Experts worry that antivirals may mask avian influenza

Aug 24, 2006 (CIDRAP News) – Avian flu experts in two of the countries with the most human H5N1 avian influenza cases to date—Vietnam and Thailand—are warning that the antiviral drug oseltamivir may mask the infection and complicate laboratory detection.

Menno de Jong, a virologist at an Oxford University clinical research unit in Ho Chi Minh City, Vietnam, told Bloomberg News this week that avian influenza may go undetected in patients who take the drug days before testing. An incorrect diagnosis is problematic because it may hamper early detection of disease spread.

Some countries are responding to local human H5N1 avian influenza outbreaks by distributing oseltamivir to local citizens. For example, the Jakarta Post reported this week that Indonesia's health ministry had distributed the drug to 2,100 villagers in Garut, a district in West Java, Indonesia, where three recent cases have been documented and authorities are investigating the possibility of human-to-human transmission.

Antiviral drugs such as oseltamivir are designed to reduce the duration of viral replication and should be taken within 48 hours of symptom onset, according to World Health Organization (WHO) recommendations. However, De Jong's team, which observed 18 cases in Vietnam, found that analysis of nasal and throat swabs taken from patients 48 to 72 hours after beginning oseltamivir treatment was unable to detect the virus.

A study of Vietnamese H5N1 cases in a September 2005 issue of The New England Journal of Medicine found that genetic evidence of the H5N1 virus could not be detected in throat swab samples until between 2 and 15 days (median 5.5 days) after illness onset.

"If a patient is on oseltamivir for 3 days before the first swab is taken for diagnostic testing, it's possible the result will be negative, but the patient could be infected," he told Bloomberg News.

To prevent the drug from masking a possible H5N1 virus infection, he advises that patients undergo testing before or soon after taking oseltamivir. Obtaining a swab sample from the patient takes only seconds and should not delay the patient's treatment, de Jong said.

Meanwhile, a public health official in Thailand expressed the same concerns about possible false-negative testing results for the H5N1 virus in patients who take oseltamivir. In an article that appeared in The Nation, a Thai daily newspaper, Paijit Warachit, director-general of the Department of Medical Sciences, said that initial laboratory tests did not detect the H5N1 virus in the country's two most recent cases.

Warachit said the disease progression may be becoming more complicated in humans, or the use of oseltamivir could be complicating the patients' lab results. He noted that the drug is able only to prevent the virus from replicating, not destroy it, and that little of the virus was in the patients' respiratory tract for testing.

With the last two Thai cases, the avian influenza virus was found to be deeper in the respiratory tract than is typically found with other influenza viruses. Warachit said the medical staff has been told to probe deeper to obtain a complete testing specimen.

Since 2004 Thailand's health ministry has tested more than 4,000 people for the H5N1 avian influenza virus, with a 3% failure rate. However, Warachit said the failure rate has risen to 20% this year. "We need to continue our studies to see whether the virus will become more and more difficult [to detect] in the future," he noted.

See also:

Sep 29, 2005, New England Journal of Medicine article on avian influenza in humans
http://content.nejm.org/cgi/content/full/353/13/1374

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