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Asymptomatic H5N1 in Pakistan

Recombinomics Commentary
December 17, 2007

Pakistan's Health Ministry issuing a statement Saturday saying six people had initially tested positive for the virus last month, while the WHO said eight had been reported. Hartl said the discrepancy was likely linked to a technicality since six patients had tested positive using an internationally recommended method while a less reliable test was used on the others.

Specimens were never collected from one of the brothers who died, and many of those who tested positive experienced only mild symptoms and were not hospitalized, Hartl said.

A doctor who treated members of the family also has tested positive for H5N1, but with a non-standard diagnostic test, Hartl said. He cautioned that further testing is needed to determine if she is indeed a case, noting she hadn't shown signs of infection.

The above comments from WHO suggest that several patients were H5N1 antibody positive and were asymptomatic.  These assays don’t address the time of the infection, because antibodies can represent a prior exposure.  Therefore, official confirmed cases are limited to those who have tested positive twice for antibodies and the two tests show a rising antibody level, either via sero-conversion from negative to positive, or an increase in titer of at least four fold.

These tests are most accurate when the initial sample is collected early, and  the second samples is collected three to four weeks post symptoms or exposure.

The testing of asymptomatic cases is important to determine if H5N1 is silently spreading, and also important to determine if transmission chains are growing.  Thus, a positive in the health care worker could signal a chain as long as H2H2H2H involving the index case, the brother who died November 19, the brother who died November 29, and the health care worker who was a contact of teh brotehrs.  These transmission chains are most accurately defined when disease onset dates as well as contact dates are known.

The asymptomatic positives are also important for identifying additional cases which may not have been reported,  If the contact is repeatedly positive, but the level doesn’t increase, the antibodies would signal an earlier exposure, indicating earlier transmissions.

Thus, antibody tests on contacts, including samples collected recently, would be useful.


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