14 January 2005
Dutch researchers reported in the January 6th issue of the journal “Eurosurveillance Weekly” that 59% of close household contacts of poultry workers infected with the H7N7 avian influenza virus had antibodies against this H7N7virus suggesting that a high rate of human-to-human transmission had occurred. The full final report is posted at:
www. eurosurveillance.org/ew/2005/050106.asp. This finding has key implications for the next human influenza pandemic, whether with a variant of H5N1 or a different virus.
This novel H7N7 virus caused a large poultry outbreak in the Netherlands (not in Asia) and some neighboring nations in March-May 2003, and caused 86 humans to become ill, mostly with conjunctivitis (Proc Natl Acad Sci 2004;101:1356-1361).One veterinarian who had close contact with infected poultry, and who did not take anti-influenza prophylaxis (oseltamivir) died of respiratory distress syndrome after being infected with H7N7.
The authors (Bosman, Meijer, and Koopmans from Biltoven and Utrecht) also reported the striking finding that based on their hemagglutination antibody testing of a subset of 500 people exposed to H7N7 infected poultry that “it was estimated that avian influenza H7N7 virus infection occurred in at least 1000, and perhaps as many as 2000 people”.
One caveat is that the researchers used a modification of the antibody assay, based on the fact that avian flu viruses are reported to bind red blood cells from horses rather than turkeys. However, they went on to demonstrate~100% specificity of their assay using a control group of 100 persons who had no epidemiologic exposure to H7N7 infected poultry (but had been vaccinated in 2002/2003) against human influenza. None were positive for H7N7. The authors also found that a lower proportioin of persons who take prophylactic medication (e.g. oseltamivir) had antibody to H7N7 using this assay.
They concluded that: (1). Avian influenza virus adaptation occurs rapidly” and, (2) that osletamivir protected against conjunctivitis (symptomatic H7N7 human infection) as well as asymptomatic H7N7 human infection. Very few of either the poultry workers or the cullers involving with killing the infected flocks wore their face masks or goggles and thus, not surprisingly no protection was seen with these two types of personal protective equipment (PPE).
Several points arise from this important study:
1) If an avian influenza virus that causes a high case fatality rate due to lung disease, such as H5N1, were to acquire the genes that allow H7N7 to spread from person-to-person then the next pandemic could be started. This has implications both for the avian influenza virus H5N1 recombining with an H7N7 avian influenza virus in the future, without any human influenza virus being involved, contrary to current dogma, and for potential bioterrorism using variants or mutants of H5N1 (i.e. combining in the laboratory H5N1 with H7N1 to develop a virus that causes fatal influenza and demonstrates efficient and sustained person-to-person transmission.
2. Genetic studies of the H7N7 viruses from the initial poultry outbreak in March 2003 in Europe in comparison with H7N7 virus isolates from later animal or human cases could prove fruitful in determining better the yet unknown genetic sequences that confer the ability to cause sustained human-to-human transmission. In addition, studies of anti-influenza drug resistance in H7N7 isolates from poultry and humans could prove valuable in predicting the future need for neuraminidase inhibitors drugs such as oseltamivir rather than the older and less expensive inhibitors of the influenza virus M2 protein rimantidine and amantidine.
3. Further studies of close contacts of persons with H5N1 infection, perhaps using the new antibody assay employed by the Dutch researchers compared with the standard assay, is key in better determining the actual case fatality rate (which currently stands at ~ 75% using laboratory-confirmed cases of H5N1).
Daniel R. Lucey, MD, MPH
Director, Center for Biologic Counterterrorism and Emerging Diseases