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WHO WER. Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus
Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus (WHO WER, 11/13/09, edited)
[Source: World Health Organization, Weekly Epidemiological Record, November 13, 2009, LINK. EDITED.]
Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus
Several countries that have experienced large epidemics caused by pandemic influenza A (H1N1) 2009 virus have now shared their findings globally. These reports have been made publically available through the web sites and offi cial updates of ministries of health as well as through papers published in peer-reviewed literature.
This report summarizes some of the key observations from selected countries regarding hospitalization rates, mortality rates and risk groups that may inform preparations being made for the winter influenza season in countries of the northern hemisphere. In addition, members of the WHO informal mathematical modelling network for the 2009 influenza pandemic are working with their respective governments to estimate the reproductive rate (R0), attack rates, incubation period and generation time using data on pandemic influenza (H1N1) 2009 cases by date of onset, cases of influenzalike illness (ILI), rates of physician visits over time, and outbreak investigations in schools and other settings.1
Hospitalization rates ranged from very low rates of 2.9/100 000 population in Japan, where the virus circulated during the summer period, to 24.5/100 000 in Argentina, where the virus circulated during the winter season (Table 1). When taken together, the countries of the southern hemisphere that experienced the arrival of the pandemic during their winter seasons had similar rates of hospitalization, with most experiencing rates of 10?24.5/100 000, much higher than in northern hemisphere temperate countries where transmission was less intense in the summer season. Brazil, partially tropical and partially subtropical, reported the lowest hospitalization rate of the group (8.8/100 000). The proportion of hospitalized patients who required intensive care ranged from 10% to 39%.2
The risk of severe disease was increased in individuals with certain characteristics. Hospitalization rates for children aged <5 years were consistently reported to be at least 2?3 times that of other age groups. However, agespecific morality rates were highest in those aged 50?60 years. The chronic medical illnesses that predispose individuals to severe illness were similar to those of seasonal influenza. Conditions such as chronic lung disease, asthma and diabetes occurred with the highest frequency among hospitalized patients in most countries. As with previous pandemics, pregnancy was also identified as a risk factor for severe disease. Although it is difficult to quantify precisely the degree of risk associated with pregnancy, pregnant women appear to be approximately 4?5 times more likely to develop severe disease as nonpregnant individuals in the general population, and this risk was highest in the third trimester.3,4
Indigenous peoples have also been reported to be at several times higher risk than the general population in Australia, New Zealand and North America.5
At a meeting held in October 2009 at the headquarters of the Pan American Health Organization in Washington DC (USA) to review the clinical management of pandemic (H1N1) 2009 influenza virus infections, many investigators expressed strong suspicion that obesity may increase the risk of severe disease. The exact contribution of obesity as an independent risk factor for severe influenza is still not completely defined, as other known risk factors, such as diabetes, are strongly associated with obesity.
A striking feature of this pandemic has been the significant proportion of individuals with no recognized underlying predisposing conditions who develop severe illness, ranging from 27% to 79%. The wide disparity was due in part to variation in which conditions were included for analysis by some countries and the inclusion by other countries of conditions that are not known to predispose individuals to severe disease, such as hypertension and hyperlipidemia in the absence of heart disease.
Given the difficulties of detecting every case of pandemic influenza (H1N1) 2009 virus infection in a community, determining a true case-fatality rate (CFR) is particularly challenging. Despite these difficulties, most countries estimate that the true CFR is <0.5%, although the range is quite broad.6,7
Another way of examining the issue of mortality is to estimate the number of deaths in the population, or mortality rate. Rates for countries in the temperate zone of the southern hemisphere ranged from 1.8 to 14.6 deaths/1 000 000 population. However, it is almost certain that estimates of the numbers of deaths significantly underestimate the actual numbers and that the degree of underestimation varied from country to country.
In addition, some countries did not report fatal cases when the direct and immediate cause of death was judged not to be influenza, while others, notably Argentina, reported all individuals who died after testing positive for pandemic influenza (H1N1) virus infection.
Analyses using data for countries of the northern and southern hemispheres have produced R0 estimates ? that is, estimates of the average number of infections caused by an index infection at the start of the epidemic ? of 1.1?1.8.8 (Table 2). In specific contexts, notably schools, values were higher.1,9 Estimates from a number of countries of the ILI clinical attack rate range from 7% to 15%.
Estimates of generation time are consistent across groups and settings, with general agreement that the mean generation time of the H1N1 pandemic is between 2.5 and 3 days. Several estimates suggest that the mean incubation period is from 1.5 to 2 days, similar to previously circulating influenza strains.1
Analyses of ILI secondary attack rates in households and other enclosed settings from Hong Kong (Special Administrative Region of China), Italy, Japan, Mexico, the United States and the United Kingdom are reasonably consistent at 7?13%.1,10,11
Attack rates in schools in Japan, which closed schools early in the pandemic, were low, ranging from <1% to 5.3%, (personal communication, H. Nishiura), whereas self-reported ILI attack rates among students and staff in school outbreaks in the USA have been much higher. Attack rates in indigenous populations may also be higher compared with the general population;5 more information is needed to evaluate the impact of pandemic (H1N1) 2009 influenza virus in such populations.
All of these data should be interpreted with caution. In addition to inherent differences among countries with respect to access to care, availability of confirmatory testing and hospital admissions practices, it is very likely that the season in which the virus first appeared significantly affected the experience of individual countries.
The northern temperate regions of the world had the first introduction of virus during their summer season and have had persistent, ongoing transmission since then. Although many large, localized outbreaks occurred in these areas, none of the northern hemisphere countries affected, with the possible exception of Mexico, experienced nationwide outbreaks to the extent one would expect during winter. As a result, it is likely that in countries of the northern hemisphere, the total portion of the population infected was lower than might otherwise have been expected in a winter season, significantly decreasing the population-based rates of hospitalization and mortality.
In contrast, countries in the temperate regions of the southern hemisphere experienced the first introduction of pandemic influenza (H1N1) 2009 virus near the beginning of their winter season. Those countries, for the most part, experienced rapid nationwide transmission, with a pattern of spread resembling the usual pattern seen with annual outbreaks of seasonal influenza. The transmission dynamics in these countries may more closely resemble what would be expected to occur in the northern hemisphere
winter.
Table 1 Selected severity characteristics of pandemic infl uenza A (H1N1) 2009 virus infections, data as of 6 November 2009 (a)
[Country ? % of hospitalized cases with no co-morbidity ? % of hospitalized cases who are pregnant ? Cumulative number of hospitalizations ? Incidence of hospitalization (per 100 000 population) ? Median age of hospitalized cases (years) ? Rate of ICU admission or hospitalization ? Number of deaths ? Mortality rate (deaths per million population)
a Adapted in part from Baker MG, Kelly H, Wilson N. Pandemic H1N1 influenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42):pii=19370. ? En partie d?apr?s Baker MG,
Kelly H, Wilson N. Pandemic H1N1 infl uenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42): pii=19370.
Table 2 Estimates of the reproductive rate of infection (R0) from selected studies
[Country ? R0 estimate (95% confidence interval)]
(*) Believed to be an overestimate of the R0 in the population, because the analysis was based on data from a school outbreak; a later estimate gave a value of 1.4
(a) WHO informal mathematical modelling network for the 2009 influenza pandemic, [unpublished data].
(b) McBryde E et al. Early transmission characteristics of influenza A(H1N1)v in Australia: Victorian state, 16 May?3 June 2009. Eurosurveillance, 2009, 14(42):1?6 (LINK, accessed November 2009).
(c) Nishiura H et al. Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan. Eurosurveillance, 2009, 14(22):1?4 (LINK, accessed November 2009).
(d) Fraser C et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science, 2009, 324:1557?1561.
(e) Nishiura H, Wilson N, Baker M. Estimating the reproduction number of the novel influenza A virus (H1N1) in a southern hemisphere setting: preliminary estimate in New Zealand. Journal of the New Zealand Medical Association, 2009, 122(1299):73?77 (LINK , accessed November 2009).
(f) Munayco CV et al. Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru. Eurosurveillance, 2009, 14(32):1?5 (LINK, accessed November 2009).
(g) de Silva UC et al. A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June?July 2009. Eurosurveillance, 2009, 14(31):1?3 (LINK, accessed November 2009).
(h) White L et al. Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A⁄H1N1 pandemic in the USA. Influenza and Other Respiratory Diseases, 3(6): 267?276 (LINK, accessed November 2009).
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1 See No. 34, 2009, pp. 341?348.
2 Baker M, Kelly H, Wilson N. Pandemic H1N1 influenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42):1?5 (LINK, accessed November 2009).
3 Novel influenza A (H1N1) virus infections in three pregnant women - United States, April?May 2009. Morbidity and Mortality Weekly Report, 2009, 58(19):541 (LINK, accessed November 2009).
4 Jamieson DJ et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet, 2009, 374:451?458.
5 La Ruche G et al. The 2009 pandemic H1N1 influenza and indigenous populations of the Americas and the Pacific. Eurosurveillance, 2009, 14(42):1?6 (LINK, accessed November 2009).
6 Baker M et al. (2009) Pandemic influenza A(H1N1)v in New Zealand: the experience from April to August 2009. Eurosurveillance, 2009, 14(34):1?6 (LINK, accessed November 2009).
7 Presanis, Anne; Lipsitch, Marc; Daniela De Angelis; Swine Flu Investigation Team, New York City Department of Health and Mental Hygiene; Hagy, Angie; Reed, Carrie; Riley, Steven; Cooper, Ben; Biedrzycki, Paul; Anonymous. The severity of pandemic H1N1 influenza in the United States, April?July 2009. Version 2. PLoS Currents Infl uenza. 2009 Sep 25 [revised 29 September 2009]:RRN1042 (LINK).
8 Fraser C et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science, 2009, 324:1557?1561.
9 Nishiura H et al. Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan. Eurosurveillance, 2009, 14(22):1?4 (LINK, accessed November 2009).
10 Odaira F et al. Assessment of secondary attack rate and effectiveness of antiviral prophylaxis among household contacts in an influenza A(H1N1)v outbreak in Kobe, Japan, May?June 2009. Eurosurveillance, 2009, 14(35):1?5 (LINK, accessed November 2009).
11 US Department of Defence. Preliminary report: Outbreak of novel H1N1 influenza aboard USS Boxer, 29 June?31 July 2009. Medical Surveillance Monthly Report, 2009, 16(9):8?9 (LINK, accessed November 2009).
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[Source: World Health Organization, Weekly Epidemiological Record, November 13, 2009, LINK. EDITED.]
Transmission dynamics and impact of pandemic influenza A (H1N1) 2009 virus
Several countries that have experienced large epidemics caused by pandemic influenza A (H1N1) 2009 virus have now shared their findings globally. These reports have been made publically available through the web sites and offi cial updates of ministries of health as well as through papers published in peer-reviewed literature.
This report summarizes some of the key observations from selected countries regarding hospitalization rates, mortality rates and risk groups that may inform preparations being made for the winter influenza season in countries of the northern hemisphere. In addition, members of the WHO informal mathematical modelling network for the 2009 influenza pandemic are working with their respective governments to estimate the reproductive rate (R0), attack rates, incubation period and generation time using data on pandemic influenza (H1N1) 2009 cases by date of onset, cases of influenzalike illness (ILI), rates of physician visits over time, and outbreak investigations in schools and other settings.1
Hospitalization rates ranged from very low rates of 2.9/100 000 population in Japan, where the virus circulated during the summer period, to 24.5/100 000 in Argentina, where the virus circulated during the winter season (Table 1). When taken together, the countries of the southern hemisphere that experienced the arrival of the pandemic during their winter seasons had similar rates of hospitalization, with most experiencing rates of 10?24.5/100 000, much higher than in northern hemisphere temperate countries where transmission was less intense in the summer season. Brazil, partially tropical and partially subtropical, reported the lowest hospitalization rate of the group (8.8/100 000). The proportion of hospitalized patients who required intensive care ranged from 10% to 39%.2
The risk of severe disease was increased in individuals with certain characteristics. Hospitalization rates for children aged <5 years were consistently reported to be at least 2?3 times that of other age groups. However, agespecific morality rates were highest in those aged 50?60 years. The chronic medical illnesses that predispose individuals to severe illness were similar to those of seasonal influenza. Conditions such as chronic lung disease, asthma and diabetes occurred with the highest frequency among hospitalized patients in most countries. As with previous pandemics, pregnancy was also identified as a risk factor for severe disease. Although it is difficult to quantify precisely the degree of risk associated with pregnancy, pregnant women appear to be approximately 4?5 times more likely to develop severe disease as nonpregnant individuals in the general population, and this risk was highest in the third trimester.3,4
Indigenous peoples have also been reported to be at several times higher risk than the general population in Australia, New Zealand and North America.5
At a meeting held in October 2009 at the headquarters of the Pan American Health Organization in Washington DC (USA) to review the clinical management of pandemic (H1N1) 2009 influenza virus infections, many investigators expressed strong suspicion that obesity may increase the risk of severe disease. The exact contribution of obesity as an independent risk factor for severe influenza is still not completely defined, as other known risk factors, such as diabetes, are strongly associated with obesity.
A striking feature of this pandemic has been the significant proportion of individuals with no recognized underlying predisposing conditions who develop severe illness, ranging from 27% to 79%. The wide disparity was due in part to variation in which conditions were included for analysis by some countries and the inclusion by other countries of conditions that are not known to predispose individuals to severe disease, such as hypertension and hyperlipidemia in the absence of heart disease.
Given the difficulties of detecting every case of pandemic influenza (H1N1) 2009 virus infection in a community, determining a true case-fatality rate (CFR) is particularly challenging. Despite these difficulties, most countries estimate that the true CFR is <0.5%, although the range is quite broad.6,7
Another way of examining the issue of mortality is to estimate the number of deaths in the population, or mortality rate. Rates for countries in the temperate zone of the southern hemisphere ranged from 1.8 to 14.6 deaths/1 000 000 population. However, it is almost certain that estimates of the numbers of deaths significantly underestimate the actual numbers and that the degree of underestimation varied from country to country.
In addition, some countries did not report fatal cases when the direct and immediate cause of death was judged not to be influenza, while others, notably Argentina, reported all individuals who died after testing positive for pandemic influenza (H1N1) virus infection.
Analyses using data for countries of the northern and southern hemispheres have produced R0 estimates ? that is, estimates of the average number of infections caused by an index infection at the start of the epidemic ? of 1.1?1.8.8 (Table 2). In specific contexts, notably schools, values were higher.1,9 Estimates from a number of countries of the ILI clinical attack rate range from 7% to 15%.
Estimates of generation time are consistent across groups and settings, with general agreement that the mean generation time of the H1N1 pandemic is between 2.5 and 3 days. Several estimates suggest that the mean incubation period is from 1.5 to 2 days, similar to previously circulating influenza strains.1
Analyses of ILI secondary attack rates in households and other enclosed settings from Hong Kong (Special Administrative Region of China), Italy, Japan, Mexico, the United States and the United Kingdom are reasonably consistent at 7?13%.1,10,11
Attack rates in schools in Japan, which closed schools early in the pandemic, were low, ranging from <1% to 5.3%, (personal communication, H. Nishiura), whereas self-reported ILI attack rates among students and staff in school outbreaks in the USA have been much higher. Attack rates in indigenous populations may also be higher compared with the general population;5 more information is needed to evaluate the impact of pandemic (H1N1) 2009 influenza virus in such populations.
All of these data should be interpreted with caution. In addition to inherent differences among countries with respect to access to care, availability of confirmatory testing and hospital admissions practices, it is very likely that the season in which the virus first appeared significantly affected the experience of individual countries.
The northern temperate regions of the world had the first introduction of virus during their summer season and have had persistent, ongoing transmission since then. Although many large, localized outbreaks occurred in these areas, none of the northern hemisphere countries affected, with the possible exception of Mexico, experienced nationwide outbreaks to the extent one would expect during winter. As a result, it is likely that in countries of the northern hemisphere, the total portion of the population infected was lower than might otherwise have been expected in a winter season, significantly decreasing the population-based rates of hospitalization and mortality.
In contrast, countries in the temperate regions of the southern hemisphere experienced the first introduction of pandemic influenza (H1N1) 2009 virus near the beginning of their winter season. Those countries, for the most part, experienced rapid nationwide transmission, with a pattern of spread resembling the usual pattern seen with annual outbreaks of seasonal influenza. The transmission dynamics in these countries may more closely resemble what would be expected to occur in the northern hemisphere
winter.
Table 1 Selected severity characteristics of pandemic infl uenza A (H1N1) 2009 virus infections, data as of 6 November 2009 (a)
[Country ? % of hospitalized cases with no co-morbidity ? % of hospitalized cases who are pregnant ? Cumulative number of hospitalizations ? Incidence of hospitalization (per 100 000 population) ? Median age of hospitalized cases (years) ? Rate of ICU admission or hospitalization ? Number of deaths ? Mortality rate (deaths per million population)
- Northern hemisphere temperate zone
- Canada 38 - 5 - 1999 - 5.8 - 24 - 0.20 - 95 - 2.8
- Japan 63 - 0.3 - 3746 - 2.9 - 8 ? ... - 35 - 0.2
- United Kingdom 43 - 7.5 ? ... - ... ? 15-24 ? ... - 135 - 2.2
- Mexico ? ... ? ... - 10337 - 9.3 ? ... ? ... - 328 - 2.9
- United States 27 - 7 - 9079 - 3.0 - 21 - 0.25 - 1004 - 3.3
- Southern hemisphere temperate zone
- South Africa ? ... ? ... ? ... ? ... ? ... ? ... - 91 - 1.8
- Argentina 47 - 9974 - 24.5 - 20 - 0.13 - 593 - 14.6
- Australia 51 - 6 - 4844 - 22.5 - 31 - 0.13 - 186 - 8.6
- Brazil 79 - 8.3 - 17219 - 8.8 - 26 ? ... - 1368 - 7.0
- Chile 47 - 2.4 - 1852 - 10.8 - 32 - 0.39 - 140 - 8.1
- New Zealand ? ... - 6.5 - 1001 - 23.3 - 20-29 - 0.12 - 19 - 4.4
a Adapted in part from Baker MG, Kelly H, Wilson N. Pandemic H1N1 influenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42):pii=19370. ? En partie d?apr?s Baker MG,
Kelly H, Wilson N. Pandemic H1N1 infl uenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42): pii=19370.
Table 2 Estimates of the reproductive rate of infection (R0) from selected studies
[Country ? R0 estimate (95% confidence interval)]
- Australia (a) 1.2?1.5
- Australia (Victoria)(b) 1.6 (1.5?1.8)
- Brazil (a) 1.3?1.4
- Chile (a) 1.2?1.4
- Japan (c) 2.0?2.6*
- Mexico (d) 1.4?1.6
- New Zealand (e) 2.0 (1.8?2.1)
- New Zealand (a) 1.3 (1.2?1.4)
- Peru (f) 1.2?1.6
- Thailand (g) 1.8?2.1
- South Africa 1.43 (1.41?1.48)
- United Kingdom (a) 1.1?1.4
- United States (h) 1.8 (1.5?2.2)
(*) Believed to be an overestimate of the R0 in the population, because the analysis was based on data from a school outbreak; a later estimate gave a value of 1.4
(a) WHO informal mathematical modelling network for the 2009 influenza pandemic, [unpublished data].
(b) McBryde E et al. Early transmission characteristics of influenza A(H1N1)v in Australia: Victorian state, 16 May?3 June 2009. Eurosurveillance, 2009, 14(42):1?6 (LINK, accessed November 2009).
(c) Nishiura H et al. Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan. Eurosurveillance, 2009, 14(22):1?4 (LINK, accessed November 2009).
(d) Fraser C et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science, 2009, 324:1557?1561.
(e) Nishiura H, Wilson N, Baker M. Estimating the reproduction number of the novel influenza A virus (H1N1) in a southern hemisphere setting: preliminary estimate in New Zealand. Journal of the New Zealand Medical Association, 2009, 122(1299):73?77 (LINK , accessed November 2009).
(f) Munayco CV et al. Epidemiological and transmissibility analysis of influenza A(H1N1)v in a southern hemisphere setting: Peru. Eurosurveillance, 2009, 14(32):1?5 (LINK, accessed November 2009).
(g) de Silva UC et al. A preliminary analysis of the epidemiology of influenza A(H1N1)v virus infection in Thailand from early outbreak data, June?July 2009. Eurosurveillance, 2009, 14(31):1?3 (LINK, accessed November 2009).
(h) White L et al. Estimation of the reproductive number and the serial interval in early phase of the 2009 influenza A⁄H1N1 pandemic in the USA. Influenza and Other Respiratory Diseases, 3(6): 267?276 (LINK, accessed November 2009).
-
1 See No. 34, 2009, pp. 341?348.
2 Baker M, Kelly H, Wilson N. Pandemic H1N1 influenza lessons from the southern hemisphere. Eurosurveillance, 2009, 14(42):1?5 (LINK, accessed November 2009).
3 Novel influenza A (H1N1) virus infections in three pregnant women - United States, April?May 2009. Morbidity and Mortality Weekly Report, 2009, 58(19):541 (LINK, accessed November 2009).
4 Jamieson DJ et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet, 2009, 374:451?458.
5 La Ruche G et al. The 2009 pandemic H1N1 influenza and indigenous populations of the Americas and the Pacific. Eurosurveillance, 2009, 14(42):1?6 (LINK, accessed November 2009).
6 Baker M et al. (2009) Pandemic influenza A(H1N1)v in New Zealand: the experience from April to August 2009. Eurosurveillance, 2009, 14(34):1?6 (LINK, accessed November 2009).
7 Presanis, Anne; Lipsitch, Marc; Daniela De Angelis; Swine Flu Investigation Team, New York City Department of Health and Mental Hygiene; Hagy, Angie; Reed, Carrie; Riley, Steven; Cooper, Ben; Biedrzycki, Paul; Anonymous. The severity of pandemic H1N1 influenza in the United States, April?July 2009. Version 2. PLoS Currents Infl uenza. 2009 Sep 25 [revised 29 September 2009]:RRN1042 (LINK).
8 Fraser C et al. Pandemic potential of a strain of influenza A (H1N1): early findings. Science, 2009, 324:1557?1561.
9 Nishiura H et al. Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan. Eurosurveillance, 2009, 14(22):1?4 (LINK, accessed November 2009).
10 Odaira F et al. Assessment of secondary attack rate and effectiveness of antiviral prophylaxis among household contacts in an influenza A(H1N1)v outbreak in Kobe, Japan, May?June 2009. Eurosurveillance, 2009, 14(35):1?5 (LINK, accessed November 2009).
11 US Department of Defence. Preliminary report: Outbreak of novel H1N1 influenza aboard USS Boxer, 29 June?31 July 2009. Medical Surveillance Monthly Report, 2009, 16(9):8?9 (LINK, accessed November 2009).
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