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Commentary

H5N1 Case Reporting Failures In Indonesia Raise Concerns
Recombinomics Commentary 13:21
June 19, 2008

The main cause of the decline in the bird flu cases on human beings is the fact that people have now become increasingly aware that one should do something as soon as he or she found out that he or she had the symptoms of being affected with this fatal virus Supari said on Wednesday.

The above comment appears to be an acknowledgement by Health Minister Siti Fadillah Supari that Indonesia is not reporting recovered H5N1 cases.  Prompt treatment does not lower the number of infected cases, but does improve recovery.  Thus, prompt treatment would lower the case fatality rate, but the rate has been above 80% for the past three years.  The case fatality rate for WHO confirmed H5N1 cases for the past four years in Indonesia has been 65.0, 81.8, 88.1, 81.3 (13/20, 45/55, 37/42, 13/16 respectively for deaths / cases in 2005-2008).

The high case fatality rate has led to speculation that milder cases that recovered were not included in the confirmed cases.  This speculation was based on testing procedures in Indonesia, which initially did not involve cases that were not transferred to infectious disease hospitals.  Thus, patients who recovered were released with an unknown diagnosis or a mis-diagnosis of dengue fever or typhus.  In addition, testing of samples collected after the start of Tamiflu treatment would also lead to false negatives, because the treatment would depress the H5N1 RNA levels.

The speculation was supported by analysis of clusters that included at least one confirmed case.  The milder cases were obvious in cluster analysis involving the initial cases in 2005, as were limited testing approaches. 

The first confirmed case in Indonesia was part of a three member cluster.  The index case was not tested initially.  Subsequent antibody tests were strongly positive, but since samples were collected three days apart, the doubling of the antibody titer did not meet the WHO requirement of a four fold increase.  The second cluster member was never tested, while the third was H5N1 positive.  Thus, initially only one of the three fatal cases was a confirmed case.

The second confirmed case in Indonesia was also part of a cluster.  The nephew of the confirmed case also was confirmed, but he did not have a severe infection, as was seen in the fatal infection of his aunt.  He was treated and quickly recovered, but was tested prior to Tamiflu treatment because he was a contact of the index cases.

A third cluster in 2005 involved three family members who recovered.  However, these cases were identified by antibody levels detected through aggressive testing.  These recovered cases helped lower the case fatality rate to 65% for 2005.

However, the number of reported clusters declined in subsequent years, and the case fatality rose to more than 80% for each year, including 2008.  The clusters in Garut in 2006 identified a series of unreported cases.  Three clusters were reported simultaneously.  The confirmed cases were linked to earlier fatal cases which had not been tested, as well as subsequent recovered cases which were tested after the start of Tamiflu treatment.  These recovered cases, including those who were hospitalized and placed in intensive care, demonstrated the limitations in testing of patients after the start of Tamiflu treatment.  Although the number of suspect cases grew to 20, only three cases were confirmed.

The more recent changes in Tamiflu treatment of at local hospitals has not led to a decline in the case fatality rate, but has led to a slight decline in the number of reported cases.  The recent clusters demonstrate that the mis-diagnosis of infected cases is lowering the number of cases.  The two clusters in March involved fatal index cases with “lung inflammation” and dengue fever, which were not confirmed cases, even though the infections were fatal and preceded confirmed fatal cases in relatives.  More recently the cluster involved three family members. The index case was diagnosed as typhus, while a recovered cases was said to have tested negative.  The initial report of negative results for a more recent case has also been reported.  This recent cluster and case, as well as additional lab confirmed cases, have not been reported to WHO and therefore have also not appeared in the WHO total for 2008 cases in Indonesia.

Thus, the decline in H5N1 confirmed cases is largely due to deliberate under-reporting of cases which appears to include the failure to report recovered cases.

The lack of reporting, coupled with oversight failures by WHO, remain causes for concern.

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