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H5N1 False Negatives in Jakarta Indonesia Raise Concerns
September 11, 2005
The minister said that one of the blood samples taken from the woman before she died tested positive for avian influenza virus but others were negative.
The above comments suggest the recent fatality (37F) will test positive for H5N1 in additional tests in Hong Kong. However, the negative tests described above again raise concerns about the use of negative lab data to excluded patients with bird flu symptoms, especially when the cases are fatal. These exclusions underestimate the true extent of the disease and create very long delays in inclusion in official case lists, which could seriously compromise intervention efforts.
The earlier familial cluster in the nearby suburb of Tangerang is a good example. Three fatal cases were initially diagnosed as bacterial pneumonia when H5N1 test were negative or equivocal. Only the father (38M) was confirmed to be H5N1 positive by PCR. He developed symptoms on July 2, died July 12, and was officially announced by the WHO on July 21. The index case, his 8 year-old daughter developed symptoms on June 24 and died July 14. The official announcement of her positive lab results for H5 antibody was made on July 29. The first family member to die was the 1 year old daughter who developed symptoms on June 29 and died July 9. There has yet to be an announcement that she was positive in lab tests.
The clustering of the dates of the fatal pneumonias leaves little doubt that all three family members died of bird flu. The gap in onset dates also strongly suggests the index case infected the two family members. The clustering and likely human-to-human transmission is frequent. Virtually all familial clusters in Vietnam, Thailand, and Cambodia show the same pattern as the Indonesian cluster. Most of the members in the cluster die and although false negatives are common, at least one family member is H5N1 laboratory confirmed and there is a 5-10 gap between onset date of the index case and additional family members.
The latest case in Indonesia follows the pattern in northern Vietnam which generated geographical clusters. All four cases in Indonesia were in the vicinity of Jakarta, as were three additional suspect cases, which were not reported as confirmed in media reports. The clustering of the four cases with reported lab confirmations is cause for concern and raises questions about negative results in the other suspect cases, especially the cook who died. Retrospective diagnosis of fatal cases are especially difficult because PCR results require collection of appropriate samples at the appropriate time, and serological detection may be limited to samples collected weeks after diseases onset dates.
The fourth laboratory confirmed case in the same geographical location in Indonesia is cause for concern.