PREVENTION AND CONTROL OF INFLUENZA

Donnie Fowler, M.D.

Louisiana State University Medical Center Shreveport, Louisiana

Page by: E.J. Mayeaux, Jr., M.D.

Introduction

• This disease has afflicted the human population at least as long as recorded history
• Well described in English texts as early as the 16th century
• It was once thought the disease was affected by celestial movement
• Viral etiology of the disease demonstrated in the 1930's
• Antigenic variation of the virus described in the 1940's and 1950

VIROLOGY

• Antigenic Drift
1. Antigenic variation within a subtype
2. Created by errors in replication of the viral DNA and the high replication rate of the virus
3. New epidemics result from new variants of the virus
4. Vaccines developed only against current circulating strains
• Influenza A
1. Subtypes based upon 2 surface antigens
2. Hemagglutinin (H) and Neuramindase(N)
3. Immunity to these antigens, especially H, confers immunity to the illness
4. High degree of antigenic drift
• Influenza B
1. No subtypes
2. Antigenic drift does occur but less so than Infuenza A

CLINICAL FEATURES

Abrupt onset of a respiratory illness

1. Fever
2. Myalgia
3. Sore throat
4. Nonproductive cough
5. Severe malaise

Complications

1. Primary Influenza pneumonia
2. Secondary bacterial pneumonia

Risk factors

1. Elderly
2. Persons with underlying health problems

Mortality Risk

1. > 20,000 deaths during each of 10 different U.S. epidemics from '72-'73 to '90-'91
2. > 40,000 deaths in 3 of those epidemics
3. > 90% of these deaths occurred among persons >65 years of age
4. Mortality rates are expected to increase due to several

PREVENTION AND TREATMENT

Immunoprophylaxis

1. Vaccination

Chemoprophylaxis

1. Amantadine
2. Rimantadine

Therapy

1. Amantadine
2. Rimantadine

IMMUNIZATION

1. Cost Effective
2. Composition - Comprised of three different strains: 2 Influenza A, 1 Influenza B
3. Inactivated , highly purified
4. Grown from eggs
5. Availablity: 1) Whole virus 2)Subvirion 3)Purified surface antigen
6. 1995-96 Trivalent vaccine
• A/Texas/36/91-like (H1N1)
• A/Johannesburg/33/94-like (H3N2)
• B/Beijing/184/93-like virus

Side Effects

1. Vaccine CANNOT cause influenza
2. around 33% will have local reaction at the site of injection
3. Systemic reaction less common - Fever, malaise
4. Allergic reaction very rare
5. No clear association with Guillian-Barre syndrome

Effectiveness

1. Age - Children and young adults: high titers
2. Immunocompetence - Elderly and chronic disease: Low titers
3. Degree of simularity between vaccine strains and infecting strains

Indications / Target groups

Those at increased risk for complications

1. Age > 65
2. Residents of Nursing Home facilities
3. Persons with pulmonary or CV disorders
4. Persons with chronic metabolic diseases
5. Children on long-term aspirin therapy

Those that can transmit Influenza to High Risk persons

1. Medical personnel
2. Nursing Home employees
3. Home Health employees
4. Household members of high risk persons

Pregnancy

1. Third trimester
2. Early puerperium
3. Underlying medical problems - regardless of the stage of pregnancy

HIV

1. Limited information but vaccine is currently recommended
2. Booster vaccine NOT recommended

Travelers

1. Tropics: Year round
2. Southern Hemisphere: April - September

Others

1. Persons who provide essential services
2. Students in dorms

Contraindications

1. Anaphylactic hypersensitivity to eggs
2. Acute febrile illness

Dosing and Administration

1. Must be given yearly
2. Children > 9 years old previously unvaccinated need 2 doses 1 month apart
3. Adults or previously vaccinated children only require 1 dose
• Adults: Any preparation is OK
• Children: Subvirion or purified surface Antigen only
• Timing: Mid-October to Mid-November is optimal
• Other Vaccines: OK to give except DTP (DTaP OK)

ANTIVIRAL AGENTS

Introduction

1. Amantadine, Rimantadine
2. Activity against Influenza A replication cycle
3. 70% - 90% effective for healthy adults given prophylactically
4. Reduces the severity and duration of acute illness
5. Resistance can arise and is cross-resistant

Indications

1. Prophylaxis
2. High risk persons exposed prior to vaccination
3. Persons with immune deficiency
4. Persons with contraindications to vaccination
5. Therapeutic when started within 48 hours of acute onset of illness
6. Rimantadine only indicated for prophylaxis in children
7. Prevention of complications in high risk groups - unknown
8. Useful in outbreak control in institutions

Side Effects / Toxicity

1. CNS - Nervousness, anxiety, lightheadedness, difficulty concentrating
2. GI - Nausea, anorexia - Amantadine > Rimantadine
3. Usually mild and resolve with cessation or continued usage > 1 week
4. Serious - Very rare - Behavioral changes, delirium, hallucinations,agitation, seizures
5. Associated with CRI, Seizure D/O, Elderly on long term therapy
6. Drug interactions: Amantadine (No Significant interactions with Ramantadine), CNS drugs - especially stimulants

Dosing

See Table II