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The new avian influenza in China: H7N9
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What in the world is going on in China with this new avian influenza virus? The answer seems to be much more than we know.
However, we do know a surprising amount already. Cases began to occur in late February and March of this year and were first reported in late March. There has been a steady stream of reporting since then, documented in virtually daily postings in Pro-MED Mail. Reports are now starting to appear in the peer-reviewed literature, notably for US readers in The New England Journal of Medicine.
This stream of reporting is the first point that merits comment. Ten years ago, an epidemic of SARS began in China and spread from there to a number of other countries. In that outbreak, the Chinese were reclusive, perhaps in denial, not at all forthcoming with information, and the rest of the world expressed its anger. It is clear a decade later that the Chinese learned its lesson well, for the Chinese openness and sharing of information, antisera and virus strains have been exemplary. Viral gene structure has been posted on a global database, available to any country that desired it. This has been enormously helpful in preparing reagents and developing candidate viruses for vaccine production, should that become necessary.
Cause of severe disease
The next striking characteristic of this disease in humans is its severity. Clinical descriptions include terms such as severe pneumonitis, respiratory failure, shock, disseminated intravascular coagulation and multi-organ failure. These are not the terms one usually uses to describe the influenza cases we are used to seeing. This is a very nasty virus. The case-fatality rate is currently about 20%, but this likely will go higher because many of the cases are still critically ill. In contrast to H5N1 influenza, which attacks mostly the very young and younger adults, the H7N9 virus seems to spare the young and attack older adults, particularly older males. Most of the older adults with the disease have had underlying conditions.
Three family clusters have been studied, and there has been no convincing documentation of direct human-to-human spread, although it cannot be ruled out that this indeed may have occurred. Household contacts of other cases, as well as health care workers caring for them, have been monitored, and there has been no documented H7N9 illness among them. Thus, human-to-human spread must be infrequent if it occurs at all, and there certainly has not been sustained person-to-person spread. However, viral geneticists have pointed out that this H7 gene possesses several mutations that place it even further along the road to facilitating person-to-person spread than the H5 gene. This issue, therefore, needs to be watched carefully.
Theodore C. Eickhoff
Origins of the virus
Where did this virus come from? Again, the viral geneticists tell us that the genes in this virus are all of avian origin — a triple reassortant virus. In this respect, at least, it is comparable to the H5N1 virus, but there the similarity ends. H5N1 is lethal in avian species and announced its presence by rapid die-offs in poultry, ducks, pigeons, etc, and perhaps some wild birds as well. Indeed, countries controlled the spread of H5N1 virus by widespread culling of domestic fowl, and this is still the principal method of control. Not so with H7N9. It causes no illness in fowl and poultry, and it announces its presence only when it infects humans. Cloacal culturing of poultry has revealed the presence on the H7N9 virus in many asymptomatic poultry. On the basis of this evidence, the Chinese believe quite firmly that colonized poultry represents the probably source of the virus. Yet, 25% or more of infected people give no history of any contact with poultry or fowl, and we don’t know how they are acquiring the infection; so there is still more to this story than we presently understand.
There were pig die-offs in several areas of China during the early weeks of the outbreak, but these were evidently not due to pig H7N9 infection. Furthermore, none of the reassortant genes are of porcine origin.
Very early in the course of this outbreak, live poultry markets in many cities were closed by the health authorities and, thus, seemed to slow the occurrence of new cases. The case count — as of May 7 — is 130 and climbing, albeit more slowly than before the markets were closed.
Another major gap in knowledge: We don’t have a good appreciation of the spectrum of illness this virus can cause. Most confirmed cases have been severe pneumonitis; there also has been one asymptomatic person from whom H7N9 virus was confirmed. How many other asymptomatic infections might have gone undetected, and is there anything in-between, such as mild influenza infections or other expressions of infection?
H7 virus infections in man have been infrequent in the past and not unusually severe. In poultry, however, H7 virus infections have resulted in serious disease and extensive economic loss. Such an outbreak occurred in the Netherlands in 2003 caused by an H7N7 virus. Among humans, it resulted mostly in mild influenza-like illness or conjunctivitis; there was one case of severe pneumonitis and one death.
Unanswered questions
Some other gaps in knowledge: There is a presumption that humans are uniformly susceptible to this virus because H7 infection has not occurred on a major scale in the past. This has not yet been documented by serologic testing; nor do we yet know anything about the human antibody response to H7N9 infection. How effective is H7 as an immunogen? Will it regularly induce hemagglutination or virus neutralizing antibody in high titer, or will it be necessary to flog the immune system with enormous quantities of antigen, as was necessary with H5N1 viruses, to obtain a satisfactory response? Are any of the severe H7N9 infections actually coinfections with an as yet unrecognized pathogen? These and many other questions remain to be answered.
WHO considers this to be one of the most lethal viruses it has ever seen and is very concerned.
Looking into the future — always a dangerous thing to do with influenza viruses — there seem to be three possible scenarios: 1) the outbreak subsides with existing control measures and disappears, just as other influenza outbreaks and SARS have done in the past; 2) the outbreak declines, but doesn’t totally disappear, and pops up again from time to time in China and perhaps in other countries as well — it behaves in a fashion comparable to how H5N1 is behaving, never acquiring the mutations necessary to spread easily and rapidly in humans; and 3) the necessary mutations occur, the virus spreads uncontrollably, and we have a highly lethal pandemic, capable of eclipsing the 1918 pandemic.
Take your pick.
References:
Li Q. N Engl J Med. 2013;doi:10.1056/NEJMoa1304617.
Uyeki T. N Engl J Med. 2013;doi:10.1056/NEJMp1304661.
For more information:
Disclosure: Eickhoff reports no relevant financial disclosures.