# 1484
From CIDRAP (Center for Infectious Disease Research & Policy) comes this synopsis of a report just issued by the World Health Organization's Second Consultation on Clinical Aspects of Human Infection With Avian Influenza A(H5N1).
Exposure source unclear in 25% of human H5N1 cases
Jan 16, 2008 (CIDRAP News) – In at least 25% of human infections with the H5N1 avian influenza virus, just how the person was exposed to the virus remains a mystery, according to a report by an expert panel set up by the World Health Organization (WHO).
"In one quarter or more of patients with influenza A (H5N1) infection virus infection, the source of exposure is unclear, and environment-to-human transmission remains possible," says the report, which appears today in the New England Journal of Medicine.
The predominant source of exposure in H5N1 cases is contact with infected poultry in the week before onset of illness, the article notes. But in cases involving no such contact, patients might have touched contaminated objects (fomites) or fertilizer containing poultry feces or have inhaled aerosolized infectious material. The only known risk factor for some patients was visiting a live-poultry market, the article says.
The discussion of exposure sources is part of a review of all aspects of human H5N1 cases, including epidemiology, clinical features, diagnosis, treatment, and prevention. The report is based on the WHO's Second Consultation on Clinical Aspects of Human Infection with Avian Influenza A (H5N1), a meeting held in Antalya, Turkey, in March 2007.
About a quarter of all human cases have occurred in clusters of two or more that were epidemiologically linked, the report says. More than 90% of the clusters have involved blood relatives, suggesting a possible genetic susceptibility to the infection. Most people in the clusters probably were infected through common exposure to poultry, "but limited, nonsustained human-to-human transmission has probably occurred during very close, unprotected contact with a severely ill patient," the article states.
Other items of note include:
- The report charts 10 clades (or lineages) of the H5N1 virus, including the original outbreak in Hong Kong in 1997.
- Changes in multiple viral genes"—not just the surface protein known as hemagglutinin—"are probably required to generate a potentially pandemic influenza A (H5N1) virus.
- The virus is not transmissible among ferrets or swine, and reassortment between an H5N1 virus and an H3N2 (seasonal flu) virus did not produce a virus transmissible among ferrets
- The report does not fully endorse the "cytokine storm" theory . . . . The tissue damage "probably results from the combined effects of unrestrained viral infection and inflammatory responses" induced by the infection, it says.
- The report repeats the advice against the routine use of corticosteroids in H5N1 patients.
- Clade 1 viruses and most clade 2 viruses from Indonesia are fully resistant to amantadine and rimantadine, but the other clade 2 viruses from other parts of Eurasia and Africa are usually susceptible to these older drugs.
- The article repeats the standard recommendation for early treatment with oseltamivir (Tamiflu), a neuraminidase inhibitor. The panel also reiterates previous WHO statements that doubling the standard oseltamivir dose and duration of treatment may be reasonable.
- The report stops short of endorsing prepandemic vaccination.
- The median age of H5N1 case-patients is about 18, and 90% of patients have been 40 years or younger.
- While the disease typically leads to severe pneumonia, febrile upper respiratory illnesses without pneumonia have been seen in children, particularly since 2005.
- About 15% to 20% of older adults have some antibodies to H5N1 and might respond to a single dose of vaccine.
The `double the dose for double the duration' treatment course with oseltamivir is something that has been discussed many times, and there are clinical trials going on to see how much more effective this would be.
The downside is, it raises the 10-pill course of treatment to 40 pills - and that would reduce the number of patients that could be treated by stockpiled antivirals by 75%.
In other words, a country with enough Tamiflu to treat 25% of their population at the 10-pill course would find they only had enough for 6.25% of their citizens at the 40-pill course.
The choices here are grim if a larger course of treatment proves to improve survivability rates.
Should a pandemic erupt doctors may have to choose between giving patients a sub-optimal course of treatment in order to treat the maximum number of patients, or accept that by giving a 40-pill course that only a small percentage of infected patients can be treated.
All in all, a fascinating report. Well worth reading.
