Giuseppe
Emeritus
[Source: World Health Organization, Weekly Epidemiological Record, full PDF document (LINK). Extract, edited.]
Weekly epidemiological record
Relev? ?pid?miologique hebdomadaire
22 APRIL 2011, 86th year / 22 AVRIL 2011, 86e ann?e
No. 17, 2011, 86, 161?172
http://www.who.int/wer
Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010
This report describes the epidemiology of the 48 human cases of symptomatic illness caused by laboratory confirmed infection with influenza A(H5N1) virus that were reported to WHO during 2010. All 48 cases occurred as sporadic cases, with no clusters reported.
Temporal and geographical distribution:
Although cases occurred throughout the year there was a marked seasonal variation with the peak occurring between December and March, during the northern hemisphere winter (Figure 1). In 2010, most human cases occurred in the northern hemisphere ? with the exception of those in Indonesia, which straddles the equator ? in both temperate and tropical areas. The number of cases in individual countries was too small to determine whether seasonality differed among countries with different climates. The seasonal variation in human cases parallels that of outbreaks in birds.(1)
The highest number of cases was reported from Egypt (29 cases), followed by Indonesia (9), Viet Nam (7), China (2) and Cambodia (1). All of these countries have reported human cases previously, including in 2009,(2, 3) and all are countries where influenza A(H5N1) virus is believed to be circulating widely in poultry. Egypt and Indonesia have officially declared the virus endemic in poultry,(4) and information from the United Nations Food and Agriculture Organization suggests that the influenza A(H5N1) virus is also endemic in poultry in Viet Nam and parts of China as well as in Bangladesh.(5) In Cambodia the virus appears to be reintroduced sporadically in poultry.
Distribution by sex and age
In 2010 most cases occurred in children and young adults; 83% (40/48) of cases occurred in people aged <40 years (Figure 2). Cases ranged in age from 1?59 years, with a median age of 25 years. The median age of cases in 2010 was slightly higher than the median of 19 years for all cases from all countries since 2003. Egypt in 2010 had a higher median age of 27 years compared with a median age of 3 years in 2009, and 10 years for all previous years combined. In 2010, there were half as many cases in male than in females (ratio of male to female cases, 1:2), although this difference was not uniformly distributed among countries nor was the sex distribution consistent among age groups. Females made up a much larger proportion of cases aged 20?29 years, which is consistent with data from previous years. The sex difference in 2010 was most notable in Indonesia (ratio of males to females, 1:8) and for Viet Nam (ratio of males to females, 1:6). In contrast, cases in Egypt were more evenly distributed: the ratio of males to females was 1:1.2. Historically, when all cases from all countries are considered, the sex of cases is almost equally distributed between males and females (ratio of males to females, 1:1.1).
Outcomes
Half (n = 24) of the 48 cases died. The case-fatality ratio (CFR) differed by country: Viet Nam had the lowest CFR (7 cases; CFR, 28%). For all countries in 2010, women had a higher CFR than men (56% versus 38%). There have been 516 cases since 2003, and the CFR has been higher for women for all years taken together (65% versus 53%); however, this difference has not been observed in every country and may be related to factors such as age.
During 2010, the CFR was highest among those aged 30?39 years (CFR, 70%) and lowest among those aged 0?9 years (CFR, 30%), but the difference was not significant. When all 516 cases from 2003 to 2010 are included, cases aged <20 years have a significantly lower risk of dying than those aged >20 years (CFR 52% versus 66%; OR, 0.56; 95% CI, 0.39?0.81); however, this observation is not consistent for every country.
Time from onset to hospitalization
The time from onset of illness to hospitalization was available for 42 cases; it ranged from 0 days to 12 days, with a median of 4 days. Cases that died were admitted to hospital later (median, 5 days) after onset than those who survived (median, 2 days). The CFR for cases who were hospitalized within ≤2 days of onset was lower than for those hospitalized >2 days after onset (CFR, 25% versus 65%; OR, 5.6; 95% CI, 1.4?22.7). For all cases from all years, those who died were hospitalized later than those who survived (median 5 days after onset versus 2 days; Kruskal?Wallis test P = 0.0001), and when cases were hospitalized ≤2 days from onset they were more likely to survive than those hospitalized >2days after onset (CFR, 29% versus 71%; OR, 5.9; 95% CI, 3.7?9.3).
Exposure data
Data on exposure were available for 37 cases. In 32 of the cases, exposure to sick or dead poultry was noted; no other exposures were reported. Of the cases reporting exposure to sick or dead poultry, 4 were reported to have slaughtered poultry and 2 disposed of dead poultry.
Three cases were associated with occupational exposure:
Virological information
Influenza A(H5N1) viruses have continued to diversify, both genetically and antigenically. During 2010, viruses characterized from human cases belonged to clade 1 (Cambodia), clade 2.2.1, group C (Egypt), clade 2.3.2 (China, Hong Kong Special Administrative Region), and clade 2.3.4 (Viet Nam). Viruses from these clades have also been isolated from poultry in each country.(6) None of 9 human isolates from 2010 that have been sequenced had the neuraminidase mutations known to predict resistance to oseltamivir.
Discussion
Human infection with influenza A(H5N1) virus remains uncommon and sporadic despite continued widespread circulation of the virus in poultry in some countries. As in previous years, countries reporting human cases were those where the virus circulates in poultry; there continues to be no evidence of sustained human-to-human transmission. The general epidemiological picture of human cases of infection with influenza A(H5N1) is unchanged.
Women seem to have a worse outcome than men, and the disease appears more likely to be mild in children. Overall, children and young adults seem to be more frequently diagnosed with the infection, although the median age increased in 2010, primarily in association with an increase in the age of cases in Egypt. Early recognition of infection and hospitalization are likely to lead to favourable outcomes. A recent analysis of 119 cases occurring in Egypt since 2006 reaffirms these observations.(7) Investigators there found a significant increase in CFR with the age of the case and among females when compared with males. In addition, early hospitalization was found to have a positive impact on survival. WHO continues to recommend that clinicians in endemic countries be encouraged to consider influenza A(H5N1) infection when patients present with compatible clinical and epidemiological features, and to treat patients early with appropriate antiviral medications.(8)
The influenza A(H5N1) virus remains an avian virus that has not substantially changed in its zoonotic behaviour since emerging. The genetic and antigenic diversification of circulating influenza A(H5N1) viruses, however, require the development of multiple candidate vaccine viruses for purposes of pandemic preparedness. There are no signs of increasing antiviral resistance to oseltamivir in influenza A(H5N1) viruses or reassortment with any of the circulating human influenza viruses.
Most human cases are exposed through direct or indirect contact with poultry or contaminated environments and, as in previous years, the exposures that result in symptomatic infection happen almost exclusively in households or markets rather than in association with commercial poultry. People who are infected are often reported to have slaughtered or prepared birds for consumption, and visits to live-bird markets continue to be reported as potential venues for exposure to infection. However, in most of the areas where human cases have been reported, multiple exposures to potentially infected poultry or to environments where poultry live are a routine part of daily life. Because of this, it is difficult to determine which specific exposures lead to human infection and disease. It is therefore important for animal health and public health partners to continue to work together to identify and manage common risks and to decrease human exposure at the human?animal interface, particularly in households and in live-bird markets. Because some risk of human exposure will remain as long as the virus circulates widely among poultry, it is also important that the animal health sector continues its efforts to control the virus at its source ? that is, in animal populations.
Current knowledge about influenza A(H5N1) infection in humans has been acquired thanks to the countries that have collected and openly shared information about their cases. WHO would like to recognize the contribution of the countries which reported cases in 2010. However, there is a need to do more, both in terms of comprehensive data collection, contextual analysis, and the sharing of linked virological, epidemiological and clinical data. There are still unanswered questions about the epidemiology of the disease in animals, and these are being addressed by the animal health sector. In addition, there are specific issues about the disease in humans and at the human?animal interface that need to be addressed through targeted research, including clearly identifying the factors that facilitate transmission to humans, further defining the spectrum of illness and the magnitude of mild or asymptomatic disease, and identifying the virological and genetic markers for transmissibility and virulence in humans. Finally, laboratories which identify influenza A viruses that are not seasonal subtypes are encouraged to submit these samples immediately for further characterization to a WHO Collaborating Centre on influenza.(9)
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Weekly epidemiological record
Relev? ?pid?miologique hebdomadaire
22 APRIL 2011, 86th year / 22 AVRIL 2011, 86e ann?e
No. 17, 2011, 86, 161?172
http://www.who.int/wer
Update on human cases of highly pathogenic avian influenza A(H5N1) virus infection, 2010
This report describes the epidemiology of the 48 human cases of symptomatic illness caused by laboratory confirmed infection with influenza A(H5N1) virus that were reported to WHO during 2010. All 48 cases occurred as sporadic cases, with no clusters reported.
Temporal and geographical distribution:
Although cases occurred throughout the year there was a marked seasonal variation with the peak occurring between December and March, during the northern hemisphere winter (Figure 1). In 2010, most human cases occurred in the northern hemisphere ? with the exception of those in Indonesia, which straddles the equator ? in both temperate and tropical areas. The number of cases in individual countries was too small to determine whether seasonality differed among countries with different climates. The seasonal variation in human cases parallels that of outbreaks in birds.(1)
The highest number of cases was reported from Egypt (29 cases), followed by Indonesia (9), Viet Nam (7), China (2) and Cambodia (1). All of these countries have reported human cases previously, including in 2009,(2, 3) and all are countries where influenza A(H5N1) virus is believed to be circulating widely in poultry. Egypt and Indonesia have officially declared the virus endemic in poultry,(4) and information from the United Nations Food and Agriculture Organization suggests that the influenza A(H5N1) virus is also endemic in poultry in Viet Nam and parts of China as well as in Bangladesh.(5) In Cambodia the virus appears to be reintroduced sporadically in poultry.
Distribution by sex and age
In 2010 most cases occurred in children and young adults; 83% (40/48) of cases occurred in people aged <40 years (Figure 2). Cases ranged in age from 1?59 years, with a median age of 25 years. The median age of cases in 2010 was slightly higher than the median of 19 years for all cases from all countries since 2003. Egypt in 2010 had a higher median age of 27 years compared with a median age of 3 years in 2009, and 10 years for all previous years combined. In 2010, there were half as many cases in male than in females (ratio of male to female cases, 1:2), although this difference was not uniformly distributed among countries nor was the sex distribution consistent among age groups. Females made up a much larger proportion of cases aged 20?29 years, which is consistent with data from previous years. The sex difference in 2010 was most notable in Indonesia (ratio of males to females, 1:8) and for Viet Nam (ratio of males to females, 1:6). In contrast, cases in Egypt were more evenly distributed: the ratio of males to females was 1:1.2. Historically, when all cases from all countries are considered, the sex of cases is almost equally distributed between males and females (ratio of males to females, 1:1.1).
Outcomes
Half (n = 24) of the 48 cases died. The case-fatality ratio (CFR) differed by country: Viet Nam had the lowest CFR (7 cases; CFR, 28%). For all countries in 2010, women had a higher CFR than men (56% versus 38%). There have been 516 cases since 2003, and the CFR has been higher for women for all years taken together (65% versus 53%); however, this difference has not been observed in every country and may be related to factors such as age.
During 2010, the CFR was highest among those aged 30?39 years (CFR, 70%) and lowest among those aged 0?9 years (CFR, 30%), but the difference was not significant. When all 516 cases from 2003 to 2010 are included, cases aged <20 years have a significantly lower risk of dying than those aged >20 years (CFR 52% versus 66%; OR, 0.56; 95% CI, 0.39?0.81); however, this observation is not consistent for every country.
Time from onset to hospitalization
The time from onset of illness to hospitalization was available for 42 cases; it ranged from 0 days to 12 days, with a median of 4 days. Cases that died were admitted to hospital later (median, 5 days) after onset than those who survived (median, 2 days). The CFR for cases who were hospitalized within ≤2 days of onset was lower than for those hospitalized >2 days after onset (CFR, 25% versus 65%; OR, 5.6; 95% CI, 1.4?22.7). For all cases from all years, those who died were hospitalized later than those who survived (median 5 days after onset versus 2 days; Kruskal?Wallis test P = 0.0001), and when cases were hospitalized ≤2 days from onset they were more likely to survive than those hospitalized >2days after onset (CFR, 29% versus 71%; OR, 5.9; 95% CI, 3.7?9.3).
Exposure data
Data on exposure were available for 37 cases. In 32 of the cases, exposure to sick or dead poultry was noted; no other exposures were reported. Of the cases reporting exposure to sick or dead poultry, 4 were reported to have slaughtered poultry and 2 disposed of dead poultry.
Three cases were associated with occupational exposure:
- 1 worked with fertilizers of animal origin, 1 worked in a live-bird market and 1 worked slaughtering and defeathering poultry.
Virological information
Influenza A(H5N1) viruses have continued to diversify, both genetically and antigenically. During 2010, viruses characterized from human cases belonged to clade 1 (Cambodia), clade 2.2.1, group C (Egypt), clade 2.3.2 (China, Hong Kong Special Administrative Region), and clade 2.3.4 (Viet Nam). Viruses from these clades have also been isolated from poultry in each country.(6) None of 9 human isolates from 2010 that have been sequenced had the neuraminidase mutations known to predict resistance to oseltamivir.
Discussion
Human infection with influenza A(H5N1) virus remains uncommon and sporadic despite continued widespread circulation of the virus in poultry in some countries. As in previous years, countries reporting human cases were those where the virus circulates in poultry; there continues to be no evidence of sustained human-to-human transmission. The general epidemiological picture of human cases of infection with influenza A(H5N1) is unchanged.
Women seem to have a worse outcome than men, and the disease appears more likely to be mild in children. Overall, children and young adults seem to be more frequently diagnosed with the infection, although the median age increased in 2010, primarily in association with an increase in the age of cases in Egypt. Early recognition of infection and hospitalization are likely to lead to favourable outcomes. A recent analysis of 119 cases occurring in Egypt since 2006 reaffirms these observations.(7) Investigators there found a significant increase in CFR with the age of the case and among females when compared with males. In addition, early hospitalization was found to have a positive impact on survival. WHO continues to recommend that clinicians in endemic countries be encouraged to consider influenza A(H5N1) infection when patients present with compatible clinical and epidemiological features, and to treat patients early with appropriate antiviral medications.(8)
The influenza A(H5N1) virus remains an avian virus that has not substantially changed in its zoonotic behaviour since emerging. The genetic and antigenic diversification of circulating influenza A(H5N1) viruses, however, require the development of multiple candidate vaccine viruses for purposes of pandemic preparedness. There are no signs of increasing antiviral resistance to oseltamivir in influenza A(H5N1) viruses or reassortment with any of the circulating human influenza viruses.
Most human cases are exposed through direct or indirect contact with poultry or contaminated environments and, as in previous years, the exposures that result in symptomatic infection happen almost exclusively in households or markets rather than in association with commercial poultry. People who are infected are often reported to have slaughtered or prepared birds for consumption, and visits to live-bird markets continue to be reported as potential venues for exposure to infection. However, in most of the areas where human cases have been reported, multiple exposures to potentially infected poultry or to environments where poultry live are a routine part of daily life. Because of this, it is difficult to determine which specific exposures lead to human infection and disease. It is therefore important for animal health and public health partners to continue to work together to identify and manage common risks and to decrease human exposure at the human?animal interface, particularly in households and in live-bird markets. Because some risk of human exposure will remain as long as the virus circulates widely among poultry, it is also important that the animal health sector continues its efforts to control the virus at its source ? that is, in animal populations.
Current knowledge about influenza A(H5N1) infection in humans has been acquired thanks to the countries that have collected and openly shared information about their cases. WHO would like to recognize the contribution of the countries which reported cases in 2010. However, there is a need to do more, both in terms of comprehensive data collection, contextual analysis, and the sharing of linked virological, epidemiological and clinical data. There are still unanswered questions about the epidemiology of the disease in animals, and these are being addressed by the animal health sector. In addition, there are specific issues about the disease in humans and at the human?animal interface that need to be addressed through targeted research, including clearly identifying the factors that facilitate transmission to humans, further defining the spectrum of illness and the magnitude of mild or asymptomatic disease, and identifying the virological and genetic markers for transmissibility and virulence in humans. Finally, laboratories which identify influenza A viruses that are not seasonal subtypes are encouraged to submit these samples immediately for further characterization to a WHO Collaborating Centre on influenza.(9)
- See H5N1 HPAI global overview May/June 2010. FAOAIDEnews, 2010, 69:5?19 (LINK), accessed 4 April 2011).
- See No. 46, 2008, pp. 413?420.
- See No. 7, 2010, pp. 49?56.
- World animal health information database: summary of immediate notifications and follow-ups ? 2010. Paris, World Organisation for Animal Health, 2011 ((LINK), accessed 4 April 2011).
- Global Programme for the Prevention and Control of Highly Pathogenic Avian Influenza: third report. Rome, United Nations Food and Agriculture Organization, 2010 ((LINK), accessed 4 April 2011).
- See No. 11, 2011, 93?100.
- Kayali G et al. The epidemiological and molecular aspects of influenza H5N1 viruses at the human-animal interface in Egypt. PLoS One 2011, 6(3): e17730; doi:10.1371/ journal.pone.0017730.
- WHO rapid advice guidelines on pharmacological management of humans infected with avian influenza A (H5N1) virus: May 2006. Geneva, World Health Organization,2006 (also available at (LINK)).
- Selection of clinical specimens for virus isolation and of viruses for shipment from National Influenza Centres to WHO Collaborating Centres ? revised: 6 Dec 2010. Geneva, WHO Global Influenza Programme, 2010 ((LINK), accessed 4 April 2011) .
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