The level of immunity to the recently circulating
H7N9 influenza virus in an urban and a rural population in Vietnam
is very low, according to the first population-level study to
examine human immunity to the virus, which was previously only
found in birds. The findings have implications for planning the
public health response to this pandemic threat.
The study used a new, high-throughput method that
allows blood samples to be analysed for antibodies to multiple
human and animal influenza viruses at the same time and is easier
to standardise than previous techniques. However, the assay is yet
to be validated clinically for the H7N9 virus, and the researchers
caution that the results must be interpreted with care.
Since the first case of H7N9 infection in humans was
reported in February 2013, there have been 131 confirmed cases and
36 deaths, all in China apart from one case in Taiwan. All of the
infections seem to have come from infected poultry and there is no
evidence of sustained transmission between people.
One of the first key pieces of information that
officials need when considering how best to respond to the threat
of a pandemic is how much, if any, immunity the human population
has to this virus. This helps to predict where the virus is likely
to affect first and how likely it is to spread further. Having this
knowledge also helps to understand the risks of severe infection,
as well as helping to target protective measures such as where to
direct antiviral medication.
Researchers at the Wellcome Trust Oxford University
Clinical Research Unit (OUCRU) in Vietnam tested 1723 blood samples
collected in southern Vietnam for the presence of antibodies to
five different bird flu viruses, including one from the H7 subtype.
The presence of antibodies would be an indication of past exposure
to these particular strains of flu. They used a new technique,
developed by their research collaborators at the National Institute
of Public Health of the Netherlands, which is faster and easier to
use than previous methods.
The results reveal that although there were more
antibodies to the H7 subtype of flu virus than that to any of the
H5 subtypes tested, antibodies to all five bird flu viruses were
much rarer than those to human flu viruses. This suggests that
people living in this particular area of Vietnam have had very
little or no exposure to H7, similar to other bird flu viruses. As
this population of people would be expected to be among the first
to be affected in the event of a pandemic, these findings have
important implications for pandemic preparedness plans in this
area.
Dr Maciej Boni, a Sir Henry Dale Fellow at the OUCRU
and first author of the study, explains: "H7N9 is a virus that
until now has only infected birds so it's not surprising that we
don't find much evidence of humans having been exposed to it. It is
reassuring that in Vietnam we don't see any evidence that the
current outbreaks represent a tip-of-the iceberg observation of
widespread H7N9 infection in people. On the other hand, the low
antibody levels indicate that there is likely to be very little
immunity to this virus."
Around half of the samples were taken from an urban
environment, Ho Chi Minh City, and half from a rural area, the
nearby Khanh Hoa province. The team found no difference in the
level of immunity to bird flu viruses between these two
populations, even though people living in rural areas are more
likely to live in close proximity to poultry.
"It has been suggested that people who live in closer
proximity to chickens and other birds will have higher levels of
immunity to bird flu viruses simply because their exposure is
likely to be greater. However we find no evidence for this. Our
findings would suggest that both rural and urban populations should
be treated the same when considering how best to respond to the
threat of an outbreak," added Dr Boni.
Professor Jeremy Farrar, Director of the Wellcome
Trust Major Overseas Programme in Vietnam and the OUCRU Hospital
for Tropical Diseases, explained: "This is the first study to give
us information about the level of antibodies and potentially human
immunity to this new bird flu virus, H7N9 in the region. But we
need to interpret the findings cautiously; these assays are
relatively new and we need to understand how they correspond to
existing assays and how they reflect past infection and true human
immunity.
"We know that antibodies are very important for
immunity to other flu viruses but at this stage, we still don't
know what level of antibody measured using this assay would provide
protection against this novel strain. Further studies will be
needed to understand the clinical relevance of these new assays,
how they compare with classic techniques and what the apparent
absence of antibodies to these viruses in the human population
means. However these new techniques do allow for much higher
throughput of samples, ease of use and once validated may allow
much more rapid assessment of the spread of infection and levels of
population immunity than do traditional assays."
The study was carried out in collaboration with
scientists at the National Institute for Public Health and the
Environment (RIVM) in the Netherlands.
Professor Marion Koopmans, who is Head of Virology at
the RIVM and senior author of the study, said: "We developed this
technique exactly to be used in the current situation: we wanted a
standardised test that allowed us to rapidly compare antibodies to
the new virus with those to influenza viruses that we already know
are common in people.
"The level of immunity to a new virus is one of the
important questions during any emerging disease outbreak. We need
only one drop of blood, so that tests can also be run when only
small sample volumes are available, for instance when testing
children. For outbreak investigations, testing of animals may be
needed, and we are currently working on that. To do the clinical
validation studies, we need blood samples from patients (and
animals) with confirmed H7N9, and we hope to be able to do that
soon through collaborations with other groups working on
H7N9."
The paper, Population level antibody estimates to novel influenza A/H7N9,
is published in the Journal of Infectious
Diseases.