Thursday, July 22, 2010

Avian influenza, human (46): InVS update

22-JUL-2010
SubjectPRO/AH/EDR> Avian influenza, human (46): InVS update
AVIAN INFLUENZA, HUMAN (46): INSTITUT DE VEILLE SANITAIRE UPDATE

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A ProMED-mail post
<http://www.promedmail.org>
ProMED-mail is a program of the
International Society for Infectious Diseases
<http://www.isid.org>

Date: Thu 22 Jul 2010
Source: Eurosurveillance, Volume 15, Issue 29 [edited]
<http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=19619>

The influenza A(H5N1) epidemic at 6 and a half years: 500 notified
human cases and more to come

-----------------------------------------------
By: A Tarantola 1, P Barboza1, V Gauthier1, S Ioos1, N El Omeiri1, M
Gastellu-Etchegorry1, and the Epidemic Intelligence team at InVS 2

1 - International and Tropical Department, Institut de Veille
Sanitaire, Saint-Maurice, France
2 - The Epidemic Intelligence team at InVS
Introduction
--------------
Since November 2003, the epidemic intelligence team at the French
Institut de Veille Sanitaire [InVS] has been gathering data on
influenza A(H5N1) circulation in poultry and on human cases
worldwide. As Indonesia notifies the world's 500th case to the World
Health Organization, we discuss the epidemiological situation and
trends of A(H5N1) influenza [A 501st case has now been reported; see:
ProMED-mail report "Avian influenza, human (45): Indonesia (SH),
archive number 20100718.2404. - Mod.CP]. Although the overall number
of cases reported worldwide has decreased, influenza A(H5N1)
continues to circulate intensely in some countries, and more cases
are to be expected, especially in Egypt and Indonesia.

The international and tropical department of the Institut de Veille
Sanitaire (InVS) conducts constant monitoring of health events
worldwide to provide French health authorities with timely
forewarning of public health events of international concern. This
process, known as epidemic intelligence (EI), has been described
elsewhere [1]. Although topics vary widely, the situation of highly
pathogenic influenza A(H5N1) influenza in the world has constantly
been monitored since 2003. This paper describes the epidemiological
situation 6 and a half years into the epidemic, as Indonesian
authorities notify the world's 500th case since November 2003 [2].
Epizootic
-----------
From the end of 2003 to 1 Jul 2010, 63 countries or territories on
the Asian, African or European continents (incl. 15 European Union
countries) have notified infections by influenza A(H5N1) virus in
poultry or wild birds to the World Organization for Animal Health
(OIE) [3]. In 2009, a total of 9 countries notified outbreaks in
poultry or were considered enzootic by OIE: Bangladesh, Cambodia,
China (Tibet and Xinjiang), Egypt, India, Indonesia, Laos, Nepal (1st
notification) and Viet Nam. Six other countries or territories
notified cases in wild birds only: China (Qinghai and Hong Kong SAR),
Germany, Mongolia and the Russian Federation (Moscow Oblast and
Republic of Tyva). In 2010, 12 countries have been affected to date:
Bangladesh, Bhutan (for the 1st time), Cambodia, Egypt, India,
Indonesia, Israel, Laos, Myanmar, Nepal, Romania and Viet Nam.
Furthermore, in 2010, cases were reported in wild birds only by
animal health authorities in Bulgaria, China (Tibet and Hong Kong SA!
R), Mongolia and the Russian Federation (Republic of Tyva). Many
other countries, notably in sub-Saharan Africa, have suspected
transmission in predominantly backyard flocks, but lack surveillance
systems to document it. [These data in those countries with
documented human cases are summarised in schematic form in the
original text].

Since 2003, cases of influenza A(H5N1) virus infection have also been
occasionally documented in wild (felines, ferrets etc.) or domestic
mammals (cats and dogs). No secondary transmission to humans,
however, has been described following contacts with animals other
than poultry or wild birds.

Wild aquatic fowl constitute the animal reservoir and have
occasionally reintroduced influenza A(H5N1) -- in European countries
along the Danube or in Viet Nam for example -- leading to sporadic
outbreaks in poultry flocks despite previous and successful
elimination efforts.
Human epidemic
----------------------
From 1 Nov 2003 to 1 Jul 2010 (by date of symptom onset), a total of
500 confirmed human cases of influenza A(H5N1) including 296 deaths
(case fatality rate (CFR) 59 percent) were notified to the World
Health Organization (WHO) by 15 countries [4]

From 1 Jan to 1 Jul 2010, 32 confirmed human cases including 14
deaths
(CFR 44 percent) were notified by 7 countries. During the same
period in 2009, 41 confirmed human cases including 12 deaths (CFR 29
percent) were notified by China, Egypt and Viet Nam. Indonesia also
reported 18 cases during that period, although data on deaths by date
are not available. In 2009, a total of 73 confirmed human cases
including 32 deaths (CFR 44 percent) were notified by these 4
countries plus Cambodia. Five countries, which had notified cases in
preceding years, have notified no new cases since 2006: Azerbaijan,
Djibouti, Iraq, Thailand and Turkey. Three additional countries
(Laos, Myanmar and Pakistan) have not notified any case since 2007.

Since November 2003, reported human cases seem to follow an overall
downward trend and occur mostly during the period from November to
April. This variation is due to seasonal patterns described also in
poultry [5,6] in the countries which were mainly affected in the
northern hemisphere, especially Egypt, Thailand and Viet Nam. In
Indonesia, however, cases tend to occur throughout the year.


Since the end of 2003, most (366 of 500; 73 percent) notified human
cases of influenza A(H5N1) occurred in Asia, notably in Indonesia,
China and Viet Nam. Since the start of the epidemic, Indonesia
remains the most affected country (33 percent of cases and 46 percent
of deaths notified worldwide). Indonesia notified 21 cases including
19 deaths (CFR 90 percent) in 2009 and 4 cases including 3 deaths
(CFR 75 percent) in 2010 up to 1 Jul 2010.

The number of cases has fallen in Asia, while it has progressively
increased in the Near East (Azerbaijan, Egypt, Iraq and Turkey).
Between November 2003 and December 2005, 100 percent of notified
cases occurred in Asia. In 2006 and 2007, the annual proportion of
cases notified by Asian countries remained somewhat stable at 63
percent and 70 percent, respectively. From January 2008 to 1 Jul
2010, 83 (56 percent) of 149 notified cases occurred in Asia; the
remaining 66 cases worldwide were notified by Egypt. The percentage
of cases notified by Egypt has risen steadily from 18 percent of
worldwide cases in 2008, to 53 percent in 2009, to 59 percent of
worldwide cases notified to date for 2010.


Changes in the H5 haemagglutinin have determined a phylogeny with
clades and sub-clades. Clade 2.2.1 viruses circulate in poultry in
Egypt, while clade 2.3.2 and 2.3.4 viruses circulate in Asia [7].
There is no conclusive evidence for differences in virulence or
resistance to oseltamivir among these viruses. The health outcomes
for humans infected with these viruses can be explained by
differences in the timeliness and type of medical management and drug
treatment.

The overwhelming majority of cases with documented exposure acquired
the influenza A(H5N1) virus from sick or dead poultry or wild birds.
Many cases lack documented exposure, while for some, although this
was never definitively proven, there is a strong suspicion of
involving environmental sources or human-to-human transmission.

Clustered cases and human-to-human transmission
---------------------------------Since 2003, there have been at least 40 clustered events involving a
total of over 100 confirmed cases in 12 countries: Azerbaijan,
Cambodia, China, Egypt, Indonesia, Iraq, Laos, Nigeria, Pakistan,
Thailand, Turkey and Viet Nam. Overwhelmingly, the suspected or
documented source was common exposure to sick or dead poultry,
although investigation concluded that limited human-to-human
transmission occurred in some instances: Most of these clusters
involved persons with close familial ties [8]. Although its relevance
remains debated [9], at least some degree of genetic susceptibility
probably plays a role, as shown by events such as the 3-generation
transmission cluster described in 2006 in the Karo district of North
Sumatra, Indonesia [10] or the family clusters described in Turkey
[11]. These clusters of limited human-to-human transmission occurred
after people had close and repeated contact with cases and did not
fully observe standard precautions to prevent infection [12]. Cases
of nosocomial influenza A(H5N1) transmission had been described in
Hong Kong hospitals in 1997 [13]. Since 2003, however, no confirmed
influenza A(H5N1) transmission in the healthcare setting has been
documented in studies done to date [14].

Quality of available information
-------------------------------
Human case detection and reporting largely depends on the
availability and intensity of reliable diagnostic efforts. The global
influenza A(H5N1) case count probably vastly under represents the
true case burden worldwide.
Since December 2009, Indonesian health
authorities have resumed their collaboration with WHO and notify
cases officially. Since January 2009, 25 cases and 22 deaths (CFR 88
percent) have been notified from the Indonesian archipelago. With the
exception of a single case documented in Riau Province (central
Sumatra), all notified cases lived on the island of Java. This
geographical distribution and the comparatively high CFR suggest that
access to diagnosis may be uneven, that severe cases are over
represented among detected cases, and/or that timely clinical
management remains a challenge. In China, human cases continue to be
reported with no prior notification of influenza A(H5N1) circulation
in poultry, pointing to the probable under detection or under
reporting of poultry outbreaks in that country.
In an area such as
upper Egypt, access to timely diagnosis and care is associated with
lower CFR, but suspected human cases occurring in remote locations
may not all be officially detected and/or reported and would have
contributed to a higher CFR.
Conclusions
----------
All these elements seem to converge and sketch out the following
situation: some countries which were heavily affected before 2007
(such as Thailand and Turkey) seem to have controlled the situation
and reduced risks to humans. The influenza A(H5N1) virus, however,
continues to circulate in poultry elsewhere, especially in
Bangladesh, Egypt and Indonesia, where the enzootic remains intense.
The A(H5N1) influenza virus is one of several which could
hypothetically give rise to a pandemic in the future
[15]. Although
this risk cannot be quantified, poultry outbreaks and human cases
now, in contrast to the period from 2003 to 2004, occur in some of
the most densely populated urban or suburban areas in the world. Not
only might this increase the risk of the virus being transmitted to
humans living in close proximity to animals, it may also challenge
usual control measures (which are easier to apply to large farms
than, for instance, backyard flocks) and make it more difficult to
contain a nascent influenza A(H5N1) pandemic should one arise
[16].

Human cases continue and will continue to occur as long as the
situation in animals is not brought under control. Authorities and
populations face a complex situation in Egypt and Indonesia, but
communication in these countries is transparent and constructive and
allows for quick reporting of cases, especially if suspected clusters
should arise. Although the global CFR reported in 2009 was lower than
that observed in 2008, it varies greatly between countries. Some
countries report a greater number of cases and fewer deaths, perhaps
due to improved surveillance and access to diagnostic techniques and
medical care [17,18]. However, cases occurring in remote locations
with no access to healthcare, although having a higher CFR, may still
not come to the attention of health authorities or be reported for
lack of biological confirmation.

Many clustered events have occurred, some of which are highly likely
to have involved human-to-human transmission.
To date, this has
remained limited with no sustained community transmission. Available
data, especially those gathered following clustered events, show
that, so far, the virus shows no sign of "humanisation," i.e. the
ability to transmit easily from human to human. The overall worldwide
situation of influenza A(H5N1), however, has not markedly improved
since 2003. This fact, and regular reintroduction of the virus by
wild birds in countries where foci have been controlled (such as
Bulgaria, Romania, Turkey or Viet Nam) underscore the importance of
maintaining adequate surveillance and response capacities for
infections in both animals and humans.

(The Epidemic Intelligence team at InVS's International and Tropical
Department as of 1 Jan 2010 in alphabetical order: Fatima Ait
el-Belghiti, Philippe Barboza, Laurence Cherie-Challine, Sandra
Cohuet, Dominique Dejour-Salamanca, Nathalie El Omeiri, Marc
Gastellu-Etchegorry, Violaine Gauthier, Myriam Gharbi, Sophie Ioos,
Guy La Ruche, Arnaud Tarantola, Laetitia Vaillant.)

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