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Vinnytsia National Pirogov Memorial Medical University
Department of Children Infectious Diseases
. “Approved”
at sub-faculty meeting
28.08.2012, protocol №_1_
Head of Department
prof. _______I.I. Nezgoda
Study guide for practical work of students
Topic: “ Acute respiratory viral infections (Influenza. Parainfluenzal infection. Adenoviral infection. Respiratory syncytial infection. Rhinoviral infection). Differential diagnosis.Emergency”.
Course VI
English-speaking Students’ Medical Faculty
Duration of the class-150min
Composed by assoc. prof. L.M. Stanislavchuk
Vinnytsa
2012
Acute respiratory viral infections (Influenza. Parainfluenzal infection. Adenoviral infection. Respiratory syncytial infection. Rhinoviral infection). Differential diagnosis.Emergency.
I. The theme urgency.
Acute respiratory viral infections (ARVIs) are the most common infectious illnesses in the general population. ARVI are the leading reasons for people missing work or school, and they represent the leading acute diagnosis in the office setting. Separately, ARVIs rarely cause permanent complications or death, although ARVIs may serve as a gateway to infection of adjacent structures. Serious complications may result in clinically significant morbidity and rare deaths. Influenza viruses also can cause pandemics, during which rates of illness and death from influenza-related complications can increase dramatically worldwide. Influenza viruses cause disease among all age groups. Rates of infection are highest among children, but rates of serious illness and death are highest among persons of any age who have medical conditions that place them at increased risk for complications from influenza.
II. Primary aims of the study.
To teach students major methods of ARVI diagnosis and treatment.
A student should know:
1. Etiology of ARVI
2. Epidemiology of ARVI
3. Pathogenesis of ARVI
4. Classification and clinical manifestations of ARVI
5. Laboratory studies of ARVI
6. Complications of ARVI
7. Treatment of ARVI
8. Prevention
9. Viral croup: clinical manifestations, differential diagnosis, management
10. Control fever in the management of influenza in children
11. Febrile seizure.Emergency management
A student should be able to:
1) Find out history
2) Interpret data of physical examination
3) Interpret data of laboratory studies
4) Formulate clinical diagnosis
5) Make differential diagnosis
6) Administer treatment in ARVI.
7) Prevention
III. Educative aims of the study.
To facilitate:
. The formation of deontology concepts and practical skills related to patients with ARVIs.
. To acquire the skills of psychological contact establishment and creation of trusting relations between the doctor and the patient and his parents.
The development of responsibility sense for timeliness and completeness of patient’s investigation.
IV. The contents of the theme.
Influenza
Influenza viral infections cause a broad array of respiratory illnesses that are responsible for significant morbidity and mortality in children.
ETIOLOGY.
Influenza viruses are members of the family Orthomyxoviridae. They are large, single-stranded RNA viruses with a segmented genome encased in a lipid-containing envelope. The two major surface proteins that determine the serotype of influenza, hemagglutinin and neuraminidase, project as spikes through the envelope. Influenza viruses are divided into three types: A, B, and C. Influenza types A and B are the primary influenzal pathogens and causes of epidemic disease. Influenza type C is a sporadic cause of predominantly upper respiratory tract disease. Influenza types A and B are further divided into serotypically distinct strains that circulate on a yearly basis through the population.
EPIDEMIOLOGY.
Influenza A viruses have a complex epidemiology involving animal hosts that serve as a reservoir for diverse strains with potential for infecting the human population. The segmented nature of the influenza genome allows reassortment to occur between an animal and human virus when coinfection occurs. Thus, potentially any of 15 hemagglutinins (H) and 9 neuraminidases (N) residing in animal reservoirs may be introduced into humans; influenza A viruses behave epidemiologically as though there were many serotypes. Minor changes within a serotype are termed antigenic drift; major changes in serotype are termed antigenic shift. In addition, migratory avian hosts may be responsible for spread of disease. A recent example occurred in Hong Kong in the winter of 1997 when a small outbreak of avian H5N1 influenza in humans was associated with a high mortality; 6 of 18 patients died. Influenza B has much less capacity for major antigenic change and no identified animal reservoir.
The worldwide epidemiology of influenza viruses demonstrates annual spread from Asia across the Pacific Ocean to North America. When a virus identified by a novel and serologically distinct hemagglutinin or neuraminidase enters the population, there is potential for a pandemic of influenza with excess morbidity and mortality on a global scale in a largely nonimmune population. The most dramatic pandemic in recent history occurred in 1918, when influenza was estimated to have killed more than 20 million people. More common is the almost yearly variation in the antigenic composition of the surface proteins, which confers a selective advantage to a new strain and results in localized epidemics of disease with mortality largely confined to the elderly and to those with underlying cardiopulmonary disease. Each year's strain is novel for infants because they have no pre-existing antibody except for maternally transferred antibody in the very young.
The attack rate and frequency of isolation of influenza is highest in young children. As many as 30-50% of children have serologic evidence of infection in a typical year. Children undergoing primary exposure to an influenza strain have higher titered and more prolonged shedding of the virus than adults, making them extremely effective transmitters of infection. Influenza is a disease of the colder months of the year in temperate climates; spread appears to occur by small-particle aerosol. Transmission through a community is rapid; the highest incidence of illness occurs within 2-3 wk of introduction. Influenza is marked by increased school absenteeism and the yearly peak in visits to the pediatrician. Influenza has been implicated in hospital spread of infection and may complicate the original illness that required hospitalization.
On a country or global basis, one or two predominant strains spread to create the annual epidemic. At present, influenza type A strains with the H1N1 and H3N2 serotypes and type B strains are co-circulating, and either type may be predominant in any one year, making predictions about the serotype and severity of the upcoming influenza season very difficult. Strain variants are identified by their hemagglutinin and neuraminidase serotypes, by the geographic area from which they were originally isolated, by their isolate number, and by year of isolation. Thus, the influenza vaccine for 1998-1999 was trivalent, having strains identified as A/Sydney/5/97/ (H3N2), A/Beijing/262/95 (H1N1), and B/Harbin/07/94.
PATHOGENESIS.
The virus attaches to sialic acid residues on cells via the hemagglutinin and, via endocytosis, makes its way into vacuoles, where, with progressive acidification, there is fusion to the endosomal membrane and release of the viral RNA into the cytoplasm. The RNA is transported to the nucleus and transcribed. Newly synthesized RNA is returned to the cytoplasm and translated into proteins, which are transported to the cell membrane. This is followed by budding of virus through the cell membrane. The packaging mechanisms for the segmented genome are not well understood. A proteolytic cleavage of the hemagglutinin occurs at some point in the assembly and release of the virus, which is essential for successful reinfection and amplification of virus titer. In humans, this replicative cycle is confined to the respiratory epithelium. With primary infection, virus replication continues for 10-14 days. Implicit in successful replication in the respiratory tract is the assumption that key proteolytic enzymes exist at this site. The effective cleavage of hemagglutinin has been demonstrated by respiratory secretions, but the cellular origin of the enzyme remains undefined.
Influenza causes a lytic infection of the respiratory epithelium with loss of ciliary function, decreased mucus production, and desquamation of the epithelial layer. These changes permit secondary bacterial invasion either directly through the epithelium or, in the case of the middle ear space, through obstruction of the normal drainage through the eustachian tube. Influenza types A and B have been reported to cause myocarditis, and influenza type B can cause myositis. Reyes syndrome can result with the use of salicylates for influenza type B infection.
The exact immune mechanisms involved in termination of primary infection and protection against reinfection are not well understood. The incubation period of influenza can be as short as 48-72 hr. The extremely short incubation period of influenza and its growth on the mucosal surface pose particular problems for invoking a protective immune response. Antigen presentation must be primarily at mucosal sites acting through the bronchial associated lymphoid tract. The major humoral response is directed against the hemagglutinin. High serum antibody levels generated by inactivated vaccine correlate with protection. Mucosally produced immunoglobulin (Ig) A antibodies are presumably directed at the same antigenic sites and are thought to be the most effective and immediate response that can be generated to protect against influenza. Unfortunately, measurable IgA antibodies against influenza persist for a relatively short period, and symptomatic reinfection with influenza can be seen at intervals of 3-4 yr. Although heterotypic immunity can be demonstrated in the mouse through cell-mediated immune mechanisms directed toward common internal proteins, heterotypic immunity has not been shown in humans.
CLINICAL MANIFESTATIONS.
Influenza types A and B cause predominantly a respiratory illness. The onset of illness is abrupt and is marked by coryza, conjunctivitis, pharyngitis, and dry cough.The predominant symptoms may localize anywhere in the respiratory tract, producing an isolated upper respiratory tract illness, croup, bronchiolitis, or pneumonia. More so than any of the other respiratory viruses, influenza is accompanied by systemic signs of high temperature, myalgia, malaise, and headache. Many of these symptoms may be mediated through cytokine production by the respiratory tract epithelium instead of reflecting systemic spread of the virus. The typical duration of the febrile illness is 2-4 days. Cough may persist for longer periods of time, and evidence of small airway dysfunction is often found weeks later. Other family members or close contacts often have a similar illness. Influenza is a less distinct illness in younger children and infants; manifestations may be localized to any region of the respiratory tract. The children may be highly febrile and toxic in appearance, prompting a full diagnostic work-up. In spite of the distinctive features of influenza, the illness is often indistinguishable from that caused by other respiratory viruses such as respiratory syncytial virus, parainfluenza viruses, and adenoviruses.
DIAGNOSIS.
The diagnosis of influenza depends on epidemiologic and clinical considerations. In the context of an epidemic, the clinical diagnosis of influenza in a young child with fever, malaise, and respiratory symptoms can be made with some certainty. The laboratory confirmation of influenza can be made in three ways. If seen early in the illness, virus can be isolated from the nasopharynx by inoculation of the specimen into embryonated eggs or a limited number of cell lines that support the growth of influenza. The presence of influenza in the culture is confirmed by hemadsorption, which depends on the capacity of the hemagglutinin to bind red cells. Rapid diagnostic tests for influenza A are available in some centers that use antigen capture in an enzyme-linked immunosorbent assay. The diagnosis can be confirmed serologically with acute and convalescent sera drawn at about the time of illness and tested by hemagglutination inhibition.
Laboratory Findings.
The clinical laboratory abnormalities associated with influenza are nonspecific. A relative leukopenia is frequently seen. Chest radiographs show evidence of atelectasis or infiltrate in about 10% of children.
TREATMENT.
Amantadine and rimantadine can be used in the prophylaxis and treatment of influenza type A outbreaks, in institutions, and in individual cases, including patients with underlying conditions that predispose them to severe or complicated influenza infection (Table 251-2) . These antivirals are not effective against influenza B and are not approved for use in children younger than 1 yr. If given within the first 48 hr, they decrease the severity and duration of influenzal symptoms. Confusion and inability to concentrate or sleep are seen in some patients given amantadine. Drug resistance develops fairly quickly during a course of therapy, but it is not widespread among circulating viruses. Both influenza A and B viruses are susceptible to ribavirin in vitro, but ribavirin is not approved for treatment of influenza infections. Drugs under investigation are modeled to fit in the crystallographic structure of the neuraminidase pocket to inhibit neuraminidase activity.
Adequate fluid intake and rest are important components in the management of influenza. Acetaminophen or ibuprofen, but not salicylates because of the risk of Reye syndrome, should be used as antipyretics to control fever. The most difficult question for parents is the appropriate timing of consultation with a health care provider. Bacterial superinfections are common, and antibiotic therapy should be administered. Bacterial superinfections should be suspected with recrudescence of fever, prolonged fever, or deterioration in clinical status. With uncomplicated influenza, children should feel at their worst over the first 48 hr.
COMPLICATIONS.
Otitis media and pneumonia are common complications of influenza in young children. Acute otitis media may be seen in up to 25% of cases of culture-documented influenza. Pneumonia accompanying influenza may be a primary viral process. An acute hemorrhagic pneumonia may be seen in the most severe cases, as may have been frequent with the highly virulent strain seen in 1918. The more common cause of pneumonia is probably secondary bacterial infection through the damaged epithelial layer. Unusual clinical manifestations of influenza include acute myositis seen with influenza type B, which follows the acute respiratory illness by 5-7 days and is marked by muscle weakness and pain, particularly in the thigh muscles, and myoglobinuria. Myocarditis also follows influenza, and toxic shock syndrome is associated with influenza type B and staphylococcal colonization. Influenza is particularly severe in children with underlying cardiopulmonary disease, including congenital and acquired valvular disease, cardiomyopathy, bronchopulmonary dysplasia, asthma, cystic fibrosis, and neuromuscular diseases affecting the accessory muscles of breathing. Virus is shed for longer periods of time in children receiving cancer chemotherapy and children with immunodeficiency.
PROGNOSIS.
The prognosis for recovery is excellent, although full return to normal levels of activity and freedom from cough usually requires weeks rather than days.
PREVENTION.
Influenza vaccine of targeted high-risk populations is the best means of prevention of severe disease from influenza. Chemoprophylaxis is a less desirable alternative, and is only effective against influenza A.
Vaccine.
An inactivated influenza vaccine becomes available each summer incorporating changes in formulation that reflect the strains anticipated to circulate in the coming winter. The American Committee on Immunization Practices publishes guidelines for their use each year when the vaccines are formulated and released. Current guidelines include the administration of vaccine intramuscularly to children at least 6 mo of age in chronic care facilities; with chronic disorders of the pulmonary or cardiovascular system, including asthma; with chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications); and receiving long-term aspirin therapy who may be at risk for Reye's syndrome after influenza. Vaccination is also recommended for women who will be in the second or third trimester (
14 wk gestation) of pregnancy during the influenza season (December-March). In addition, vaccine is recommended for individuals who may transmit influenza to persons at high risk, including health care workers and household members.
Because of the decreased potential for causing febrile reactions, only the split-virus vaccine is recommended for children younger than 12 yr. Two doses of vaccine (0.25 mL for 6-36 mo of age; 0.5 mL for 3-8 yr of age) at least 1 mo apart are recommended for primary immunization of children younger than 9 yr. Live, attenuated vaccines that are administered intranasally are in clinical trials and have been demonstrated to have an efficacy comparable to that of inactivated vaccine in adults. Trials in children have shown efficacy of 90%. These vaccines are likely to be licensed soon. Their ease of administration could serve to increase influenza vaccination among children.
Chemoprophylaxis.
Amantadine and rimantadine are licensed for prophylaxis of influenza A infections. They are recommended for prophylaxis for vaccinated and unvaccinated high-risk patients and their unvaccinated health care providers during influenza A outbreaks in closed settings, unvaccinated persons and health care providers during community influenza A outbreaks, and during the period of peak influenza A activity in immunodeficient persons and those for whom the influenza vaccine is contraindicated.
Parainfluenzal infection
Viruses in the parainfluenza family are common causes of respiratory illness in infants and young children. They cause a spectrum of upper and lower respiratory tract illnesses, but are particularly associated with laryngotracheitis, bronchitis, and croup.
ETIOLOGY.
The parainfluenza viruses are members of the Paramyxoviridae family. There are four viruses in the parainfluenza group that cause illness in humans, designated types 1-4. The viruses have a nonsegmented, single-stranded RNA genome with a lipid-containing envelope derived from budding through the cell membrane. The major antigenic moieties are envelope spike proteins that exhibit hemagglutinating (HN protein) and cell fusion (F protein) properties.
EPIDEMIOLOGY.
Parainfluenza viruses are spread from the respiratory tract by aerosolized secretions or direct hand contact with secretions. By 3 yr of age, most children have experienced infection with types 1, 2, and 3. Type 3 is endemic and can cause disease in the infant younger than 6 mo. Serious illness is seen with parainfluenza type 3 in immunocompromised patients. Types 1 and 2 occur in a seasonal pattern in the summer and fall and alternate years in which their serotype is most prevalent. Parainfluenza type 4 is more difficult to grow in tissue culture; thus, its epidemiology is less well defined. However, it does not appear to be a major cause of illness.
PATHOGENESIS.
Parainfluenza viruses replicate in the respiratory epithelium without evidence of systemic spread. The propensity to cause illness in the upper large airways is presumably related to enhanced replication in the larynx, trachea, and bronchi compared with other viruses. The destruction of cells in the upper airways can lead to secondary bacterial invasion and resultant bacterial tracheitis. Eustachian tube obstruction can lead to secondary bacterial invasion of the middle-ear space and acute otitis media.
Illness caused by parainfluenza occurs shortly after inoculation with the virus. The mechanisms by which viral injury occurs are not known. Some parainfluenza viruses induce cell-to-cell fusion. During the budding process, cell membrane integrity is lost, and viruses can induce cell death through the process of apoptosis. The severity of illness correlates with the amount of viral shedding. Immune destruction of virally infected cells may also occur, but appears to be less important with mucosal than systemic infection. The level of immunoglobulin A antibody is the best predictor of susceptibility to infection. Reinfection is seen particularly with parainfluenza type 3 as mucosal immunity wanes. The inability of children with serious T-cell defects to clear parainfluenza type 3 suggests a cell-mediated component of immunity.
CLINICAL MANIFESTATIONS.
Most parainfluenza virus infections are confined to the upper respiratory tract. The parainfluenza viruses account for 50% of hospitalizations for croup and 15% of cases of bronchiolitis and pneumonia. Parainfluenza type 1 causes more cases of croup, whereas parainfluenza type 3 causes a broad spectrum of lower respiratory tract diseases.
Parainfluenza virus infections are not associated with fever. Aside from low-grade fever, systemic complaints are rare. The illness usually lasts 4-5 days; however, virus may be recovered in low titers for 2-3 wk. Rarely, parainfluenza viruses have been implicated in parotitis.
DIAGNOSIS.
The diagnosis of parainfluenza virus infection in children is usually based only on clinical and epidemiologic criteria. The virus should be specifically sought in persistent pneumonias in immunosuppressed children. The radiographic "steeple sign" of progressive narrowing of the subglottic region is characteristic of parainfluenza virus respiratory tract infections.
Laboratory Findings.
There are no distinctive laboratory findings. The laboratory diagnosis of parainfluenza virus infection can be accomplished by inoculation of nasal secretions into tissue culture, with presumptive diagnosis based on finding a hemadsorbing agent and final serotypic diagnosis based on hemadsorption inhibition. Direct immunofluorescent staining is available in some centers for rapid identification of virus antigen in oropharyngeal sections.
TREATMENT.
The possibility of rapid respiratory compromise during severe croup should influence the level of care given (Chapter 385) . Careful attention to symptomatic care is important. Parents should be provided a description of the parameters of increasing respiratory distress that should lead to reassessment by a health care provider. Humidification and exposure to cold air are both classically associated with a decrease in mucosal edema and liquefaction of secretions that may help to relieve obstruction; however, their value has never been proved in a controlled trial. Aerosolized racemic epinephrine may temporarily improve aeration, but has the possibility of rebound. Aerosolized or systemic corticosteroids are helpful in the management of croup in the emergency room setting and after hospitalization. The indications for antibiotics are limited to well-documented secondary bacterial infections of the middle ears or lower respiratory tract.
Ribavirin has some antiviral activity against parainfluenza virus, and should be considered in the immunocompromised child with persistent parainfluenza viral pneumonia.
COMPLICATIONS.
In children with fever or more severe respiratory compromise, the possibility of a bacterial tracheitis with purulent infection below the epiglottis and vocal cords should be considered. The high frequency of otitis media complicating parainfluenza virus indicates that careful pneumatic otoscopy should be performed in all children with suspected parainfluenza virus infection.
PROGNOSIS.
The prognosis for full recovery is excellent in the normal child. No long-term pulmonary residua of parainfluenza virus infection have been described.
PREVENTION.
Work is progressing with both live and subunit parainfluenza type 3 vaccines. The live vaccines include a cold-adapted virus of human origin and a bovine parainfluenza virus, which is attenuated because of host range adaptation. The measure of protection afforded by vaccines will be difficult to assess because symptomatic reinfection is seen and the frequency of serious infection in the general population is low. Nonetheless, it is clear that prevention of acute respiratory illness that results from parainfluenza virus is a worthwhile goal.
Respiratory syncytial infection
Respiratory syncytial virus (RSV) is the major cause of bronchiolitis and pneumonia in children younger than 1 yr. It is the most important respiratory tract pathogen of early childhood.
ETIOLOGY.
RSV is a medium-sized, membrane-bound RNA virus that develops in the cytoplasm of infected cells and matures by budding from the plasma membrane. It belongs to the family Paramyxoviridae, along with parainfluenza, mumps, and measles viruses, but is the sole member of the genus Pneumovirus. Although different strains of RSV show some antigenic heterogeneity, this variation is primarily in one of the two surface glycoproteins, and it is not clear that this degree of difference is clinically or epidemiologically significant.
RSV grows in a number of types of tissue culture, in which it produces characteristic syncytial cytopathology. Specimens for culture should be delivered rapidly on wet ice to the laboratory because the virus is heat labile and very susceptible to destruction by freezing and thawing.
EPIDEMIOLOGY.
The occurrence of annual outbreaks and the high incidence of infection during the first months of life are unique among human viruses. RSV is distributed worldwide and appears in yearly epidemics. In temperate climates, these epidemics occur each winter and last 4-5 mo. During the remainder of the year, infections are sporadic and uncommon. In the Northern Hemisphere, epidemics usually peak in January, February, or March, but peaks have been recognized as early as December and as late as June. At these times, hospital admissions for bronchiolitis and pneumonia of children younger than 1 yr increase and decrease in proportion to the number of RSV infections in the community. In the tropics, the epidemic pattern is less clear.
Placentally transmitted anti-RSV antibody, when present in high concentration, has some protective effect. This may account for low frequency of severe infections in the first 4-6 wk of life, except in infants born prematurely who receive less than a full complement of maternal immunoglobulin (Ig)G. Nevertheless, serum antibody is not fully protective, and the age at which an infant undergoes first infection depends also on the opportunities for exposure. It is estimated that in an urban setting about half of the susceptible infants undergo primary infection in each epidemic. Thus, infection is almost universal by the 2nd birthday. Reinfection occurs at a rate of 10-20% per epidemic throughout childhood; the frequency is lower in adults. In situations of high exposure such as daycare centers, attack rates are higher: nearly 100% for first infections and 60-80% for second and subsequent infections.
Estimates of the severity of primary infections have emerged from studies of outbreaks in nurseries and institutions. Under these circumstances asymptomatic infection is rare. Most infants experience coryza and pharyngitis, usually with fever and occasionally with otitis media. In 10-40% of patients, the lower respiratory tract is involved to a varying degree. Bronchitis, bronchopneumonia, and bronchiolitis all occur. Calculations based on hospital admissions in the United States and Britain yield a ratio of 1-3 infants hospitalized with bronchiolitis or pneumonia for every 100 primary infections with the virus.
Reinfection may occur as early as a few weeks after recovery, but usually takes place during subsequent annual outbreaks.
The severity of illness during reinfection is usually lower, and appears to be a function of both partial immunity and increased age. Nevertheless, instances of severe RSV bronchiolitis occurring twice in succession have been documented.
Bronchiolitis is the most common clinical diagnosis in infants hospitalized with RSV infections, although the syndrome is often indistinguishable from RSV pneumonia in infants, and, indeed, the two frequently coexist. All RSV diseases of the lower respiratory tract (excluding croup) have their highest incidence from 2-7 mo of age and decrease in frequency thereafter. The syndrome of bronchiolitis becomes uncommon after the 1st birthday; acute infective wheezing attacks after that age are often termed "wheezy bronchitis," "asthmatoid bronchitis," or simply asthma attacks. Viral pneumonia is a persistent problem throughout childhood, although RSV becomes less prominent as the etiologic agent after the 1st year. RSV is responsible for 45-75% of cases of bronchiolitis, 15-25% of childhood pneumonias, and 6-8% of cases of croup.
Bronchiolitis and pneumonia resulting from RSV are more common in boys than in girls by a ratio of about 1.5:1. Racial factors make little difference. Lower respiratory tract involvement occurs more often and earlier in life in lower socioeconomic groups and in crowded living conditions.
The incubation period from exposure to 1st symptoms is about 4 days. The virus is excreted for variable periods, probably depending on severity of illness and immunologic status. Most infants with lower respiratory tract illness shed virus for 5-12 days after hospital admission. Excretion for 3 wk and longer has been documented. Spread of infection occurs when large, infected droplets, either airborne or conveyed on hands, are inoculated in the nose or conjunctiva of a susceptible subject. RSV is probably introduced into most families by schoolchildren undergoing reinfection. Typically, in the space of a few days, older siblings and one or both parents acquire colds, but the infant becomes more severly ill with fever, otitis media, or lower respiratory tract disease.
Nosocomial infection during RSV epidemics is an important concern. Virus is usually spread from child to child on the hands of caregivers. Adults undergoing reinfection have also been implicated in spread of the virus.
PATHOGENESIS.
Bronchiolitis is characterized by virus-induced necrosis of the bronchiolar epithelium, hypersecretion of mucus, and round cell infiltration and edema of the surrounding submucosa. These changes result in formation of mucous plugs obstructing bronchioles with consequent hyperinflation or collapse of the distal lung tissue. In interstitial pneumonia, infiltration is more generalized, and epithelial necrosis may extend to both the bronchi and the alveoli. Infants are particularly apt to experience small airway obstruction because of the small size of the normal bronchioles.
Several facts suggest immunologic injury as a factor in the pathogenesis of bronchiolitis caused by RSV: (1) Anti-RSV IgE antibody is found in the secretions of convalescent infants with bronchiolitis; (2) recent studies in infants and in various animal models of RSV infection indicate that a large number of soluble factors (interleukins, leukotrienes, and chemokines) with the potential to stimulate inflammation and tissue damage are liberated during RSV infection; (3) children who received a highly antigenic, inactivated, parenterally administered RSV vaccine experienced, on subsequent exposure to wild-type RSV, more severe and more frequent bronchiolitis than did their age-matched controls; and (4) bronchiolitis merges into asthma in older infants, and RSV is a frequently recognized cause of acute asthma attacks in children 1-5 yr old.
It is not clear how often superimposed bacterial infection plays a pathogenic role in RSV lower respiratory tract disease. The present view is that RSV-induced bronchiolitis in infants is an exclusively viral disease, and that bacteria are of little importance even when the disease is accompanied by atelectasis or interstitial pneumonia.
CLINICAL MANIFESTATIONS.
The first signs of infection of the infant with RSV are rhinorrhea and pharyngitis. Cough may appear simultaneously but more often after an interval of 1-3 days, at which time there may also be sneezing and a low-grade fever. Soon after the cough develops, the child begins to wheeze audibly. If the disease is mild, the symptoms may not progress beyond this stage. Auscultation often reveals diffuse rhonchi, fine rales or crackles, and wheezes. Clear rhinorrhea usually persists throughout the illness, with intermittent fever. Roentgenograms of the chest at this stage are frequently normal.
If the illness progresses, cough and wheezing increase and air hunger ensues with increased respiratory rate, intercostal and subcostal retractions, hyperexpansion of the chest, restlessness, and peripheral cyanosis. Signs of severe, life-threatening illness are central cyanosis, tachypnea of more than 70 breaths/min, listlessness, and apneic spells. At this stage, the chest may be greatly hyperexpanded and almost silent to auscultation because of poor air exchange.
Chest roentgenograms of infants hospitalized with RSV bronchiolitis are normal in about 10% of cases; air trapping or hyperexpansion of the chest is evident in about 50%. Peribronchial thickening or interstitial pneumonia is seen in 50-80%. Segmental consolidation occurs in 10-25%. Pleural effusion is rarely, if ever, seen.
In some infants, the course of the illness may be more like that of pneumonia with the prodromal rhinorrhea and cough followed by dyspnea, poor feeding, and listlessness, with a minimum of wheezing and hyperexpansion. Although the clinical diagnosis is pneumonia, wheezing is often present intermittently and the chest roentgenogram may show air trapping.
Fever is an inconstant sign in RSV infection. Rash and conjunctivitis each occur in a few cases. In young infants, particularly those who were born prematurely, periodic breathing and apneic spells have been distressingly frequent signs, even with relatively mild bronchiolitis. It is likely that a small portion of deaths included in the category of sudden infant death syndrome are due to RSV infection.
RSV infections in profoundly immunocompromised hosts may be severe at any age. The mortality associated with RSV pneumonia in the first few weeks after bone marrow or solid organ transplantation is 50% or higher. RSV infection does not seem to be severe in HIV-infected patients.
DIAGNOSIS.
Bronchiolitis is a clinical diagnosis. The involvement of RSV in any particular child's disease can be suspected with varying degrees of certainty from the season of the year and the presence of a typical outbreak at the time. Other epidemiologic features that may be helpful are the presence of colds in older household contacts and the age of the child, because, aside from RSV, the only respiratory virus that attacks infants frequently during the first few months of life is parainfluenza virus type 3.
Routine laboratory tests offer little helpful information in most cases of bronchiolitis or pneumonia caused by RSV. The white cell count is normal or elevated, and the differential count may be normal with either a neutrophilic or mononuclear predominance. Bacterial cultures of the throat grow only normal flora. Hypoxemia is frequent, and tends to be more marked than anticipated on the basis of the clinical findings. When it is severe, it is frequently accompanied by hypercapnia and acidosis.
The diagnostic dilemma of greatest import is the question of possible bacterial or chlamydial involvement. When bronchiolitis is clinically mild or when infiltrates are absent by roentgenogram, there is little likelihood of a bacterial component. In infants 1-4 mo of age, interstitial pneumonitis may be caused by Chlamydia trachomatis. In C. trachomatis
pneumonia, there may be a history of conjunctivitis, and the illness tends to be of subacute onset. Coughing and rales are prominent; wheezing is not. There may also be eosinophilia. Fever is usually absent.
Consolidation without other signs or with pleural effusion is considered of bacterial origin until proved otherwise. Other signs suggesting bacterial pneumonia are elevation of the neutrophil count, depression of the white cell count in the presence of severe disease, ileus or other abdominal signs, high temperature, and circulatory collapse. In such instances, there is rarely any doubt about the need for antibiotics.
Definitive diagnosis of RSV infection is based on the detection of virus or viral antigens in respiratory secretions. An aspirate of mucus or a nasopharyngeal wash from the child's posterior nasal cavity is the optimal specimen. Nasopharyngeal or throat swabs are less preferred but acceptable. A tracheal aspirate is unnecessary. The specimen should be placed on ice, taken directly to the laboratory, and processed for antigen detection or inoculated onto susceptible cell monolayers.
TREATMENT.
In uncomplicated cases of bronchiolitis, treatment is symptomatic. Humidified oxygen is usually indicated for hospitalized infants because most are hypoxic. Many infants are slightly to moderately dehydrated; therefore, fluids should be carefully administered in amounts somewhat greater than maintenance. Often intravenous or tube feeding is helpful when sucking is difficult due to tachypnea. Infants may breathe more easily when propped up at an angle of 10-30 degrees.
A trial of a bronchodilator administered either parenterally or by aerosol may relieve wheezing and improve clinical status, and should be repeated if initial benefit is shown. Studies have indicated that epinephrine is more often useful in bronchiolitis than albuterol. Corticosteroids are not indicated except in older children with an established diagnosis of asthma.
In most instances antibiotics are not useful, and their indiscriminate use in presumed viral bronchiolitis and pneumonia should be discouraged. Interstitial pneumonia in infants 1-4 mo old may be chlamydial; therefore, erythromycin (40 mg/kg/24 hr) or clarithromycin (7.5 mg/kg every 12 hr) may be beneficial. When infants with interstitial pneumonia are older, or when consolidation is found, parenteral antibiotics may be indicated. In the critically ill child, antibiotics may also be indicated.
The antiviral drug ribavirin, delivered by small-particle aerosol and breathed, along with the required concentration of oxygen, for 20 of 24 hr/day for 3-5 days, has a modest beneficial effect on the course of RSV pneumonia. Shortened hospital stay and reduced mortality have not been demonstrated, and long-term effects are still unknown. Its use is, therefore, indicated only in very sick infants or in high-risk infants, such as those with underlying cyanotic congenital heart disease, significant bronchopulmonary dysplasia, or severe immunodeficiency. If indicated, it should be administered early in the course of the infection.
PROGNOSIS.
The mortality of hospitalized infants with RSV infection of the lower respiratory tract is about 2%. Almost all deaths occur in young, premature infants or those with underlying disease of the neuromuscular, pulmonary, cardiovascular, or immunologic system.
Many children with asthma have a history of bronchiolitis in infancy. There is recurrent wheezing in 33-50% of children with typical RSV bronchiolitis in infancy. The likelihood of recurrence is increased in the presence of an allergic diathesis (eczema, hay fever, or a family history of asthma). In bronchiolitis, in patients older than 1 yr there is an increasing probability that, although the episode may be virus induced, this is the first of multiple wheezing attacks that will later be called asthma.
PREVENTION.
Within the hospital, the most important preventive measures are aimed at blocking nosocomial spread. During RSV season, high-risk infants should be separated from infants with respiratory symptoms. Separate gowns and gloves and careful handwashing should be used for the care of all infants with suspected or established RSV infection.
Passive Immunoprophylaxis.
Administration of either palivizumab (15 mg/kg intramuscularly), a monoclonal antibody against RSV, or high-titered RSV intravenous immunoglobulin (RSV-IVIG; 750 mg/kg) is recommended for protecting high-risk children against serious complications from RSV disease. Immunoprophylaxis reduces the frequency and total days of hospitalization for RSV infections in high-risk infants. These agents are administered monthly from the beginning (October-December) to the end (March-May) of the RSV season. Palivizumab is preferred for most children because of ease of intramuscular administration and lack of interference with live virus vaccinations (measles-mumps-rubella and varicella). RSV-IVIG provides some protection against other respiratory pathogens and may be substituted for IVIG during the RSV season for children with immunodeficiency receiving monthly IVIG.
Candidates for immunoprophylaxis include children with lung disease and children who were born very prematurely. Children younger than 2 yr with bronchopulmonary dysplasia requiring supplemental oxygen therapy currently or within the 6 mo before the RSV season should receive prophylaxis for the first two RSV seasons if they have severe lung disease and only the first RSV season for less severe lung disease. Infants without bronchopulmonary dysplasia should receive prophylaxis up to 12 mo of age if they were born at 28 wk of gestation or earlier and up to 6 mo of age if they were born at 29-32 wk of gestation. One dose of immunoprophylaxis may be considered for premature infants to be discharged from the hospital during the RSV season. RSV-IVIG is contraindicated and palivizumab is not recommended for children with cyanotic congenital heart disease. Adverse events with palivizumab are uncommon.
Vaccine.
There is not currently a vaccine against RSV. Vaccine development for RSV has proceeded cautiously since the experience in the 1960s with an alum-precipitated formalin-inactivated vaccine. This vaccine was excellent for inducing serum antibodies, but vaccinees had augmented disease after natural infection. Live, attenuated vaccines have produced unacceptable symptoms or reverted to wild-type virus. Current candidate vaccines are either purified subunit vaccines against the fusion (F) protein or attenuated, cold-adapted live vaccines.
Adenoviral infection
Adenoviruses cause 5-8% of acute respiratory disease in infants, plus a wide array of other syndromes, including pharyngoconjunctival fever, follicular conjunctivitis, epidemic keratoconjunctivitis, myocarditis, hemorrhagic cystitis, acute diarrhea, intussusception, and encephalomyelitis. Only a third of the 49 serotypes have been associated with disease. Fatal disease is rare, but is associated with infection by certain serotypes (particularly type 7) and infection in severely immunocompromised hosts.
ETIOLOGY.
The Adenoviridae are DNA viruses of intermediate size, which are classified into subgenera A to F. The virion has an icosahedral coat (capsid) made up of 252 subunits (capsomers) of which 240 are "hexons" and 12 are "pentons." The hexons have a cross reacting antigen common to all mammalian adenoviruses. The penton confers type specificity, and antibody to it is protective. It is cytotoxic in tissue culture, and toxic properties have been ascribed to it in vivo as well. Adenoviruses can also be classified by their characteristic DNA "fingerprints" on gels after being digested with restriction endonucleases, and this classification generally conforms to their antigenic types.
All adenovirus types, except types 40 and 41, grow in primary human embryonic kidney cells, and most grow in HEp-2 or HeLa cells, producing a typical destructive cytopathic effect. Types 40 and 41 (and other serotypes as well) grow in 293 cells, a line of human embryonic kidney cells into which certain "early" adenovirus genes have been introduced.
Many adenovirus types, but particularly the common childhood types (1, 2, and 5), are shed for prolonged periods from both the respiratory and gastrointestinal tracts. These types also establish low-level and chronic infection of the tonsils and adenoids.
EPIDEMIOLOGY.
Adenoviral infections are distributed worldwide. They occur year-round but are most prevalent in spring or early summer and again in midwinter in temperate climates. Certain types tend to occur in epidemics, notably types 4 and 7 in outbreaks of febrile respiratory disease, types 3, 7, and 21 in severe pneumonia; type 3 in pharyngoconjunctival fever; type 11 in hemorrhagic cystitis; and types 8, 19, and 37 in epidemic keratoconjunctivitis. For unexplained reasons, adenovirus types 3 and 7 cause severe epidemics of pneumonia in the children of northern China and Korea, with mortality rates of 5-15%.
More than 60% of school-age children have antibodies to the common respiratory types. Almost all adults have serum antibody to types 1-7. Infections with types 1 and 2 tend to occur during the 2nd yr of life, and types 3 and 5 occur a little later. Spread occurs by the respiratory and fecal-oral routes, although it is not clear whether spread is by large- or small-particle aerosol. Hospital outbreaks of respiratory disease and keratoconjunctivitis have been described.
PATHOGENESIS.
Adenoviruses are among the few "respiratory" viruses that grow well in the epithelium of the small intestine. Although mucosal surfaces are the primary target early in infection and typically the site of the most common pathology, viremia probably occurs frequently, with accompanying fever.
Adenoviral pneumonia produces characteristic microscopic changes, with dense lymphocytic infiltrates, destruction of the bronchial and bronchiolar epithelium, focal necrosis of mucous glands, hyaline membrane formation, and several types of nuclear inclusion bodies.
CLINICAL MANIFESTATIONS.
Adenoviruses cause a wide array of clinical syndromes.
Acute Respiratory Disease.
This is the most common manifestation of adenovirus infection in children and adults. Acute adenovirus respiratory tract infections in infants and children are not clinically distinctive and are usually caused by types 1, 2, 3, 5, or 6. Primary infections in infants are frequently associated with fever and respiratory symptoms and are complicated by otitis media in more than half of the patients. Adenovirus respiratory infections are associated with a significant incidence of diarrhea.
Pharyngitis due to adenovirus typically has symptoms of coryza, sore throat, and fever. Adenoviruses can be identified in 15-20% of children with isolated pharyngitis, mostly in preschoolers and infants.
Pneumonia is uncommon, but 7-9% of hospitalized children with acute pneumonia have adenovirus infection. Any of the "respiratory" types can cause pneumonia, but severe infections are most likely due to type 3, 7, or 21. Such infections have a mortality as high as 10%, and survivors may have residual airway damage, manifested by bronchiectasis, bronchiolitis obliterans, or, rarely, pulmonary fibrosis. Neonatal adenovirus pneumonia occurs rarely, but may be severe or fatal.
A pertussis-like syndrome has been described in association with adenovirus infections. In these cases, adenoviruses frequently accompany Bordetella pertussis as coinfecting agents, but occasionally they may also be causative on their own.
Pharyngoconjunctival fever is a clinically distinct syndrome that occurs particularly in association with type 3 adenovirus. Features include a high temperature that lasts 4-5 days, pharyngitis, conjunctivitis, preauricular and cervical lymphadenopathy, and rhinitis. Nonpurulent conjunctivitis occurs in 75% of patients and is manifested by inflammation of both the bulbar and palpebral conjunctivae of one or both eyes; it often persists after the fever and other symptoms have resolved. Headache, malaise, and weakness are common, and there is considerable lethargy after the acute stage.
Conjunctivitis and Keratoconjunctivitis.
Adenovirus is one of the most common causes of follicular conjunctivitis and keratoconjunctivitis. The former is a relatively mild illness. The latter, which may occur, in epidemics, is associated with infection by adenovirus types 8, 19, and 37. Keratitis begins as the conjunctivitis wanes, and may cause corneal opacities that last several years.
Myocarditis.
In several series of acute myocarditis or idiopathic cardiomyopathy, investigated by the application of polymerase chain reaction (PCR) in the search for microbial agents, adenovirus has been found as commonly as, or more commonly than, nonpolio enteroviruses. It is widely assumed that adenovirus has an important etiologic role in this disease. It has also been associated with heart transplant rejection and with some cases of endocardial fibroelastosis.
Gastrointestinal Infections.
Adenoviruses can be found in the stools of 5-9% of children with acute diarrhea. About one half of these are the "enteric" types, 40 or 41. It is also clear that enteric infection with any adenovirus serotype is often asymptomatic, so the causative role in these episodes is frequently uncertain.
The pathogenesis of intussusception is thought by many to include enlarged lymph nodes as an initiating factor. Adenoviruses have been recovered from mesenteric lymph nodes or appendices at surgery and also from surface cultures in a higher percentage of children with intussusception than of controls. Adenoviruses have also been found in the appendices of children with appendicitis.
Hemorrhagic Cystitis.
This syndrome has a sudden onset of bacteriologically sterile hematuria, dysuria, frequency, and urgency lasting 1-2 wk. Infection with adenovirus types 11 and 21 has been found in some affected children and young adults.
Reye's Syndrome and Reye's-like Syndromes.
Typical Reye's syndrome has followed confirmed adenovirus infection of several serotypes, particularly in very young children. In addition, several cases of a Reye's-like syndrome have been reported, all of which are caused by infection with adenovirus type 7. The latter disease, which is frequently fatal, is characterized by severe bronchopneumonia, hepatitis, seizures, and disseminated intravascular coagulation. Circulating adenovirus penton antigen has been found in several patients and has been implicated in the pathogenesis.
Infections in Immunocompromised Hosts.
Adenoviruses are important pathogens in immunocompromised hosts with either B- or T-cell deficiencies. In B-cell-deficient (hypogammaglobulinemic) patients, a chronic meningoencephalitis similar to that caused by enteroviruses has been described. In T-cell-deficient patients, regardless of whether this deficiency is congenital, acquired, or iatrogenic, fulminant hepatitis and pneumonia, frequently with a fatal outcome, have been described. There is also a close association between adenovirus infection and both hemorrhagic cystitis and tubulointerstitial nephritis in immunosuppressed children.
DIAGNOSIS.
The laboratory diagnosis of adenovirus infection in children may be made by suggestive pathologic changes in biopsy material, detection of virus by culture or PCR, demonstration of a rise in antibody titers, or a combination of virus detection and serologic testing. PCR has proven a very useful method in the detection of adenovirus in biopsy tissues. If virus is found in a "privileged" site, such as blood, urine, or cerebrospinal fluid, or in a biopsy of the lung or liver, the implication of infection with disease and organ damage is strong. Likewise, detection of certain adenovirus types in respiratory secretions (type 7 or 21) probably indicates their etiologic involvement. The presence of untyped virus or the common childhood types (1, 2, and 5) in respiratory secretions or stool does not, however, indicate clinical adenovirus infection because these viruses may be excreted chronically and asymptomatically. In these instances, discovery of a coincident rise in antibody by complement fixation (group specific) or neutralization or hemagglutination inhibition (type specific) is helpful in assigning a specific adenovirus type to disease. Adenovirus infection may also be considered etiologic if a rise in antibody is found between sera drawn in the acute stage and in convalescence from a patient with an appropriate illness. Adenovirus infection often results in a high erythrocyte sedimentation rate and white blood cell count.
TREATMENT.
There are at present no recognized antiviral agents that are effective in treating adenovirus infections. Ribavirin can inhibit viral growth of some strains in vitro, but evidence of its clinical efficacy is lacking.
PREVENTION.
Vaccines that contain either killed or live virus have been developed to prevent type 4 and 7 infections in military recruits. These vaccines have not, however, been used in children.
Rhinoviral infection
Rhinoviruses are collectively the most common cause of the "common cold" in adults. They are also very common in young children, but because of the frequency of other viral respiratory tract infections in this age group, their relative importance is somewhat less than in adults. They are difficult to grow in tissue culture, however, and studies using polymerase chain reaction (PCR) indicate that their frequency and importance in respiratory illnesses are considerably greater than has been thought in the past.
ETIOLOGY.
There are 101 serologically distinct rhinoviruses (numbered 1-100, and subtype 1A), members of the Picornaviridae family of small RNA viruses. They are best identified in clinical samples by PCR performed on nasal secretions from infected individuals. Tissue culture is approximately one third as sensitive as PCR. Routine serologic testing for development of antibody is not practical because of the multiplicity of serotypes.
Not all rhinovirus infections are associated with symptoms, even in infants and children. In longitudinal studies, 75% of pediatric rhinovirus infection (detected by culture) is associated with illness, usually rhinitis or pharyngitis. Rhinoviruses have also been associated with serious lower respiratory tract disease, particularly in very young infants and those with underlying illnesses. They are frequent precipitators of asthma in children and of chronic bronchitis in adults.
EPIDEMIOLOGY.
Rhinoviruses are distributed worldwide with no predictable pattern of infection by serotype. Multiple types may be present in a community at one time.
In temperate climates the incidence of rhinovirus infection peaks in September and again in April or May, but infections occur year-round. The peak incidence in the tropics occurs during the rainy season.
Rhinoviruses are recovered in highest concentration in nasal secretions, and experimental infection is most easily accomplished by nasal or conjunctival instillation. Virus persists for several hours in secretions on hands or other surfaces. Transmission occurs when infected secretions carried on contaminated fingers are rubbed into the nasal or conjunctival mucosa. Evidence also implicates spread through prolonged contact with aerosols produced by talking, coughing, or sneezing.
PATHOGENESIS.
Rhinoviruses, like other picornaviruses, infect cells only after interaction with specific cell receptors. For most rhinovirus types, this is ICAM-1, an intercellular adhesion molecule present on the epithelium covering the adenoids (lymphoepithelium) and on other epithelial cells of the nose after stimulation by various interleukins (interferon-gamma, tumor necrosis factor, interleukin 1). Thus, for these types, infection probably begins in the nasopharynx and then, as interleukins are produced, spreads forward to the nasal mucosa. The peak nasal inflammatory response occurs when virus growth is at its greatest, 2-4 days after experimental infection, and is accompanied by the production of multiple proinflammatory mediators. Immune responses include specific nasal immunoglobulin (Ig) A and serum IgG antibody, which may contribute to modifying the illness and limiting viral shedding.
CLINICAL MANIFESTATIONS.
The primary clinical response to rhinovirus infection, like that to most respiratory viral infections, is the common cold (see Chapter 381 .1). There is an incubation period of 2-4 days; then sneezing, nasal obstruction and discharge, and sore throat ensue. Cough and hoarseness occur in 30-40% of cases. Fever is neither as frequent nor as high as in primary infections with respiratory syncytial virus, parainfluenza virus, influenza virus, or adenovirus. Headache and other systemic symptoms are not as common as with influenza virus. Symptoms are worse in the first 2-3 days of illness and last for 1 wk in a majority of patients; they persist for more than 14 days in 35% of young children.
DIAGNOSIS.
Because other viral agents can produce the same manifestations, a clinical diagnosis is only presumptive but is usually adequate. Laboratory diagnosis is not practical under ordinary circumstances. Bacterial antigen testing or cultures should be performed to exclude streptococcal nasopharyngitis if this is suspected.
TREATMENT.
Relief of acute symptoms may be provided by acetaminophen or ibuprofen for antipyresis and mild analgesia and by saline or decongestant (in children >6 mo of age) nose drops used for a short time for nasal discharge and obstruction.
Several antiviral drugs have been developed with potent activity against rhinoviruses. Tests in volunteers have shown that, although these reduce the titer of virus in the nose, they do not lessen symptoms or decrease the duration of illness. It seems likely that successful treatment will have to target the host response as well as the virus.
COMPLICATIONS.
As with any infection causing edema and inflammation in the nasopharynx, complications include otitis media and sinusitis. In one study rhinoviruses were the most common virus recovered from the middle-ear fluids of infants and children with otitis media. In very young infants bronchiolitis may occur. Rhinoviruses are the most common cause of acute exacerbations of asthma in school-age children.
PREVENTION.
The best approach to reducing spread includes careful handwashing and avoidance of manual nose and eye manipulation.
LARYNGOTRACHEITIS AND LARYNGOTRACHEOBRONCHITIS (CROUP)
The most common upper-airway infections are viral laryngotracheitis (LT) or laryngotracheobronchitis (LTB), also known as viral croup, and viral bronchitis. Serious subglottic infections include bacterial tracheitis and severe viral croup.
Viral LT/LTB usually spreads downward from the nasopharynx into the larynx, trachea, and the smaller airways. The source of obstruction in viral croup is below the glottis and usually results from inflammatory edema and mucus production of the subglottic tracheal submucosa, without direct viral invasion. Exfoliation of the damaged mucosal lining of the trachea can intensify the obstruction. The level of glottic and subglottic infection – namely, the larynx, trachea, or bronchi – determines and is predicted by the clinical features of the disease, particularly the quality of the voice or cry and the frequency and quality of cough.
Epidemiology
Croup is the most common infectious cause of obstruction of the upper airway in young children. It occurs most often in children between the ages of 6 months and 2 years, and more often in boys than in girls.
Croup is traditionally divided into spasmodic and infectious (viral) types; however, this distinction is not necessary for practical purposes, since both are managed in the same way. Epidemics begin in October or November and peak in early winter; in some years, there is a smaller outbreak in mid-August. The virus is transmitted by contact with unwashed hands or sneezing, coughing, or breathing virus-laden microdroplets. The incubation period is 2 to 3 days, and the typical course of croup is about 3 days, with a range of 1 to 6 days.
Etiologic Agents
Parainfluenza virus types 1, 2, and 3 are the most common causes of croup; together, they account for about 60% of cases.Type 1 virus, the most common, characteristically causes fall or winter epidemics; type 3 virus is less common but can cause more severe illness. Respiratory syncytial virus, influenza virus A and B, human adenoviruses that affect the respiratory tract (types 1, 2, 3, 4, 7, 8, 11, 14, and 21), human metapneumovirus, certain echoviruses, coxsackieviruses, and other viruses can also cause croup, and the inflammatory changes and clinical symptoms are similar to those of the prototypical parainfluenza-associated croup. Measles is sometimes associated with severe croup.The most common causes of outbreaks of croup in closed communities are influenza virus and adenovirus infections.
Clinical Manifestations
Croup is heralded by symptoms characteristic of a nonspecific upper respiratory tract illness. These are followed by a seal-like barking or brassy cough, dysphonia that may progress to aphonia, intermittent inspiratory stridor, and suprasternal retractions. The onset is usually unexpected and dramatic and can become manifest after the child has been sleeping. Nonspecific antecedent upper respiratory tract symptoms are not always present; in this case, the condition is called spasmodic croup.
Ninety percent of children with croup have mild symptoms. Some children develop significant symptoms during daylight hours, with or without a high fever. They are often evaluated by primary care physicians, who may prescribe antibiotic agents injudiciously. Moderate or severe croup can lead to airway occlusion and is potentially life-threatening. Stridor and barking cough are the predominant symptoms. The leukocyte count is generally normal or mildly elevated, with lymphocytes predominating. Radiographs demonstrate the classic “steeple sign” of subglottic edema, with a 5- to 10-mm segment of narrowed subglottic air column. The lateral radiographic view of the neck can show widening of the hypopharyngeal air space resulting from a distal obstruction.
Differential Diagnosis
Unusual infectious causes of croup syndrome include Corynebacterium diphtheriae, Mycobacterium tuberculosis, endotracheal infection and Candida albicans secondary to overuse of steroid inhalations. Laryngeal diphtheria can present as severe croup. In an unimmunized child, a degree of toxicity and tachycardia that is out of proportion to fever may help focus the clinician's attention on this rare disease.
The history can help differentiate true LTB from other causes of a croupy cough. A history of recent aspiration or choking on a foreign body, the presence of croup in the first 90 days of life, or more than two or three recurrences of croup in a year suggest that the obstruction may have an anatomic cause. Noninfectious causes of recurrent croup include foreign-body aspiration, tracheomalacia, gastroesophageal reflux, paradoxical vocal cord dysfunction, and subglottic stenosis from prolonged tracheal intubation in the neonatal period. Anatomic causes of airway compromise include a vascular ring. Infrequent causes of a croupy cough and stridor include laryngeal papillomatosis, laryngeal webs or cysts, vascular ring, allergic or hypocalcemic laryngospasm, H-type tracheoesophageal fistula, and laryngeal trauma. CT, MRI, or MR angiography can help differentiate noninfectious from infectious causes of obstruction.
Croup is not expected as a complication of viral infection in children older than age 5 because of the greater diameter of the lumen of the trachea and because previous infections with parainfluenza virus and other typical agents of croup have led to immunity. Another diagnosis or predisposition must be sought, particularly aspiration of a foreign body. Older children and adolescents with parainfluenza laryngotracheitis usually have symptoms of simple laryngitis, i.e., dysphonia, without a barking cough or stridor.
Management
Maintenance of an adequate airway, humidification of room air, and oxygenation are tenets of management. Six percent of young children with viral croup are hospitalized for severe obstructive symptoms, hypoxia, dehydration, or fatigue. Endotracheal intubation is necessary for less than 1% of such patients. The condition is rarely fatal. Recovery from LTB occurs in 3 to 7 days. The most common complication of LTB is extension of infection to other regions of the respiratory tract, such as the middle ear, the bronchioles, and the parenchyma of the lung (bronchopneumonia). Recurrences can be expected in about one-third of children. Bacterial tracheitis sometimes complicates LT/LTB and can be life-threatening.
General Care and Management of Airway
Decisions concerning where the child with croup will be managed depend on the degree of parental or physician uneasiness with the clinical, geographic, and social setting; the course of previous episodes; the rapidity and degree of progression of upper-airway obstruction and respiratory distress (i.e., croup score); progression of weakness and fatigue; and symptoms or signs of moderate-to-severe dehydration or poor intake of fluids.
As long as a responsible caretaker remains with the child at all times, a telephone is in the home, immediate transportation is available, and an emergency medicine facility is close by, most children with mild or moderate croup do not require hospitalization. All children, however, require periodic reassessment by a caretaker during the hyperacute phase of the disease. Humidification of air may reduce edema of the airway and facilitate clearing of secretions. The relative therapeutic merit of hot steam over cold mist vaporizer is not supported by evidence. Exposure to a steam-filled bathroom or to night air (via an open window or a ride in an automobile with the windows down) is traditional advice of unproven merit. Ipecac syrup, once a popular treatment, has no role in modern treatment.
Racemic Epinephrine
Nebulized racemic epinephrine can be useful in the treatment of moderate or severe cases of LTB. The adrenergic effects of racemic epinephrine induce vasoconstriction, which decreases subglottic edema. Racemic epinephrine 2.25% diluted 1:8 in saline is administered via nebulizer at a dose of 0.25 mL (4 drops) for children younger than 6 months and 0.5 mL for older children. The onset of drug action occurs in less than 10 minutes, and the effects last 60 to 90 minutes. The dose can be repeated in 1 hour. Continuous nebulization over 30 to 60 minutes may also be effective.
Close observation in the emergency department or office is standard practice after this treatment to reassess in the period after waning of drug effect. Discharge is appropriate when there is minimal stridor at rest, and air entry, color, and level of consciousness are normal. If the child's upper respiratory distress worsens following discharge, the patient should be immediately transported to a medical facility for re-evaluation.
Corticosteroid Therapy
Corticosteroid treatment reduces symptoms in children with mild, moderate, or severe croup. In double-blind, placebo-controlled studies, children who receive corticosteroids have significant reductions in duration of severe symptoms, shorter observation times in an emergency medical facility, less need for return visits, less need for hospitalization and critical care observation when hospitalized, and less need for endotracheal intubation. A Cochrane review of benefit highlighted the efficacy of corticosteroids in the management of croup. Dosage options are dexamethasone phosphate (0.6 to 1 mg/kg) once intramuscularly; dexamethasone syrup or crushed tablets (0.6 to 1 mg/kg) once orally; or prednisolone (2 mg/kg per day) orally in two or three divided doses. There is no significant difference in efficacy between single dexamethasone doses administered orally or intramuscularly. No adverse effect from single-dose dexamethasone has been noted. It seems prudent to administer dexamethasone to any child with croup whose airway obstruction is severe enough to warrant treatment with racemic epinephrine.
Nebulized budesonide is nearly as effective as dexamethasone but is more expensive, takes longer to administer, and is less available. The addition of inhaled budesonide to oral dexamethasone offers no advantage in the treatment of children hospitalized with croup.
Supplemental oxygen is often prescribed for hospitalized children with LT/LTB, particularly when the resting pulse oximetry reading in room air is less than 92%. The hypoxic child must be carefully monitored for impending respiratory failure. A small study has documented the benefits of heliox for children with LTB.
Control fever in the management of influenza in children
Definition of fever: rectal temperature >= 38.0o C (100.4o F )
Pathophysiology: raising of hypothalamic set point in CNS
Treatment:
1. Antipyretics (lower the central set point: inhibit cyclo-oxygenase enzyme, prevent synthesis of prostaglandin; do not interfere with immune response to infection)
Doses:
- acetaminophen 10-15 mg/kg every 4 hours
- ibuprofen 5-10 mg/kg every 6-8 hours
- salicylates can’t be used as antipyretic to control fever in the management of influenza because of the risk of Reye syndrome(Reye’s syndrome is characterized by protracted vomiting, hepatitis, and neurologic abnormalities)
2. Treatment( adjunctive measures)
- Adequate hydration
- Comfortable surroundings: temperature 72o F (22o C)
- Not bundled in extra clothing or blankets
- Sponging with tepid water(28o C); sponging with cold water or alcohol should be avoided: lead to shivering which may increase body temperature and is uncomfortable
Febrile seizure
Convulsion that occurs in association with a febrile illness in children between 6 months and 5 years of age in the absence of an identifiable cause.
Febrile seizures are the most common type of seizure in young children, with a 2% to 5% incidence of children experiencing at least one seizure before the age of 5 years.
|Simple febrile seizure |Complex febrile seizure |
|Lasts less than 15 minutes |Lasts 15 minutes or longer |
|Occurs once in a 24-hour period |Occurs more than once in a-24-hour period |
|Generalized |Focal |
|No previous neurologic problems |Patient has known neurologic problems, such as cerebral |
| |palsy |
| | |
The peak age for febrile convulsions is between 18 and 24 months.
The exact pathophysiology is unknown, but it seems that a fever lowers the seizure threshold.
Family history of febrile seizures present in 25% to 40% of children with febrile seizures.
When to do a lumbar puncture?
• Every child < 1 year of age with a febrile convulsion.
• Presence of meningeal signs and symptoms.
• In case of doubt, if LP is not performed , the paediatrician is advised to review the case within a few hours.
• Not necessary in most cases, but exceptions in a child with
• papilledema
• cranial nerve palsies (eg. 6th nerve palsy)
• other persisting focal neurological signs (eg. hemiparesis)
marked depression in mental status
EEG:
- rarely indicated in the management of a simple febrile convulsion
- complex febrile seizure
Blood chemistry:
- electrolytes and sugar in a child who is drowsy or dehydration
- toxicology screening if suspicious
Emergency management
General:
← Same as other type of seizure
← Maintain a clear airway (ABC!!!)
← Give oxygen if available
← Apply suction for nasal or oral secretions if facility available
← Place the child in a semi-prone position
← Protect the child from injury
← Loosen clothing or remove excess clothing
← Monitor vital sign
Benzodiazepines are the first drug of choice for persistent seizure activity.
Diazepam is the most common drug used
- administer rectal diazepam 0.2-0.5 mg/kg/dose
- IV dose is 0.3 mg/kg/dose
- The same dose can be repeated every 10 to 30 minutes to a total of 3 doses, if necessary
Administer intravenous anticonvulsant if the child is still convulsing for >15 minutes
← Diazepam
← lorazepam 0.05-0.10 mg/kg/dose (maximum rate: 1 mg/minute) to a maximum dose of 4 mg can be given
← phenobarbital 15-20 mg/kg (rate: 30 to 100 mg/minute)
Observation for several hours after a febrile convulsion
Patients with a simple febrile seizure may be safely discharged to home with parental reassurance and seizure education.
Follow up care
Hospital Admission ( indications ):
Complex febrile seizure
Suspicious of possibility of meningitis and encephalitis
Age < 18 months
Anxious parents or inadequate home care
Croup. Emergency management
[pic]
V. Sources of information.
Basic literature:
|№ |Author(s) |Name of the source |City, |Year of |Number of |
|№ | |(textbook, manual, monograph, etc) |Publish-ing house |edition, vol.,|pages |
| | | | |issue | |
|1 |Mikhailova A.M., Minkov | | Odessa | | |
| |I.P., Savchuk A.I. |Infection diseases in children | |2003 |102-114 |
| | | | | | |
|2 |E. Nikitin, | | | | |
| |M. Andreychin |Infectious diseases |Ukrmedkniga |2004 | |
Additional literature:
|№ |Author(s) |Name of the source |City, |Year of |Number of |
|№ | |(textbook, manual, monograph, etc) |Publishing house |edition, vol.,|pages |
| | | | |issue. | |
|1 |Robert M. Kliegman, MD, | |W.B.Saunders |2007, 16 th |987-996; |
| |Richard E. Behrman, MD, |Nelson Textbook of pediatrics |company |edition |1275-1278 |
| |Hal B. Jenson, MD and | | | | |
| |Bonita F. Stanton, MD | | | | |
VIII. Tests &Tasks
Topic: “ Acute respiratory viral infections (Influenza. Parainfluenzal infection. Adenoviral infection. Respiratory syncytial infection. Rhinoviral infection). Pertussis . Differential diagnosis.Emergency”.
Tests
Influenza
1. Influenza viruses are members of the family:
A. Paramyxoviridae
B. Picornaviridae
C. Orthomyxoviridae
D. Herpesviridae
E. Retroviridae
2. Influenza viruses are:
A. DNA viruses
B. RNA viruses
3. Major changes in serotype of influenza A virus are termed:
A. Antigenic drift
B. Antigenic shift
4. Minor changes within a serotype of influenza A virus are termed:
A. Antigenic shift
B. Antigenic drift
5. What type of influenza viruses is the major cause of epidemic disease:
A. Type A
B. Type B
C. Type C
6. The attack rate of influenza is highest in:
A. Infants (new-born)
B. Young children.
C. Adult
7. What viruses more so than any of the other respiratory viruses is accompanied by systemic signs of high temperature, myalgia, malaise, and headache:
A. Parainfluenza viruses
B. Adenoviruses
C. Influenza viruses
D. Respiratory syncytial virus
8. Common complication of influenza in children is:
A. Inflammation of intestine
B. Hepatitis
C. Otitis media
9. Common complication of influenza in children is:
A. Otitis media
B. Pneumonia
C. All answers are correct
10. What viruses have etiologic role in myocarditis:
A. Influenza viruses
B. Parainfluenza viruses
C. Respiratory syncytial virus
D. Rhinoviruses
E. All answers are correct
11. What disease is characterized by severe bronchopneumonia, hepatitis, and disseminated intravascular coagulation:
A. Reye’s syndrome
B. Reye’s-like syndrome
C. Pertussis-like syndrome
12. What disease is characterized by protracted vomiting, hepatitis, and neurologic abnormalities:
A. Reye’s syndrome
B. Reye’s-like syndrome
C. Pertussis-like syndrome
13. The laboratory diagnosis of influenza virus infection can be accomplished by:
A. Inoculation of nasal secretions into tissue culture
B. Serologic testing
C. Direct immunofluorescent staining
D. All answers are correct
14. What medicine can be used as antipyretic to control fever in the management of influenza:
A. Acetaminophen
B. Ibuprofen
C. All answers are correct
15. What medicine can’t be used as antipyretic to control fever in the management of influenza:
A. Acetaminophen
B. Salicylates
C. Ibuprofen
D. All answers are correct
16. Reyes syndrome can result with the use of ( in case of influenza type B infection):
A.Immunoglobulin
B.Rimantadine
C.Acetaminophen
D.Salicylates
17. Oseltamivir and zanamivir are effective against influenza:
A. Type A
B. Type B
C. All answers are correct
18. Rimantadine and amantadine are effective against influenza:
A. Type A
B. Type B
C. Type C
D. All answers are correct
19. Amantadine and rimantadine aren’t approved for use in children younger than:
A. 1 yr
B. 7 yr
C. 12 yr
20. Antiviral decrease the severity and duration of influenza symptoms if given within the first:
A. 48 hr
B. 72 hr
C. 3-5 days
21. What influenza vaccine isn’t recommended for children younger than 12 yr:
A. Live, attenuated vaccine
B. Split-virus vaccine
C. Subunit-virus vaccine
D. All answers are correct
22. What influenza vaccine is recommended for children younger than 12 yr:
A. Split-virus vaccine
B. Subunit-virus vaccine
C. All answers are correct
23. What vaccines have been used in children:
A. Against parainfluenza viruses infections
B. Against adenoviruses infections
C. Against influenza viruses infections
D. Against respiratory syncytial virus infections
E. Against rhinoviruses infections
Parainfluenza
1. Parainfluenza viruses are members of the family:
A. Picornaviridae
B. Paramyxoviridae
C. Orthomyxoviridae
D. Herpesviridae
E. Retroviridae
2. Parainfluenza viruses are:
A. DNA viruses
B. RNA viruses
3. Parainfluenza viruses have propensity to cause illness associated with:
A. high temperature, myalgia, malaise, and headache
B. the upper respiratory tract illness
C. the lower respiratory tract illness
4. Parainfluenza viruses are particularly associated with:
A. Laryngotracheitis
B. Bronchitis
C. Croup.
D. All answers are correct
5. The major causes of croup in children are:
A. Parainfluenza viruses
B. Adenoviruses
C. Influenza viruses
D. Respiratory syncytial virus
6. Viral croup has his highest incidence from:
A. 1-6 mo of age
B. 6 mo-5yr of age
C. 5-7yr of age
7. What disease typically has symptoms of hoarse voice, barking cough and inspiratory stridor:
A. Croup
B. Bronchitis
C. Bronchiolitis
D. Pneumonia
8. What sign is characteristic of croup:
A. The radiographic “steepl sign”
B. Koplik sign
C. Kernig sign
9. The laboratory diagnosis of parainfluenza virus infection can be accomplished by:
A. Gram stain
B. Direct immunofluorescent staining
C. Bacteriologically
D. All answers are correct
10. The laboratory diagnosis of parainfluenza virus infection can be accomplished by:
A. Inoculation of nasal secretions into tissue culture;
B. Serologically
C. Direct immunofluorescent staining
D. All answers are correct
11. What antiviral has some antiviral activity against parainfluenza viruses:
A. Amantadine
B. Rimantadine
C. Ribavirin
D. Zanamivir
12. The most effective method to control of croup:
A. Aerosolized racemic epinephrine
B. Aerosolized or systemic corticosteroids
C. Aerosolized or systemic antibiotics
13. The indications for antibiotics in the management of parainfluenza are:
A. Secondary bacterial infections of the middle ears
B. Secondary bacterial infections of lower respiratory tract
C. All answers are correct
Adenoviral infection
1. The Adenoviridae are:
A. DNA viruses
B. RNA viruses
2. What viruses are shed for prolonged periods from both the respiratory and gastrointestinal tracts:
A. Parainfluenza viruses
B. Adenoviruses
C. Influenza viruses
D. Respiratory syncytial virus
E. Rhinoviruses
3. What viruses spread by the respiratory and fecal-oral routes:
A. Influenza viruses
B. Parainfluenza viruses
C. Adenoviruses
D. Respiratory syncytial virus
E. Rhinoviruses
4. Clinical manifestation of adenoviral infection:
А. Acute respiratory disease
B. Pharyngoconjunctival fever
C. Conjunctivitis and keratoconjunctivitis
D. Encephalomyelitis
E. All answers are correct
5. Clinical manifestation of adenoviral infection:
A. Myocarditis.
B. Gastrointestinal infection
C. Intussusception
D. Hemorrhagic cystitis
E. Reye’s syndrome and Reye’s-like syndromes
F. All answers are correct
6. What syndrome is associated with a high temperature that lasts 4-5 days, pharyngitis, conjunctivitis, preauricular and cervical lymphadenopathy, and rhinitis:
A. Reye’s syndrome and Reye’s-like syndromes
B. Conjunctivitis and keratoconjunctivitis
C. Pharyngoconjunctival fever
7. What viruses are one of the most common causes of follicular conjunctivitis and keratoconjunctivitis:
A. Influenza viruses
B. Parainfluenza viruses
C. Adenoviruses
D. Respiratory syncytial virus
E. Rhinoviruses
8. What viruses establish chronic infection of the tonsils and adenoids:
A. Parainfluenza viruses
B. Adenoviruses
C. Influenza viruses
D. Respiratory syncytial virus
E. Rhinoviruses
9. What syndrome of adenoviral infection has a sudden onset of bacteriologically sterile hematuria, dysuria :
A. Pertussis-like syndrome
B. Reye’s syndrome and Reye’s-like syndromes
C. Hemorrhagic cystitis
D. Acute myositis
10. What viruses have etiologic role in myocarditis:
A. Parainfluenza viruses
B. Adenoviruses
C. Respiratory syncytial virus
D. Rhinoviruses
E. All answers are correct
11. What viruses have etiologic role in myocarditis:
А. Adenoviruses
B. Influenza viruses
C. All answers are correct
12. The pathogenesis of intussusception in children with adenovirus infection to include as an initiating factor:
A. Enlarged lymph nodes
B. Enlarged liver
C. Enlarged spleen
13. What respiratory infections are associated with diarrhea:
A. Influenza viruses
B. Parainfluenza viruses
C. Adenoviruses
D. Respiratory syncytial virus
Е. Rhinoviruses
14. What antiviral agents are effective in treating adenovirus infection:
A. Ribavirin
B. Oseltamivir
C. Zanamivir
D. There are at present no recognized antiviral agents that are effective
15. What vaccines against adenovirus infections have been used in children:
A. Subunit vaccines
B. Attenuated live vaccines
C. Vaccines against adenovirus infections have not been used in children
Respiratory syncytial virus infection
1. What viruses belong to the family Paramyxoviridae:
A. Parainfluenza viruses
B. Mumps virus
C. Measles virus
D. RSV (respiratory syncytial virus)
E. All answers are correct
2. RSV have propensity to cause illness in infants associated with:
A. High temperature, myalgia, malaise, and headache.
B. The upper respiratory tract illness
C. The lower respiratory tract illness
3. What viruses are responsible for 45-75% of cases of bronchiolitis:
A. Influenza viruses
B. Parainfluenza viruses
C. Adenoviruses
D. Respiratory syncytial virus
E. Rhinoviruses
4. Placentally transmitted anti-RSV antibody, when present in high concentration, has some protective effect during:
A. The first 4-6 wk of life
B. The first 4-6 mo of life
C. The first 6-12 mo of life
D. There are at present no placentally transmitted anti-RSV antibody in infants
5. All RSV diseases of the lower respiratory tract (excluding croup) have their highest incidence from:
A. 4-6 wk of age
B. 2-7 mo of age
C. 12-18 mo of age
6. Infants are particularly apt to experience small airway obstruction because:
A. Of the large size of the normal bronchiolar epithelium
B. Of the small size of the normal bronchioles.
7. What diseases typically has symptoms of cough, wheezing, intercostal and subcostal retractions, hyperexpansion of the chest(auscultation often reveals diffuse rhonchi, fine rales or crackles, and wheezes):
A. Croup
B. Bronchitis
C. Bronchiolitis
D. Pneumonia
8. What medicine may relieve wheezing in infants with RSV bronchiolitis:
A. Bronchodilator
B. Clarithromycin
C. Zanamivir
9. What antiviral drug, delivered by aerosol, has a modest beneficial effect on the course of RSV pneumonia:
A. Dexamethazone
B. Zanamivir
C. Ribavirin
D. Adrenaline
10. What viruses are a frequently recognized cause of acute asthma attacks in children 1-5 yr old:
A. Parainfluenza viruses
B. Adenoviruses
C. Influenza viruses
D. Respiratory syncytial virus
E. Measles virus
F. All answers are correct
11. Passive immunoprophylaxis against RSV infection include administration of:
A. Monoclonal antibody against RSV
B. High-titered RSV intravenous immunoglobulin (RSV-IVIG, 750 mg/kg)
C. All answers are correct
12. What vaccines against RSV infections have been used in children:
A. Subunit vaccines
B. Attenuated live vaccines
C. There is not currently a vaccine against RSV.
Rhinoviral infection
1. Rhinoviruses are members of the family:
A. Paramyxoviridae
B. Orthomyxoviridae
C.Herpesviridae.
D. Picornaviridae
E. Retroviridae
2. The most common comlication of rhinoviral infection is:
A. Otitis media
B. Sinusitis
C. All answers are correct
3. What viruses are the most common cause of acute exacerbations of asthma in school-age children and of chronic bronchitis in adults:
A. Parainfluenza viruses
B. Adenoviruses
C. Respiratory syncytial virus
D. Rhinoviruses
E. Influenza viruses
F. All answers are correct
4. Decongestant may be indicated in children:
A. >6 mo of age
B. >12 mo of age
C. >6 yr of age
Task 1.
A 8 years-old child fell ill abrupt in winter: fever up to 39,5 C, myalgia, malaise, headache and dry cough. His mother and old sister had cold and high fever too.
Questions:
1.Make the preliminary diagnosis.
2.What laboratory examinations should be administered for the definition of etiology?
3.Make the plan of treatment.
4. What methods of specific prophylaxis against this infection do you know?
Task 2.
A 9-months-old child fell ill acutely(a child is vaccinated according with the schedule of immunization). The onset was marked by fever up to 37,5°C, dry "barking" cough. The condition has sharply worsened at night: began restless, barking cough, hoarseness, inspiratory a short wind; jugular fossa, subclavian fossa and intercostal retractions.
Questions:
1.Make the preliminary diagnosis.
2.What laboratory examinations should be administered for the definition of etiology?
3. Administer pathogenetic therapy. What indications are for antibiotics in the management of this disease.
4. What methods of prophylaxis against this infection do you know?
Task 3.
A 3-years-old child fell ill acutely. Complaints: a high temperature, headache, malaise, and weakness. Examination: nonpurulent conjunctivitis of both eyes, pharyngitis, rhinitis, preauricular and cervical lymphadenopathy.
Questions:
1.Make the preliminary diagnosis.
2. What clinical manifestations of this infection do you know?
3. What routes of spread this infection do you know?
4. Make the plan of treatment.
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