VinnytsiaNationalPirogovMemorialMedicalUniversity
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 ARVIdiagnosis and treatment.
A student should know:
- Etiology of ARVI
- EpidemiologyofARVI
3. Pathogenesis of ARVI
4. Classification and clinical manifestationsof ARVI
5. Laboratory studiesofARVI
6. Complications ofARVI
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 treatmentinARVI.
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.