posted on Sep, 28 2005 @ 12:13 PM
Thanks to Dr. Niman for his commentary on this very important subject.
Quote..It seems that much of the testing in Indonesia is destined to give false negatives. Detecting H5N1 by PCR or serum antibodies requires
collection of the right sample at the right time. For PCR, samples from the throat should be collected early, before the virus has moved to the lungs.
Alternatively, H5N1 can be detected at autopsy by collecting infected tissues. For antibody, samples need to be collected late, such as 30 days after
symptoms which allows for antibody levels to rise. For WHO confirmation, a titer rise of greater than 4 X is required, so at least two collections
need to be made. An early collection followed by a late collection would clearly show the required 4X titer increase.
However, the patients in Indonesia have been going to local facility, which do not collect samples. By the time the patient is referred to the
infectious disease hospital, H5N1 has moved out of the throat and into the lungs. Thus, PCR test are negative. If the patient recovers, there is no
autopsy. If the patient dies, there ay be no autopsy because of religious prohibition. Thus, positive PCR results are unlikely.
For serum, the antibody levels are not high enough when transferred, so they also are negative most of the time. If positive, they still won't be
confirmed unless another sample is collected and its level is at least 4 X higher than the first.
Thus, the lack of testing at the primary care center coupled with late PCR testing and early antibody testing at the referral center, produces false
In the June/Jily family cluster, only the father was PCR positive because by the time he was admitted both of his daughters were dying, so they took a
throat sample early (at the correct time). For his older daughter, both of her serum samples were strongly positive, but they were collected just 3
days apart so the second samples was not 4X the first (and therefore she was not a confirmed case).
In the second familial cluster, the sample from Rini Dina was collected at the right time (possibly because she worked at the airport and concern
levels were high). Her nephew developed symptoms a week later so he was also tested early and was also PCR positive, but has recovered and has been
discharged. Although PCR positive, he was never that sick.
Thus, the sample collection procedures are destined to return false negatives and the true level of H5N1 infections in humans in Indonesia is largely
So basically, we might already be in sustained human-to-human transmission. I think that the WHO should mandate that all samples and tests be turned
over to a reliable source. It would be nice to have a qualified testing center on site. This might clear up some of the misdiagnosed cases also.