Evolution of H5N1 With Pandemic Potential
Recombinomics Commentary 04:43
January 22, 2008
Dr. Paul A. Offit, a vaccine specialist at Children’s Hospital in Philadelphia, was one of those who, he jokes, “dared to be stupid” by bucking the alarmist trend in 2005.
“H5 viruses have been around for 100 years and never caused a pandemic and probably never will,” he said.
The above comments ignore the well documented evolution of the H5N1 with pandemic potential which is clearly at odds with the above statements. Although everyone has a right to “be stupid”, the comments on pandemic potential are at odds with the facts.
H5N1 evolution is clear in the sequence changes of various H5 isolates collected over the years. The first H5N1 was found about 50 years ago, in a chicken in Scotland in 1959. However, that H5N1 was really a “European” sequence, and quite distinct from the H5N1 which was first reported in Asia in 1996. Low path H5 has been circulating worldwide, but those strains tend to cause problems in poultry when they acquire a polybasic cleavage site through non-homologous recombination. However, such high path variants have caused problems for poultry, but have not have been isolated from humans or other mammals.
The H5N1 of concern was not reported prior to 1996, when it was found in a goose in Guangdong province in China. The following year, it caused a human outbreak in Hong Kong, which led to infections of 16 people, including 6 fatal infections. The WHO official count of fatal human infections by bird flu is 220. 219 of the 220 were due to H5N1. Thus, H5N1 has a lethality and pandemic potential not seen in other bird flu serotypes.
Although the first recorded fatalities were in 1997/1998, there were no further reported fatalities until 2003. Thus, of the 219 H5N1 reported fatalities, 213 of them have been since 2003.
The pandemic potential of H5N1 can also be seen in the recent spread and evolution of H5N1. In 2004, H5N1 exploded out of China, resulting in the first human cases in Vietnam and Thailand, as well as poultry outbreaks in most countries to the east of China. Human cases were reported in 2005 in Indonesia, multiple provinces in mainland China, and Cambodia.
In 2005 H5N1 was also detected in long range migratory birds at Qingahi Lake, China, which led to an expansion into 50 countries west of China. None of these countries had reported “Asian” H5N1 prior to 2005 and all subsequent human, mammal, and bird infections were the Qinghai strain of H5N1. The Qinghai strain led to human fatalities in Turkey, Iraq, Azerbaijan, and Egypt in 2006 and Nigeria and Pakistan in 2007. The Qinghai strain is distinct from the Fujian strain, which has caused the deaths in China and more recently in southeast Asia. Both strains are distinct from the strain causing the fatal infections in Indonesia.
In 2007 the Qinghai strain in Europe was replaced by the Uva Lake strain, a Qinghai Lake variant. It is likely responsible for the confirmed cases in Pakistan, and the current outbreak in India (as well as poultry infections in Europe since the summer of 2007).
Thus, the evolution of H5N1 into a human killer with a markedly expanded geographic reach has developed in the past few years, not the 100 years cited above. Moreover, the recent trend has been quite clear and although there was somewhat of a lull in 2007 when the Qinghai strain was being replaced by the Uva Lake strain, this strain caused the longest H5N1 sustained transmission chain reported to date (in Pakistan).
The recent activity, especially in West Bengal, India, signals more significant evolution and pandemic potential in the upcoming weeks.
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