Isolation of Avian Influenza A(H5N1) Viruses from Humans -- Hong Kong, May-December 1997

A strain of influenza virus that previously was known to infect only birds has been associated with infection and illness in humans in Hong Kong. The first known human case of influenza type A(H5N1) occurred in a 3-year-old child who died from respiratory failure in May 1997. In Hong Kong, the virus initially was identified as influenza type A, but the subtype could not be determined using standard reagents. By August, CDC; the National Influenza Center, Rotterdam, the Netherlands; and the National Institute for Medical Research, London, United Kingdom, had independently identified the virus as influenza A(H5N1). An investigation conducted during August-September by the Hong Kong Department of Health and CDC excluded the possibility of laboratory contamination. Since this initial case was identified, six additional persons in Hong Kong have been confirmed to have influenza A(H5N1) infection, and two possible cases have been identified. This report summarizes the nine cases identified thus far and describes preliminary findings from the ongoing investigation, which indicate that multiple influenza A(H5N1) infections have occurred and that both the source and mode of transmission are uncertain at this time. Confirmed Cases

Patient 1. On May 9, 1997, a previously healthy 3-year-old boy developed fever, sore throat, and cough. The child's symptoms persisted, and on May 15, he was hospitalized. His illness progressed, and on May 18, he was admitted to the pediatric intensive care unit (ICU). On May 21, the child died from acute respiratory distress secondary to viral pneumonia. Influenza A(H5N1) virus was isolated from a tracheal aspirate collected on May 19. The child may have been exposed to ill chickens before he became ill.

Patient 2. On November 6, a 2-year-old boy with a congenital heart disease developed high fever, cough, and sore throat and was hospitalized the next day for presumed pneumonia. He had an uneventful recovery and was discharged from the hospital on November 9. A nasopharyngeal swab collected from the child on November 8 yielded influenza A(H5N1) virus.

Patient 3. On November 20, a previously healthy 13-year-old girl developed fever, sore throat, and cough; she was hospitalized on November 26 because of pneumonia. On November 27, she was transferred to the ICU and placed on mechanical ventilation. As of December 17, she remained hospitalized. Influenza A(H5N1) virus was isolated from a tracheal aspirate collected on November 28.

Patient 4. On November 24, a previously healthy 54-year-old man developed fever and cough and on November 29, he was hospitalized because of pneumonia. His condition deteriorated, and he died on December 5. A broncho-alveolar lavage specimen collected on December 1 yielded influenza A(H5N1) virus.

Patient 5. On December 4, a 24-year-old woman developed fever, sore throat, cough, and dizziness. Her symptoms worsened, and she was hospitalized on December 7. Her condition deteriorated, and on December 9, she was transferred to the ICU and placed on mechanical ventilation; as of December 17, she remained in the ICU. Influenza A(H5N1) was isolated from a tracheal aspirate collected on December 9.

Patient 6. On December 7, a 5-year-old girl developed fever, rhinitis, cough, sore throat, and vomiting. As of December 17, she remained hospitalized in satisfactory and stable condition. A nasopharyngeal aspirate collected on December 10 yielded influenza A(H5N1).

Patient 7. On December 12, a 2-year-old boy developed fever and was admitted to the hospital in good condition. The child is a cousin of patient 6, who frequently visited him and his family at their home. On December 16, a culture from the child was reported positive for influenza A(H5N1) virus. Possible Cases

On November 24, a previously healthy 37-year-old man was hospitalized because of pneumonia; onset of illness was November 17. He recovered and was discharged from the hospital on December 9. Although respiratory specimens were unavailable for testing, preliminary results of serologic tests suggest infection with influenza A(H5N1); results of a neutralization assay, which is required to confirm infection, are pending.

The other possible case-patient is the 3-year-old sister of patient 7 and cousin of patient 6. She lived in the same apartment as patient 7 and had onset of fever on December 13 and was hospitalized in good condition. Preliminary laboratory results were positive for influenza A(H5N1) virus; confirmation of these results by virus isolation is pending. Ongoing Investigation

The Hong Kong Department of Health and CDC are investigating these cases. The primary objectives of the ongoing investigation are to detect and investigate new cases and to identify potential sources, including whether and to what extent infection is being transmitted from person to person, birds to humans, or both. Blood specimens for measurement of antibody against influenza A(H5N1) and information concerning respiratory illness, exposure to birds, the type and degree of exposure to cases, and other relevant information are being collected from persons who had contact with case-patients and from control groups that did not have contact with case-patients.

Patients 1-6 lived in different parts of Hong Kong, had no contact with each other, and had no apparent common exposures. Patients 6 and 7 and the 3-year-old girl possible case-patient have all had contact with each other and common exposures. Influenza A(H5N1) viruses isolated from these patients are being fully characterized both antigenically and genetically by CDC.

Surveillance for influenza has been intensified in Hong Kong and Guangdong Province, China, following the identification of the first case of human A(H5N1) infection. Although some of the increased surveillance was conducted through outpatient facilities, most surveillance has occurred in hospitals. Beginning December 8, influenza surveillance was further intensified to include all government outpatient clinics in Hong Kong. Surveillance among poultry in Hong Kong indicates continued circulation of A(H5N1) viruses since March, when outbreaks on poultry farms were first detected.

Reported by: TA Saw, FHKAM (Community Medicine), Hong Kong Dept of Health; W Lim, FRCP, Virus Unit, Hong Kong Dept of Health; K Shortridge, PhD, The Univ of Hong Kong; J Tam, PhD, Chinese Univ of Hong Kong; KK Liu, DRVS, Dept of Agriculture and Fisheries; KH Mak, FHKAM (Community Medicine); T Tsang, MPH, YY Ho, MSC, FY Lee, MBBS, H Kwong, MMED (Public Health), Hong Kong Dept of Health. Queen Mary Hospital; Queen Elizabeth Hospital; Prince of Wales Hospital; Yan Chai Hospital, Hong Kong. World Health Organization, Geneva, Switzerland. Influenza Br, Div of Viral and Rickettsial Diseases, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The cases described in this report represent the first documented human infections with avian influenza A(H5N1) virus. One of the most important aspects of the investigation is to determine the source of infection and mode of transmission. However, this effort is complicated by the high prevalence of exposure to live poultry among residents of Hong Kong.

Although the spectrum of illness caused by human influenza virus infection can range from asymptomatic to fatal, most human influenza infections cause acute febrile respiratory illnesses that resolve without complications. Many of the cases of human infection with type A(H5N1) identified so far in Hong Kong have been unusually severe. However, because influenza surveillance in Hong Kong has been conducted primarily in hospitals, milder cases may not have been recognized, and the severity of infections identified to date may not be representative of the spectrum of illness caused by A(H5N1) infection in humans.

Infection with this influenza strain that is new to humans prompts consideration about whether this virus has the potential to spread globally and cause a pandemic. For an influenza pandemic to occur, a novel human influenza strain against which all or most of the human population has no antibody must be capable of sustained person-to-person transmission, causing widespread illness (1). As of December 17, acute respiratory illness among the population of Hong Kong apparently had not increased.

Although the potential for widespread transmission of this strain is presently unknown, as a precautionary measure, laboratory studies have been initiated to identify a candidate A(H5N1) vaccine strain. At this time, there are no plans for commercial vaccine production.

Two antiviral drugs, amantadine and rimantadine, inhibit replication of virtually all naturally occurring human and animal strains of influenza type A and therefore can be useful for prophylaxis and treatment of influenza A infections (2-4). Influenza A viruses resistant to amantadine and rimantadine can emerge during treatment, but drug-resistant influenza viruses have only rarely been isolated from specimens collected as part of routine influenza surveillance (5,6). Influenza A(H5N1) isolates from Hong Kong that have been tested are sensitive to amantadine and rimantadine.

Persons considering travel to Hong Kong should consider that

1. the number of clinical cases of influenza A(H5N1) identified to date is small despite the intensive surveillance that has been conducted among the 6.5 million residents of Hong Kong and 2) there has been no detected increase in the incidence of acute respiratory illness among residents of Hong Kong. However, the risk for infection to persons living in or visiting Hong Kong cannot be determined with certainty, and the risk may change over time. Although no human influenza A(H5N1) infections have been identified outside Hong Kong, worldwide surveillance for influenza is critical to monitor the circulation of various influenza strains. Human influenza types A(H3N2), A(H1N1) and B continue to circulate worldwide (7,8).

References

1. Cox N, Patriarca P. Influenza pandemic preparedness plan for the United States. J Infect Dis 1997;176(suppl 1):S4-S7.

2. Douglas RG. Drug therapy: prophylaxis and treatment of influenza. N Engl J Med 1990;322:443-50.

3. Tominack RL, Hayden FG. Rimantadine hydrochloride and amantadine hydrochloride use in influenza A virus infections. Infect Dis Clin North Am 1987;1:459-78.

4. Hayden FG. Antivirals for pandemic influenza. J Infect Dis 1997;176(suppl 1):S56-S61.

5. Belshe RB, Burk B, Newman F, Cerruti RL, Sim IS. Resistance of influenza A virus to amantadine and rimantadine: results of one decade of surveillance. J Infect Dis 1989;159:430-5.

6. Ziegler T, Hemphill M, Zeigler ML, Klimov A, Cox N. Rimantadine resistance of influenza A viruses: an international surveillance. Presented at the 7th ISAR Conference, Charleston, South Carolina, March 1994.

7. CDC. Update: influenza activity -- worldwide, March-August 1997. MMWR 1997;46:815-8.

8. CDC. Update: influenza activity -- United States, 1997-98 season. MMWR 1997;46:1192-4.

   
   

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