respiratory viral infections

ACUTE RESPIRATORY VIRAL INFECTIONS

Main Statements ARVI is the group of infectious diseases which includes known for a long time

viruses (influenza virus) and recently discovered ones (bocavirus, metapneumovirus) which are transmitted predominantly by airway route and which damage respiratory tract mucosa

The highest morbidity of ARVI is seen in 6 months-3 years of age children Influenza virus A is prone to mutations by mechanisms of antigenic shift and drift Viremia is possible, but it plays a role in pathogenesis of only adenoviral infection Majority of diseases in immunocompetent people have spontaneous recovery Effective etiotropic drugs are rimantadine, oseltamivir (for influenza), ribavirin

(for RS infection) The only indication for antibiotic prescription at ARVI is development of bacterial

complications Vaccination prevents development of influenza

ARVI is a group of infectious diseases caused by viruses with airborne way of

transmission which are characterized by symptoms of infectious toxicosis and

predominant involvement of respiratory tract mucosa.

Etiological structure of ARVI in children.

Causative agent Children under 2 years Children older than 2 years

Influenza 10%-15% 40%-50%

Parainfluenza 20%-30% 7%-10%

Rhinovirus 20% 50%

RS-virus 25%-30% 7%-10%

Metapneumovirus 3%-10% 25%-33%

Bocavirus 35%-60% 3%-20%

Adenovirus 10%-15% 12%-15%

Other viruses До 5% До 10%

Influenza

Influenza (Flu) is an acute infectious disease caused by different serotypes of

influenza virus and characterized by damage of respiratory tract and intoxication.

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Etiology. Virus of influenza belongs to family Ortomixoviruses, contains

RNA. Virion has spherical form of 80-120 nm in diameter. According to

differences of inner antigens (nucleoprotein and matrix protein), influenza virus is

divided into three types: А, В, С. Types А and В belong one genus, type С to

another. Particularity of influenza A virus is instability of antigenic properties of

superficial proteins: hemagglutinin (Н) and neuraminidase (N). Pointed mutations

of hemagglutinin and neuraminidase, which lead to changes in immunological

properties of the virus, are called antigenic drift. Mutations which simultaneously

cause changes of two antigens and appearance of new combination of H and N, are

called shift. Drift occurs every 2-3 years whereas shift is observed once every 20-

30 years. Drift provides evolvement of epidemics of influenza whereas shift is

responsible for pandemics. For influenza A virus currently 16 subtypes of

hemagglutinin (Н1-Н16) are described and 9 subtypes of neuraminidase (N1 - N9).

3 subtypes of hemagglutinin (Н1, Н2, Н3) and 2 subtypes of neuraminidase (N1

and N2) cause disease in humans. Other subtypes of influenza A viral antigens

cause diseases in animals and birds. However, in the world, cases of human

infections with subtypes (Н5N1, Н7N2, Н9N2, Н7N3, Н7N7) of avian influenza A

virus are described. Influenza B virus is prone to lesser changeability and influenza

C virus has constant antigenic structure.

Epidemiology. The source of influenza infection is only sick person with

overt, low-grade and subclinical forms of the disease.

The way of transmission is airborne. Maximal contagiosity is observed at the

first days of the disease when during coughing and sneezing the virus is excreted

into outer environment with droplets of mucus. Viral excretion at uncomplicated

course finishes before the 5th day from disease onset. At the same time, if

pneumonia complicates the course of influenza, the virus persists in the body till 2-

3 weeks from disease onset.

Epidemics caused by influenza A virus are repeated every 2-3 years and have

outbreak character. Disease morbidity reaches its peak on the 2-3rd week.

Epidemics continue 2-3 months and finish as abruptly as they begin. Epidemics of

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influenza B spread more slowly, continue 2-3 months and affect not more than

25% of population. Influenza C does not produce epidemic outbreaks; the disease

cases are only sporadic.

Influenza A pandemias appear once per 10-40 years and affect 30%-50% of

global population.

Influenza affects all age groups and has distinct seasonality. Maximal

morbidity is in winter season.

Pathogenesis. Leading role belongs to epithelial tropic and neural toxic

actions of influenza virus. Entering upper respiratory tract mucosa, the virus

penetrates epithelial cells where it replicates; replication is accompanied by cell

damage unless dystrophy. Antigens are produces during this process, which

“provoke” cytotoxic reactions. They are pointed to organization of damaged foci

and elimination of affected cells and viral antigens. Morphologically it presents

with local inflammation; clinically with catarrh of upper respiratory tract.

Capillaries and precapillaries are affected until their complete paresis, which leads

to slowing down of blood flow. Due to increased vessel permeability brain edema

can develop. Due to microcirculation damage, hemodynamic disturbances in

different organs and systems develop; the latter are the leading points in

pathogenesis of severe forms of influenza in children.

Prominent circulatory disturbances in CNS cause development of

encephalopathy. In lungs they cause segmental or polysegmental hemorrhagic

edema. General toxic action of influenza virus inhibits both cellular and humoral

parts of immunity. This inhibition, together with elimination of protective function

of superficial epithelium and depression of local factors of immune system,

promotes activation of saprophytic bacterial infection in respiratory tract.

Processes of sensitization with viral antigens, products of semi-destruction of

epithelial cells and bacterial antigens play role in pathogenesis of influenza. At the

presence of previous sensitization this can lead to appearance of allergic and

autoimmune reactions: influenza encephalitis, polyradiculoneuritis, polyarthritis,

myocarditis, glomerulonephritis, etc.

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Considerable changes at influenza are seen in respiratory tract with

predominant involvement of larynx, trachea and large bronchi. Dystrophic changes

of respiratory mucosa epithelium with further detachment are typical. In

pulmonary tissue blood flow disturbances with small hemorrhages and presence of

serous fluid in some alveoli are mainly detected. Small hemorrhages can be seen in

pleura, under epicardium and in other organs. In case of bacterial superinfection,

viral-bacterial pneumonia can develop.

Severity of lung damage caused by respiratory viruses depends on alveolar

antigenic load and intensity of CD8 Т-cell response of immune system. CD8 Т-

lymphocytes play the key part in eradication of the virus from macroorganism; this

process is accompanied by release of a number of biologically active substances:

perfolin, CD95L, IFN, TNF. At the same time these substances (first of all

IFN, TNF) cause damage of lung tissue. If bacterial superinfection is not joined,

restoration of these epithelial cells occurs during the following 3-5 days. However,

complete recovery of cilia unction and adequate mucus production continues at

least 2 weeks. Main particularity of respiratory tract reparation process is

metaplasia of mucosal cylindrical epithelium and vessel reticulum, which is most

intense in trachea.

Clinical manifestations. For typical form of influenza the combination of two

leading syndromes is characteristic: general intoxication and catarrhal

inflammation of upper respiratory tract. Atypical forms include low-grade

(afebrile, acatarrhal) and hypertoxic forms of influenza.

Incubational period is between several hours and 1-2 days. The disease begins

acutely with chills and fever till 380С-400С. Chills are rapidly changed by feeling

of heat. General weakness, headache with predominate localization in forehead and

temporal areas are typical. The patient suffers from pain in eyeballs, muscles, light

phobia, malaise, sweating, sleep disorders, ear tinnitus. In severe cases nausea,

vomiting and decreased consciousness are observed.

Fever continues 3-5 days. Face hyperemia, sclera vessel injection, moderate

lip cyanosis and eye shining attract attention. The skin is hot to palpation and

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moist. Previous tachycardia is substituted for bradycardia. During heart

auscultation decreased II tone and sometimes functional systolic murmur at apex

are heard.

Diffuse inflammation of respiratory tract is seen (rhinopharyngitis, laryngitis,

tracheitis). Mucosa of nasopharynx, soft and hard palate is hyperemic and

edematous. At influenza B granular palate enanthema appears – Morozkin

symptom. Nasal congestion without rhinorrhea is observed. Typical signs of

laryngotracheitis include feeling of irritation or pain behind sternum and along

trachea, persistent dry cough. The face becomes red, eye conjunctiva is hyperemic;

lacrimation is seen. Temporal improvement of condition is only seen after

discharge of small amount of mucus.

If influenza course is not complicated, in 2-3 days the patient begins to

recover: fever decreases, cough becomes softer, headache and myalgia disappear.

General weakness and malaise can remain for several more days and longer.

Catarrhal syndrome disappears later.

Hypertoxic form of influenza is characterized by prominent general

intoxication: hyperthermia, neurological symptoms (dizziness, loss of

consciousness, seizures, meningeal signs), hemorrhagic syndrome (nasal

bleedings, petechial rash on face and upper part of trunk, vomiting with “coffee

grounds”, hemorrhagic lung edema, microhematuria), disturbances of

cardiovascular function (prominent tachycardia or bradycardia, muffled heart

sounds, systolic murmur, arrhythmias, decreased blood pressure). Development of

hemorrhagic lung edema is the most common cause of death at influenza.

Influenza in newborns and 1st year of age children. The disease often

begins gradually with mild fever. Intoxication symptoms are absent or are not so

prominent. Clinically the disease presents with skin paleness and refusal of

feeding. Catarrhal signs (cough, nasal congestion, heavy breathing through the

nose) are mild. However, in spite of mild primary clinical signs of influenza, the

disease course in 1st year old children is usually severe due to frequent joining of

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bacterial infection and development of purulent complications (otitis, pneumonia,

etc.). Mortality in this age is three times higher than in older children.

Influenza course in children from 1 to 3 years of age is especially severe

with prominent intoxication, frequent development of meningeal and encephalitic

syndrome, segmental lung damage, croup and asthmatic syndrome.

Diagnosis. Diagnosis of influenza can be made based on presence of typical

disease presentations, especially during epidemic outbreaks:

- acute onset;

- fever till 38.0 – 400С, sometimes it can be subfebrile or absent;

- prominent symptoms of general condition disturbance which develop during

the first days of the disease (headache, pain in muscles, joints, eyeballs,

hyperesthesia, malaise, adynamia, vomiting);

- hemorrhagic syndrome is possible: nasal and other bleedings, petechial rash

on the face, neck and upper part of the trunk;

- moderate signs of rhinopharyngitis (nasal congestion, moderate serous nasal

discharge, discomfort and pain in the throat, hyperemia of posterior

pharyngeal wall, soft palate with vessel injection and petechial hemorrhages

on the mucosa);

- sclera vessel injections;

- signs of tracheitis (dry, painful cough with retrosternal pain);

- sometimes diarrhea and vomiting can be present.

In the period between epidemics, as well as for diagnosis of atypical forms of

the disease, laboratory methods of investigation are used.

Paraclinical investigations at influenza.

1. Detection of viral antigen in nasopharyngeal washing with the reaction of

immune fluorescence and immune chromatography analysis;

2. Detection of viral antibodies with the reaction of complement fixation and

reaction of hemagglutination delay. The method of paired serum is used: 4-fold

antibody titer increase during 10-14 days is diagnostic;

3. Molecular genetic methods (PCR for detection of hemagglutinin (Н));

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4. Virusological methods – isolation of influenza virus;

5. Electronic microscopy.

Virologic diagnosis and electronic microscopy due to time and effort

difficulties currently are only used for scientific goals.

Complications of influenza.

Respiratory complications:

- acute bronchitis;

- secondary bacterial pneumonia;

- primary viral pneumonia;

- exacerbation of bronchial asthma;

- exacerbation of chronic diseases of respiratory tract;

- pulmonary abscess;

- lung empyema;

- sinusitis.

Non-respiratory complications:

- febrile seizures;

- otitis media;

- sepsis;

- myositis;

- myocarditis;

- Rey syndrome;

- encephalitis;

- myelitis;

- Guillain-Barre syndrome.

Parainfluenza

Parainfluenza is аn acute respiratory viral disease caused by different

serotypes of parainfluenza virus, characterized by involvement of upper and

medium parts of respiratory tract, predominantly larynx and trachea, with

presentation of moderate intoxication and catarrhal syndrome.

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Etiology. Parainfluenza virus belongs to family Paramyxoviridae, genus

Paramixovirus, which includes 5 types of human parainfluenza virus, Sendai virus

and Newcastle disease virus.

Main serotypes of parainfluenza virus are:

- parainfluenza virus type 1 (PI1) which includes hemadsorbing virus (НА1)

and Sendai virus with antigenic similarity;

- parainfluenza virus type 2 (PI2);

- parainfluenza virus type 3 (PI3);

- parainfluenza virus type 4 (PI4).

The most studied are parainfluenza viruses of 1st, 2nd and 3rd types. Serotypes

1 and 2 are associated with development of stenosing laryngitis; serotype 3 is

associated with damage of lower respiratory tract. Serotypes 4 and 5 involve both

upper and lower respiratory tract.

In the outer environment the viruses are not stable. They lose their activity at

room temperature in 2-4 hours, they are inactivated at +500С during 30-60 minutes,

lose virulence under the action of ether, ultraviolet radiation, chloroform,

proteolytic enzymes. In frozen condition at -60-700С the virus preserves activity

during several months and years.

Epidemiology. Susceptibility to parainfluenza is high, especially among

early age children. Index of contagiosity is 55-95%. Diseases caused by

parainfluenza are diagnosed in all age groups but children of the first 3 years of life

are predominantly affected.

Typical increase of parainfluenza morbidity is observed since October till

April with peak in February and March. Between influenza epidemics the

morbidity of parainfluenza infection posses the first place in respiratory pathology

of children.

The source of infection is sick person who is contagious during 7-10 days.

Infection is transmitted by airborne route.

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The immunity is type-specific and short-lasting (its duration in the mean is 6

months), that’s why the child can have parainfluenza infection several times during

a year.

Pathogenesis. Entrance route for the infection is respiratory tract mucosa,

where the virus is replicating; most often larynx is affected. Dystrophy, more

seldom necrosis of cilia epithelium develops; barrier function of respiratory tract

mucosa is decreased. After replication the virus and its metabolites are absorbed

into blood causing general intoxication. Viremia at parainfluenza infection is short-

lasting, but immune complexes can precipitate in capillaries, causing different

immune pathologic reactions.

The most prominent inflammatory changes at parainfluenza are seen in

nasopharynx and larynx. Parainfluenza viruses of 1st and 2nd types are more often

fixated in larynx and trachea; viruses of the 3rd type damage lower parts of

respiratory tract in early age children.

Due to inhibition of immune system functional activity and destruction of

cilia epithelium caused by parainfluenza virus, favorable conditions for joining of

bacterial flora are created with further development of secondary complications.

Parainfluenza infection causes type specific immunity for several months

but practically does not protect from repeated infection with other serotypes of

parainfluenza virus. Parainfluenza in children older than 3 years of age with

antibodies in blood has milder and shorter course than in younger children.

Clinical manifestations. Incubational period is 1-7 days (in the mean, 3-4

days).

Primary period (prodromal) is almost absent.

Period of height. The disease begins with mild intoxication (malaise,

decreased appetite, headache, seldom vomiting) and moderate catarrhal syndrome

with symptoms of rhinitis, pharyngitis, laryngitis. Abundant serous mucous nasal

discharge, pharyngeal and hyperemia, prominent and long-lasting dry cough and

coarse voice are observed. Subcordal stenosis and false croup can develop. Unlike

influenza, intoxication symptoms are milder; in older age children general

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condition can often be disturbed mildly or can be normal. Fever up to 38-38.50С

continues till 3-5 days, though it can be subfebrile or even absent. Recovery is

delayed till 2-3 weeks due to long-lasting rhinitis and persistent cough.

In recovery period, which begins in 7-14 days from disease onset, there is

increased susceptibility of the children to bacterial infections due to decreased

immunity.

Particularities of influenza course in children under three years of age

and in immunocompromised children. Children can develop parainfluenza since

birth. During the first year of life the infection with the 3rd type of the virus is seen

most often. Gradual disease onset with normal temperature or short-term subfebrile

fever is typical for it. Intoxication at parainfluenza infection in this age group can

be prominent and accompanied by anorexia, adynamia, repeated vomiting and

seizures.

Catarrhal syndrome is moderate but long-lasting; laryngitis seldom

develops. In children of the first 4 months of age the syndrome of false croup is

almost never diagnosed. In majority of this age children the course of

parainfluenza infection is complicated by development of viral and bacterial

diseases (bronchitis, bronchiolitis, pneumonia).

Complications. Specific: stenosing laryngotracheitis (false croup) and

obstructive bronchitis. Non-specific: bronchitis, bronchiolitis, pneumonia, otitis,

etc.

Diagnosis.

1) clinical signs:

- typical epidemiological history (contact);

- age more often 1-5 years;

- acute onset;

- moderate intoxication;

- prominent catarrhal syndrome;

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- typical clinical signs - laryngitis syndrome which develops at the beginning

of the disease: “barking” cough, coarse voice, loud breathing with impeded

inspiration.

2) laboratory signs:

- virusological investigation (virus extraction on cell culture);

- express methods: immunoenzyme, immunofluorescent;

- serological methods (reaction of indirect hemagglutination, reaction of

complement fixation, reaction of neutralization, immunoenzyme analysis,

immunochromatographic analysis). Investigation is performed in paired serum

taken with interval of 10-14 days. Confirmatory is 4-fold titer and higher increase

(retrospective method);

- non-specific methods: complete blood count in acute period of the disease

shows leucopenia and lymphocytosis are seen;

Etiological diagnosis is confirmed by laboratory investigation. At its absence

the diagnosis of “ARVI” is made and its leading clinical syndrome is pointed out.

Adenoviral infection

Adenoviral infection is an acute infectious disease caused by different

serotypes of adenovirus with airborne way of transmission which is characterized

by predominant involvement of nasopharynx, conjunctiva, lymphoid tissue, with

signs of intoxication, catarrhal syndrome with prominent exudative component.

Etiology. The causative agent of adenoviral infection is DNA-containing

virus from family of Adenoviride, genus Mustadenovirus. Adenoviruses include 49

serotypes with different antigenic, biophysical and hemagglutination properties,

but common soluble antigen; they are divided into 7 subgroups (A, B, C, D, T, F,

G). The disease is mainly caused by representatives of B-, C-, E-subgroups,

serotypes 1, 2, 3, 4, 5, 7, 14 and 21. Clinically prominent infections are caused by

viral serotypes 3, 4, 7, 14, 21. Adenoviruses of 1st, 2nd, 5th and 6th types are latent;

they cause subclinical disease forms in children. However, at unfavorable host

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conditions they can activate and cause typical ARVI. Serotypes 8, 19, 29 cause

conjunctiva inflammation; serotypes 12, 18, 31, 40, 41 initiate development of

enteritis. Adenoviruses are resistant to low temperatures, are epithelium tropic and

cytopathogenic.

Epidemiology. Adenoviral infection is a wide spread disease, affecting all

age groups. The sources of infection are sick people, people during recovery and

healthy carriers. The patient is contagious since first days of the disease and till 2-3

weeks from disease onset. In acute period the virus is excreted with mucus from

nose, pharynx and conjunctiva; later with stool. Patients excrete the virus in the

mean up till 7-12 days, some of them till 50 days and longer.

Main way of transmission is airborne; alimentary way is not excluded. Index

of contagiosity is till 50%.

Outbreaks of adenoviral infection can be notices around the year; they can

be seen in pediatric medical institutions. Their typical particularity is a long course

(till 1-1.5 months).

Pathogenesis. Adenovirus has tropism to mucosal epithelial cells, first of all

that of respiratory tract, and lymphoid tissue. The entrance routes for the infection

are most often upper parts of respiratory tract and conjunctiva, where the virus

intensively replicates and penetrates the blood, both from foci of replication and

through lymphatic ways. The virus damages vessel endothelium. It leads to

exudative inflammation, predisposition to fibrin formation, necrotic changes in

mucosa (exudative pharyngitis, pseudomembranous tonsillitis, pseudomembranous

conjunctivitis). Duration of viremia is from 1 till 3 weeks and depends on repeated

penetration of the virus into blood.

First of all respiratory tract epithelium is involved. Necrosis of superficial

layers of epithelium and its desquamation develop. In deeper layers of large

bronchi and trachea walls moderate lymphoid infiltration develops. In bronchial

lumen serous exudate with admixture of macrophages and single leukocytes is

observed; alveolar changes are similar to those in cilia epithelium. Affected cells

are destroyed; released viruses damage other cells and penetrate regional lymph

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nodes where they continue to replicate. Directly from infection focus the virus

penetrates into blood through lymphatic ways. The virus affects vessel

endothelium. In severe cases edema, vessel widening, dissection of their walls and

in some cases lumen clots develop.

The virus penetrates gastrointestinal system from upper respiratory tract

with mucus or hematogenically. At all forms of adenoviral infection the virus

replicates in small intestinal epithelium during 1.5-2 weeks; from this place the

virus penetrates regional lymph nodes through lymphatic ways and causes

mesenteric lymphadenitis, inflammation of intra-abdominal lymph nodes. Giant

cell transformation is seen on separate areas of small intestinal epithelium. In cells

of distal parts of renal tubules and bladder there are also dystrophic and necrotic

changes. For this infection giant cell metamorphosis is typical, which is seen in

many organs: in CNS, adrenal glands, lymphatic system.

Immunity after disease episode is type specific and long-lasting.

Clinical manifestations. Typical forms of adenoviral infection include

intoxication syndrome, predominant involvement of nasopharynx, conjunctiva and

lymphoid tissue.

Incubational period continues from 4 till 14 days, in the mean 5-7 days.

Primary (prodromal) period is absent.

Period of height. The disease can have both acute and gradual onset.

Independent from onset acuteness, in disease course new symptoms keep

appearing. It is typical for adenoviral infection to present with different damage of

respiratory tract and conjunctiva with prominent exudative component.

Intoxication syndrome is less prominent than at influenza and presents with

malaise, decreased appetite, headache, sometimes vomiting. Irregular fever

continues 5-7 days, can have wavy course.

Clinical forms of adenoviral infection:

- upper respiratory tract catarrh;

- rhinopharyngitis;

- tracheobronchitis;

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- pharyngoconjunctival fever;

- conjunctivitis, keratoconjunctivitis;

- tonsillopharyngitis;

- adenoviral pneumonia;

- gastroenteritis;

- hemorrhagic cystitis;

- mesenteric lymphadenitis.

Particularities of the course of adenoviral infection in children under three

years of age include combination of symptoms, prominence of intoxication and

catarrhal syndromes, presence of diarrhea and mesenteric lymphadenitis, liver and

spleen increase. Damage of respiratory tract can present with stenosing laryngitis

(in 5% of cases) with milder course than at influenza or parainfluenza, tracheitis,

obstructive bronchitis (in 3-4% of cases), pneumonia (in 50% of sick children).

With development of adenoviral pneumonia the child condition is severe; shortness

of breath, prominent nasolabial cyanosis, frequent dry cough are observed. In lungs

with the disease course amount of rales increases, wet fine rales appear, the cough

increases, cyanosis worsens. Fine and coarse rales are heard in lungs for 2-3 weeks

and sometimes longer. The disease can be accompanied by hyperthermia or normal

body temperature. Conjunctivitis and polyadenitis are seen not often, in newborns

they are not seen at all. Severity of the course, predisposition to recurrences and

exacerbations, length of the disease – all these are typical signs of adenoviral

infection. At X-ray examination massive lung damage with involvement of several

segments with tendency of development of confluent pneumonia.

Catarrhal signs include considerable impediment of nasal breathing which

makes more difficult the feeding of the child and is the reason for restlessness.

In this age group children generalization of adenoviral infection is seen with

frequent joining of bacterial flora. Lethal outcome is possible.

The most common complications at adenoviral infection are the following:

otitis, sinusitis, polysegmental serous-desquamating pneumonia, obstructive

bronchitis.

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Diagnosis.

1) clinical criteria:

- typical epidemiological history;

- acute disease onset with gradual symptoms development;

- polymorphism of clinical signs: simultaneously respiratory tract, lymphatic

tissue, conjunctiva and bowel involvement are observed;

- presence of prominent catarrhal syndrome from the first days of the

disease; this syndrome predominates over intoxication syndrome;

- duration of fever is 5-7 days; wave-like temperature curve;

- prominent exudative character of inflammation;

- combination of upper respiratory tract and conjunctiva catarrhal

inflammation;

- syndrome of polyadenitis;

- hepatosplenomegaly;

- possibility of intestinal disorders development (secretory viral diarrhea);

- long-term wave-like course.

2) laboratory criteria:

- virusological method (virus growth on cell culture);



complement fixation, reaction of neutralization): examination is performed with

paired serum taken with interval of 10-14 days in between. Diagnostic is titer

increase 4 times and higher.

Respiratory syncytial infection

Respiratory syncytial (RS) infection is and acute infectious disease caused

by respiratory syncytial virus with airborne way of transmission and predominant

damage of lower respiratory tract with development of fever, mild intoxication and

catarrhal syndrome.

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Etiology. The causative agent is a highly contagious RS virus from family

paramyxoviruses, genus Pneumovirus, with single stranded RNA. The virus lacks

hemagglutinin and neuraminidase. All detected strains of RS virus have common

complement fixating antigen. According to the structure of surface antigen 3

serovars of RS virus are described.

Virus is unstable in outer environment (at temperature 550С it is inactivated

in 5 minutes), stable to low temperatures but is inactivated at freezing. In mucus

droplets the virus preserves activity during several hours (from 20 minutes till 6

hours).

Epidemiology. Susceptibility of early age children is 75-100%; in older age

children the index of contagiosity is 40%. Mechanism of transmission is airborne.

The sources of infection are sick people from the end of incubational period

till 12-17 days after appearance of first disease symptoms (maximal till 30 days).

The virus causes both sporadic diseases and epidemic outbreaks in winter and

spring, more seldom in autumn. RS viral infection comprises up till 70% of all

ARVI in early age children.

Immunity is unstable, reinfection is possible. The morbidity is increased

since January till March. Periodic increase of RS infection frequency is seen every

6 years.

Pathogenesis. Entrance route for the infection is upper respiratory tract

(nasopharynx); at penetration of infection rhinitis and rhinopharyngitis develop.

Viremia continues till 10 days. The virus finds the best conditions for further

replication in small bronchi and bronchioles where the virus is brought with blood

flow. In those organs typical for infection clinical picture of bronchiolitis and

obstructive bronchitis develop. Important role in pathogenesis of the disease

belongs to joining of secondary bacterial flora. The virus is capable to persist for a

long time in bronchiolar epithelium, which leads to development of chronic

bronchitis. Virus elimination from the host and clinical recovery occur due to

formation of virus specific secretory and serum antibodies.

Clinical manifestations. Incubational period continues from 2 till 7 days.

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Primary period is 2-3 days. The disease onset is gradual. Catarrhal

syndrome is mild. Since the first days of the disease nasal congestion, throat

tickling, rare dry cough are seen. Body temperature is normal or subfebrile and

continues 2-7 days.

Height period. Younger children develop respiratory insufficiency due to

involvement into pathological process of lower parts of respiratory tract with

predominant damage of small bronchi, bronchioles and alveoli. Obstructive

bronchitis and bronchiolitis develop. Discordance between height of fever

(subfebrile), not prominent intoxication syndrome and severe respiratory

insufficiency is typical. Body temperature increases till 380С or remains normal.

Symptoms of intoxication present with sleep disturbance, appetite decrease and

moderate worsening of general condition. The most typical presentation of RS

infection is bronchiolitis. Cough becomes frequent, persistent, pertussis-like.

Severity of the condition is due to progressing respiratory insufficiency: prominent

expiratory shortness of breath appears with breath rate 60-80 per minute which is

accompanied by retraction of thoracic complient places, paleness, skin marble

color, perioral or total cyanosis, agitation or adynamia, tachycardia. In severe cases

hypoxia and hypercapnia develop. For bronchiolitis it is typical to have

emphysema of thorax. On percussion tympanic tone of the sound is heard. Liver

and spleen are palpable due to lowering of diaphragm. At lung auscultation

prolonged expiration is heard with large amount of fine and coarse wet rales, more

seldom wheezes. After cough the auscultation picture is not changed. At X-ray

examination pulmonary emphysema without foci of inflammation is seen.

In older age children at RS infection acute bronchitis develops which mainly

present with dry cough rapidly changing to moist. Shortness of breath is seldom

seen. At auscultation spread dry, fine and coarse wet rales are heard which

decrease or disappear after cough.

At RS infection obstructive bronchitis can develop which presents with

prolonged and noisy expiration. At auscultation spread dry and wet rales are heard;

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their amount decreases after cough. Lung emphysema is detected. Severity of the

disease is caused by degree of respiratory insufficiency.

Particularities of RS infection course in children under three years of age.

In first year old children the disease has a very sever course. On the 2-7 th day the

process involves lower respiratory tract. Prominent signs of respiratory

insufficiency appear due to development of obstructive bronchitis or bronchiolitis.

Respiration becomes frequent, till 60-80 per minute; prolonged expiration is

observed (expiratory dyspnea), retraction of compliant parts of thorax; the skin

becomes cyanotic. In lungs a large amount of dry and wet fine rales appear. Lung

emphysema causes lowering of liver and spleen borders beyond costal rib. Reverse

development of lower respiratory tract changes is observed during 5-7 days; in

premature children it can prolong till 2-3 weeks. RS infection can seldom cause

stenosing laryngitis (false croup) in early age children.

Besides, early age children can present with possible generalization of the

process, involving other organs. In these organs growth of epithelial and reticular

cells occurs (blood, lymphatic vessels, bile ducts, pancreatic ducts, renal tubules).

All early age children with signs of RS infection must be obligatory

hospitalized to pediatric medical settings with required equipment for performance

of artificial lung ventilation if required due to high probability of bronchiolitis and

obstructive bronchitis development with respiratory insufficiency of different

degree.

Complications are caused by bacterial flora. Most commonly pneumonia

and otitis are seen.

Diagnosis.



- the disease is more often seen in first year children

- gradual disease onset;

- mild intoxication signs;

- body temperature is subfebrile as a rule;

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- mild catarrhal syndrome;

- typical involvement of lower parts of respiratory tract (bronchiolitis,

obstructive bronchitis) on the 2-3rd day from disease onset;

- prominent respiratory insufficiency with rapid reverse dynamics;

- discordance between severity of lower tract involvement (a lot of dry and

wet fine crackles over the whole lung surface, thorax emphysema) and degree of

fever and intoxication.


- virusological method (virus growth on cell culture);



complement fixation, reaction of neutralization): investigation is performed with

paired serum taken with interval of 10-14 days in between. Diagnostic is titer

increase 4 times and higher.

Rhinoviral infection

Rhinoviral infection or prolonged common cold is an acute infectious

disease caused by different serotypes of rhinoviruses with airborne way of

transmission and with predominate involvement of nasal mucosa and absent or

mild intoxication.

Etiology. The causative agent belongs to family Picornoviridae, genus

Rhinovirus. Currently there are about 114 serotypes of human rhinoviruses

described, which provide different clinical presentation of rhinitis. They do not

have any common group antigen, every serotype posses specific virus neutralizing

and complement fixating antigens. Viral genome is presented by non-fragmentated

single stranded viral RNA. There are no lipids and carbohydrates in virion

structure, which leads to ether resistance of the virus. Viral replication occurs in

cytoplasm. Rhinoviruses have tropism to respiratory epithelium, predominantly of

nasal mucosa.

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Rhinoviruses are not stable in outer environment; they are rapidly

inactivated at low pH, at high temperature (they are killed during 10 minutes at

temperature 560С), at drying, but are stable to lipid solvents, can preserve

pathogenicity and remain contagious on surrounding objects and hands.

Epidemiology. The source of infection is sick person and carrier. Duration

of contagious period in the mean is 5-7 days (from 1 till 28 days). The person

becomes contagious at the end of incubational period.

Mechanism of infection transmission is airborne, more seldom contact.

Susceptibility to infection is high. Very often 2 and more viral serotypes

participate simultaneously in development of rhinoviral infection.

Seasonality. Sporadic cases of rhinoviral infection are registered annually;

small outbreaks are detected in autumn and spring.

Rhinoviral infection is widely spread and is diagnosed in all age groups

which can be explained by extreme variability of rhinovirus types and short-term

type-specific immunity.

Pathogenesis. The virus penetrates respiratory tract mucosa and replicates in

epithelial cells of nasal channels, causing inflammatory reaction with prominent

swelling, edema, desquamation of epithelium and abundant secretion (rhinorrhea).

Regeneration of mucosa continues 2 weeks. The role of rhinoviruses in

development of inflammatory processes in ear and pharynx is proved.

The immunity is type-specific and is connected with appearance of secretory

antibodies.

Clinical manifestations. Incubational period is 1-6 days.

Primary period is not prominent.

Period of height. The disease onset is acute: on the background of mild

intoxication (headache, moderate malaise, muscle pain) and subfebrile fever local

signs of respiratory mucosa involvement appear acutely (sneezing, throat tickling).

The main symptom is abundant watery rhinorrhea with redness and maceration of

outer nasal canals, impeded nasal breathing, lacrimation and eyelids edema. Sense

of smell, taste and hearing are disturbed; ear congestion feeling is seen. During

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mouth examination mild hyperemia of palate arches, tonsils, soft palate, more

seldom of posterior pharyngeal wall is detected.

Diagnosis.



- prominent rhinorrhea;

- mild intoxication;

- normal or subfebrile body temperature.




complement fixation, reaction of neutralization): investigation is performed with

paired serum taken with interval of 10-14 days in between.

Metapneumoviral infection

Metapneumoviral infection is an acute infectious disease caused by

metapneumovirus with predominantly airborne way of transmission which is

characterized by involvement of upper respiratory tract and gastro-intestinal tract

with catarrhal signs and frequent diarrhea syndrome.

Etiology. Metapneumovirus is RNA containing virus from family of

paramyxoviruses; by its biological characteristics it is close to RS viruses.

Epidemiology. Two seasonal increases of metapneumoviral infection

morbidity are observed. The first one is begins in November and gradually

decreases by the end of winter, giving way to RS viruses, influenza and

parainfluenza. The second increase begins in May. In the countries with moderate

climate metapneumovirus circulates predominantly during the second part of

winter and early spring; the peak of its activity often coincides or appears right

after RS virus. In the countries with tropical climate the virus is predominantly

detected in April-June (during the season of rains). In some countries the virus is

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extracted from sick people with respiratory syndrome around the whole year.

Metapneumoviruses affect different age groups with various frequency and are

mostly diagnosed in children from 3 till 7 years. In healthy children the virus is

detected in 0.6-1.2% of cases.

Clinical manifestations. The most common presentations of

metapneumoviral infection are rhinorrhea, cough, hyperthermia, development of

bronchitis, bronchiolitis and pneumonia.

Metapneumoviral infection more often begins acutely with appearance of

catarrhal signs (cough, rhinorrhea, nasal mucosa edema) and fever. The disease is

more often accompanied by febrile fever which is present during 4-6 days in the

mean. Prominent intoxication syndrome is observed in half of patients. All the

children present with oropharyngeal mucosal hyperemia. Shortness of breath of

mostly inspiration character is seen from the first days of the disease in half of

patients. In 20% of sick children with metapneumoviral infection dyspeptic

syndrome is diagnosed: vomiting with diarrhea without pathological admixtures.

Diagnosis.



- intoxication syndrome, shortness of breath;

- combination of nasopharyngitis, bronchitis or bronchiolitis and enteritis;

- hepatomegaly and not rarely splenomegaly;

- possible diarrhea syndrome.


- for detection of RNA hMPV real time polymerase chain reaction is used

with hybridization and detection of fluorescence (RT-PCR).

Bocaviral infection

Bocaviral infection is an acute infectious disease caused by bocaviruses with

predominantly airborne way of transmission characterized by upper respiratory

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tract and gastrointestinal tract involvement which presents with catarrhal signs and

frequent diarrhea syndrome.

Etiology. Human bocavirus belongs to family Parvoviridae. It was identifies

in 2005 year. The virus is still understudied.

Epidemiology. The most often bocaviral infection affects children of 1-3

years of age. In healthy children bocavirus is detected in 2.6% of cases.

Peak of morbidity is in autumn (October – December).

Clinical manifestations. Clinical presentation of bocaviral infection is

characterized by acute disease onset, combination of respiratory syndrome,

intoxication signs and dyspepsia syndrome.

Cough, running nose, enlargement and hyperemia of tonsils, intoxication

and hyperthermia (39-400С) appear simultaneously during the first days of the

disease. Length of fever is 4-6 days.

At bocaviral infection the following clinical forms develop: pneumonia,

rhinopharyngitis, acute bronchitis, obstructive bronchitis, acute tonsillopharyngitis.

One third of patients with hBoV infection develop gastroenteritis; its duration is

usually not longer than 8-9 days. Symptoms of gastrointestinal tract involvement

are more often seen simultaneously with catarrhal signs.

Diagnosis.

1)clinical criteria:


- intoxication syndrome, shortness of breath;

- combination of nasopharyngitis, bronchitis or bronchiolitis and enteritis.


- for detection of RNA hBoV real time polymerase chain reaction is used

with hybridization and detection of fluorescence (RT-PCR).

Treatment of influenza and other ARVI

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Patients with severe forms of the disease, people with increased risk of

complication development, at inability to isolate the patient in ambulatory

conditions, people from closed groups should be hospitalized.

Etiotropic treatment of influenza.

The first generation of anti-influenza drugs include drugs of adamantadine

group, amantadine and rimantadine. These drugs are blockers of ion channels.

Formed transmembrane parts of viral protein М2 cause proton transfer through

membrane and decrease of pH inside the virion. This condition is necessary for

release of viral ribonucleoprotein from M1 protein and initiation of viral genome

transcription. It was shown that molecules of amantadine and rimantadine are

similar in diameter to these ion channels. These dugs block proton transfer with

subsequent increase of pH inside endosomes and depression of viral reproduction.

М2-cannels are only present in influenza A virus, so inhibitors of М2-channels are

not effective against influenza B and C.

Nowadays influenza A virus is resistant to M2-channel inhibitors in more

than 90% of cases, so these drugs are not currently recommended for empirical

therapy of the disease.

Anti-influenza drugs of second generation include inhibitors of

neuraminidase: oseltamivir and zanamivir. These drugs block function of viral

enzyme neuraminidase, which precludes release of new virions from the cells and

their further spread in the body. Prescription of these drugs within the first 48

hours from disease onset decreases prominence and duration of influenza

symptoms, risk of complications and mortality.

Antiviral therapy with neuraminidase inhibitors is recommended for any

patient with severe and complicated forms of influenza.

Antiviral treatment of influenza is indicated to children with any forms of

influenza and high risk of complication development:

- chronic pathology of respiratory system;

- chronic diseases of cardiovascular system;

- immunodeficient conditions;

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- diabetes mellitus;

- obesity;

- chronic diseases of kidneys;

- disorders of nervous system;

- children under 5 years of age.

Antiviral therapy with neuraminidase inhibitors at mild and moderate forms

of influenza is not recommended.

Oseltamivir. It is prescribed to children older than 12 years of age in capsules

75 mg twice a day during 5 days. Children from 1 till 12 years are given this drug

in form of solution for dinking.

Recommended dosages of oseltamivir for children from 1 year and older:

Body weight Recommended dose for 5 days course≤ 15 kg 30 mg twice a day > 15-23 kg 45 mg twice a day> 23-40 kg 60 mg twice a day> 40 kg 75 mg twice a day

Zanamivir is prescribed as a dosed powder for inhalations. Children older 2

years of age are given 2 inhalations (5 mg * 2) twice a day during 5 days.

At the absence of indications to antiviral therapy of influenza and other ARVI

by neuraminidase inhibitors other antiviral drugs can be used, whose efficacy is

proved at seasonal, pandemic influenza and ARVI (interferon preparations and

inductors of interferon).

Symptomatic therapy of influenza and ARVI.

At hyperthermia in children paracetamol is used in dosage 10-15 mg / kg in 4

hours, maximal daily dosage is 60 mg / kg, or ibuprofen in dosage 5-10 mg / kg in

6-8 hours, maximal daily dosage is 25-30 mg / kg of body weight. Preparations of

acetylsalicylic acid are contraindicated in children under 28 years of age due to risk

of Reye syndrome development.

Additional amount of fluid should be given to febrile children for prophylaxis

of dehydration. First year of age children should be given glucose and salt

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solutions for oral rehydration, fruit and vegetable decoction without sugar, mineral

water with low contain of minerals and without gas.

At nasal congestion in children under 6 months of age the nasal mucosa is

moisten with 0.65% sodium chloride solution. Decongestants (vasopressors) can

cause irritation and sleeplessness in this age. Children older than 6 months of age

can be given vasopressing pediatric nasal solutions but not longer than 3-5 days, as

they can cause development of drug-associated rhinitis.

At acute cough the optimal remedies are drugs which moist and protect

respiratory mucosa (mucolytics, tussive drugs). Anti-tussive drugs can only be

given to children in case of dry cough secondary to irritation of upper respiratory

tract mucosa when this cough disturbs child’s sleeping, eating and drinking.

Prophylaxis of influenza and ARVI.

Vaccination against influenza is a reliable method of prophylaxis. Optimal

terms for vaccination are October-November. In pandemia period it is possible to

use vaccination against influenza annually to protect people from high risk group

of influenza.

First of all vaccination is indicated to children:

- with chronic diseases of broncho-pulmonary system, including

bronchial asthma, to children who require permanent or repeated usage of

bronchodilating drugs or systemic corticosteroids;

- with diseases of cardiovascular system (inborn heart defects,

hypertonic disease, heart insufficiency);

- with hemolytic anemias;

- with diabetes mellitus;

- with obesity;

- those on immune suppressive therapy (patients taking systemic

steroids longer than a month in dosage equivalent to 20 mg of prednisone daily (for

any age), for children with body weight under 20 kg - 1 mg or more per kg per day;

chemotherapy, radiation therapy;

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- with chronic kidney diseases (nephrotic syndrome, chronic renal

insufficiency and kidney transplantation);

- with chronic liver diseases (liver cirrhosis, biliary duct atresia,

chronic hepatitis);

- those receiving prolonged therapy with aspirin;

- with HIV infection and asplenia;

- from confined populations.

At the absence of vaccination against influenza, its chemoprophylaxis is

indicated, especially to children from high risk groups. Influenza

chemoprophylaxis can be post-exposure and pre-seasonal.

Influenza chemoprophylaxis must begin no later than 48 hours after contact

with sick person. For influenza chemoprophylaxis first of all oseltamivir and

zanamivir are used. Other antiviral drugs, whose efficacy is proven at ARVI

(recombinant interferons, inductors of interferons) can also be used for influenza

prophylaxis. The latter antiviral drugs can also be used for other ARVI

prophylaxis.

Non-specific prophylaxis of influenza include healthy life style, rational

nutrition, adherence to rules of private hygiene (frequent hand washing, face

washing), air moistening in the room air.

Questions for self-control:

1. Characteristics of ARVI causative agents.2. Epidemiological particularities of different ARVI.3. Pathogenesis of influenza and other ARVI.4. Classification of clinical forms of ARVI.5. Clinical manifestations of different ARVI depending on children age.6. Complications of ARVI.7. Clinical and laboratory diagnostic criteria of ARVI.8. Principles of ARVI treatment.9. Specific prophylaxis of influenza.10. Anti-epidemic activities in nidus of ARVI.

Tests for self-control:

1. Which family does the influenza virus belongs to:А. Orthomixoviruses В. Paramixoviruses

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С. Arboviruses D. Picornaviruses Е. Retroviruses 2. Children of which age are most commonly affected by RS infection:А. 0-2 years В. 2-5 years С. 5-10 years D. 10-15 years Е. Independently of age 3. Which ARVI typically has fecal-oral way of transmission:А. Influenza В. Parainfluenza С. Adenoviral infection D. RS infection Е. All the answers are correct 4. What is most commonly affected at parainfluenza in children:А. Nasopharynx В. Larynx, trachea С. Bronchi, bronchiolesD. TonsilsЕ. Alveoli 5. Which ARVI typically has hemorrhagic syndrome:А. Influenza В. Parainfluenza С. Adenoviral infection D. RS infection Е. Rhinoviral infection6. Which ARVI typically presents with rrhynopharyngoconjunctival fever:А. Influenza В. Parainfluenza С. Adenoviral infection D. RS infection Е. Rhinoviral infection7. What is most commonly affected at RS infection in early age children:А. Nasopharynx В. Larynx, trachea С. Bronchi, bronchiolesD. TonsilsЕ. Alveoli 8. Which ARVI typically has wavy course:А. Influenza В. Parainfluenza С. Adenoviral infection D. RS infection Е. Rhinoviral infection9. What drug is neuraminidase inhibitor:А. Rimantadine В. TyloroneС. Oxoline D. Acyclovir Е. Oseltamivir 10. What drug is interferon inducer:

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А. Rimantadine В. TyloroneС. Oxoline D. Acyclovir Е. Oseltamivir

Test answers

1-А, 2-А, 3-С, 4-В, 5-А, 6-С, 7-С, 8-С, 9-Е, 10-В.

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respiratory viral infections

Health & Medicine