H5N1 / Avian Influenza Essentials. Quick Reference for Providers and Public Health Officials

Transcription

1 H5N1 / Avian Influenza Essentials Quick Reference for Providers and Public Health Officials December 2005

2 INFLUENZA Family: Orthomyxoviridae Genus: influenza virus Subtypes: A, B, and C Influenza A INFLUENZA Hemagglutinin (HA or H): 9 subtypes (H1-9) Neuraminidase (NA or N): 16 subtypes (N1-16) Management Summary Isolation and negative pressure room (up to 7 days after symptom resolution) Specimen collection and testing Empiric antibiotic and antiviral therapy Respiratory support Manage complications + / steriods (weigh individual patient risks and benefits) Healthcare and visitor personal protective equipment Investigation Summary Plan investigation strategy, questions, and timeline Devise questionnaire and database for analysis Supplies (specimen collection, epidemiology data collection, personal protective equipment, prophylaxis) Carry out investigation Analyze data Make response recommendations

3 H5N1 VERSUS Influenza A (nonh5 and nonh7) Responsible for seasonal outbreaks (H3 and H1 subtypes predominantly). Associated with significant mortality among very young and very old. Vaccine-preventable. Nasal swabs yield higher virus than throat swabs. Influenza B Responsible for seasonal outbreaks Associated with little mortality. Influenza C Responsible for little significant human disease. Avian Influenzas 144 different strains H5 and H7 (human cases) INFLUENZA Common Cold / (Picornavirus, rhinovirus, echovirus,coronavirus, coxsackivirus) Common colds caused by different viruses. Symptoms may appear similar but common colds are milder and more likely to be associated with a runny nose. Common colds do not results in moderate to severe complications, such as hospitalization and pneumonia. Severe Acute Respiratory Syndrome (SARS) / (Coronavirus) Caused by different viruses. Symptoms may appear clinically similar and require laboratory testing to distinguish.

4 EPIDEMICS VS PANDEMICS Seasonal Community or Regional Epidemics (Antigenic Drift) Small changes to influenza virus strains that already infect humans Gradual small genetic changes (point mutations) to the influenza virus HA gene. Human antibodies produced during past infections are unable to prevent infection with this new strain. Mortality and morbidity in very young, very old and immuncompromised. Vaccines are produced based on a significant few of the previous season s circulating influenza strains. Global Pandemics (Antigenic Shift) Gene reassortment of HA gene in an influenza virus that infects non-human hosts. New HA gene allows transmission of animal virus to human hosts. New influenza subtype emerges. No human immunity lead to morbidity and mortality in all age groups. Vaccines must be developed for this new subtype. INFLUENZA

5 INFLUENZA BIRDS AND PANDEMICS Global Pandemics (Antigenic Shift) Belshe, Robert B. The Origins of Pandemic Influenza -- Lessons from the 1918 Virus. N Engl J Med :

6 PANDEMIC THREAT Periodic Pandemics cause millions of deaths. INFLUENZA

7 INFLUENZA H5N1 virus is making changes to adapt to humans and our treatment strategies Compared to the 1997 Hong Kong H5N1 subtype, more recent strains of H5N1... last longer in the environment higher level resistance to existing therapies strain requires higher oseltamivir doses and longer duration (8 days) - Some recent isolates resistant to M2 inhibitors (amantadine and rimantidine) Viral shedding In children under 12 years old, viral shedding may be prolonged (up to 21 days) Certain bird species (e.g., ducks) shed virus without displaying flu symptoms. INFLUENZA

8 EPIDEMIOLOGY Incubation Period mean 4 days (2-4 days) Risk Factors Contact with poultry, especially sick, dying or dead poultry within 7 days Close contact with person ill with H5N1 infection Healthcare workers Laboratory staff works Poor Prognostic Factors Delay to medical care > 48 hours from onset of symptoms On admission, evidence of pneumonia or ARDS, leukopenia, lymphopenia Infectivity Human-to-human transmission remains inefficient as of Dec 2005 and likely requires close, unprotected contact and the person to be shedding high virus concentrations. Patients remain capable of infecting others up to 7 days after symptom resolution. Asymptomatic to Symptomatic Case Ratio Unknown Mortality Rate 67 deaths in 130 cases (52%) as of 17 Nov 2005 Human Cases Cambodia, China, Indonesia, Thailand, Vietnam as of 17 Nov 2005 Animals Infected Domesticated/wild birds Domesticated/wild cats INFLUENZA

9 CLINICAL DESCRIPTION Clinical Characteristics Acute onset fever (>38 C) with one or more of the following +/- cough +/- sore throat +/- muscle aches +/- sputum (sometimes bloody) +/- acute respiratory distress (median 5 days after onset) * * dyspnea, tachypnea, and/or inspiratory crackles Other less frequent symptoms associated with human H5N1 cases include rhinorrhea, conjunctivitis, headache, diarrhea, mental status changes FEVER (>38 C) +/- cough +/- sore throat +/- shortness of breath +/- muscle aches CLINICAL Epidemiological Characteristics a) History of travel in the 14 days prior to onset of symptoms to an area affected by avian influenza A (H5N1) AND b) close contact (within 1 meter) with live or dead domestic fowl, wild birds, or pigs in any setting, including bird markets. OR c) close contact (within 1 meter) with a person known or thought to be ill with H5N1 influenza.

10 CLINICAL DESCRIPTION Common Admission Laboratory Characteristics Leukopenia, especially lymphopenia Thombocytopenia (mild to moderate) Elevated aminotransferase (moderate) Common Admission Radiology Characteristics Usually appear within 7 days of onset of symptoms Pneumonia: Diffuse, multifocal or patchy infiltrates Complications Rapid respiratory failure (ARDS) within median 6 days of onset (range 4 to 13) Renal failure Cardiovascular collapse Ventillator-associated pneumona Pneumothorax Pancytopenia Sepsis (without documented bacteremia) Low white cell count Low platelet count Elevated liver enzymes CLINICAL

11 SPECIMEN COLLECTION To test for virus and viral antigens. Throat swabs have a higher viral yield than nasal swabs. Virus detectable from 2 to up to 18 days after onset of illness (median 6 days) Test to order: PCR or Rapid Diagnostic Kit Nasal Swab 1. Insert a dry swab past the nares until the tip reaches the area below the inferior turbinate. 2. Allow swab to remain there for 5-15 seconds to absorb secretions. 3. Rotate the swab gently two to three times and withdraw. 4. Place the swab back in the protective sheath. 5. Label the container with patient name, date of collection, and type of specimen. 6. Break the ampule of transport medium by squeezing it. Throat Swab 1. Depress the tongue with a tongue blade and gently swab the posterior pharynx in an up and down motion several times. 2. Place the swab back in the protective sheath. 3. Label the container with patient name, date of collection, and type of specimen. 4. Break the ampule of transport medium by squeezing it. Storage < 2 days: 4 C > 2 days: - 70 C Transport ice or liquid nitrogen

12 SPECIMEN COLLECTION To test for antibodies. Antibodies will be detectable approximately 7 days after onset of symptoms. Test to order: Hemagglutination Inhibition, Microneutralization Collect sera at least in the following time intervals 1. acute phase (7-14 days after symptom onset) 2. convalescent phase (21-28 days after symptom onset) Serum 1. Collect 5-ml whole blood 2. Label containter with patient name, date of collection, and type of specimen Storage < 7 days: 4 C > 7 days: - 70 C Transport ice or liquid nitrogen

13 SPECIMEN COLLECTION 1. Label Specimen Patient Full Name Date of Birth Date of Collection Type of Specimen Unique specimen identifier 2. Complete a data collection form to accompany

14 IMMUNOLOGY AND THE VIRUS Laboratory Rationale

15 SUMMARY OF TESTS

16 MANAGEMENT Hospitalization Isolation Negative Pressure room Diagnostic testing Empiric therapy with antivirals until testing returns Supportive care - Oxygen* and ventilator support (if necessary) * nebulizers and high-flow oxygen masks should be used under strict airborne precautions because they are implicated in spread of nosocomial infections. Antiviral Agents Neuraminidase inhibitor class effective but M2 inhibitors generally ineffective. Optimal dose and duration of therapy of neuraminidase inhibitors remains uncertain. CLINICAL

17 MANAGEMENT Neuraminidase Inhibitor Mechanism of Action CLINICAL Immunomodulators Corticosteroids (e.g., dexamethasone) Uncertain efficacy. In a randomized control trial in Vietnam, all 4 patients treated with Dexamethasone died. Immune suppression may lead to increased risk of secondary infections. Interferon Alfa Antiviral activity and potent regulator of the immune system. Not recommended at this time because it has not been appropriately studied.

18 OUTBREAK DESCRIPTIONS Describe the suspected outbreak Case Definition Create a definition based on the clinical symptoms Time Date of first case Total number of cases since the first case and number of new cases per day or week or month Place Specify location where cases live Number of people at risk for infection (e.g., population of hospital, community, household ) Case Characteristics Number of people ill by genders Number of people ill by age group (0-4, 5-14, 15-29, 30-44, 45-60, >60) Epidemic Curve Create a graph of the number of new cases per day or per week since the first case presented EPIDEMIOLOGY

19 OUTBREAK DESCRIPTIONS Quantitatively describe the suspected outbreak For example: In the last week... EPIDEMIOLOGY Gender (Case) Ratio = # male cases / # female cases Mean age + (age range) Median age + (age range)

20 INFECTION CONTROL Healthcare Worker Precautions INFLUENZA

21 WHO COLLABORATING CENTERS TOKYO (JAPAN) WHO Collaborating Centre for Influenza for Reference and Research on Influenza Department of Viral Diseases and Vaccine Control, National Institute of Infectious Diseases Gakuen 4-7-2, Musashi-Murayama, Tokyo Japan Telephone: Fax: MELBOURNE (AUSTRALIA) WHO Collaborating Centre for Influenza for Reference and Research on Influenza 45 Poplar Rd, Parkville, Victoria 3052 Australia Telephone: Fax: whoflu@influenzacentre.org web site: ATLANTA (USA) WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza Influenza Branch, National Centers for Infectious Diseases, Centers for Disease Control and Prevention 1600 Clifton Road, Mailstop G16, Atlanta, Georgia 30333, USA Telephone: Fax: cdcinfo@cdc.gov web site: LONDON (UNITED KINGDOM) WHO Collaborating Centre for Reference and Research on Influenza National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA United Kingdom Telephone: Fax: RESOURCES

22 H5N1 Influenza and the Pandemic Threat Internet Resources World Health Organization US Centers for Disease Control and Protection , The Spanish Flu "It is only a matter of a few hours until death comes, and it is simply a struggle for air until they suffocate." - US Army Physician, letter