No evidence was found of nosocomial transmission of H5N1 viruses among 83 hospital employees with exposure to 4 confirmed and 1 probable H5N1 case-patients or their clinical samples. A number of possible factors may explain these findings: a lack of infectivity of the patients at the time of admission; the effective use of personal protective equipment (PPE) and infection control; low sensitivity of the antibody detection method; lack of susceptibility of HCWs, or a lack of transmissibility of this particular H5N1 strain.
No data are available on the duration of H5N1 virus shedding in children. However, for human influenza virus, viral shedding at high titers is generally more prolonged in children, and virus can be recovered up to 6 days before and 21 days after the onset of symptoms. The H5N1 patients in this study were admitted with severe illness 3–7 days after onset of symptoms and PCR-positive specimens were obtained from the 4 confirmed case-patients on the day 1 (1 patient), day 2 (1 patient), and day 3 (2 patients) after admission. In addition, live virus was cultured from samples taken from 2 of the patients on days l and 3 after admission, respectively. None of the patients were treated with oseltamivir because this was not available at the time (9
). Two of the patients were treated orally with the nucleoside analogue ribavirin during their admission, 1 on day 4 after admission, and the other on day 1 (9
). However, the 2 other confirmed case-patients and the probable case-patient did not receive antiviral treatment and, if human infection with H5N1 is associated with viral shedding, these patients would be expected to be contagious during their admission.
Most hospital employees (94.8%) reported that they always wore masks while caring for H5N1 patients, and often the reported type of mask was an N95 respirator. However, N95 respirators were first available in NPH on January 7, and some employees reported wearing N95s before this date. Therefore, reported PPE use in this study may be biased by inaccurate recall or a tendency to report behavior that HCWs know is recommended. Enhanced infection control practices and PPE were instituted on January 7, and the diagnosis of avian influenza was first confirmed on January 9. Therefore some HCWs in this study were likely exposed to H5N1 patients without optimal PPE or infection control.
Oseltamivir prophylaxis was not used by any of the staff in this study and therefore did not play a role in protecting HCWs. Whether the HCWs in the study were protected by cross-reactive immunity to other influenza A subtypes is hard to assess. One possible explanation for the observation that most confirmed H5N1 case-patients are reported in children or young adults is that older adults are protected by cross-reactive immunity from previous exposure to other influenza A viruses. This hypothesis requires further investigation.
Serum samples were taken from HCWs at least 29 days after last possible exposure and at a time when the antibody response to exposure would be expected to be detectable (4
). Based on a small number of samples, the sensitivity of microneutralization test in detecting antibodies to H5N1 in children and adults is 88% and 80%, respectively, while the specificity is 100% and 93%, respectively (10
). Also, the microneutralization assay utilized H5N1 strains isolated from human patients in North Vietnam, so the negative results are unlikely to be false negatives due to a poor match between antigen and antibody. False-positive results are perhaps more likely, and 1 sample was initially positive but appeared to be due to cross-reacting anti-N1 antibody.
Epidemiologic evidence from Vietnam and Thailand clearly indicates that sustained human-to-human transmission of H5N1 has not yet occurred. Most reports of H5N1-infected patients have been sporadic, and despite the evidence from Hong Kong of human-to-human transmission and the occurrence of family clusters of H5N1 in Vietnam and Thailand, no evidence indicates that influenza A H5N1 has ever caused >1 generation of human-to-human transmission. Although this study has not distinguished the inherent transmissibility of the virus from the influence of infection control or host resistance, the data provides further reassurance that the risk for human-to-human transmission of currently circulating avian H5N1 viruses is low. Studies among household members of confirmed H5N1 case-patients will provide additional information on the risk for human-to-human transmission in the absence of infection control measures.
While the absolute risk for human-to-human transmission of avian H5N1 viruses may be low at this time, the high case-fatality proportion seen among recent human H5N1 patients demonstrates that the individual consequences of infection are very serious and intensive measures to protect healthcare workers and laboratory staff against infection remain warranted. The risk of human-to-human transmission of H5N1 viruses could increase in the future. Consequently, every H5N1 case should be managed by clinicians and public health professionals with the assumption that human-to-human transmission can occur and that the risk for such transmission is unpredictable.