:

Base ntherapy:

• Bed regimen till body ntemperature normalization, disappearance of general cerebral and considerable nimprovement of focal neurological signs, not less than 14-16 days;

• A diet (before stable vital nfunctions is due to adequate parenteral infusion therapy);

• Brest feeding or bottle nfeeding by adopted formulas for infants, in the first day

1/2-1/3 of average volume with na next increase to the complete volume during 2-3nd days;

• A milk vegetable diet (№5) nis appointed for preschoolers or school children, 5-6 times per day with the nnext passing to the diet №2 whether №15 (depending the age) in the recovery nperiod;

• Oral fluids intake ncorresponds to age norms (with including the IV fluids);

• Antibacterial therapy: for ninfants at presence of concomitant bacterial infection, chronic infection, ninflammatory changes in the CBC (by the broadspectrum antibiotic in average ntherapeutic doses, a short course).

Etiologic therapy: specific therapy is absent.

Pathogenetic therapy:

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

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

• In posthypoxia period – nnootrops, vitamins group B;

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

• In case of seizures – nAnticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) 0.3-0.5 mg/kg IV, nif they are ineffective – 1 % hexenalum or thiopenthalum sodii in 3-5 mg/kg IV. nDehydration therapy: lasix 2-3 mg/kg IM or IV.

 

Prognosis:

• Recovery;

• Invalaidization (in case of nthe innate Rubella).

 

Prophylaxis:

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

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

 

 

n  nPassive prophylaxis to seronegative pregnant, (to nchildren does not performed).

 

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

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

meningoencephalitis, specific and nonspecific prophylaxis.

 

VARICELLA (Chickenpox)

 

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

 

ETIOLOGY.

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

VZ-Virus

 

PATHOLOGY.

Varicella begins with mucosal inoculation of virus ntransferred in respiratory secretions or by direct contact with skin lesions of nvaricella or herpes zoster. Inoculation is followed by an incubation period of n10–21 days, during which subclinical viral spread occurs. Widespread cutaneous nlesions result when the infection enters a viremic phase; peripheral blood nmononuclear cells carry infectious virus, generating new crops of vesicles for n3–7 days. VZV is also transported back to respiratory mucosal sites during the nlate incubation period, permitting spread to susceptible contacts before the nappearance of rash. The transmission of infectious virus by respiratory ndroplets distinguishes VZV from other human herpes viruses. Visceral disseminatioof the virus follows the failure of host responses to terminate viremia, which nresults in infection of lungs, liver, brain, and other organs. VZV becomes nlatent in dorsal root ganglia cells in all individuals who experience primary ninfection. Its reactivation causes a localized vesicular rash that usually ninvolves the dermatomal distribution of a single sensory nerve; necrotic nchanges are produced in the associated ganglia, sometimes extending into the nposterior horn. The histopathology of varicella and herpes zoster lesions is nidentical; infectious VZV is present in herpes zoster lesions, as it is ivaricella lesions, but is not released into respiratory secretions. Varicella nelicits humoral and cell-mediated immunity that is highly protective against nsymptomatic reinfection. Suppression of cell-mediated immunity to VZV ncorrelates with an increased risk of VZV reactivation as herpes zoster.

 

EPIDEMIOLOGY.

In the United States and other temperate climates, n90–95% of individuals acquire VZV in childhood. Annual nvaricella epidemics occur in winter and spring. Wild-type VZV strains that ncause the annual epidemics of varicella do not exhibit changes in virulence as njudged by the clinical severity of primary VZV infections from year to year. nHousehold transmission rates are 80–90%; more casual contact, such as school nclassroom exposure, is associated with attack rates of 30% or less. Varicella nis contagious from 24–48 hr before the rash appears and while uncrusted nvesicles are present, which is usually 3–7 days. Susceptible childreacquire varicella after close, direct contact with adults who have herpes nzoster; this route of transmission maintains the circulation of the virus ithe population. For unexplained reasons, varicella is much less common in tropical nareas, so that susceptibility rates among adults are as high as 20–30%. Herpes nzoster shows no seasonal variation in incidence because it is due to the nreactivation of endogenous, latent virus. Despite anecdotal reports, nepidemiologic studies demonstrate that exposure to varicella does not cause nherpes zoster. Herpes zoster is very rare in children younger than 10 yr except namong those given immunosuppressive therapy for malignancy or other diseases, nthose who have human immunodeficiency virus (HIV) infection, and those who have nbeen infected in utero or during the first year of life. The risk of severe or nlife-threatening primary or recurrent VZV infection is related primarily to nhost factors rather than variations in the pathogenicity of VZV strains.

 

CLINICAL MANIFESTATIONS OF VARICELLA.

 

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

 

  

Typical rash in varicella

 

 

Pustular rashes and hemorrhagic rashes

 

 

 Hemorrhagic nform of varicella

 

Ulcerative lesions involving the oropharynx and vagina nare common; many children have vesicular lesions on the eyelids and nconjunctivae, but serious ocular disease is rare. The average number of nvaricella lesions is about 300, but healthy children may have from fewer tha10 to more than 1,500 lesions. In secondary household cases and cases involving nolder children, more days of new lesion formation and more lesions are likely. nThe exanthem is more extensive in children with skin disorders, such as eczema nor recent sunburn. Hypopigmentation of lesion sites persists for days to weeks isome children, but scarring is unusual.

 

 An element othe palate

 

Varicella Convalescent

 

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

 

COMPLICATIONS OF VARICELLA.

 

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

 

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

 

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

 

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

 

CLINICAL MANIFESTATIONS OF HERPES nZOSTER.

 

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

 

The rash is mild, with new lesions appearing for a few ndays, symptoms of acute neuritis are minimal, and complete resolution usually noccurs within 1–2 wk. Immunocompromised children have more severe dermatomal ndisease and may experience viremia, causing pneumonia, hepatitis, encephalitis, nand disseminated intravascular coagulopathy. Severely immunocompromised nchildren, particularly those with HIV infection, may have unusual, chronic, or nrelapsing cutaneous disease, retinitis, or central nervous system disease nwithout rash. Transverse myelitis with transient paralysis is a rare ncomplication of herpes zoster. In contrast to adults, postherpetic neuralgia is nvery unusual in children.

  

 

 

The rash in herpes Zoster

 

LABORATORY FINDINGS AND DIAGNOSIS.

 

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

 

TREATMENT.

 

Acyclovir—9-[(2-hydroxyethoxy) methyl] guanine—is the ndrug of choice for varicella and herpes zoster when specific therapy is nindicated. Any patient who has signs of disseminated VZV including pneumonia, nhepatitis, thrombocytopenia, or encephalitis should receive immediate treatment nwith intravenous acyclovir. Acyclovir therapy given within 72 hr prevents nprogressive varicella and visceral dissemination in high-risk patients; the ndosage is 500 mg/m2 every 8 hr, administered intravenously for 7 days or until nno new lesions have appeared for 48 hr. Delaying antiviral treatment until nprolonged new lesion formation is evident is not an option because visceral ndissemination occurs during the same time period. Recent large, nplacebo-controlled clinical studies have shown that oral acyclovir diminishes nthe clinical symptoms of varicella in otherwise healthy children, adolescents, nand adults when it is administered within 24 hr after the appearance of the ninitial cutaneous lesions. Drug efficacy was established for all groups, but nthe clinical benefit may be considered more significant in older children and nin secondary household cases. Acyclovir therapy does not interfere with the inductioof VZV immunity.

 

Acyclovir is also effective for treatment of herpes nzoster in healthy and immunocompromised patients. Patients at high risk for ndisseminated disease should receive 500 mg/m2 nor 10 mg/kg every 8 hr intravenously. Onset of VZV reactivation reduces nthe duration of new lesion formation to only about 3 days. Oral acyclovir is aoption for immunocompromised patients who are considered at low risk for nvisceral dissemination. Antiviral drug resistance is rare but has occurred ichildren with HIV infection; foscarnet is the only drug now available for the ntreatment of acyclovir-resistant VZV infections.

 

PREVENTION.

 

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

 

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

 

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

 

The live, attenuated varicella vaccine, made from the nOka strain, is the first human herpesvirus vaccine. The live, attenuated nvaricella vaccine (Oka-Merck strain) has been given to more than 8,500 healthy nchildren and adults in clinical trials in the United States. The vaccine ninduced seroconversion rates of more than 95%, with complete protection against ndisease in 85–95% of exposures. Persistence of humoral and cell-mediated nimmunity has been documented in 94–100% of vaccine recipients monitored for 1–6 nyr. The Oka-Merck varicella vaccine can be given to children with acute nleukemia in remission, with careful attention to the status of their underlying ndisease 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 nfever, appearance on a skin, mucus membranes small vesicles

with transparent content.

 

Etiology: DNA containing Varicella-Zoster virus.

 

Epidemiology:

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

• Chickenpoxis is ntransmitted from person to person by respiratory route or by the direct ncontact.

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

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

time.

 

Pathogenesis:

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

2.                     nWith lymph nit enters to the blood and viremia develops.

3.                     nDamage of nthe skin epithelium and mucosa epithelium.

4.                     nDamage of nthe nervous system – (intravertebral ganglia, brain and cerebellum cortex, nsubcortical region).

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

 

Clinical npresentation

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

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

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

• The rashes, noften pruritic, begin as a maculae and progresses rapidly through the nstages of papule, vesicle (photo 12), and crusted lesion (photo 13). The spots nfirst appear on the face or trunk, obvious on the scalp (photo 14) and, at the nheight of the illness, are more numerous centrally than distally (photo 15). Isevere cases may be present on palms and soles (as spots and papules) (photo n16). The lesions erupt in crops for 3 to 4 days (sometimes to 7 days) and it is ncharacteristic of the rashes that lesions in different stages of development nmay be found on one area (false polymorphism) (photo 17). The vesicle is a 2 to n3 mm oval nfilled with clear fluid surrounded by an erythematous base. The fluid clouds nand a crust forms appear within 1 day. Lesions occurring on the mucous nmembranes do not crust but form a shallow ulcer (photo 18, 19). Posterior ncervical 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 ncongenital varicella syndrome in case of ninfection in the 1st trimester of pregnancy by VZ-virus – may occur embryopathies. nMaternal varicella 5-10 days before delivery result in mild chickenpox inewborn from the first days of his life. Maternal varicella 4 days or less nbefore delivery may result in severe disseminated or total chickenpox in the nnewborn.

 

Clinical nclassification

Type

• Typical forms

• Atypical forms:

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

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

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

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

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

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

 

n

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 infectio 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 – ninfection of lesions (with staphylococci as pustulosis (photo 21) or nb-hemolytic group A streptococci as erysipelas, phlegmona (photo 22) are the nmost common complications; also may be otitis, pneumonia, lymphadenitis, nstomatitis, purulent conjunctivitis and keratitis, sepsis, osteomyelitis.

 

Pustulosis

 

Phlegmona

 

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

– Rare ncomplications: idiopathic nthrombocytopenic purpura, nephritis, myocarditis, arthritis, acute adrenal ninsufficiency because of adrenal hemorrhages.

 

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

• Immune Fluorescent method;

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

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

used;

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

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

 

Diagnosis nexample: Chickenpox, typical form, nmoderate severity, complicated by

the nbilateral medial otitis.

 

Differential ndiagnosis should be performed among nearly impetigo, insect bites, scabies,

and urticarial lesions.

 

Features of nchicken pox in infants

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

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

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

·Neurotoxicosis (cramps, nmeningeal symptoms).

· Possible visceral signs.

· Frequent is secondary nbacterial infection.

 

Evidences nfor obligatory hospitalization of patients with infectious exanthema

·                        nThe severe nform of disease, when appears need in undertaking of intensive therapy; npatients with moderate forms at age before 3 years.

7.                     nSick childrefrom families with bad social-home conditions, especially in the event of nimpossibility of their isolation to prevent infections transmission.

8.                     nAbsence of nconditions for examination and treatment at home.

9.                     nSick childrefrom closed children institutions.

 

Advantages nof the home treatment

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

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

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

 

Treatment ihome conditions is possible

1. In conditions nof isolated flat.

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

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

 

Treatment

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

• Antiseptic fluids for skilesions to prevent secondary bacterial infection (1 % brilliant green, 1-2 % nKMnO4);

• Gurgling with oral antiseptic nfluids after the food intake;

• Antihistamines for itching;

• Acetaminophen for fever ncontrol.

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

n Patients with noncohematologic diseases;

n Patients after bone marrow nor inner organs transplantation;

n Patients who achieve ncorticosteroids;

n Patients with the primary nimmune deficit;

n Patients with HIV-infection;

n Inborn Chicken pox;

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

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

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

 

In case of encephalitis:

Base ntherapy:

• Bed regimen till body ntemperature normalization, disappearance of general cerebral and considerable nimprovement of focal neurological signs, not less than 14-16 days;

• A diet (before stable vital nfunctions is due to adequate parenteral infusion therapy);

• Brest feeding or bottle nfeeding by adopted formulas for infants, in the first day 1/2-1/3 of average nvolume with a next increase to the complete volume during 2-3th days;

• A milk vegetable diet (№5) nis appointed for preschoolers or school children, 5-6 times per day with the nnext passing to the diet №2 whether №15 (depending the age) in the recovery nperiod;

• Oral fluids intake ncorresponds to age norms (with including the IV fluids);

• Antibacterial therapy: for ninfants at presence of concomitant bacterial infection, chronic infection, ninflammatory changes in the CBC (by the broadspectrum antibiotic in average ntherapeutic doses, a short course).

Etiologic ntherapy:

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

• In meningitis IV acyclovir n10-15 mg/kg 3 times per day during 5-7 days.

Pathogenetic ntherapy:

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

• vascular medicine (penthoxyphyllin, nnicergolin and others like that);

• In posthypoxia period – nnootrops, vitamins group B.

• In case of CSF hypertensio– dehydration by 25 % MgSO4 IM, lasix 1-3 mg/kg IV or IM, acethazolamid orally.

• In case of seizures – nAnticonvulsant therapy: benzodiasepins (seduxenum, sibasonum)

0.3-0.5 mg/kg IV, if they are nineffective – 1 % hexenalum or thiopenthalum sodii

in 3-5 mg/kg IV. Dehydratiotherapy: lasix 2-3 mg/kg IM or IV.

 

Prevention:

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

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

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

after exposure).

 

Key words nand phrases: Varicella-Zoster, chickenpox, npolymorphism, congenital

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

immune globulin, nimmunocompromised children.

 

HERPES VIRUS INFECTION

 

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

 

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

 

Herpes nzoster is the viral disease, that is ncaused by the Varicella-Zoster virus, is characterized by inflammation of nintravertebral or cranial nerves nodes and is shown up by a vesicles rash on a nskin along the nerves and symptoms of intoxication.

 

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

 

Epidemiology:

• The source are npatients and virus carriers;

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

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

• Seasonality: infectiomore 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 iintravertebral ganglia, ganglia of cerebrum).

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

· Relapses (on a background of URT viral infections, ultraviolet irradiation, ncooling).

 

Herpes nSimplex diagnostic criteria

• Latent period is 2-14 days.

• Acute beginning, toxic nsigns.

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

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

• Skin damage (lips (photo n26), nose (photo 27), eyelids, face, hands, other localization) – painful npapules on the red base, than their evolution to small vesicles with the ntransparent content, they may be connected, clouding of the content, erosions, ncrusts formation.

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

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

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

• Relapsed course.

 

stomatitis

 

Stomatitis

 

 

Skin damage

 

 

Skin damage

 

 

 

Herpetic whitlow

→→→→

 

Herpes Zoster diagnostic ncriteria

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

• Acute beginning from high nbody temperature, toxic signs.

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

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

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

 

 

Additional ninvestigations

• Virology research of nvesicular content, nasopharyngeal smears.

• IF method, PCR.

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

• CSF investigation (in case nof meningoencephalitis signs).

 

Diagnosis nexample: Herpes Simplex 1st type local nform: stomatitis, severe degree.

 

Differential ndiagnostics with herpangina, enterovirus nencephalitis, adenoviral keratoconjunctivitis, chicken pox, streptococcus nimpetigo, erysipelas, eczema, mumps

encephalitis.

 

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

 

Treatment:

Local damage nof the skin and mucous membranes:

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

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

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

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

• ultraviolet irradiation.

Keratitis:

• locally n5-iodine-2-desoxyuridin, adenine arabinosid.

 

In severe forms (encephalitis):

Etiologic ntherapy:

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

Pathogenetic ntherapy:

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

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

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

• In case of seizures – nAnticonvulsant therapy: benzodiasepins (seduxenum, sibasonum) 0.3-0.5 mg/kg IV, nif they are ineffective – 1 % hexenalum or thiopenthalum sodii in 3-5 mg/kg IV. nDehydration therapy: lasix 2-3 mg/kg IM or IV;

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

Base ntherapy:

• Bed regimen till body ntemperature normalization, disappearance of general cerebral and considerable nimprovement of focal neurological signs, not less than 14-16 days;

• A diet (before stable vital nfunctions is due to adequate parenteral infusion therapy);

• Brest feeding or bottle nfeeding by adopted formulas for infants, in the first day 1/2-1/3 of average nvolume with a next increase to the complete volume during 2 – 3th days;

• A milk vegetable diet (№5) nis appointed for preschoolers or school children, 5-6 times per day with the nnext passing to the diet №2 whether №15 (depending the age) in the recovery nperiod.

Antibacterial ntherapy: in case of possible nconcomitant bacterial infection (by the broadspectrum antibiotic in average ntherapeutic doses, as cephalosporines 3rd generation or aminoglycosides 3rd ngeneration).

Irehabilitation period:

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

• In posthypoxia period – nnootrops, vitamins group B.

 

In case of nrelapsed course:

· adaptogens (eleutherocock, npyrogenal and other);

· vitamins of group B (B1, B2, nB12);

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

daily during 5-10 days;

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

At secondary nbacterial infection: (penicillins, ncefalosporins, aminoglycosides).

 

Prophylaxis:

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

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

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

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

• Delivery by the caesareasection at Herpes simplex 2 infection.

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

• Ventilation and moist ncleaning up.

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

 

Key words nand phrases: Varicella-Zoster, Herpes nsimplex, polymorphism, congenital herpes syndrome, multinuclear giant cells, nacyclovir, Varicella-Zoster immune globulin, immunocompromised children.

 

References:

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

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

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

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

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

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