Lesson No 5

LessoNo 5

Theme 5. Acute respiratory tract viral infections n(Influenza, Parainfluenza, Adenoviral, Respiratory-syncitial, Rinoviral ninfection).

ACUTE VIRAL nUPPER RESPIRATORY TRACT

INFECTIONS

 

Acute Viral Upper Respiratory nTract Infections – is a large ngroup of infectious diseases,

which are caused by viruses, ntransmitted by droplet way, characterized by intoxication and catarrhal nsyndrome with predominant changes in mucous membranes of the upper respiratory ntract.

Etiology:

• Parainfluenza, 5 types of nhuman parainfluenza virus that belong to paramyxovirus family (large RNA nviruses 150-200 nm, contain hemagglutinine and neuraminidase with stable nantigen structure).

• Respiratory syncitial (RS) virus, nbelong to paramyxovirus family (large polymorph RNA viruses 120-200 nm) doesn’t nhave neuraminidase and without hemagglutination ability, grew only on the ntissues cultures.

• Rhinoviruses, with over n100 serotypes, belong to picornavirus family (small RNA viruses 20-30 nm, ninstable in the environment).

• Adenoviruses – a stable nDNA-viruses of medium size, 70-90 nm, have A, B, C

antigens, could agglutinate nthe blood.

• Rheoviruses – 3 serotypes nRNA-viruses of medium size, 70-80 nm, stable in the

environment.

• Enteroviruses

• Coronaviruses

 

Epidemiology   

·        nA source of infection are patients with URT viral ninfection, and virus-carriers (Adenovirus, Rhinovirus,  Rheovirus and RS-virus)

·        nMechanism of transmission

o   ndroplet with inhalation of small or nlarge airborne drops during coughing, sneezing, speaking, by contact with contaminated nhands, toys ets.

o   nalso fecal-oral (for Adenovirus, Rheovirus infection)

·        nReceptivity – early age children, from 6 nmonth and under-fives, contagiousness is high (40-80%)

·        nSeasonality – autmn-winter or winter-spring flashes and sporadic ndiseases during a year

 

Pathogenesis       – inoculatioof viruses in upper respiratory tract epitheliocytes, conjunctiva, lymph nnodes

–         nLocal reproduction of virus

–         nDevelopment of inflammatory process in upper respiratory tract, destructive nchanges

–         nStart of immune nreactions

 

delete of the virus                   n      immune factors            possible viremia

                                               suppression                                  

                                                                                     damage of organs

                                                 bacterial                          and nsystems

                                             complications

 

Clinical classification of aAcute Upper Respiratory Tract Viral Infections

 

 

Clinical criteria

 

Commoclinical symptoms:

·        nComplaints: nmore or less severe symptoms of general intoxication, catarrhal symptoms are nsore throat (considerably rarer is pharyngeal pain), cold, dry cough.

·        nModerate nhyperemia, mainly palatal arch, soft palate, uvula, back pharyngeal wall with nthe presence of grittiness (lymphoidc follicles are enlarged).

·        nHyperemia nof nasal mucosa.

·        nTonsils nare mainly intact (except adenoviral infection).

·        nConjunctivitis n(more or less severe, in dependence on the type of URTI).

·        nSigns nof a few parts of upper respiratory tract inflammation.

·        nFor nevery type of infection the prominent inflammation of one part of upper nrespiratory tract is characteristic with development of typical clinical signs.

 

 Parainfluenza:

·        nSporadic morbidity, grows in winter.

·        nLatent period is 2-7 days.

·        nAcute beginning.

·        nToxic syndrome is mild or moderate.

·        nCatarrhal phenomena are not severe.

·        nA basic clinical sign is a catarrh of upper nrespiratory tract.

·        nPeculiarities in infants and under-fives: a croup syndrome is oftethe first display.

 

Adenovirus infection:

·        nSporadic morbidity and epidemic flashes.

·        nWinter seasonality, possible flashes in summer.

·        nLatent period is 2-12 days.

·        nAcute beginning.

·        nThe first symptom is a catarrh of upper nrespiratory ntract

·        nToxic syndrome is moderate.

·        nConjunctivitis (photo 89, 90).

·        nLymphoprolipherative syndrome (acute viral ntonsillitis, neck lymph nodes enlargement, hepatomegaly (rare splenomegaly).

·        nIntestinal syndrome.

·        nPeculiarities in infants: often dyspeptic syndrome (vomiting, ndiarrhea), bronchitis, interstitial pneumonia,  nrare – lymph nodes enlargement, conjunctivitis

 

 

Conjunctivitis

 

Conjunctivitis

 

RS-infection:

·        nLatent period is 3-7 days.

·        nWinter seasonality, acute beginning.

·        nThe children of senior age have mild nforms (as an acute nbronchitis).

·        nCroup nis less common.

·        nPeculiarities nin infants: often bronchiolitis, interstitial pneumonia

 

Rhinovirus ninfection:

·        nEpidemic flashes (in winter, in autumn).

·        nLatent period is 1-5 days.

·        nIntoxicatiois absent or mild,

·        nAcute nrhinitis with large effusion (mucus) from the nfirst days of illness

·        nOftebacterial complications (later – purulent effusion from the nose).

·        nPeculiarities in infants: rhinoviral ninfection with often development of tracheobronchitis

 

Common peculiarities iinfants:

·        nPoor feeding,

·        nDecrease of nbody weight,

·        nLess nacute beginning,

·        nLess intoxication,

·        nBacterial complications (otitis, pneumonia, netc.) and mortality appear more often.

 

Laboratory and instrumental ninvestigations

·        nIdentification of virus from nasopharyngeal smears n(also feces or blood in Adenovirus infection ) by culture, nimmunofluorescence, or ELISA.

·        nSerologic diagnosis to find antibodies against nviruses (CBR, DHAR) with fourfold increasing of antibodies title in 10-14 days may be used.

·        nICBC,  mainly leucopenia (normocytosis) nwith a shift to the left and relative lymphomonocytosis.

·        nDuring nX-ray  – strengthening of the pulmonary npicture

 

Etiological ndiagnosis may be put nin case of the virus identification, in other case diagnosis will be URT nviral infection + leading clinical syndrome (for example: URT viral infection: rhinopharyngitis, nor URT viral infection: obstructive nbronchitis, Respiratory insufficiency 2^nd degree; with intestinal nsyndrome.

 

Differential ndiagnosis nshould be performed between other viral respiratory tract infections, allergic nrhinitis, foreign body aspiration, epiglottitis, bacterial tracheitis, npertussis, measles, Epstein-Bar Virus infection, bacterial croup.

·        nRhinoviral infection: with nallergic rhinitis, foreign body of the nose.

·        nRS–infection: whooping ncough, chlamidiosis, mycoplasmosis.

·        nAdenoviral infection: with ninfectious mononucleosis, micoplasmosis, and measles.

·        nParainfluenza: with ntrue croup in diphtheria, other viral croup (i.e. in measles).

 

Differential Diagnosis between Viral Respiratory nInfections

 

 

INFLUENZA VIRAL INFECTIONS

 

Influenza viral infections cause a broad array of nrespiratory illnesses that are responsible for significant morbidity and nmortality in children.

 

ETIOLOGY.

 

Influenza viruses are classified as Orthomyxoviridae. They nare large, single-stranded RNA viruses with a segmented genome encased in a nlipid-containing envelope. The two major surface proteins that determine the nserotype of influenza, the hemagglutinin and neuraminidase, project as spikes nthrough the envelope. Influenza viruses are divided into three types: A, B, and nC. Influenza types A and B are the primary influenzal pathogens and causes of nepidemic disease. Influenza type C is a sporadic cause of predominantly upper nrespiratory tract disease. Influenza types A and B are further divided into nserotypically distinct strains that circulate on a yearly basis through the npopulation.

 

EPIDEMIOLOGY.

 

Influenza A viruses have a complex epidemiology ninvolving animal hosts that serve as a reservoir for diverse strains with npotential for infecting the human population. The segmented nature of the ninfluenza genome allows reassortment to occur between an animal and human virus nwhen coinfection occurs. Thus, potentially any of 13 hemagglutinins and 9 nneuraminidases residing in animal reservoirs may be introduced into humans. Iaddition, avian hosts that are migratory may be responsible for spread of ndisease. Influenza B has a lesser capacity for major antigenic change and no nidentified animal reservoir.

 

When a virus identified by a novel and serologically distinct nhemagglutinin or neuraminidase enters the population, there is potential for a npandemic of influenza with excess morbidity and mortality on a global scale ia largely nonimmune population. The most dramatic pandemic in recent history noccurred in 1918 when influenza was estimated to have killed more than 20 nmillion people. More common is the almost yearly variation in the antigenic ncomposition of the surface proteins, which confers a selective advantage to a nnew strain and results in localized epidemics of disease with mortality largely nconfined to the elderly and to those with underlying cardiopulmonary disease. nEach year’s strain is novel for infants because they have no pre-existing nantibody except for maternally transferred antibody in the very young.

 

The attack rate and frequency of isolation of influenza is highest iyoung children. As many as 30–50% of children have serologic evidence of ninfection in a typical year. Children undergoing primary exposure to ainfluenza strain have much higher and more prolonged shedding of the virus thaadults, making them extremely effective transmitters of infection. Influenza is na disease of the colder months of the year in temperate climates; spread appears nto occur by small-particle aerosol. Transmission through a community is rapid, nwith the highest incidence of illness occurring within 2–3 wk of introduction. nIt is marked by increased school absenteeism and the yearly peak in visits to nthe pediatrician. Influenza has been implicated in hospital spread of infectioand may complicate the original illness that required hospitalization.

 

On a country or global basis, one or two predominant strains spread to ncreate the annual epidemic. At present, influenza type A strains with the H1N1 nand H3N2 serotypes and type B strains are cocirculating, and either type may be npredominant in any one year, making predictions about the serotype and severity nof the upcoming influenza season very difficult. Strain variants are identified nby their hemagglutinin and neuraminidase serotypes, by the geographic area from nwhich they were originally isolated, by their isolate number, and by year of nisolation. Thus, the current influenza vaccine for 1994–1995 is trivalent, nhaving strains identified as A/Shangdong/9/93(H3N2), A/Texas/36/91(H1N1), and nB/Panama/46/90.

 

PATHOLOGY.

 

Influenza causes a lytic infection of the respiratory nepithelium with loss of ciliary function, decreased mucus production, and ndesquamation of the epithelial layer. These changes permit secondary bacterial ninvasion either directly through the epithelium or, in the case of the middle near space, through obstruction of the normal drainage through the eustachiatube. Influenza types A and B have been reported to cause myocarditis, and ninfluenza type B can cause myositis. When influenza type B is accompanied by nthe administration of salicylates, the fatty liver, cerebral edema, and nmitochondrial changes that are the hallmarks of Reye syndrome can be seen.

 

Hemorrhagic npneumonia in influenza

 

PATHOGENESIS.

 

The incubation period of influenza can be as short as n48–72 hr. The virus attaches to sialic acid residues on cells via the nhemagglutinin and, via endocytosis, makes its way into vacuoles, where, with nprogressive acidification, there is fusion to the endosomal membrane and nrelease of the viral RNA into the cytoplasm. The RNA is transported to the nnucleus and transcribed. Newly synthesized RNA is returned to the cytoplasm and ntranslated into proteins, which are transported to the cell membrane. This is nfollowed by budding of virus through the cell membrane. The packaging nmechanisms for the segmented genome are not well understood. A proteolytic ncleavage of the hemagglutinin occurs at some point in the assembly and release nof the virus which is essential for successful reinfection and amplification of nvirus titer. In humans, this replicative cycle is confined to the respiratory nepithelium. With primary infection, virus replication continues for 10–14 days. nImplicit in successful replication in the respiratory tract is the assumptiothat key proteolytic enzymes exist at this site. The successful cleavage of nhemagglutinin has been demonstrated by respiratory secretions, but the cellular norigin of the enzyme remains undefined.

 

The exact immune mechanisms involved in termination of nprimary infection and protection against reinfection are not well understood. nThe extremely short incubation period of influenza and its growth on the nmucosal surface pose particular problems for invoking a protective immune nresponse. Antigen presentation must be primarily at mucosal sites acting nthrough the bronchial associated lymphoid tract. The major humoral response is ndirected against the hemagglutinin and high serum antibody levels generated by ninactivated vaccine correlate with protection. Mucosally produced nimmunoglobulin (Ig) A antibodies are presumably directed at the same antigenic nsites and are thought to be the most effective and immediate response that cabe generated to protect against influenza. Unfortunately, measurable IgA nantibodies against influenza persist for a relatively short period, and nsymptomatic reinfection with influenza can be seen at intervals of 3–4 yr. nAlthough heterotypic immunity can be demonstrated in the mouse through ncell-mediated immune mechanisms directed toward common internal proteins, nheterotypic immunity has not been shown in humans.

 

CLINICAL MANIFESTATIONS.

 

 Influenza types nA and B cause predominantly a respiratory illness. The onset of illness is nabrupt and is marked by coryza, conjunctivitis, pharyngitis, and dry cough. The npredominant symptoms may localize anywhere in the respiratory tract, producing nan isolated upper respiratory tract illness, croup, bronchiolitis, or npneumonia. More so than any of the other respiratory viruses, influenza is naccompanied by systemic signs of high fever, myalgia, malaise, and headache. nMany of these symptoms may be mediated through cytokine production by the nrespiratory tract epithelium instead of reflecting systemic spread of the nvirus. The typical duration of the febrile illness is 2–4 days. Cough may npersist for longer periods of time, and evidence of small airway dysfunction is noften found weeks later. Other family members or close contacts often have a nsimilar illness. Influenza is a less distinct illness in younger children and ninfants, with manifestations that may be localized to any region of the nrespiratory tract. The children may be highly febrile and toxic in appearance, nprompting a full diagnostic workup. In spite of the distinctive features of ninfluenza, the illness is often indistinguishable from that caused by other nrespiratory viruses such as respiratory syncytial virus, parainfluenza virus, nand adenovirus.

Conjunctive hyperemia

Injection of the pharyngeal vessels in influenza npatient

 

LABORATORY FINDINGS.

 

The clinical laboratory abnormalities associated with ninfluenza are nonspecific. A relative leukopenia is frequently seen. Chest nradiographs show evidence of atelectasis or infiltrate in about 10% of nchildren.

 

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

 

The diagnosis of influenza depends on epidemiologic nand clinical considerations. In the context of an epidemic, the clinical ndiagnosis of influenza in a young child with fever, malaise, and respiratory nsymptoms can be made with some certainty. The laboratory confirmation of ninfluenza can be made in three ways. If seen early in the illness, virus can be nisolated from the nasopharynx by inoculation of the specimen into embryonated eggs nor a limited number of cell lines that support the growth of influenza. The npresence of influenza in the culture is confirmed by hemadsorption, which ndepends on the capacity of the hemagglutinin to bind red cells. Rapid ndiagnostic tests for influenza A are being introduced that use antigen capture nin an enzyme-linked immunosorbent assay format. The diagnosis can be confirmed nserologically with acute and convalescent sera drawn around the time of illness nand tested by hemagglutination inhibition.

 

COMPLICATIONS.

Otitis media and pneumonia are common complications of ninfluenza in young children. Acute otitis media may be seen in up to 25% of ncases of culture-documented influenza. Pneumonia accompanying influenza may be na primary viral process. An acute hemorrhagic pneumonia may be seen in the most nsevere cases, as may have been frequent with the highly virulent strain seen i1918. The more common cause of pneumonia is probably secondary bacterial ninfection through the damaged epithelial layer. Unusual clinical manifestations nof influenza include acute myositis seen with influenza type B, which follows nthe acute respiratory illness by 5–7 days and is marked by muscle weakness and npain, particularly in the thigh muscles, and myoglobinuria. Myocarditis also follows ninfluenza, and toxic shock syndrome is associated with influenza type B and nstaphylococcal colonization. Influenza is particularly severe in children with nunderlying cardiopulmonary disease including congenital and acquired valvular ndisease, myocardiopathy, bronchopulmonary dysplasia, asthma, cystic fibrosis, nand neuromuscular diseases affecting the accessory muscles of breathing. Virus nis shed for longer periods of time in children receiving cancer chemotherapy nand children with immunodeficiency.

 

PREVENTION.

 

An inactivated influenza vaccine becomes available neach summer with changes in formulation that reflect the strains anticipated to ncirculate in the coming year. When the vaccines are released, the AmericaCommittee on Immunization Practices publishes guidelines for their use. Current nguidelines include the administration of vaccine intramuscularly to children 6 nmo of age and older in chronic care facilities; those with chronic disorders of nthe pulmonary or cardiovascular system, including asthma; those with chronic nmetabolic diseases (including diabetes mellitus), renal dysfunction, nhemoglobinopathies, or immunosuppression (including immunosuppression caused by nmedications); and children receiving long-term aspirin therapy who may be at nrisk for Reye syndrome after influenza. In addition, vaccine is recommended for nindividuals who may transmit influenza to persons at high risk, including nhealth care workers and household members. The split-virus vaccine is nrecommended for children younger than 12 yr. Two doses of vaccine are nrecommended for primary immunization of children younger than 8 yr. The dosage nis divided in half to a volume of 0.25 mL for children younger than 3 yr. Live, nattenuated intranasally administered vaccines are in clinical trials and have nbeen demonstrated to have an efficacy comparable to that of inactivated nvaccine. Their ease of administration could serve to increase their use. nAmantadine hydrochloride is the only licensed antiviral drug for influenza type nA. It has been used prophylactically in high-risk patients and their care nproviders during influenza epidemics and in immunodeficient persons and those nfor whom the influenza vaccine is contraindicated.

 

TREATMENT. Amantadine hydrochloride can be used in the control of ninfluenza type A outbreaks, in institutions, and for therapy in individual ncases. If given within the first 48 hr, it decreases the severity and duratioof influenzal symptoms. Confusion and inability to concentrate or sleep are nseen in a minority of people given amantadine hydrochloride. Drug resistance ndevelops fairly quickly during a course of therapy, but it is not widespread namong circulating viruses. Because amantadine hydrochloride has no efficacy nagainst influenza type B, knowledge of the circulating strain is essential to nthe rational use of the drug.

 

Adequate fluid intake and rest are important components in the nmanagement of influenza. Non-salicylate-containing antipyretics can be used for nhigh fever. The most difficult question is the appropriate timing of nconsultation with a health care provider. Bacterial superinfections are common, nand antibiotic therapy should be administered. Bacterial superinfections should nbe suspected with recrudescence of fever, prolonged fever, or deterioration iclinical status. With uncomplicated influenza, children should feel at their nworst over the 1st 48 hr.

 

PROGNOSIS.

 

The prognosis for recovery is excellent although full return to normal nlevels of activity and freedom from cough usually requires weeks rather than days.

 

 

PARAINFLUENZA VIRUS

 

 Viruses in the nparainfluenza family are common causes of respiratory illness in infants and nyoung children. They cause a spectrum of upper and lower respiratory tract nillnesses, but are particularly associated with laryngotracheitis, bronchitis, nand croup.

 

ETIOLOGY.

There are four viruses in the parainfluenza family nthat cause illness in humans, designated types 1–4. The viruses have a nnonsegmented, single-stranded RNA genome with a lipid-containing envelope nderived from budding through the cell membrane. The major antigenic moieties nare envelope spike proteins that exhibit hemagglutinating (HN protein) and cell nfusion (F protein) properties.

 

EPIDEMIOLOGY.

 Parainfluenza viruses are spread nfrom the respiratory tract by aerosolized secretions or direct hand contact nwith secretions. By age 3 yr, most children have experienced infection with ntypes 1, 2, and 3. Type 3 is endemic and can cause disease in the infant nyounger than 6 mo. Serious illness is seen with parainfluenza type 3 in the immunocompromised nchild. Types 1 and 2 are more seasonal. They occur in the summer and fall and nalternate years in which their serotype is most prevalent. Parainfluenza type 4 nis more difficult to grow in tissue culture; thus, its epidemiology is less nwell defined. However, it does not appear to be a major cause of illness.

 

PATHOLOGY.

Parainfluenza viruses replicate in the respiratory nepithelium without evidence of systemic spread. The propensity to cause illness nin the upper large airways is presumably related to enhanced replication in the nlarynx, trachea, and bronchi compared with other viruses. The destruction of ncells in the upper airways can lead to secondary bacterial invasion and nresultant bacterial tracheitis. Eustachian tube obstruction can lead to nsecondary bacterial invasion of the middle ear space and acute otitis media.

 

PATHOGENESIS.

 

Illness caused by parainfluenza occurs shortly after ninoculation with the virus. The mechanisms by which viral injury occurs are not nknown. Some parainfluenza viruses induce cell to cell fusion. During the nbudding process, cell membrane integrity is lost, and viruses can induce cell ndeath through the process of apoptosis. The severity of illness correlates with nthe amount of viral shedding. Immune destruction of virally infected cells may nalso occur but appears to be less important with mucosal than systemic ninfection. The level of immunoglobulin A antibody is the best predictor of nsusceptibility to infection. Reinfection is seen particularly with parainfluenza ntype 3 as mucosal immunity wanes. The inability of children with serious T-cell ndefects to clear parainfluenza type 3 suggests a cell-mediated component of nimmunity.

 

CLINICAL MANIFESTATIONS.

Most parainfluenza virus infections are confined to the nupper respiratory tract. Selected signs, symptoms, and clinical diagnoses, nbased on a culture from young children with respiratory illness, are shown iTable 217–1 Table 217–1. The relative frequency of parainfluenza type 3 ncompared with types 1 and 2 is consistent with other epidemiologic studies. nThis relatively mild-appearing illness is belied by a spectrum of rarer but nmore serious illnesses that result in hospitalization. The parainfluenza nviruses account for 50% of hospitalizations for croup and 15% of cases of nbronchiolitis and pneumonia. Parainfluenza type 1 causes more cases of croup, nwhereas parainfluenza type 3 causes a broad spectrum of lower respiratory tract ndiseases. Clinical descriptions of croup, bronchitis, bronchiolitis, and npneumonia are presented in Chapters 170, 327, and 332. Parainfluenza virus ninfections are not associated with high fever. Aside from low-grade fever, nsystemic complaints are rare. The illness usually lasts 4–5 days; however, nvirus may be recovered in low titers for 2–3 wk. Rarely, parainfluenza viruses nhave been implicated in parotitis.

Sites of retructions in croup

 

Viral laryngitis, treated viral laryngitis

 

 

LABORATORY FINDINGS.

There are no distinctive hematologic or chemistry nfindings. The laboratory diagnosis of parainfluenza virus infection can be naccomplished by inoculation of nasal secretions into tissue culture, with npresumptive diagnosis based on finding a hemadsorbing agent and final serotypic ndiagnosis based on hemadsorption inhibition. Direct immunofluorescent staining nhas been used in some centers to identify infected cells in secretions rapidly.

A “pencil” sign in the croup syndrome

 

 

DIAGNOSIS.

The diagnosis of parainfluenza virus infection is nbased on clinical and epidemiologic criteria in most pediatric settings. The nvirus should be specifically sought in persistent pneumonias iimmunosuppressed children. The radiographic “steeple” sign of nprogressive narrowing of the subglottic region is characteristic of parainfluenza nvirus infections.

 

COMPLICATIONS.

In more febrile children and those with more severe nrespiratory compromise, the possibility of a bacterial tracheitis with purulent nmaterial below the epiglottis and vocal cords should be considered. The high nfrequency of otitis complicating parainfluenza virus means that careful npneumatic otoscopy should be performed in all children with suspected nparainfluenza virus infection.

 

PREVENTION.

Work is progressing with both live nand subunit parainfluenza type 3 vaccines. The live vaccines include a ncold-adapted virus of human origin and a bovine parainfluenza virus, which is nattenuated because of host range adaptation. The measure of protection afforded by vaccines will nbe difficult to assess because symptomatic reinfection is seen and the nfrequency of serous infection in the general population is low. Nonetheless, it nis clear that prevention of acute respiratory illness that results from nparainfluenza virus is a worthwhile goal.

 

TREATMENT.

The possibility of rapid respiratory compromise during nsevere croup should influence the level of care given. Careful attention to nsymptomatic care is important as is a description for parents of the parameters nof increasing respiratory distress that should lead to reassessment by a health ncare provider. Humidification and exposure to cold air are both classically nassociated with a decrease in mucosal edema and liquification of secretions nthat may relieve obstruction; however, their value has never been proved in a ncontrolled trial. Aerosolized racemic epinephrine may temporarily improve naeration, but one must be convinced that the improvement will be sustained nbefore discharging the child. Recent nstudies have suggested that aerosolized or systemic steroids were helpful ithe management of croup in the emergency room setting and after nhospitalization. The indications for antibiotics are limited to well-documented nsecondary bacterial infections of the middle ears or lower respiratory tract.

 

Ribavirin has some antiviral activity against parainfluenza virus and nshould be considered in the immunocompromised child with persistent pneumonia.

 

PROGNOSIS.

The prognosis for full recovery is excellent in the normal child. No nlong-term pulmonary residua of parainfluenza virus infection have beedescribed.

 

 

RESPIRATORY SYNCYTIAL VIRUS

 

Respiratory syncytial virus (RSV) is the major cause nof bronchiolitis  and pneumonia iinfants younger than 1 yr. It is the most important respiratory tract pathogen of nearly childhood.

 

ETIOLOGY.

 

RSV is a medium-sized, membrane-bound RNA virus that ndevelops in the cytoplasm of infected cells and matures by budding from the nplasma membrane. It belongs to the family Paramyxoviridae, along with nparainfluenza, mumps, and measles viruses but is classified in a separate ngenus: the pneumoviruses.

 

Although different strains of RSV show some antigenic heterogeneity, nthis variation is primarily seen in only one of the two surface glycoproteins, nand the virus behaves in the human host like a single serotype.

 

RSV grows in a number of types of tissue culture, iwhich it produces characteristic syncytial cytopathology. Specimens for culture nshould be delivered rapidly on wet ice to the laboratory because the virus is nheat labile and very susceptible to destruction by freezing and thawing.

 

EPIDEMIOLOGY. The occurrence of annual outbreaks and the high incidence of infectioduring the first months of life are unique among human viruses. RSV is ndistributed worldwide and appears in yearly epidemics. In temperate climates nthese epidemics occur each winter and last 4–5 mo. During the remainder of the nyear infections are sporadic and uncommon. Epidemics usually peak in January, nFebruary, or March, but peaks have been recognized as early as December and as nlate as June. At these times hospital admissions for bronchiolitis and npneumonia of infants younger than 1 yr increase and decrease in proportion to nthe number of RSV infections in the community. In the tropics, the epidemic npattern is less clear.

 

Placentally transmitted antibody probably has some protective effect, nparticularly when present in high concentration. This may account for the fact nthat severe infections are uncommon in the first 4–6 wk of life. Nevertheless, serum nantibody is not fully protective, and the age at which an infant undergoes nfirst infection depends also on the opportunities for exposure. It is estimated nthat in an urban setting about half of the susceptible infants undergo primary ninfection in each epidemic. Thus, infection is almost universal by the 2nd nbirthday. Reinfection occurs at a rate of 10–20% per epidemic throughout nchildhood; the frequency is lower in adults. In situations of high exposure nsuch as day-care centers, attack rates are higher: nearly 100% for first ninfections and 60–80% for second and subsequent infections.

 

Estimates of the severity of primary infections have nemerged from studies of outbreaks iurseries and institutions. Under these ncircumstances asymptomatic infection is rare. Most infants experience coryza nand pharyngitis, usually with fever and occasionally with otitis. In 10–40% of npatients the lower respiratory tract is involved to a varying degree. nBronchitis, bronchopneumonia, and bronchiolitis all occur. Calculations based non hospital admissions in the United States and Britain yield a ratio of 1–3 ninfants hospitalized with bronchiolitis or pneumonia for every 100 primary ninfections with the virus.

 

Reinfection may occur as early as a few weeks after nrecovery but usually takes place during subsequent annual outbreaks. The nseverity of illness during reinfection is probably as much influenced by age as nby prior experience with this virus; older children are generally less ill. nNevertheless, several instances of severe RSV bronchiolitis occurring twice isuccession have been recorded.

 

Bronchiolitis is the most common clinical diagnosis iinfants hospitalized with RSV infections, although the syndrome is ofteindistinguishable from RSV pneumonia in infants, and, indeed, the two nfrequently coexist. All RSV diseases of the lower respiratory tract (excluding ncroup) have their highest incidence in the 2nd–7th mo of life and decrease ifrequency thereafter. The syndrome of bronchiolitis becomes uncommon after the n1st birthday; acute infective wheezing attacks after that age are often termed n”wheezy bronchitis,” “asthmatoid bronchitis,” or, simply, nasthma attacks. Viral pneumonia is a persistent problem throughout childhood, nalthough RSV becomes less prominent as the etiologic agent after the 1st year. nRSV is responsible for 45–75% of cases of bronchiolitis, 15–25% of childhood npneumonias, and 6–8% of cases of croup.

 

Bronchiolitis and pneumonia resulting from RSV are more common in boys nthan in girls by a ratio of about 1.5:1. Racial factors make little difference. nLower respiratory tract disease, however, occurs more often and earlier in life nin low socioeconomic groups and in crowded living conditions.

 

The incubation period from exposure to 1st symptoms is nabout 4 days. The virus is excreted for variable periods, probably depending oseverity of illness and immunologic status. Most infants with lower respiratory ntract illness shed virus for 5–12 days after hospital admission. Excretion for n3 wk and longer has been documented. Spread of infection occurs when large, ninfected droplets, either airborne or conveyed on hands, are inoculated in the nnose or conjunctiva of a susceptible subject. RSV is probably introduced into nmost families by school children undergoing reinfection. Typically, in the nspace of a few days older siblings and one or both parents acquire colds, but nthe infant becomes more severely ill with fever, otitis, or lower respiratory ntract disease.

 

Hospital cross infection during RSV epidemics is important. Virus is nusually spread from child to child on the hands of caregivers. Symptomatic, ninfected adults have also been implicated in the spread of the infection.

 

PATHOLOGY AND PATHOGENESIS.

Bronchiolitis is characterized by virus-induced nnecrosis of the bronchiolar epithelium, hypersecretion of mucus, and round cell ninfiltration and edema of the surrounding submucosa. These changes result iformation of mucous plugs obstructing bronchioles with consequent nhyperinflation or collapse of the distal lung tissue. In interstitial npneumonia, infiltration is more generalized, and epithelial necrosis may extend nto both the bronchi and the alveoli. Infants are particularly apt to experience nsmall airway obstruction because of the small size of the normal bronchioles.

 

Several facts suggest immunologic injury as a factor nin the pathogenesis of bronchiolitis caused by RSV: (1) infants dying of nbronchiolitis have shown both immunoglobulin and virus in the injured nbronchiolar tissues; (2) children who received a highly antigenic, inactivated, nparenterally administered RSV vaccine experienced, on subsequent exposure to nwild-type RSV, more severe and more frequent bronchiolitis than did their nage-matched controls; (3) bronchiolitis merges into asthma in older infants, nand RSV is a frequently recognized cause of acute asthma attacks in childre1–5 yr old; and (4) immunoglobulin E (IgE) antibody directed toward RSV has nbeen found in the secretions of convalescent infants with bronchiolitis.

 

It is not clear what role, in addition to the ndestructive effect of the virus and the attendant host response, is played by nsuperimposed bacterial infection. In most infants with bronchiolitis, with or nwithout interstitial pneumonia, clinical experience suggests that bacteria play nan insignificant role.

 

CLINICAL MANIFESTATIONS.

 

The first signs of infection of the infant with RSV nare rhinorrhea and pharyngitis. Cough may appear simultaneously but more ofteappears after an interval of 1–3 days, at which time there may also be sneezing nand a low-grade fever. Soon after the cough has developed, the child begins to nwheeze audibly. If the disease is mild, the symptoms may not progress beyond nthis stage. Auscultation often reveals diffuse rhonchi, fine rales, and nwheezes. Rhinorrhea usually persists throughout the illness, with intermittent nfever. Roentgenograms of the chest at this stage are frequently normal.

 

If the illness progresses, cough and wheezing nincrease, and air hunger and evidence of hyperexpansion of the chest and of nintercostal and subcostal retraction occur. The respiratory rate increases, and ncyanosis occurs. Signs of severe, life-threatening illness are central ncyanosis, tachypnea of more than 70 breaths/min, listlessness, and apneic nspells. At this stage the chest may be greatly hyperexpanded and almost silent nto auscultation because of poor air exchange.

 

Chest roentgenograms of infants hospitalized with RSV nbronchiolitis are normal in about 10% of cases; air trapping or hyperexpansioof the chest occurs in about 50%. Peribronchial thickening or interstitial npneumonia is seen in 50–80%. Segmental consolidation occurs in 10–25%. Pleural neffusion is rarely, if ever, seen.

 

Peribronchial nthickening

 

Segmental nconsolidation

 

In some infants the course of the illness may be more nlike that of pneumonia. In these instances, the prodromal rhinorrhea and cough nare followed by dyspnea, poor feeding, and listlessness, with a minimum of nwheezing and hyperexpansion. Although the clinical diagnosis is pneumonia, nwheezing is often present intermittently and the chest roentgenogram may show nair trapping.

 

Fever is an inconstant sign in RSV infection. Rash and nconjunctivitis each occur in a few cases. In young infants, particularly those nwho were born prematurely, periodic breathing and apneic spells have beedistressingly frequent signs, even with relatively mild bronchiolitis. It is nlikely that a small portion of deaths included in the category of sudden infant ndeath syndrome are due to RSV infection.

 

RSV infections in profoundly immunocompromised hosts nmay be severe at any age. The mortality associated with RSV infection in the n1st few weeks after bone marrow or solid organ transplantation may be as high nas 50%.

 

Routine laboratory tests offer little helpful ninformation in most cases of bronchiolitis or pneumonia caused by RSV. The nwhite cell count is normal or elevated, and the differential count may be nnormal or shifted either to the right or left. Bacterial cultures usually grow nnormal flora. Hypoxemia is frequent and tends to be more marked thaanticipated on the basis of the clinical findings. When it is severe, it is nfrequently accompanied by hypercapnia and acidosis.

 

DIAGNOSIS.

Bronchiolitis is a clinical diagnosis. The involvement nof RSV in any particular child’s disease can be suspected with varying degrees nof certainty from the season of the year and the presence of a typical outbreak nat the time. Other features that may be helpful are the age of the child (aside nfrom RSV, the only respiratory virus that attacks infants frequently during the nfirst few months of life is parainfluenza virus type 3) and the family nepidemiology (colds in siblings and parents).

 

The diagnostic dilemma of greatest import is the questioof possible bacterial or chlamydial involvement. When bronchiolitis is mild or nwhen infiltrates are absent by roentgenogram, there is little likelihood of a nbacterial component. In infants 1–4 mo of age, interstitial pneumonitis may be ncaused by Chlamydia trachomatis. In this instance there may be a history of nconjunctivitis, and the illness tends to be of subacute onset. Coughing is nprominent; wheezing is not. There may also be eosinophilia. Fever is usually nabsent.

 

Consolidation without other signs or with pleural neffusion is considered of bacterial origin until proved otherwise. Other signs npointing to bacterial pneumonia are elevation of the neutrophil count, ndepression of the white cell count in the presence of severe disease, ileus or nother abdominal signs, high fever, and circulatory collapse. In such instances nthere is rarely any doubt about the need for antibiotics.

 

Definitive diagnosis of RSV infection is based on the ndetection of virus or viral antigens in respiratory secretions. The specimeshould be put on ice, taken directly to the laboratory, and processed for nantigen detection or inoculated onto susceptible cell monolayers. An aspirate nof mucus from the child’s posterior nasal cavity is the optimal specimen. nNasopharyngeal or throat swabs are also acceptable. A tracheal aspirate is nunnecessary.

 

PROGNOSIS.

 

The mortality of hospitalized infants with RSV ninfection of the lower respiratory tract is about 2%. The prognosis is clearly nworse in young, premature infants or those with underlying disease of the nneuromuscular, pulmonary, cardiovascular, or immunologic system.

 

Many children with asthma have a nhistory of bronchiolitis in infancy. There is recurrent wheezing in 33–50% of nchildren with typical RSV bronchiolitis in infancy. The likelihood of nrecurrence is increased in the presence of an allergic diathesis (eczema, hay nfever, or a family history of asthma). In bronchiolitis in patients older tha1 yr there is an increasing probability that, though it may be virus induced, nthis is the first of multiple wheezing attacks that will later be called asthma.

 

TREATMENT.

 

In uncomplicated cases of bronchiolitis, treatment is nsymptomatic. Humidified oxygen is usually indicated for hospitalized infants nbecause most are hypoxic. Many infants are slightly to moderately dehydrated; ntherefore, fluids should be carefully administered in somewhat greater thamaintenance amounts. Often intravenous or tube feeding is helpful when sucking nis difficult. Most infants seem to breathe better when propped up at an angle nof 10–30 degrees.

 

Bronchodilators should not be routinely used. However, na trial of albuterol aerosols should be made in wheezing children and nbronchodilators administered if aerosols are beneficial. Corticosteroids are nnot indicated except as a last resort in critical cases. Sedatives are rarely nnecessary.

 

In most instances antibiotics are not useful, and ntheir indiscriminate use in presumed viral bronchiolitis and pneumonia should nbe discouraged. Interstitial pneumonia in infants 1–4 mo old may be chlamydial, nand erythromycin (40 mg/kg/24 hr) may, therefore, be beneficial. When infants nwith interstitial pneumonia are older, or when consolidation is found, nparenteral antibiotics may be indicated. In the critically ill child nantibiotics may also be indicated.

 

The antiviral drug ribavirin, delivered by nsmall-particle aerosol and breathed, along with the required concentration of noxygen, for 20 of 24 hr per day for 3–5 days, has a modest beneficial effect othe course of RSV pneumonia. Shortened hospital stay and reduced mortality have nnot been demonstrated, and long-term effects are still unknown. Its use is, ntherefore, indicated only in very sick infants or in high-risk infants, such as nthose with underlying cyanotic congenital heart disease, significant nbronchopulmonary dysplasia, or severe immunodeficiency. It should be nadministered early in the course of the infection.

 

PREVENTION.

 

Within the hospital the most important preventive nmeasures are aimed at blocking nosocomial spread. During RSV season high-risk ninfants should be separated from infants with respiratory symptoms. Separate ngowns and gloves and careful handwashing should be used for the care of all ninfants with suspected or established RSV infection.

 

Attempts to develop useful inactivated or attenuated nvaccines have been unsuccessful. Indeed, the insufficiency of protectiofollowing natural RSV infection diminishes the likelihood that an attenuated nvaccine will prevent subsequent disease. Trials of monthly high-titered nintravenous Ig have demonstrated some reduction in the severity of RSV ninfections in high-risk infants. Passive immunoprophylaxis appears to be a npromising approach to prevention.

 

 

ADENOVIRUSES

 

 Adenoviruses cause n5–8% of acute respiratory disease in infants, plus a wide array of other nsyndromes including pharyngoconjunctival fever, follicular conjunctivitis, nepidemic keratoconjunctivitis, hemorrhagic cystitis, acute diarrhea, nintussusception, and encephalomyelitis. Only a third of the 37-plus serotypes nhave been associated with disease. Although fatalities are rare, they are nassociated with infections by certain serotypes (particularly type 7) and with ninfections in severely immunocompromised hosts.

 

ETIOLOGY.

 

Adenoviruses are DNA viruses of intermediate size, nwhich are classified into subgenera A to G. Types 1–39 are in subgenera A to E, ntype 40 is subgenus F, and type 41 is subgenus G. The virion has an icosohedral ncoat made up of several proteins, the most abundant of which is the n”hexon,” a cross-reacting antigen common to all mammaliaadenoviruses. The “penton” confers type specificity, and antibody to nit is protective. It is also cytotoxic in tissue culture, and toxic properties nhave been ascribed to it in vivo as well. Adenoviruses can also be classified nby the “fingerprints” their DNA make on gels after being digested nwith restriction endonucleases, and this classification generally conforms to ntheir antigenic types.

 

All adenovirus types except types 40 and 41 grow iprimary human embryonic kidney cells, and most grow in HEp-2 or HeLa cells, nproducing a typical destructive cytopathic effect. Types 40 and 41 (and other nserotypes as well) grow in 293 cells, a line of human embryonic kidney cells ninto which certain “early” adenovirus genes have been introduced.

 

Many adenovirus types, but particularly the commochildhood types (1, 2, and 5), are shed for prolonged periods from both the nrespiratory and gastrointestinal tracts. These types also establish low-level nand chronic infection of the tonsils.

 

EPIDEMIOLOGY.

 

Adenoviral infections are distributed worldwide. They noccur year-round but are most prevalent in spring or early summer and again imidwinter in temperate climates. Certain types tend to occur in epidemics, nnotably types 4 and 7 iepidemics of febrile respiratory disease, types 3, 7, and 21 in severe pneumonia, type 3 in pharyngoconjunctival nfever, type 11 icystitis, and types 8, 19, and 37in epidemic keratoconjunctivitis. For unexplained nreasons, adenovirus types 3 and 7 cause frequent severe epidemics of pneumonia nin the children of northern China, with mortality rates of 5–15%.

 

Over 60% of school-age children have antibodies to the ncommon respiratory types. Almost all adults have serum antibody to types 1–7. nInfections with types 1 and 2 tend to occur during the 1st yr or 2 of life, and ntypes 3 and 5 occur a little later. Spread occurs by the respiratory and nfecal-oral routes, although it is not clear whether spread is by large- or small-particle naerosol. Hospital outbreaks of respiratory disease and keratoconjunctivitis nhave been described.

 

PATHOLOGY AND PATHOGENESIS.

 

Adenoviruses are one of the few n”respiratory” viruses that grow well in the epithelium of the small intestine. nAlthough mucosal surfaces are the primary target early in infection, it is nlikely that viremia is common, accompanying fever. Viremia is, however, of nlittle consequence except in rare instances or in the immunocompromised npatient.

 

Adenoviral pneumonia produces characteristic nmicroscopic changes, with dense lymphocytic infiltrates, destruction of the nbronchial and bronchiolar epithelium, focal necrosis of mucous glands, hyaline nmembrane formation, and several types of nuclear inclusion bodies.

 

CLINICAL MANIFESTATIONS.

Adenoviruses cause a wide array of syndromes:

Acute Respiratory Disease. This is the most common manifestation of adenovirus ninfection in children and adults. Acute respiratory infections in infants and nchildren are not clinically distinctive and are usually caused by types 1, 2, n3, 5, or 6. They are usually mild but may be complicated or severe. Primary ninfections in infants are frequently associated with fever and respiratory nsymptoms and in some series are complicated by otitis in more than half of the npatients. Adenovirus respiratory infections are associated with a significant nincidence of diarrhea.

 

Pharyngitis is a characteristic clinical syndrome, and nadenoviruses can be identified in 15–20% of children with isolated pharyngitis, nmostly in preschoolers and infants. The pharyngitis may be exudative and is noften febrile. Most cases are due to type 1, 2, 3, or 5.

 

Pneumonia is uncommon but 7–9% of hospitalized children with nacute pneumonia have adenovirus infection. Any of the “respiratory” ntypes can cause pneumonia, but severe infections are most likely due to type 3, n7, or 21. Such infections have a mortality as high as 10%, and survivors may nhave residual airway damage, manifested by bronchiectasis, bronchiolitis nobliterans, or, rarely, pulmonary fibrosis.

 

A pertussis-like syndrome has been described in association with adenovirus ninfections. In such instances adenoviruses frequently accompany Bordetella npertussis as coinfecting agents, but they may also be causative on their own. nIn many cases this illness represents activation of latent or low-level chronic nrespiratory or tonsillar infection by the virus. With improved methods for ndetecting B. pertussis, doubt has increased that adenovirus (or any respiratory nvirus) can produce the classic pertussis syndrome on its own.

 

Pharyngoconjunctival fever is a clinically distinct syndrome that occurs nparticularly in association with type 3 adenoviral infection. Features include na high fever that lasts 4–5 days, pharyngitis with characteristic involvement nof pharyngeal lymphoid tissue, conjunctivitis, preauricular and cervical nadenopathy, and rhinitis. Nonpurulent conjunctivitis occurs in 75% of patients nand is manifested by inflammation of both the bulbar and palpebral conjunctivae nof one or both eyes; it often persists after the fever and other symptoms have nresolved. Headache, malaise, and weakness are common, and there is considerable nlethargy after the acute stage.

 

Conjunctivitis and Keratoconjunctivitis. Adenovirus is one of the most common causes of nfollicular conjunctivitis and keratoconjunctivitis. The former is a relatively nmild illness. The latter, which may occur in epidemics, is associated with ninfection by adenovirus types 8, 19, and 37. The disease may cause corneal opacities nthat last several years.

 

 

 

 

Gastrointestinal Infections. Adenoviruses can be found in the stools of 5–9% of nchildren with acute diarrhea. About one half of these are the n”enteric” types, 40 or 41. It is also clear that enteric infection with nany adenovirus serotype is often asymptomatic, so the causative role in these nepisodes is frequently uncertain.

 

The pathogenesis of intussusception is thought by many nto include enlarged lymph nodes as an initiating factor. Adenoviruses have beerecovered from mesenteric lymph nodes at surgery and also from surface cultures nin a higher percentage of children with intussusception than from controls. nAdenoviruses have also been found in the appendices of children with nappendicitis. Whether these findings represent acute etiologic relationships or nare manifestations of a protracted, low-level intestinal infection analogous to nthat described in the tonsils is not clear.

 

Hemorrhagic Cystitis. This syndrome has a sudden onset of bacteriologically nsterile hematuria, dysuria, frequency, and urgency lasting 1–2 wk. Infectiowith adenovirus types 11 and 21 has been found in some affected children and nyoung adults.

 

Reye Syndrome and Reye-like Syndromes. Typical Reye syndrome has followed demonstrated nadenovirus infection of several serotypes, particularly in very young children. nIn addition, several cases of a Reye-like syndrome have been reported, all of nwhich are caused by infection with adenovirus type 7. The latter disease, which nis frequently fatal, is characterized by severe bronchopneumonia, hepatitis, nseizures, and disseminated intravascular coagulation. Circulating adenovirus npenton antigen has been found in several patients and has been implicated ithe pathogenesis.

 

Infections in Immunocompromised Hosts. Adenoviruses are important pathogens in the nimmunocompromised host. This includes those with either B- or T-cell ndeficiencies. In B cell–deficient children, a chronic meningoencephalitis very nsimilar to that caused by enteroviruses has been described. In T cell–deficient npatients, regardless of whether this deficiency is congenital, acquired, or niatrogenic, fulminant hepatitis and pneumonia, frequently with a fatal outcome, nhave been described. There is also a close association between adenovirus infectioand both hemorrhagic cystitis and tubulointerstitial nephritis iimmunosuppressed children.

 

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

 

The laboratory diagnosis of adenovirus infection ichildren may be made by culture (or other method of identifying the presence of nthe virus), demonstration of a rise in serum antibody level, or some ncombination of the two. If virus is found in a “privileged” site, nsuch as blood, urine, or cerebrospinal fluid, or in a biopsy of the lung or nliver, the implication of infection with disease and organ damage is strong. nLikewise, detection of certain adenovirus types in respiratory secretions (type n7 or 21) probably indicates their etiologic involvement. The presence of nuntyped virus or the common childhood types in respiratory secretions or stool ndoes not, however, indicate clinical adenovirus infection because these viruses nmay be excreted chronically and asymptomatically. In these instances, discovery nof a coincident rise in antibody by either complement fixation or some more ntype-specific test is helpful in assigning a specific microorganism to disease. nAdenovirus infection may also be considered etiologic if a rise in antibody is nfound between sera drawn in the acute stage and in convalescence from a patient nwith an appropriate illness. Adenovirus infection often results in a high nerythrocyte sedimentation rate and white cell count.

 

Differential diagnosis is complex and depends on which nsyndrome is seen.

 

PREVENTION AND TREATMENT.

 

Vaccines that contain either killed or live virus have nbeen developed to prevent types 4 and 7 infections in military recruits. These nvaccines have not, however, been used in children. There are at present no nrecognized antiviral agents that are effective in treating adenovirus ninfections. Ribavirin can inhibit viral growth of some strains in vitro, but nevidence of its clinical efficacy is lacking.

 

 

RHINOVIRUS

 

 Rhinoviruses, ncollectively the most common cause of the “common cold” in adults, nrepresent a smaller proportion of infections in young children because of the nfrequency of other viral respiratory infections. Also rhinoviral infections iyoung children often do not produce respiratory illness. However, rhinoviruses nspread readily, producing illness iursery and other school groups, and these nchildren provide a major link in their spread within families.

 

ETIOLOGY.

There are 111 serologically distinct rhinoviruses, all nmembers of the Picornavirus family of small RNA viruses. They are best identified nby inoculating human embryonic kidney or human diploid cell cultures with nasal nsecretions from infected individuals and waiting to observe a cytopathic neffect. Routine serologic testing for acquisition of antibody is not practical nbecause of the multiplicity of types and infrequency of their cross-reactivity.

 

Several cross-sectional studies indicate that a low npercentage of control children or children with diarrhea (1%) yield nrhinoviruses at the time of sampling; similarly, only 2.2% of children with respiratory ntract illness yield rhinoviruses. In longitudinal studies, however, 75% of npediatric rhinovirus infection is associated with illness, usually rhinitis or nthe pharyngitis-bronchitis syndrome. Rhinoviruses have also occasionally beeassociated with serious lower respiratory tract disease, particularly iinfants with underlying illnesses. They are frequent precipitants of asthma ichildren and chronic bronchitis in adults.

 

EPIDEMIOLOGY. Rhinoviruses are distributed worldwide with no npredictable pattern of infection by serotype. Multiple types may be present ia community at one time.

In temperate climates the incidence of rhinoviral ninfection peaks in September and again in April or May, but some infections noccur year-round. The peak incidence in the tropics occurs during the rainy nseason.

 

Rhinoviruses are recovered in highest concentration inasal secretions, and experimental infection is most easily accomplished by nnasal or conjunctival instillation. Infection via aerosol is less efficient. Virus npersists for several hours in secretions on hands or other surfaces. nTransmission probably occurs when infected secretions carried on contaminated nfingers are rubbed into the nasal or conjunctival mucosa. More recent evidence nalso implicates spread through prolonged contact with aerosols produced by ntalking, coughing, or sneezing.

 

PATHOGENESIS.

The peak nasal inflammatory response occurs when virus ngrowth is at its greatest, 2–4 days after experimental infection. Immune nresponses include specific nasal immunoglobulin (Ig) A and serum IgG antibody, nwhich may contribute to modifying the illness and limiting viral shedding. nInterferon and a nonspecific factor induced by infection with a heterotypic nrhinovirus may be a part of the resistance mechanism. Usually the inflammatory nresponse is limited to the nose, throat, and upper bronchial passages, but npneumonia has occurred.

 

CLINICAL MANIFESTATIONS.

The primary clinical response to rhinoviral infection, nlike that to most respiratory viral infections, is the common cold. There is aincubation period of 2–4 days; then sneezing, nasal obstruction and discharge, nand sore throat ensue. Cough and hoarseness occur in 30–40% of cases. Headache nand other systemic symptoms are not as common as in influenza. Fever is neither nas frequent nor as high as in primary infections with respiratory syncytial nvirus, parainfluenza virus, influenza virus, or adenovirus. Symptoms are worse nin the first 2–3 days of illness and last for a week in a majority of patients; nthey persist for over 14 days in 35% of young children.

 

COMPLICATIONS.

These are like those of any infection causing edema nand inflammation in the nasopharyngeal area. They include otitis media, nsinusitis, local spread down the respiratory tract, bacterial superinfection, nand, in certain atopic children, acute wheezing. In one study rhinoviruses were nthe most common virus recovered from the middle ear fluids of infants and nchildren with otitis media.

 

DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS.

Because other viral agents can produce the same nmanifestations, a clinical diagnosis is only presumptive. Laboratory diagnosis nis not practical under ordinary circumstances. If any question exists, nbacterial cultures should be taken to exclude streptococcal infection.

 

TREATMENT AND PREVENTION.

There is no specific preventive or ameliorative ntreatment. Careful hand washing and avoidance of manual nose and eye nmanipulation is the best approach to reducing spread. For relief of acute nsymptoms, a mild analgesic and saline or decongestant nose drops may be used nfor a short time. Interferon administered by nasal spray may be of value ipreventing rhinovirus infection.

 

Short statement of the material

Influenza is a communicable acute infectious disease that is caused by nRNA-containing viruses and is characterized by the specific symptoms of nintoxication and catarrhal signs of the upper respiratory tract.

 

Etiology:  Influenza nviruses are negative-strand RNA viruses (ortomyxoviruses) of three major nantigenic types – A, B, C. All have the property hemagglutination and possess nthe enzyme neuraminidase.

 

Epidemiology: n

·                       nSource nof infection is ill person with typical or atypical influenza.

·                       nWay of spreading n- droplet with infected drops produced by coughing and sneezing.

·                       nSusceptible norganisms – people of all age groups.

During periods nof epidemic or pandemic spreading, respiratory infections by influenza may nexceed all other etiology. Influenza infections have marked seasonality; nepidemic occurs almost exclusively in winter month.

 

Pathogenesis:

1.                    nInoculatioof virus in upper respiratory tract epithelial cells.

2.                    nDestructioand necrosis of epithelial cells.

3.                    nImmune nresponse.

4.                    nViremia.

5.                    nToxic influence of cardiovascular and ncentral nervous systems.

6.                    nDepression of immunity response – nbacterial complication.

7.                    nAllergy to viral parts – autoallergic ncomplication.

 

Clinical ncriteria:

The incubatioperiod of influenza ranges from few hours to 1-2 days, if contact transmissio– up to 7 days, but is commonly 2 to 3 days.  nThe symptoms and signs of ”classic” influenza in older childreinclude abrupt onset, with fever and associated flushes face, chills, headache, nmyalgia and malaise. The temperature range is from 39º C to 41º C. nAlthough a dry cough and corryza are also early manifestation of influenza. A nsore throat occurs in over half the cases and is associated with nonexudative nPharyngitis. Ocular symptoms include tearing, photophobia, burning, and paiwith eye movement [ophthalmodynia]. In severe cases signs of toxic capillaritis nwith petechia on the face, chest, or hemorrhages into sclera may be present (photo 87, 88). In uncomplicated illness, the fever usually persists nfor 2 to 3 days, but may last up to 5 days. By the second to the fourth days, nrespiratory symptoms become more prominent, and the systemic complaints begito subside. The cough is dry and hacking, and usually persists for 4 to 7 days. nIn young children laryngotracheitis, bronchitis, bronchiolitis, pneumonia, and nthe common cold all occur. Affected children appear moderately toxic, with nclear nasal discharge, cough and irritability. Pharyngitis is usually present, nwith diffuse erythema and boggy, enlarged tonsilar tissue. Gastrointestinal nsymptoms have beeoted in young children. Febrile convulsion may be iseveral studies. Acute laryngotracheitis [croup] has beeoted as a prominent nfeature of influenza A.

 

 

 

Petechia non the face

 

Hemorrhage ninto sclera

 

Classification of influenza, diagnostic criteria

 

 

By the type:

 ––  typical forms (catarrhal, subtoxic, toxic, toxic–catarrhal)

–– natypical forms (subclinical, hypertoxic)

 

Variants (by the main syndrome):

·        nCroup syndrome,

·        nObstruction syndrome,

·        nPrimary lung’s damage,

·        nSegmentary  lung’s damage,

·        ncerebral syndrome,

·        nabdominal syndrome,

·        nhemorrhagic syndrome,

 

Peculiarities nin infants:

·        nless nacute beginning,

·        nless nintoxication,

·        nsmall nrespiratory  symptoms,

·        nrare croup syndrome,

·        noften dyspeptic syndrome (vomiting, ndiarrhea),

·        npoor feeding,

·        ndecrease of body weight,

·        nbacterial infection complications n[otitis, pneumonia] and mortality appear more often.

 

Complications:    

1.     nViral: nencephalitis, meningitis, neuritis.

2.     nBacterial: npneumonia, otitis, laryngotracheitis.

3.     nReye’s nsyndrome.

   

Laboratory nwork-up:

·        nIdentifying of virus antigens iasopharyngeal smears by nimmunefluorescence reaction.

·        nSerologic diagnosis to find antibodies against nviruses (CBR, DHAR) with fourfold increasing of antibodies title in 10-14 days may be used.

 

Diagnosis nexample: Influenza A, typical catarrhal form: tracheitis, nmoderate degree

 

Differential diagnosis between other respiratory viruses as parainfluenza, nRS-infection, adenovirus infection and group A streptococcal diseases [angina, nscarlet fever], typhoid fever, enterovirus infection, intestinal infections n(shigella, salmonella, rotavirus ets.), meningococcal infection, pertussis, nmeasles, viral hepatitis A.

  

Treatment: 

Hospitalization for patients nwith:

1. Flu-like diseases that are accompanied:

–         nby ncyanosis;

–         nby ndyspnea;

–         nby nphysical changes in lungs;

–         nby nhemorrhagic displays: hemorrhagic rash, hemathemesis;

–         nmultiple nvomit and diarrhea (over 3 times per day);

–         nbradycardia nas compared to an age-old norm; arrhythmia of other character;

–         nby nhypotension on 30% below the norm;

–         nby nviolation of consciousness, cramps, surplus excitation or expressed languor.

2. Flu-like syndrome in children with concomitant diseases, which are nrisked to develop complications:

–         nchronic npulmonary diseases, as bronchial asthma;

–         nendocrine npathology – excessive weight more than 30%; severe diabetes mellitus;

–         nimmunedefficiencies n– hemolytic anemia, primary immunedefficiencies, asplenia, hemoglobinopathies, nHIV-infection, prolong immunosuppressive therapy, oncologic and noncohemathologic diseases, decompensated chronic cardio-vascular diseases; nkidneys insufficiency.

3. Hospitalization by epidemiologic evidences:

–         nchildren, nthat are in the closed child’s collectives;

–         nchildrefrom social risky families.

Treatment of patients with the severe flu mast be in hospital in the nisolated boxes.

 

Basic therapy (for all npatients independantly from the disease severity):

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

2.     nVitaminized nmilk-vegetable food.

3.     nAdequate nrehydration with oral fluids (lemon tea, raspberry tea, warm alkalic drinks).

4.     nControl of nfever and myalgia (when the temperature is more than 38.5 °C in childreelder 3 months); in children before 3 months and in case of perinatal CNS ndamage, seizures in the history, severe heart diseases – when the temperature nis more than 38 °C nwith acetaminophen (paracetamol 10-15 mg/kg not often than every 4 hours (not nmore than 5 times per day) or ibuprophen 5-10 mg/kg per dose, not often thaevery 6 hours. For better effect those two drugs may be given in order one by nanother with 4 hours interval between them (paracetamol 10 mg/kg, ibuprophen 5 nmg/kg per dose). Acetylsalicylic nacid medicine as antipyretic is contraindicated because of possible ncomplication by the Reye’s syndrome!!!

5.     nNasal drops n(in infants before 6 mo – only physiologic saline solutions as Salin; in elder nchildren – decongestants: naphtizin, rhinasolin, nasivin for children 1-2 drops n3 t.d. in the nostrils, not more than 3-5 days).

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

7.     nMucolytics nin case of the moist nonproductive cough (ambroxol, acetylcystein etc.), are not nrecommended for the infants before 1 year.

8.     nHistamine nblockers of the 1st generation (2nd and 3rd are ineffective) as chlorpyramine n(suprastin) 1-3 mg/kg decrease cough and sneezing. They should be used not more nthan 3-5 days because of the sleepiness effect.

• Combined mucolytics and nantihystamines are not recommended before 6 years, and it is better not to use nthem in 6-12 years.

Before hospitalization to the ndepartment in severe cases SpO2 is nmeasured:

·        nIf it is less nthan 90 % – an inhalation of 100 % O2 for an hour:

–         nIf it nbecomes normal – hospitalisation to the infectious department,

–         nIf it is nstill less thaormal – hospitalisation to the intensive care unit.

·        nIf it is nnormal – hospitalisation to the infectious department.

 

Antiviral treatment (specific for influenza virus)

Antiviral treatment of severe, ncomplicated forms, for the children with the chronic respiratory or ncardiovasculary diseases, immune defficit, diabetes mellitus or obesity, nchildren before 5 years, with chronic decompensated liver and kidneys diseases:

1. Oseltamivir (Tamiflu) – is neffective against influenza A and B. It is given for children elder than 12 nyears 75 mg/dose in capsules 2 times a day, for children 1-12 years – in oral nsolution:

to 15 kg – 30 mg twice a day

15-23 kg – 45 mg twice a day

23-40 kg – 60 mg twice a day

* Solution is prepared naccording the instruction.

This medicine is appointed at nfirst 48 hours from the disease beginning for 5 days.

2. Zanamivir (Relenza) is neffective against influenza A and B – in inhalations from 5 years as medicine nof the 2nd row (could provoke bronchial obstruction).

 

Broad spectrum Antiviral ntherapy (for mild and moderate forms nin children elder than 5 years without concomitant diseases)

1. Arbidolum from 2 years (2-6 nyears 50 mg 4 times per day, 6-12 years 100 mg 4 times per day) for 5 days.

2. Remantadin is effective nagainst seasonal influenza A, is given for children elder than 7 years for 3-5 ndays.

3. Inosini pranobex 50-100 nmg/kg/daily in 3-4 doses for 5 days.

4. Synthetic interferoinductors: tiloron (amixin) from 7 years, cycloferon from 4 years, amizonum nfrom 6 years.

Virus of influenza А (H1N1 California) is stable nto Amantadine or Remantadine,

Amizonum.

Antiviral ntherapy of influenza А n(H1N1 California) is nindicated in severe cases

For mild and moderate forms antiviral therapy is not used.

Antiviral therapy influenza А (H1N1 California) also is indicated to people who are risked to develop complications.

Oseltamivir – to the children elder than 13 years is appointed icapsules 75 mg 2 times a day during 5 days. This medicine is appointed at first n48 hours from the disease beginning.

for children from 1 year and elder – in solution:

to 15 kg n– 30 mg twice a day

15-23 kg n– 45 mg twice a day

23-40 kg n– 60 mg twice a day

* Solution is prepared according the instruction.

Virus of influenza А (H1N1 California) is stable to amantadine or nremantadine.

Virus of influenza А (H1N1 California) is stable to Amizon.

 

Antibiotics are appointed

1. In case of ncomplications caused by bacteria, micoplasm or chlamydia, as:

• Middle otitis

• Sinusitis

• Acute tonsillitis

• Bronchitis

• Pneumonia

2. At suspicion of secondary bacterial ninfection, children that are risky for bacterial infection development, with nbody temperature > 38°C more than 3 days, leucocytosis more than 15 x 10⁹/l. nAntibiotics from the following groups are used:

• Macrolydes (clarythromycin, nazithromycin, spiramycin);

• Aminopenicillines protected nby clavulanic acid (amoxacillin clavulanate);

• Cefoperason in combinatiowith sulbactam (cefuroxim, cefpodoxim);

• Cephalosporines of 3rd-4th ngeneration also are used;

• At presence of the nmethycillinresistant staphylococcus – vancomycin,

·        nin case of nnosocomeal pneumonia carbapenems are appointed.

 

Prevention specific

1.     nSpecial nprevention by immunization .Only inactivated influenza vaccines are licensed nfor use [whole virus vaccines and split-product]. Influenza vaccine is nspecially recommended for children 6 months of age and older. First time nvaccineers less than 9 year of age need to receive two doses of vaccine nseparated by a 1-month interval.

2.     nRemantadin, narbidol, recombined interpheron during 10-14 days.

 

An evidences to the obligatory nvaccination of children:

–         nChildrewith chronic broncho-pulmonary diseases;

–         nChildrewith cardiac diseases with the changed hemodynamics;

–         nChildrewith hemolytic anemia;

–         nChildrewith diabetes mellitus;

–         nChildren, nwhich receive immunosuppressive therapy;

–         nChildrewith metabolic diseases;

–         nChildrewith the chronic kidneys’ diseases;

–         nChildren, nwhich get Acetylsalicylic acid therapy because of rheumatoid arthritis, and nothers like that;

–         nChildrewith HIV-infection;

–         nChildren, which nare in the closed child’s establishments.

A vaccine must be entered n1-1,5 months prior to the seasonal growth of influenza morbidity (iSeptember-November).

All other people vaccinatioagainst influenza can be done because of necessity or at pleasure.

 

Prophylaxis of influenza n(nonspecific):

–         nTo avoid a ncontact with people which have displays of influenza infection;

–         nTo limit nvisits of places with large accumulation of people;

–         nTo ventilate nan apartment oftenly;

–         nTo teach nchildren to wash hands with soap during 20 seconds;

–         nTo teach nchildren to cough and sneeze in a serviette;

–         nTo aim not nto touch eyes, nose or mouth by unwashed hands;

–         nTo avoid ncuddles, kisses and greeting by hands;

–         nTo cover a nnose and mouth at a sneeze or cough by nasal serviette which at once it is nneeded to throw out after the use;

–         nTo teach nchildreot to stay with the patients nearer than on one and a half – two nmeters;

–         nIll childremust stay at a home (not to visit preschool establishments and schools);

–         nThe moist ncleaning up of apartments is needed not less than two times a day.

 

Croup Syndrome

 

The lumen of an infant’s or child’s airway is narrow; nbecause airway resistance is inversely proportional to the 4th power of the radius, nminor reductions in cross-sectional area due to mucosal edema or other ninflammatory processes cause an exponential increase in airway resistance and a nsignificant increase in the work of breathing. The larynx is composed of 4 nmajor cartilages (epiglottic, arytenoid, thyroid, and cricoid cartilages, ordered from superior to inferior) and the soft tissues that surround nthem. The cricoid cartilage encircles the airway just below the vocal cords and ndefines the narrowest portion of the upper airway in children <10 yr of nage.

Inflammation involving the vocal cords and structures ninferior to the cords is called laryngitis, laryngotracheitis, orlaryngotracheobronchitis, and inflammation of the structures superior to the ncords (i.e., arytenoids, aryepiglottic folds [“false cords”], epiglottis) is ncalled supraglottitis. The nterm croup refers to a heterogeneous group of mainly acute and ninfectious processes that are characterized by a bark-like or brassy cough and nmay be associated with hoarseness, inspiratory stridor, and respiratory ndistress. Stridor is a harsh, high-pitched respiratory sound, which is nusually inspiratory but can be biphasic and is produced by turbulent airflow; nit is not a diagnosis but a sign of upper airway obstruction. Croup typically naffects the larynx, trachea, and bronchi. When the involvement of the larynx is nsufficient to produce symptoms, they dominate the clinical picture over the ntracheal and bronchial signs. Traditionally, a distinction has been made nbetween spasmodic or recurrent croup and laryngotracheobronchitis. Some nclinicians believe that spasmodic croup might have an allergic component and nimproves rapidly without treatment, whereas laryngotracheobronchitis is always nassociated with a viral infection of the respiratory tract. Others believe that nthe signs and symptoms are similar enough to consider them within the spectrum nof a single disease, in part because studies have documented viral etiologies nin both acute and recurrent croup.

Infectious Upper nAirway Obstruction

Etiology and nEpidemiology

With the exceptions of diphtheria, bacterial ntracheitis, and epiglottitis, most acute infections of the upper airway are caused nby viruses. The parainfluenza viruses (types 1, 2, and 3;   account for ∼75% of ncases; other viruses associated with croup include influenza A and B, nadenovirus, respiratory syncytial virus (RSV), and measles. Influenza A has nbeen associated with severe laryngotracheobronchitis. Mycoplasma pneumoniae has rarely been isolated from children with croup and ncauses mild disease .Most patients with croup nare between the ages of 3 mo and 5 yr, with the peak in the 2nd yr of nlife. The incidence of croup is higher in boys; it occurs most commonly in the nlate fall and winter but can occur throughout the year. Recurrences are nfrequent from 3-6 yr of age and decrease with growth of the airway. nApproximately 15% of patients have a strong family history of croup.

In the past, Haemophilus influenzae type b was the most commonly identified etiology of nacute epiglottitis. Since the widespread use of the HiB vaccine, invasive ndisease due to H. influenzae type b in pediatric patients has been reduced by n80-90% . Therefore, other agents, such as Streptococcus pyogenes, Streptococcus pneumoniae, and Staphylococcus naureus, now represent a larger nportion of pediatric cases of epiglottitis in vaccinated children. In the prevaccine nera, the typical patient with epiglottitis due to H. influenza type b was 2-4 yr of age, although cases were seen in the 1st year nof life and in patients as old as 7 yr of age. The typical patient with nepiglottitis is an adult with a sore throat, although cases still do occur iunderimmunized children; vaccine failures have been reported.

Clinical nManifestations

Croup n(Laryngotracheobronchitis)

Viruses most commonly cause croup, the most commoform of acute upper respiratory obstruction. The termlaryngotracheobronchitis refers to viral infection of the nglottic and subglottic regions. Some clinicians use the termlaryngotracheitis for the most common and most typical form of croup and nreserve the termlaryngotracheobronchitis for the more severe form that is considered aextension of laryngotracheitis associated with bacterial superinfection that noccurs 5-7 days into the clinical course.

Most patients have an upper respiratory tract ninfection with some combination of rhinorrhea, pharyngitis, mild cough, and nlow-grade fever for 1-3 days before the signs and symptoms of upper airway nobstruction become apparent. The child then develops the characteristic n“barking” cough, hoarseness, and inspiratory stridor. The low-grade fever capersist, although temperatures can reach 39-40°C (102.2-104°F); some childreare afebrile. Symptoms are characteristically worse at night and often recur nwith decreasing intensity for several days and resolve completely within a nweek. Agitation and crying greatly aggravate the symptoms and signs. The child nmay prefer to sit up in bed or be held upright. Older children usually are not nseriously ill. Other family members might have mild respiratory illnesses with nlaryngitis. Most young patients with croup progress only as far as stridor and nslight dyspnea before they start to recover.

Physical examination can reveal a hoarse voice, ncoryza, normal to moderately inflamed pharynx, and a slightly increased nrespiratory rate. Patients vary substantially in their degrees of respiratory distress. nRarely, the upper airway obstruction progresses and is accompanied by aincreasing respiratory rate; nasal flaring; suprasternal, infrasternal, and nintercostal retractions; and continuous stridor. Croup is a disease of the nupper airway, and alveolar gas exchange is usually normal. Hypoxia and low noxygen saturation are seen only when complete airway obstruction is imminent. nThe child who is hypoxic, cyanotic, pale, or obtunded needs immediate airway nmanagement. Occasionally, the pattern of severe laryngotracheobronchitis is ndifficult to differentiate from epiglottitis, despite the usually more acute nonset and rapid course of the latter.

Croup is a clinical diagnosis and does not require a nradiograph of the neck. Radiographs of the neck can show the typical subglottic nnarrowing, or steeple sign, of croup on the posteroanterior view (Fig. 1). However, the steeple sign may be nabsent in patients with croup, may be present in patients without croup as a nnormal variant, and may rarely be present in patients with epiglottitis. The nradiographs do not correlate well with disease severity. Radiographs should be nconsidered only after airway stabilization in children who have an atypical npresentation or clinical course. Radiographs may be helpful in distinguishing nbetween severe laryngotracheobronchitis and epiglottitis, but airway management nshould always take priority.

n

Figure 1  Radiograph of an airway of a patient with croup, showing typical subglottic narrowing (steeple sign).

n

Acute Epiglottitis n(Supraglottitis)

This dramatic, potentially lethal condition is ncharacterized by an acute rapidly progressive and potentially fulminating ncourse of high fever, sore throat, dyspnea, and rapidly progressing respiratory nobstruction. The degree of respiratory distress at presentation is variable. nThe initial lack of respiratory distress can deceive the unwary clinician; nrespiratory distress can also be the 1st manifestation. Often, the otherwise nhealthy child suddenly develops a sore throat and fever. Within a matter of nhours, the patient appears toxic, swallowing is difficult, and breathing is nlabored. Drooling is usually present and the neck is hyperextended in an attempt nto maintain the airway. The child may assume the tripod position, sitting nupright and leaning forward with the chin up and mouth open while bracing othe arms. A brief period of air hunger with restlessness may be followed by nrapidly increasing cyanosis and coma. Stridor is a late finding and suggests nnear-complete airway obstruction. Complete obstruction of the airway and death ncan ensue unless adequate treatment is provided. The barking cough typical of ncroup is rare. Usually, no other family members are ill with acute respiratory nsymptoms.

The diagnosis requires visualization of a large, ncherry red, swollen epiglottis by laryngoscopy. Occasionally, the other nsupraglottic structures, especially the aryepiglottic folds, are more involved nthan the epiglottis itself. In a patient in whom the diagnosis is certain or nprobable based on clinical grounds, laryngoscopy should be performed nexpeditiously in a controlled environment such as an operating room or nintensive care unit. Anxiety-provoking interventions such as phlebotomy, nintravenous line placement, placing the child supine, or direct inspection of nthe oral cavity should be avoided until the airway is secure. If epiglottitis nis thought to be possible but not certain in a patient with acute upper airway obstruction, nthe patient can undergo lateral radiographs of the upper airway first. Classic nradiographs of a child who has epiglottitis show the thumb sign (Fig. 2). Proper positioning of the patient for nthe lateral neck radiograph is crucial in order to avoid some of the pitfalls nassociated with interpretation of the film. Adequate hyperextension of the head nand neck is necessary. In addition, the epiglottis can appear to be round if nthe lateral neck is taken at an oblique angle. If the concern for epiglottitis nstill exists after the radiographs, direct visualization should be performed. A nphysician skilled in airway management and use of intubation equipment should naccompany patients with suspected epiglottitis at all times. An older ncooperative child might voluntarily open the mouth wide enough for a direct nview of the inflamed epiglottis.

n

2  Lateral roentgenogram of the upper airway reveals the swollen epiglottis (thumb sign).

n

Establishing an airway by nasotracheal intubation or, nless often, by tracheostomy is indicated in patients with epiglottitis, nregardless of the degree of apparent respiratory distress, because as many as n6% of children with epiglottitis without an artificial airway die, compared nwith <1% of those with an artificial airway. No clinical features have beerecognized that predict mortality. Pulmonary edema can be associated with acute nairway obstruction. The duration of intubation depends on the clinical course nof the patient and the duration of epiglottic swelling, as determined by nfrequent examination using direct laryngoscopy or flexible fiberoptic nlaryngoscopy. In general, children with acute epiglottitis are intubated for n2-3 days, because the response to antibiotics is usually rapid (see later). nMost patients have concomitant bacteremia; occasionally, other infections are npresent, such as pneumonia, cervical adenopathy, or otitis media. Meningitis, narthritis, and other invasive infections with H. influenzae type b are rarely found in conjunction with epiglottitis.

Acute Infectious nLaryngitis

Laryngitis is a common illness. Viruses cause most cases; ndiphtheria is an exception but is extremely rare in developed countries. The onset is usually characterized by an upper nrespiratory tract infection during which sore throat, cough, and hoarseness nappear. The illness is generally mild; respiratory distress is unusual except nin the young infant. Hoarseness and loss of voice may be out of proportion to nsystemic signs and symptoms. The physical examination is usually not remarkable nexcept for evidence of pharyngeal inflammation. Inflammatory edema of the vocal ncords and subglottic tissue may be demonstrated laryngoscopically. The nprincipal site of obstruction is usually the subglottic area.

Spasmodic Croup

Spasmodic croup occurs most often in childre1-3 yr of age and is clinically similar to acute laryngotracheobronchitis, nexcept that the history of a viral prodrome and fever in the patient and family nare often absent. The cause is viral in some cases, but allergic and npsychologic factors may be important in others.

Occurring most commonly in the evening or nighttime, nspasmodic croup begins with a sudden onset that may be preceded by mild to nmoderate coryza and hoarseness. The child awakens with a characteristic nbarking, metallic cough, noisy inspiration, and respiratory distress and nappears anxious and frightened. The patient is usually afebrile. Usually, the nseverity of the symptoms diminishes within several hr, and the following day, nthe patient often appears well except for slight hoarseness and cough. Similar, nbut usually less severe, attacks without extreme respiratory distress can occur nfor another night or 2. Such episodes often recur several times. Spasmodic ncroup might represent more of an allergic reaction to viral antigens thadirect infection, although the pathogenesis is unknown.

Differential Diagnosis

These 4 syndromes must be differentiated from one nanother and from a variety of other entities that can present as upper airway nobstruction. Bacterial ntracheitis is the most important ndifferential diagnostic consideration and has a high risk of airway nobstruction. Diphtheritic croup is extremely rare in North America, although a nmajor epidemic of diphtheria occurred in countries of the former Soviet Uniobeginning in 1990 from the lack of routine immunization. Early symptoms of ndiphtheria include malaise, sore throat, anorexia, and low-grade fever. Withi2-3 days, pharyngeal examination reveals the typical gray-white membrane, which ncan vary in size from covering a small patch on the tonsils to covering most of nthe soft palate. The membrane is adherent to the tissue, and forcible attempts nto remove it cause bleeding. The course is usually insidious, but respiratory nobstruction can occur suddenly. Measles croup almost always coincides with the nfull manifestations of systemic disease and the course may be fulminant

Sudden onset of respiratory obstruction can be caused nby aspiration of a foreigbody . The child is usually n6 mo-3 yr of age. Choking and coughing occur suddenly, usually without nprodromal signs of infection, although children with a viral infection can also naspirate a foreign body. A retropharyngeal or peritonsillar nabscesscan mimic respiratory nobstruction. CT scans of the upper airway are helpful in evaluating the possibility nof a retropharyngeal abscess. A peritonsillar abscess is often a clinical ndiagnosis. Other possible causes of upper airway obstruction include extrinsic ncompression of the airway (laryngeal web, vascular ring) and intraluminal nobstruction from masses (laryngeal papilloma, subglottic hemangioma); these ntend to have chronic or recurrent symptoms.

Upper airway obstruction is occasionally associated nwith angioedema of the subglottic areas as part of anaphylaxis and ngeneralized allergic reactions, edema after endotracheal intubation for general nanesthesia or respiratory failure, hypocalcemic tetany, infectious nmononucleosis, trauma, and tumors or malformations of the larynx. A croupy ncough may be an early sign of asthma. Vocal cord dysfunction can also occur. nEpiglottitis, with the characteristic manifestations of drooling or dysphagia nand stridor, can also result from the accidental ingestion of very hot liquid.

Complications

Complications occur in ∼15% of patients with viral croup. The most common is nextension of the infectious process to involve other regions of the respiratory ntract, such as the middle ear, the terminal bronchioles, or the pulmonary nparenchyma. Bacterial tracheitis may be a complication of viral croup rather nthan a distinct disease. If associated with S. aureus, toxic shock syndrome can develop. Bacterial tracheitis can produce a ntwo-phased illness, with the second phase associated with high fever, toxicity, nand airway obstruction. Alternatively, the onset of tracheitis occurs without a nsecond phase and appears as continued but higher fever and worsening nrespiratory distress rather than the usual recovery after 2-3 days of viral ncroup. Pneumonia, cervical lymphadenitis, otitis media, or, rarely, meningitis nor septic arthritis can occur in the course of epiglottitis. Mediastinal nemphysema and pneumothorax are the most common complications of tracheotomy.

Treatment

The mainstay of treatment for children with croup is airway management and treatment of hypoxia. Treatment nof the respiratory distress should take priority over any testing. Most nchildren with either acute spasmodic croup or infectious croup can be managed nsafely at home. Despite the observation that cold night air is beneficial, a nCochrane review has found no evidence supporting the use of cool mist in the nemergency department for the treatment of croup. Children with both wheezing nand croup can experience worsening of their bronchospasm with cool mist.

Nebulized racemic epinephrine is an accepted treatment nfor moderate or severe croup. The mechanism of action is believed to be nconstriction of the precapillary arterioles through the β-adrenergic nreceptors, causing fluid resorption from the interstitial space and a decrease nin the laryngeal mucosal edema. Traditionally, racemic epinephrine, a 1:1 nmixture of the d– and l-isomers of epinephrine, has been administered. A dose nof 0.25-0.5 mL of 2.25% racemic epinephrine in 3 mL of normal saline ncan be used as often as every 20 min. Racemic epinephrine was initially nchosen over the more active and more readily available l-epinephrine nto minimize anticipated cardiovascular side effects such as tachycardia and nhypertension. There is evidence that l-epinephrine (5 mL of n1:1,000 solution) is equally effective as racemic epinephrine and does not ncarry the risk of additional adverse effects. This information is both npractical and important, because racemic epinephrine is not available outside nthe USA.

The indications for the administration of nebulized nepinephrine include moderate to severe stridor at rest, the possible need for intubation, respiratory ndistress, and hypoxia. The duration of activity of racemic epinephrine is n<2 hr. Therefore, observation is mandated. The symptoms of croup might nreappear, but racemic epinephrine does not cause rebound worsening of the nobstruction. Patients can be safely discharged home after a 2-3 hr period nof observation provided they have no stridor at rest; have normal air entry, nnormal pulse oximetry, and normal level of consciousness; and have received nsteroids (see later). Nebulized epinephrine should still be used cautiously ipatients with tachycardia, heart conditions such as tetralogy of Fallot, or nventricular outlet obstruction because of possible side effects.

The effectiveness of oral corticosteroids in viral ncroup is well established. Corticosteroids decrease the edema in the laryngeal nmucosa through their anti-inflammatory action. Oral steroids are beneficial, neven in mild croup, as measured by reduced hospitalization, shorter duration of nhospitalization, and reduced need for subsequent interventions such as nepinephrine administration. Most studies that demonstrated the efficacy of oral ndexamethasone used a single ndose of 0.6 mg/kg; a dose as low nas 0.15 mg/kg may be just as effective. Intramuscular dexamethasone and nnebulized budesonide have an equivalent clinical effect; oral dosing of ndexamethasone is as effective as intramuscular administration. A single dose of noral prednisolone is less effective. There are no controlled studies examining nthe effectiveness of multiple doses of corticosteroids. The only adverse effect nin the treatment of croup with corticosteroids is the development of Candida albicans laryngotracheitis in a patient who received ndexamethasone, 1 mg/kg/24 hr, for 8 days. Corticosteroids should not nbe administered to children with varicella or tuberculosis (unless the patient nis receiving appropriate antituberculosis therapy) because they worsen the nclinical course.

Antibiotics are not indicated in croup. Over-the-counter ncough and cold medications should not be used in children <4 yr of age. nA helium-oxygen mixture (Heliox) may be effective in children with severe croup nfor whom intubation is being considered. Children with croup should be hospitalized nfor any of the following: progressive stridor, severe stridor at rest, nrespiratory distress, hypoxia, cyanosis, depressed mental status, poor oral nintake, or the need for reliable observation.

Epiglottitis is a medical emergency and warrants immediate treatment nwith an artificial airway placed under controlled conditions, either in aoperating room or intensive care unit. All patients should receive oxygen eroute unless the mask causes excessive agitation. Racemic epinephrine and ncorticosteroids are ineffective. Cultures of blood, epiglottic surface, and, iselected cases, cerebrospinal fluid should be collected after the airway is nstabilized.Ceftriaxone, cefotaxime, or meropenum should be given parenterally, pending culture and nsusceptibility reports, because 10-40% of H. influenzae type b cases are resistant to ampicillin. After insertion of the nartificial airway, the patient should improve immediately, and respiratory ndistress and cyanosis should disappear. Epiglottitis resolves after a few days nof antibiotics, and the patient may be extubated; antibiotics should be ncontinued for 7-10 days. Chemoprophylaxis is not routinely recommended for nhousehold, child-care, or nursery contacts of patients with invasive H. influenzae type b infections, but careful observation is mandatory, with prompt nmedical evaluation when exposed children develop a febrile illness. Indications for rifampin prophylaxis (20 mg/kg orally once a day for 4 days; maximum ndose, 600 mg) for all household members are any contact <48 mo of nage who is incompletely immunized, any contact <12 mo who has not nreceived the primary vaccination series, or an immunocompromised child in the nhousehold.

Acute laryngeal swelling on an allergic basis responds to epinephrine (1:1,000 ndilution in dosage of 0.01 mL/kg to a maximum of 0.5 mL/dose) nadministered intramuscularly or racemic epinephrine (dose of 0.5 mL of n2.25% racemic epinephrine in 3 mL of normal saline) Corticosteroids are noften required (2-4 mg/kg/24 hr of prednisone). After recovery, the patient nand parents should be discharged with a preloaded syringe of epinephrine to be nused in emergencies. Reactive mucosal swelling, severe stridor, and respiratory ndistress unresponsive to mist therapy may follow endotracheal intubation for ngeneral anesthesia in children. Racemic epinephrine and corticosteroids are nhelpful.

Tracheotomy and nEndotracheal Intubation

With the introduction of routine nasotracheal nintubation or, less often, tracheotomy for epiglottitis, the mortality rate for nepiglottis has dropped to almost zero. Both procedures should always be nperformed in an operating room or intensive care unit if time permits; prior nintubation and general anesthesia greatly facilitate performing a tracheotomy nwithout complications. The use of a nasotracheal tube that is 0.5-1.0 mm nsmaller than estimated by age is recommended to facilitate intubation and nreduce long-term sequelae. The choice of procedure should be based on the local nexpertise and experience with the procedure and the postoperative care involved nwith each.

Endotracheal intubation or tracheotomy is required for nmost patients with bacterial tracheitis and all young patients with nepiglottitis. It is rarely required for patients with laryngotracheobronchitis, nspasmodic croup, or laryngitis. Severe forms of laryngotracheobronchitis that nrequire intubation in a high proportion of patients have been reported during nsevere measles and influenza A virus epidemics. Assessing the need for these nprocedures requires experience and judgment because they should not be delayed nuntil cyanosis and extreme restlessness have developed.

The endotracheal tube or tracheostomy must remain iplace until edema and spasm have subsided and the patient is able to handle nsecretions satisfactorily. It should be removed as soon as possible, usually nwithin a few days. Adequate resolution of epiglottic inflammation that has beeaccurately confirmed by fiberoptic laryngoscopy, permitting much more rapid nextubation, often occurs within 24 hr. Racemic epinephrine and dexamethasone n(0.5 mg/kg/dose every 6 hr as needed) may be useful in the treatment nof croup associated with extubation.

Prognosis

In general, the length of hospitalization and the nmortality rate for cases of acute infectious upper airway obstruction increase as nthe infection extends to involve a greater portion of the respiratory tract, nexcept in epiglottitis, in which the localized infection itself can prove to be nfatal. Most deaths from croup are caused by a laryngeal obstruction or by the ncomplications of tracheotomy. Rarely, fatal out-of-hospital arrests due to nviral laryngotracheobronchitis have been reported, particularly in infants and nin patients whose course has been complicated by bacterial tracheitis. nUntreated epiglottitis has a mortality rate of 6% in some series, but if the ndiagnosis is made and appropriate treatment is initiated before the patient is nmoribund, the prognosis is excellent. The outcome of acute nlaryngotracheobronchitis, laryngitis, and spasmodic croup is also excellent. As na group, children who need to be hospitalized for croup have somewhat increased nbronchial reactivity compared with normal children when tested several yr nlater, but the significance is uncertain.

 

Croup nSyndrome

Stenotic nlaryngotracheitis, or false croup, exists in case of ARVI (influenza, nparainfluenza, аdenoviral infection), measles, Chickenpox. Diphtheria of the nrespiratory ways has clinic of true croup, which necessary to differentiate nwith false croup.

 

 

Differential Diagnosis of the nRespiratory Tract Diphtheria

 

 

TREATMENT: n

Basic:

1.     nBed rest up to the normalization of body ntemperature, n

2.     nadequate rehydration with oral fluids n(lemon tea, nraspberry tea, warm alkalic drinks

3.     nvitaminized milk-vegetable food;

4.     nControl nof fever and myalgia (when the temperature is more than 38.5-39˚C); ichildren before 2 mo and in case of perinatal CNS damage, seizures in the nhistory, severe heart diseases – when the temperature is up to 38˚C with acetaminophen (paracetamol 10-15 mg/kg nnot often than every 4 hours (not more than 5 times per day) or ibuprophen 10 mg/kg per dose, not oftethan every 6 hours. Aspirin is ncontraindicated for children before 12 years.

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

6.     nIcase of dry cough – cough supressors (such as dextramethorphan, synecod)

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

 

Antiviral ntreatment may be used

·        nArbidol to the children elder than 12 nyrs. — 0.2 g; nchildren of 6-12 yrs. — for 0,1g,  children of n2-6 yrs. — 0.05 g n4 t.d. for 3-5 days

·        nThiloron to the children elder than 7 nyrs. through a mouth: 60 mg/day in 1, 2, 4, 6 day of treatment

·        nInnosini pranobex 50 mg/kg daily for n5 days

·        nAdenovirus conjunctivitis treatment – antiviral eye drops: poludanum, ninterferon, 0.05% deoxyribonuclease or 0.5% tebrophen ointment; corticosteroids nas  Dexamethazonum for 4-5 days.

 

Antibiotics are appointed

1. In case of ncomplications caused by bacteria, micoplasm or chlamydia, as:

• Middle otitis

• Sinusitis

• Acute tonsillitis

• Bronchitis

• Pneumonia

2. At suspicion of secondary nbacterial infection, children that are risky for bacterial infectiodevelopment, with body temperature > 38 °C more than 3 days, leucocytosis more nthan  15×10⁹/l. Antibiotics nfrom the following groups are used:

• Aminopenicillines protected nby clavulanic acid (amoxicillin clavulanate);

• Cefoperason in combinatiowith sulbactam, cefuroxim, cefpodoxim

• Macrolydes (clarythromycin, nazithromycin, spiramycin);

• Cephalosporines of 3rd-4th ngeneration also are used.

• At presence of the nmethycillin resistant staphylococcus – vancomycin, in case of nosocomeal npneumonia carbapenems are appointed.

 

Management nof croup depends on the nseverity of disease.

At the 1^st degree of stenosis treatment of the child nshould be started at home:

·        nAir nin an apartment must be moistened. An emotional and physical comfort is nprovided for a child.

·        nLocal ntherapy is directed on the improvement of venous outflow and normalization of nlymph outflow:  warming of interscapular narea, shin muscles, heels.

·        nA ndry heat should be placed on a neck.

·        nWarm ndosed alkalic drink.

·        nInhalations nby antioedematous mixture, steam inhalations.

·        nFrom nmedicinal therapy:  vitamin C and P, and nantihistaminic medicine in age-old doses.

·        nHospitalizatioonly in the case of presence of problems in a transport connection between a nhospital and child’s placement.

 

At the 2^nd degree of stenosis a child must be transported ninto the hospital, where is possibly of artificial pulmonary ventilation.

Treatment of child must begin on the prehospital stage with continuatioin the hospital.

·        nInhalatioof water-wet and warmed oxygen.

·        nSedative nmedicine with the purpose of diminishing the inspiratory efforts.

·        nGlucocorticoids n10 mg/kg per day by prednisolon. A dose is distributed on 4-6 receptions nwithout the observance of biological rhythm.

·        nAntihistaminic npreparations in age-old doses (dimedrolum).

·        nCareful ntreatment of bronchial obstructive syndrome: broncholytics, mucosolvents. At a nconsiderable obstruction tracheobronchial tree lavage is done during a few nhours.

·        nA ndecrease of child’s body weight on 3-4% (stimulation of urination with nreduction of daily liquid receipts to 80% of physiological amount).

·        nSanatioof tracheobronchial tree and feeding the child before next introduction of nSedative medicines.  

 

At the 3^rd degree of stenosis next is added:

·        nObligatory nproviding of artificial respiratory ways ventilation (intubation of trachea, ntracheotomy if it’s impossible to put an intubation tube into the trachea)

·        nUnder nthe heart rate control it is possible to use adrenalin inhalations (1:20, 1:15) nthat enables the edema of subvocal space decrease quickly, but not for a long ntime.

 

At the 4^th degree of stenosis a pneumo-cardial nreanimation, treatment of cerebrum edema-swelling is performed.

 

Prophylaxis of URT viral ninfection

1.     nIntranasal nalpha₂-interferon was active only against rhinoviruses and prevented na cold in only 40% of cases. It must be giveot longer than 1-2 weeks.

2.     nArbidol nto the children elder than 12 yrs. — 0,2 gs; children of 6-12 yrs. — for 0,1 ngs,  children of 2-6 yrs. — 0,05 gs 1 nt.d. for 10-15 days, or Thiloron to nthe children elder than 7 yrs. through a mouth: 60 mg once a week during 6 wks. n

3.     nAdaptogens, nmultivitamins

·        nTo navoid a contact with persons which have displays of URT infection;

·        nTo nlimit visits of places with large accumulation of people;

·        nTo nventilate an apartment often;

·        nTo nteach children to wash hands often with soap during 20 seconds;

·        nTo nteach children to cough and sneeze in a serviette;

·        nTo naim not to touch eyes, nose or mouth by unwashed hands;

·        nTo navoid cuddles, kisses and greeting by hands;

·        nTo ncover a nose and mouth at a sneeze or cough by nasal serviette which at once it nis needed to throw out after the use;

·        nTo nteach childreot to suit to the patients nearer than on one and a half – two nmeters;

·        nIll nchildren must stay at a home (not to visit preschool establishments and nschools);

·        nThe nmoist cleaning up of apartments is needed not less than two times a day.

 

References

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

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

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

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

5.           nOxford Textbook of nMedicine: Infection by David Warrell, Timothy M. Cox, John Firth nand Mili Estee Torok , Published nby Wiley-Blackwell, 2012

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