Lecture 1. Infectious diseases with exanthema syndrome

 

Exanthema – rashes on the skin, which occurs in many infectious diseases. Some rashes are typical only for one disease; other may be present in several diseases. They differ by the rash morphology, localization, time of appearing, and dynamics of development. That’s why it is very important to differentiate them and perform right diagnosis for adequate etiological and pathogenetical treatment.

 

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

 

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

   genus Morbillivirus.

  

Epidemiology:

– 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).

– Infection is spread by inhalation of large and small airborne droplets.

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

 

Pathogenesis:

·        The primary site of infection is the respiratory epithelium.

·        Local replication followed by viremia. During this phase, virus is spread by leukocytes to the reticuloendothelial system.

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

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

 

Clinical presentation   

1.     The incubation period is 10 – 14 (from 9 to 21) days.

2.     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.

3.     Exanthema period: Second increase of temperature. Initial lesions are noted 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.

4.     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 duration:    – 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;

                                      – digestive system;

                                      – nervous system;

                                      – eyes;

                                      – ears;

                                      – skin;

                                      – urinary system.

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 titer 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 2^nd 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, Rheumathoid arthritis systemic form, and allergic rashes.

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

                           

Cool allergy

 

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

3.     vitaminized milk-vegetable food;

4.     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.

5.     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

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

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

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

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

10.  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: steroids, dehydrates, parenteral detoxication (albumin, plasma), anticonvulsants.

 

  Prevention

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

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

3.     Nonspecifically: – isolation of ill person until 5^th day of the exanthema period, isolation of contact person from 8 to 21 day after exposure.

 

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.

 

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.

2. hematogenous distribution (viremia).

3. Damage of organs and systems.

4. Immunological answer, recovery.

Innate Rubella:  

1.     Transplacental infection of the fetus.

2.     destruction of the cells by the virus, violation of the correct organs’ development.

3.     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)

– toxic syndrome (mild)

– increase of  cervical, occipital lymph nodes (rarer – polyadenopathy)

 

Diagnostic criteria of the innate Rubella:

Classical Triad:        

1.     Cataract

2.     Inborn heart disease (open aortic channel, aortic valves defect, aortic stenosis, coarctation of aorta, intraventricular septal defect and pulmonary atery stenosis, intraatrial septal defect, large arteries transposition)

3.     Deafness

Exept enumerated:

ü Microcephalus

ü Microphthalmia

ü Rhetinopathy

ü Cornea clouding

ü Glaucoma

ü Clift palate

ü Intersticial pneumonia

ü Hepatitis

ü Myocarditis

ü Meningoencephalitis

ü Damage of the vestibular organ

ü Yrinary tract and sexual organs defect

ü Dermatitis

ü Thrombocytopenia

ü Hemolytic anemia

ü Hypogammaglobulinemia

ü Secondary immune deficit

ü Low birth weight

 

Classification of the acquired Rubella:

By the type:  typical forms 

    atypical forms (effaced, asymptomatic)

 

By the severity:     ­- mild

– moderate

– severe

 

By the duration:     – 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

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

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

4.     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)

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

 

Differential diagnosis with measles, Scarlet fever, allergic exanthema, infectious mononucleosis (see Measles)

 

Treatment:

Basic therapy:

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

ü Hygienic regime, often room ventilation

ü 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:

ü Glicocorticoids 2-5 mg/kg/day (equivalent to prednisone)

ü IV detoxication 50 ml/kg/day (5% glucose, 0.9% NaCl not more than 20 ml/kg on 1 infusion)

ü lasix 1-3 mg/kg

ü seduxen 0.3 mg/kg (if indicated)

ü trental, curantil, cavinton (0.2-0.5 ml/kg)

ü noothropil (50 ml/kg/day)

Etiologic therapy:

·        Preparations of recombinant interferon (in case of acquired Rubella with the CNS defeat, innate Rubella)

 

Prognosis:

·        Recovery

·        Invalaidization (in case of the innate Rubella)

 

Prophylaxis:

·        Isolation of patients on 4 days from the disease beginning, new-born with innate German measles – 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).

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

 

 

VARICELLA (Chickenpox)

 

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).

·        Chickenpox spread 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 2^nd 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 persons.

 

Clinical presentation. 

·        The incubation period ranges from 10 to 21 days (most cases 14-17days).

·        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), and crusted lesion (photo). The spots first appear on the face or trunk, obvious on the scalp (photo) and, at the height of the illness, are more numerous centrally than distally (photo). In severe cases may be present on palms and soles (as spots and papules) (photo). 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). 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). Posterior cervical lymph nodes usually are enlarged (photo).

 

The congenital varicella syndrome may develop, in babies whose mothers have clinical varicella before 29 weeks gestation. 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:

ü 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)

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

ü 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

ü 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

ü 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 3.      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:

ü Secondary bacterial – infection of lesions (with staphylococci as pustulosis (photo) or b-hemolytic group A streptococci as erysipelas, phlegmona (photo) are the most common complications; also may be otitis, pneumonia.

 

 

ü 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, less  common – Guillain-Barre syndrome, transverse  myelitis, optic neuritis, and facial  nerve  palsy.

ü Rare complications: idiopathic thrombocytopenic purpura, nephritis, myocarditis, arthritis.

 

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.

 

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.

 

Treatment

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

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

ü Gurgling with oral antiseptic fluids after the food intake

ü antihistamines for itching;

ü 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:

§  Patients with oncohematologic diseases

§  Patients after bone marrow or inner organs transplantation

§  Patients who achieve corticosteroids

§  Patients with the primary immune deficit

§  Patients with HIV-infection

§  Inborn Chicken pox

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

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

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

In case of encephalitis

ü acyclovir,

ü parenteral detoxication,

ü dexamethasone 0.15 mg/kg 4 t.d. (every 6 hours) for 4 days,

ü dehydration with mannitol 1-1.5 g/kg,

ü symptomatic treatment.

Prevention:

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

2.     To isolate contact persons from 9 till 21 day after exposure.

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

 

The Herpetic 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 rash 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

Epidemiology   

·   The source are patients and virus carriers

·   The way of transmission 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.

·   Winter seasonality is typical (for HSV 2).

 

Pathogenesis    

1.     An entrance gate is the injured mucus membranes and skin.

2.     Reproduction of virus.

3.     Local changes.

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

5.     viremia

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

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

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

 

Herpes Simplex diagnostic criteria

·        Latent period is 2–14 days,

·        Acute beginning, toxic signs.

·        Mucosa membranes damage (gingivitis, stomatitis (photo), tonsillitis) as vesicles, that ruin, forming erosions, accompanied by the pain.

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

·        Skin damage (lips (photo), nose (photo), 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 duration.

 

 

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 1^st,  on the 2^nd 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), than hyperemied base pales, epithelization ® slight hyperpigmentation (in a week).

 

Additional investigations

·        Virology research of vesicular content, nasopharyngeal smears

·        IF method, PCR

·        serology: BCR, IEА, PHAR, NR with paired sera (growth of antibodies title in the dynamics)

·        CSF investigation (in case of meningoencephalitis signs).

 

Diagnosis example: Herpes Simplex 1^st 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 (aspirin 50-100 g/kg)

·         ultraviolet irradiation

Keratitis:

·         locally 5-iodine-2-desoxyuridin, adenine arabinosid

In severe forms (visceral, spread, encephalitis):

·         bonaphton 0,025 х 2 (4) times per days 5-7 days with simultaneous local application of bonaphton ointment 3-4 times per day, 10-15 days

·         5-iodine-2-desoxyuridin intravenously 50 mg/kg per day in 50 ml of 5% glucose solution 4-6 times per days, 5 days

·         adenine arabinosid, acyclovir, virolex, ghancyclovir, ribavirin 15 mg/kg per day, 7-10 days

In case of relapsed duration:

·        adaptogens (eleutherocock, pyrogenal and other)

·        vitamins of group B (В1, В2, В12)

·        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 on a year

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

In case of encephalitis, meningoencephalitis also glicocorticoids (1-2 mg/kg by prednisolone).

 

Prophylaxis:

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

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

·         Carrying of masks by mothers-wet nurses in case of Herpes simplex 1, observance of hygienic norms.

·         To infected pregnant enter immunoglobulin IM 0.2 ml/kg.

·         Caesar section at Herpes simplex 2 infection in pregnant.

·         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.

 

Scarlet Fever

 

Scarlet fever is an acute infectious disease, that is caused by group A b hemolytic streptococcus, is transmitted by an air-droplet way, is characterized by intoxication, rashes on a skin, tonsillitis, regional lymphadenitis, and strawberry tongue.

 

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

 

Epidemiology:

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

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

–         Susceptible organism – children 2-9 years old.

 

Pathogenesis

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

 

Pathogenesis has three lines:

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

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

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

 

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

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

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

 

Clinical diagnostic criteria:

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

2.  Initial or prodromal period (from the first signs of illness to rashes appearance): up to 1 -2 days

·        acute beginning;

·        toxic syndrome, hyperthermia;

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

·        catarrhal regional lymphadenitis (photo).

 

3.  Period of exanthema (rashes):

а) Phase of height (1 – 2 days)

·        maximal intoxication, fever up to 39 – 40 °С;

·        tonsillitis: bright hyperemia of the throat marked off  a hard palate (photo), pin-point enanthema, hypertrophied tonsils, catarrhal, lacunar (photo), follicle (photo) or necrotizing (photo) tonsillitis;

·        regional lymphadenitis;

·        pin-point rashes for a few hours spread all over the body, intensified on the front and lateral surface of neck, lateral surfaces of trunk (photo), abdomen (photo), lumbar region (photo), iatural skin folds (photo), on the red background of skin, typical intensified in skin folds with hemorrhagic elements (Pastia’s lines) (photo), a skin is rough (“sand paper” sign), pale perioral triangle (Filatov’s sign) (photo)

·        white dermographysm;

·        coated tongue (photo) within 2-3 days clears up (photo), on 4th – 5th day becomes  “strawberry” (photo);

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

 

 

b) Fading phase:

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

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

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

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

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

·        a tongue turns pale till 10th – 12th day, keeps expressed follicles.

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

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

·        tongue with enlarged follicles;

·        the vagus-phase of scarlet fever heart remains for 2-4 weeks;

·        rise sensitivity to the streptococcus infection, possibility of complications

 

Classification

1.  Form:   a) typical;

   b) atypical:

·        without rashes;

·        effaced;

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

·        with aggravated symptoms (hypertoxic, hemorrhagic).

2.  Severity:      a) mild;

b) moderate;

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

3.  Duration:    a) smooth;

b) uneven (relapses, complications).

 

Complications

By the character:

·        are infectious (streptodermia (photo), necrotizing tonsillitis (photo), secondary tonsillitis, peritonsilitis (photo) peritonsilar abscess (photo), otitis, purulent lymphadenitis, sepsis);

·        and allergic (rheumatism, myocarditis, arthritis, nephrite).

By the time of development:

·        early (first week of the disease);

·        late (2nd – 3rd week).   

By the etiology:

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

·        secondary (caused by the other bacteria).     

 

 

Laboratory tests

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

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

3.      The complete blood cell count is helpful: usually white blood cell count higher 12500 cells/mm³, neutrophyllosis, left shift, eosynophylia, elevated ESR.

 

Diagnosis example:

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

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

 

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

Treatment  

1.     Bed regime during an acute period.

2.     Etiological treatment for scarlet fever is:

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

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

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

3.     Detoxication therapy:

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

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

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

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

6.     Control of fever (when the temperature is more than 38.5-39˚C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours.

7.     Local treatment with antiseptic fluids (gurgling), UV-insolation.

 

Patient may go home from infection department not earlier the 10^th day of the illness, in 10 days blood analysis, urinalyses, ECG must be done.

 

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

 

YERSINIA PSEUDOTUBERCULOSIS

 

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

Etiology: Yersinia pseudotuberculosis, gram-negative bacillus

 

Epidemiology:

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

·        Way of spreading – alimentary;

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

 

Pathogenesis:

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

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

3.     Regional lymphadenitis (regional infection).

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

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

6.     Immunological response, recovering from disease.

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

 

Clinical criteria

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

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

·        Rashes: maculopapulous (like in scarlet fever), may be erythematosus.

ü The eruption is characterized by dusky red, tiny papules.

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

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

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

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

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

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

·        Dyspepsia: nausea, vomiting, liquid feces.

·        Hepatomegaly, rare – splenomegaly, lymphadenopathy.

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

·        Hepatitis with or without the jaundice.

·        Toxic myocarditis.

·        Toxic nephritis, pyelonephritis.

·        Bronchitis or pneumonia may also develop.

 

 

Clinical forms classification

 

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

 

Diagnosis example:

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

 

Features of pseudotuberculosis at the children of early age

·        High and prolong fever;

·        expressed hepatolienal syndrome;

·        systemic increase of lymphnodes;

·        dyspeptic syndrome;

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

·        rarely: scarlatina rashes, damage of joints;

·        prolong,  undulating duration with exacerbation and relapses;

Frequent complications.

 

Laboratory finding 

ü Complete blood analyses: leucocytosis, neutrophyllosis with left shift, eosynophylia, ERS is enlarged.

ü Bacteriological – Yersinia Pseudotuberculosis may be found in feces, urine, blood and mucus.

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

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

 

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

 

 

Treatment

Children with mild form of pseudotuberculosis may be treated at home symptomatically without the etiological medicine.

Hospitalization is obvious for:

ü Children with moderate form of pseudotuberculosis

ü Children with severe form of pseudotuberculosis

Regimen

ü half-bed regimen in mild cases,

ü bed regimen in moderate cases

ü straight bed regimen in severe cases

Diet:

ü Icteric (jaundice) form – N 5

ü Abdominal (intestinal) form – N 4

ü Other forms – N 15

 

Etiological:

·        By chloramphenicol (orally) 10-15 mg/kg 3 or 4 times per day during all period of pyrexia and plus 3 days (average duration is 14 days).

·        Alternative antibiotics (Reserve): cefalosporins of the 3^rd or 4^th generation (IM, IV),

·        In severe cases combination together with aminoglycosides of the 3^rd generation (IM, IV).

Pathogenetical:

·        Disintoxication: oral with large amount of alkaline fluids (in mild cases), or parenteral with glucose-saline solutions (in moderate, severe cases);

·        Protease inhibitors (contrical 10-20 IU/kg),

·        Glicocorticoids 1-3 mg/kg (in equivalent to prednisolone) as a short course 3-5 days (in severe cases), for 2-4 wks in case of myocarditis,

·        Control of fever and myalgia (when the temperature is more than 38.5-39˚C); in children before 2 mo and in case of perinatal CNS damage, seizures in the history, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not often than every 6 hours.

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

·        NSAIDs in case of arthritis, carditis, nodular erythema (ibuprophen, aspirin, voltaren, indomethacin in average doses).

 

Prophylaxis:

1.     Deratization, disinfection.

2.     Right keeping of products.

3.     Looking after persons from the epidemic focus for 18 days with bacteriological investigation.

 

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

 

Material has been prepared by Associate Professor I. L. Horishna, MD, PhD

Assistant V. B. Furdela, MD, PhD