Dr. Seid is a physician at Messiah College, Grantham, Pa., and a reviewer for DynaMed. Dr. Alper is medical director of clinical reference products for EBSCO Publishing, in Ipswich, Mass., and editor-in-chief of DynaMed (www.dynamicmedical.com), a database of comprehensive updated summaries covering nearly 2,000 clinical topics.

Description
• Influenza (H5N1) infection in poultry that rarely mutates to cause disease in humans
• Current widespread epidemic in Asia of highly pathogenic avian influenza in chickens; some human cases associated with high mortality and potential for development of pandemic viral strain

ICD-9 codes
• 487.0 influenza with pneumonia
• 487.1 influenza with other respiratory manifestations
• 487.8 influenza with other manifestations
• V04.81 need for prophylactic vaccination and inoculation, influenza

Prevalence
• Human cases of avian influenza (H5N1)
— The 12 countries that have reported confirmed human cases 2003-2007 include Azerbaijan, Cambodia, China, Djibouti, Egypt, Indonesia, Iraq, Lao People’s Democratic Republic, Nigeria, Thailand, Turkey, and Vietnam.
— Total 291 cases with 172 deaths as of April 11, 2007
• Avian influenza widespread in Asian poultry and spreading
• H7N2 virus infection confirmed in four humans in United Kingdom, May 2007
• Prior avian influenza outbreaks (H7N2, H7N3, H7N7, H5N1) have been associated with human cases.
• Pandemic viruses (1918, 1957, 1968) were due to avian influenza virus that adapted to humans or to reassortments of human and avian subtypes of influenza A.

Etiology
• Influenza virus A — H5 and H7 strains cause avian influenza and rarely human disease.
— H1 and H3 strains cause human influenza.
• Genetic reassortment of avian and human influenza strains can occur during co-infection, with potential for highly pathogenic strain leading to human pandemic.
• Transmitted via respiratory droplets
• Incubation period unknown but estimated to be longer than two to three days
• Virus-induced destructive changes to respiratory epithelium may predispose to secondary bacterial infection.

Complications
• Include pneumonia, GI symptoms, hepatitis, renal failure, pancytopenia, encephalitis

Clinical presentation
• Fever, sore throat, and cough were common presentations of avian influenza in 1997 outbreak.
• Insufficient experience with avian influenza to determine if symptoms will be different
• Other symptoms reported include diarrhea, vomiting, abdominal pain, chest pain, bleeding from nose and gums, and encephalitis.
• Look for signs of pneumonia (e.g., decreased breath sounds, rales).
• No specific signs rule in or rule out influenza.

Diagnosis
• CDC recommends testing for influenza A (H5N1)
— In hospitalized patients with both
• Radiographically confirmed pneumonia, acute respiratory distress syndrome, or other severe respiratory illness without established diagnosis, and
• History of travel within 10 days of symptom onset to country with documented H5N1 avian influenza in poultry or humans
— On case-by-case basis; consult with local and state health departments for patients who have
• Documented temperature >38°C (100.4°F), and
• Cough, sore throat, or shortness of breath, and
• History of contact with domestic poultry or known or suspected case of influenza A (H5N1) in H5N1-affected country within 10 days of symptom onset
• Confirmation of avian influenza based on at least one of:— Positive viral culture for influenza A/H5
— Positive polymerase chain reaction for influenza A/H5
— Positive immunofluorescence antibody test for H5 antigen using H5 monoclonal antibodies
— Fourfold rise in H5-specific antibody titer in paired serum samplesDifferential diagnosis
• Consider influenza (non-avian), severe acute respiratory syndrome, other viral flulike illness, bacterial respiratory infection, carbon monoxide poisoning.

Treatment
• CDC 24-hour toll-free hotline 877.554.4625 to answer clinician questions• CDC recommends 14 days’ isolation for symptoms suggesting avian influenza.
• Oseltamivir (Tamiflu) 75 mg p.o. twice daily for five days— Recommendations based on in vitro testing
— Most recent H5N1 strains susceptible to oseltamivir but resistant to amantadine and rimantadine
— Resistance in some human cases (Egypt and Vietnam)
• Pediatric dosing of oseltamivir— FDA-approved for treatment at age 1 year and older
— Dose in children 30 mg if weight <15 kg, 45 mg if 15-23 kg, 60 mg if 23-40 kg; all given twice daily
— Tamiflu labeling updated by FDA to warn of self-injury and delirium, mostly in children from Japan
• Adverse effects with oseltamivir include nausea, vomiting, headache, bronchitis, insomnia, vertigo.

Prevention
• Avian influenza vaccines— Immunogenic in studies, not tested during epidemic
— Tested vaccines may not be active against mutated strain that spreads among people.
— H5N1 influenza vaccine FDA-approved
• In persons aged 18-64 years at increased risk
• As two IM injections one month apart
• Vaccine will not be sold commercially but will be used by federal government from U.S. Strategic National Stockpile maintained by CDC.
• Seasonal influenza vaccine—limit co-infections of human and avian influenza viruses, avoid genetic reassortment
• Medication for prophylaxis not currently recommended
• Travel precautions—CDC advises travelers to Asian countries with documented H5N1 outbreaks to
— Avoid live poultry and any surfaces that appear contaminated with animal feces.
— Conduct careful and frequent hand hygiene.
— Cook thoroughly all food from poultry: 70°C (158°F) in all parts of food, i.e., no “pink” parts, and no runny egg yolks.

For references, see www.dynamicmedical.com.