References: 
Influenza:

http://www.cdc.gov/flu/professionals/treatment/

http://www.cdc.gov/flu/professionals/vaccination/

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/rr4903a1.htm

Pertussis vaccines:

http://www.cdc.gov/epo/mmwr/preview/mmwrhtml/00048610.htm http://www.postgradmed.com/issues/1999/06_99/conrad.htm  

Committee on Infectious Diseases and Committee on Fetus and Newborn, American Academy of Pediatrics. Policy statement. Revised indications for the use of palivizumab and respiratory syncytial virus immune globulin intravenous for the prevention of respiratory syncytial virus infections. Pediatrics 2003;112:1442-6

Acute Bronchitis

The following agents can cause bronchitis:

• Respiratory viruses that infect the upper respiratory tract (refer to previous handout)
• Mycoplasma pneumoniae
• Chlamydia pneumoniae (TWAR agent)- 5% of cases
• Bordetella pertussis
• Salmonella typhi
• Measles virus
• Streptococcus pyogenes

Several hours before bronchitis develops the patient experiences malaise, headache, coryza, and sore throat. A cough soon develops that is nonproductive at first but with time will become mucopurulent. Substernal pain and a moderate fever are seen. Physical findings demonstrate an infected pharynx, rhonchi, and moist crackles. Roentgenography is not useful in diagnosis of bronchitis but will help in differentiating bronchitis from atypical pneumonias. Blood leukocyte count is normal.

When cough is present the diagnosis is quite simple. Differentiation between bronchitis and viral or mycoplasmal pneumonias is nearly impossible to determine on clinical grounds unless roentgenograms demonstrate infiltrates consistent with atypical pneumonia. Check patient's temperature. If the fever is elevated then a bacterial bronchitis maybe present.

Supportive therapy is most useful unless the sputum becomes purulent and the patient has a fever. Elucidation of the bacterial pathogen may be required and treatment with antimicrobial agents.

No good preventative measures are available to cover all the possible agents able to cause bronchitis. An influenza virus and B. pertussis vaccine are available to prevent bronchitis due to these agents.

Bronchiolitis

This is an acute viral infection with a favorable outcome. Rarely, fatalities occur. The infection is usually self-limiting and is normally occurs in infants (less than one year old). The following agents cause bronchiolitis:

• Respiratory Syncytial virus (RSV is the most common)
• Influenza viruses
• Adenoviruses
• Rhinoviruses
• Parainfluenza viruses = type 3
• Mycoplasma pneumoniae

The onset is insidious, following an upper respiratory infection, with coryza and cough. Fever is moderate. If disease progresses dyspnea, cyanosis, and suprasternal and intercostal retractions during inspiration are evident. Physical findings include hyperresonance on percussion, expiratory wheezing, and medium and fine sibilant or musical crackles are heard. Breathing sounds may become inaudible if bronchiolar obstruction is extensive.

Demonstration of RSV antigen in the sputum or in cultures of RSV grown in tissue culture. Serologic tests can also be helpful in determining the etiologic agent.

Provision of warm water saturated air. Proper replacement of electrolytes and fluids is essential. Digitalis preparations should be given as soon as cardiac failure is detected. Treatment of RSV with ribavirin is very controversial may only be useful for select patients with high risk of serious infection (e.g. patients with congenital heart disease, cystic fibrosis, etc.).

Based on the efficacy and safety demonstrated in clinical trials, in December 2003, America Academy of Pediatrics released a new policy statement revising their recommendations on the use of palivizumab. The updated policy recommends that RSV prophylaxis be considered in:

• infants and children younger than 2 years of age who have required medical therapy for Chronic Lung Disease (CLD) within the 6 months prior to the start of RSV season; patients with severe CLD may benefit from prophylaxis with palivizumab through 2 RSV seasons
•  infants born at or prior to 32 weeks gestation 
• infants born between 32 and 35 weeks gestation with known risk factors, such as birth within 6 months of RSV season, child care attendance, school-age siblings, exposure to environmental pollutants, airway abnormalities, or severe neuromuscular disease infants and children younger than 2 years of age with hemodynamically significant Congenital Heart Disease, particularly patients with pulmonary hypertension or cyanotic heart disease, and those who require medication for congestive heart failure.

III. Influenza

The causative agent of the flu or influenza is the influenza virus. There are 3 different antigenic types of the virus, A, B, and C. This virus is a segmented single strand RNA virus. The RNA codes for 5 structural proteins and 3 nonstructural proteins. Protein M and nucleoprotein NP are used to place the virus into types A, B, and C. It is the hemagglutinins (H antigen) and the neuraminidases (N antigen) that are important in pathogenesis. The H antigen is required for binding of the virus to the cell. The N antigen helps the mature virus escape from the cell. The type A and B viruses cause most of the epidemics and sporadic outbreaks of flu in the world. Type C is usually seen as a mild disease of the very young and by age 15 nearly everyone has developed antibodies to the type C influenza virus. Rarely, does type C cause an epidemic of flu. Not only are there major types of the influenza virus but there are also subtypes of the type A and B influenza viruses. These subtypes are determined by the H and N antigens. There are 3 antigenic types of H antigen (H1, H2, and H3) and 2 different antigenic types of N antigen (N1 and N2). Antibodies to one type of H or N antigen do not react with another type of the H or N antigen. Therefore, when influenza virus/H1N1 becomes influenza virus/H2N1 then the virus can cause disease. These changes in H and/or N are called shifts. Slight changes in H and/or N antigens can occur which can help the virus avoid destruction by the immune system. This is called drift; slight changes in the H or N antigens which do not change the type of the antigen.

Epidemic flu is cyclic and is usually caused by type B or type A. Epidemics of type A occur every 2 to 3 years. Epidemics of type B occur every 4 to 6 years. Epidemics usually occur from late autumn to early spring. The overall mortality rate is about 1%. At highest risk for complications such as pneumonia are the very young, the very old, pregnant patients, and persons with underlying cardiopulmonary, metabolic, and renal diseases.

A special terminology is used when discussing an influenza virus. It involves the type of influenza virus, the place it was first located, and the year it was first discovered. Each of the parameters are separated by a /. Example: A/Ann Arbor/ 1/86 is an influenza virus type A/first found in Ann Arbor, Michigan/in January of 1986.

Editorial Note from CDC: Worldwide surveillance for influenza viruses provides the basis for selecting influenza vaccine strains. Vaccine strains are chosen approximately 9-10 months before the start of the following influenza vaccination season. The vaccine for the 2005-2006 flu season will contain A/New Caledonia/20/99-like (H1N1), A/California/7/2004-like (H3N2), and B/Shanghai/361/2002-like viruses .  

LAST YEAR'S EPIDEMIC:
The 2004-05 U.S. influenza season began earlier than most seasons and was moderate; influenza A (H1), A (H3N2), and B viruses co-circulated. The predominant strain was influenza A (H3N2).

Widespread outbreaks of avian influenza A (H5N1) among poultry were reported in Southeast Asia in early 2004. In Vietnam and Thailand, these outbreaks were associated with severe human illnesses and deaths. CDC issued recommendations for enhanced surveillance in the United States to increase the likelihood of timely detection of an imported human avian influenza virus infection.

Influenza viruses are spread from person to person primarily through the coughing and sneezing of infected persons. The incubation period for influenza is 1–4 days, with an average of 2 days. Adults typically are infectious from the day before symptoms begin through approximately 5 days after illness onset. Children can be infectious for >10 days, and young children can shed virus for <6 days before their illness onset. Severely immunocompromised persons can shed virus for weeks or months.

Abrupt onset with fever (102°-104° F), chilliness, rigors, headache, congested conjunctiva, extreme prostration with myalgia in the back and limbs, nonproductive cough, and injection of the pharynx and conjunctiva. Among children, otitis media, nausea, and vomiting are also commonly reported with influenza illness. Fever abates in 3 to 4 days and recovery is complete in a week. The cough and malaise may persist for 2 weeks or more. 

However, in debilitated patients the condition may worsen with persistent fever, marked prostration, cough associated with rales, and pneumonia (poor prognostic signs). Usually, the pneumonia is due to a secondary bacterial infection and can include S. aureus, Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus pyogenes.

Unfortunately, there are no pathognomonic signs of influenza and it can be easily confused with other respiratory tract infections. The common cold is an afebrile disease with coryza. Acute respiratory disease cause by adenovirus is difficult to differentiate from influenza. Differentiating influenza pneumonia from atypical pneumonia may be difficult however, the onset of atypical pneumonia is usually insidious whereas influenza is rapid in onset. Definitive diagnosis requires laboratory procedures such as isolation of the virus and/or serological tests. A fluorescent antibody directed against the influenza virus is available to directly test specimens collected from febrile acutely ill patients.

Influenza can exacerbate underlying medical conditions (e.g., pulmonary or cardiac disease) and lead to secondary bacterial pneumonia or primary influenza viral pneumonia. In some patients it can occur as part of a coinfection with other viral or bacterial pathogens. Young children with influenza infection can have initial symptoms mimicking bacterial sepsis with high fevers. Some children hospitalized with influenza (<20 percent) can have febrile seizures. Influenza infection has also been associated with encephalopathy, transverse myelitis, Reye syndrome, myositis, myocarditis, and pericarditis.

Supportive care for normal individuals. Antipyretics and analgesics can prove relief from fever and muscle pain.

Antiviral drugs for influenza are an adjunct to influenza vaccine for controlling and preventing influenza. However, these antiviral agents are not a substitute for vaccination. Four licensed influenza antiviral agents are available in the United States: amantadine, rimantadine, zanamivir, and oseltamivir.

Amantadine and rimantadine are chemically related antiviral drugs known as adamantanes with activity against influenza A viruses but not influenza B viruses. Amantadine is for chemoprophylaxis and treatment of influenza type A virus infections among adults and children aged >1 year. Rimantadine is approved i treatment and chemoprophylaxis of influenza A infection among adults and prophylaxis among children. Although rimantadine is approved only for chemoprophylaxis of influenza A infection among children, certain specialists in the management of influenza consider it appropriate for treatment of influenza A among children.

Zanamivir and oseltamivir are chemically related antiviral drugs known as neuraminidase inhibitors that have activity against both influenza A and B viruses. Both zanamivir and oseltamivir are approved treating uncomplicated influenza infections. Zanamivir is approved for treating persons aged >7 years, and oseltamivir is approved for treatment for persons aged >1 year. Oseltamivir is also approved for chemoprophylaxis of influenza among persons aged >13 years.

No antibiotics should be given as prophylaxis for bacterial pneumonia. This only selects for more resistant bacteria which when causing a secondary bacterial pneumonia will be much more difficult to eliminate.

Vaccination (usually contains three different influenza viruses; 2 A's, 1 B) and chemoprophylaxis with amantadine are useful for prevention of disease in high risk groups. Usually, normal individuals do not require preventative measures unless their occupations are an essential human service (examples: health and public service personnel).

Vaccination campaigns start in mid-October and end in mid-November. Vaccination is recommended for the following groups of persons who are at increased risk for complications from influenza or who have a higher prevalence of chronic medical conditions that place them at risk for influenza-related complications (MMWR; April 14, 2000 / 49(RR03);1-38):

1. persons aged >50 years;
2. residents of nursing homes and other chronic-care facilities that house persons of any age who have chronic medical conditions;
3. adults and children who have chronic disorders of the pulmonary or cardiovascular systems, including asthma;
4. adults and children who have required regular medical follow-up or hospitalization during the preceding year because of chronic metabolic diseases (including diabetes mellitus), renal dysfunction, hemoglobinopathies, or immunosuppression (including immunosuppression caused by medications or by HIV);
5. children and teenagers (aged 6 months to 18 years) who are receiving long-term aspirin therapy and therefore might be at risk for developing Reye syndrome after influenza infection; and
6. women who will be in the second or third trimester of pregnancy during the influenza season.

CDC collects and reports U.S. influenza surveillance data during October--May. This information is updated weekly and is available through the CDC at: http://www.cdc.gov/flu/

Bordetella pertussis, is a Gram-negative small bacillus. The pertussis toxin is believed responsible for most of the tissue damage. The toxin ADP-ribosylates guanine nucleotide-binding proteins affecting regulatory mechanisms in the cells. Other products of importance are the tracheal cytotoxin, a hemolysin, and a filamentous hemagglutinin.

Pertussis occurs worldwide and results in one million deaths a year. Most of these deaths occur in underdeveloped countries. People are the only natural hosts and the disease is transmitted person to person by droplets. A primary infection does not ensure protection from a second infection with Bordetella pertussis. A carrier state does not exist however, people in close contact with symptomatic patients may transiently harbor the organism. Up to 50% of the children getting pertussis can be traced to adults with chronic cough, a minority of cases are traced to children passing on the disease, and a significant number have no obvious source. Most of the severe cases are in children less than 1 year old.

Bacterial superinfection by Staphylococcus aureus, Streptococcus pneumoniae, and the usually nosocomial Gram-negative organisms can complicate the situation.

The neurological effects of infection are associated with hypoxia, lymphocyte plugging, and intracerebral hemorrhage.

Adults may complain of chronic cough. Lymphocytosis is sometimes seen. The presence of a whoop makes pertussis infection highly likely. The paroxysmal phase blends into the convalescent phase and may last for months.

The presence of the whoop is pathognomonic for pertussis. Nasopharyngeal aspirates can be plated on Regan-Lowe medium (shelf life of 6-8 weeks) or Bordet-Gengou medium (shelf life less than a week). Immunofluorescent staining of secretions for B. pertussis is also useful. A serologic test (ELISA) with acute and convalescent sera is quite accurate.

Prognosis is dependant on age of the patient, the state of health, and availability of supportive care. Prognosis is better in the U.S. than in developing nations. The older the patient the better the outcome. The percentage of children, in the U.S., with complications from pertussis are as follows; pneumonia (20%), seizures (2.5%), and death (0.7%). The risk of nonfatal neurologic damage due to infection is at least 6 to 10 times greater than the risk associated with immunization.

Antibiotics are useless once the patient has entered the paroxysmal stage except to prevent super infections. Antibiotics will eliminate the organisms from incubating contacts and perhaps abort symptoms. Erythromycin is the drug of choice. Supportive care is essential in the prevention of hypoxia and pulmonary complications.

The most commonly used vaccine is the acellular vaccine (DTaP). It is mixed with diphtheria and tetanus toxoids. The Food and Drug Administration (FDA) has licensed three DTaP vaccines (ACEL-IMUNE®, Tripedia®, and Infanrix®) for use among children aged 6 weeks-6 years. The vaccines contain diphtheria and tetanus toxoids and the acellular pertussis vaccine (DTaP).

Acellular pertussis vaccines contain inactivated pertussis toxin (PT) and may contain one or more other bacterial components (e.g., filamentous hemagglutinin {FHA}, a 69-kilodalton outer-membrane protein -- pertactin {Pn}, and fimbriae {Fim} types 2 and 3). PT is detoxified either by treatment with a chemical (e.g., hydrogen peroxide, formalin and/or glutaraldehyde) or by using molecular genetic techniques. Acellular pertussis vaccines contain substantially less endotoxin than whole-cell pertussis vaccines.

Three acellular pertussis vaccines (Tripedia and Infanrix for the first four doses and ACEL-IMUNE for all five doses) are licensed for the diphtheria, tetanus, and pertussis vaccination series. FDA has not approved Tripedia or Infanrix as the fifth dose among persons who have received only Tripedia or only Infanrix for the first four doses in the vaccination series, because data are insufficient to evaluate their safety in this situation. However, such data should be available before infants vaccinated with four doses of these vaccines require a fifth dose at age 4-6 years.

Diph.= Diphtheria; Tet.= Tetanus
*= Approved for the first 4 doses of the 5 dose series, beginning at ages 2, 4, and 6 months.

A whole cell pertussis (DTP) vaccine combined with the diphtheria and tetanus toxoids is available in the U.S. and is also effective in preventing disease. However, 1/330,000 develop neurological sequelae. This is an association not a cause and effect relationship. Pertussis vaccine is given at an age when there is a high background of neurological disease and the complications associated with the vaccine may well be caused by something else. There is still considerable debate on whether the cellular vaccine causes these neurological problems. It is agreed upon, by most in the field, that the acellular vaccines (DTaP) have fewer severe side-effects than the cellular vaccine (DTP).