Giuseppe
Emeritus
Epidemiological summary of pandemic influenza A (H1N1) 2009 virus ? Ontario, Canada, June 2009 (Wkly Epidemiol Rec., edited)
[Full PDF Document: LINK. EDITED.]
Weekly epidemiological record - 20 november 2009, 84th year - No. 47, 2009, 84, 485?492 - http://www.who.int/wer
Epidemiological summary of pandemic influenza A (H1N1) 2009 virus ? Ontario, Canada, June 2009
Background
In March and April 2009, a novel strain of influenza A (H1N1) virus was detected in Mexico and the United States. The virus has since spread worldwide, and there have been >340 000 laboratory-confirmed cases and >4100 deaths reported to WHO as of 27 September 2009. Given the evidence of sustained community-level outbreaks of novel influenza A (H1N1) in >1 WHO region, WHO declared a global pandemic of influenza A (H1N1) on 11 June 2009, designating the virus ?pandemic influenza A (H1N1) 2009 virus?.
Canada was one of the first countries to detect imported cases of pandemic (H1N1) 2009 virus; 6 cases were reported on 26 April 2009 by the provinces of Nova Scotia (4 cases) and British Columbia (2 cases). Two days later, the province of Ontario confirmed 4 cases of infection with the pandemic (H1N1) 2009 virus.
This report describes the epidemiology of the first cases of pandemic (H1N1) 2009 virus in Ontario, Canada, during the early course of the pandemic to assist health officials in developing policies related to the identification, prevention and treatment of infection with this virus.1
Methods
Setting
Ontario is Canada?s largest province, with a population of 12.2 million. The province?s public health system consists of 36 local health authorities that are responsible for delivering local health-promotion and disease-prevention programmes, as well as 1 central and 11 regional public health laboratories.
Public health surveillance
On 21 April 2009, the Ontario Ministry of Health and Long-Term Care issued to local health authorities an enhanced surveillance directive for severe respiratory illness and febrile respiratory illness occurring in people with a history of travel to Mexico. Additionally, a notice was distributed to health-care professionals recommending that nasopharyngeal swabs be collected from patients presenting with severe respiratory illness or febrile respiratory illness in emergency departments and ambulatory care settings. Travel criteria were removed on 19 May 2009, once sustained community spread had been established.
The Toronto laboratory of the Ontario Agency for Health Protection and Promotion performed the majority of tests for the virus in Ontario. All respiratory specimens submitted to the agency?s laboratories were tested, although specimens from patients had been triaged, thus patients at higher risk were given greater priority for testing. Testing practices and triaging remained consistent for the duration of this report period. Specimens were initially tested using reverse transcriptase (RT) polymerase chain reaction (PCR) for the influenza A virus matrix gene and Sanger sequencing on the PCR product. Specimens submitted after 15 May 2009 were tested using more sensitive real-time RT-PCR for the pandemic (H1N1) 2009 influenza virus (H and N genes) developed at the Toronto laboratory. The Luminex Respiratory Viral Panel multiplex assay and viral culture (Luminex Corporation, Austin, TX) were used to test approximately 6% of specimens.2
All laboratory-confirmed cases of pandemic (H1N1) 2009 virus were reported to local public health officials, who performed detailed case investigations and entered case information into the integrated Public Health Information System. Detailed case follow-up by public health authorities ceased on 29 May 2009; thus, data were extracted from the integrated system as of this date. Data on specimens submitted to and tested at the laboratory were extracted from the laboratory information system (known as Labware) as of 9 June 2009; all pending and indeterminate results were excluded from analysis. Given the different time periods examined, dates are specified throughout.
Case definition
A confirmed case was defined as a person with influenza-like illness3 and laboratory confirmation of infection with pandemic (H1N1) 2009 virus by >1 of the following tests:4 RT-PCR with genotyping of H1 or N1 novel influenza virus, or both; viral culture with strain typing; or a 4-fold rise in pandemic (H1N1) 2009 virus specific antibodies by serological testing. In practice, any patient who tested positive for the virus was classified as a case, irrespective of symptomatology.
Results
Laboratory submission patterns and test results
From 22 April 2009 to 9 June 2009, 11 560 specimens from patients were tested for pandemic (H1N1) 2009 virus, of which 1820 (15.7%) were positive. Pending (992) results and indeterminate (44) results were excluded from further analysis, producing a test denominator of 10 524. The highest submission rates occurred in the most densely populated regions of the province, including the Greater Toronto Area and Ottawa. More than half (55% or 5730) of all patients tested were female; sex was unknown for 114 patients. Submissions of specimens from school-aged children (5?19 years) accounted for 24.6% (2572) of all submissions, while 40.2% (4202) were from adults aged 20?49 years. Specimens were least likely to come from people aged >65 years (10.3% or 1072). Age was unknown for 78 patients.
Early in the outbreak, seasonal influenza A strains (H1 and H3) were predominant; however, from 10 May onwards, pandemic (H1N1) 2009 virus was detected in higher proportions. During the week beginning 31 May, 38.1% (658/1727) of specimens submitted tested positive for pandemic (H1N1) 2009 virus, and 0.7% (12) tested positive for seasonal influenza A, compared with 2.8% (57/2033) testing positive for pandemic (H1N1) 2009 virus and 5.1% (103) testing positive for seasonal influenza A during the week beginning 26 April.
Summary of confirmed cases
During the reporting period 28 April?29 May 2009, a total of 863 cases were laboratory-confirmed; the earliest reported date of symptom onset was 13 April 2009. Despite higher rates of submission for samples from females, there was a slight male predominance in cases (448 males, 414 females, 1 unknown). Cases occurred in people ranging in age from 2 months to 80 years (median, 16 years), with 52.6% (454) of cases aged 5?19 years.
Among those aged 10?19 years, more cases were confirmed in males than in females. Only 2.7% (23) of cases were aged >55 years (Fig. 1).
Clinical characteristics and underlying conditions
A total of 805 (93.3%) confirmed cases reported symptoms. The most commonly reported symptoms were cough (92.2% or 742), fever (91.3% or 735) and sore throat (40.5% or 326). Gastrointestinal symptoms, including vomiting and diarrhoea, were present in
189 cases (23.5%). Pneumonia (0.9% or 7) and respiratory distress (1.7% or 14) were not commonly reported.
The duration of symptoms was reported for 165 cases; the mean duration of illness was 4.7 days (95% confidence interval [CI], 4.2?5.2 days; median, 4 days; range, 0?23 days).
Altogether, 72 cases (8.3%) reported chronic or underlying medical conditions, including pregnancy. The most commonly reported conditions were cardiac or pulmonary disorders (77.85% or 56 cases), followed by diabetes and other metabolic diseases (15.3% or 11 cases), and cancer or other diseases that suppress the immune system (12.5% or 9 cases). Two cases (2.8%) reported they were pregnant. Information on obesity was not systematically collected.
Morbidity and mortality
A total of 31 (3.6%) cases were hospitalized, resulting in a crude hospitalization rate of 0.24 hospitalizations/100 000 population (95% CI, 0.16?0.34). At the time of data extraction, 5 cases remained in hospital. The median length of hospital stay for cases who had been discharged was 4.0 days (range, <24 hours to 20 days). Almost one third (32.2%) of hospitalized cases were aged 0?4 years. Cases with a chronic or underlying medical condition were significantly more likely to be hospitalized than cases without such conditions (X2, 57.00; P< 0.001).
Two deaths were reported, resulting in a crude mortality rate of 0.02 deaths/100 000 population (95% CI, 0.00?0.06) and a case-fatality rate of 0.2%. Both deaths occurred in males aged >40 years who had underlying medical conditions.
Exposure
The place of acquisition was known for 633 cases (73.3%). The majority of these cases (568, 89.7%) acquired the virus in Ontario; only 8.5% (54) of cases with a known exposure reported having travelled to Mexico within 7 days of symptom onset. In the early stages of the outbreak, most cases reported having travelled to Mexico; however, after initial importations of the virus, the vast majority of cases acquired it in Ontario (Fig. 2).
Among cases who acquired the infection in Ontario, 334 (58.8%) did not have known contact with a case. A number of school-related clusters were detected. In total, 351 (40.7%) of all cases reported a known connection to a school, either as a site where exposure occurred or as a transmission location; 70.7% (133/188) of cases in primary school (aged 6?12 years) and 71.4% (162/227) of those in secondary school (aged 13?17 years) reported either exposure at school or attending school while infectious.
Seasonal vaccination status
The Ontario government funds a universal influenza immunization programme that provides free vaccination to all residents aged >6 months; vaccination status during 2008?2009 was available for 714 (82.7%) cases, of which 27.3% (195) reported they had received the vaccine.
Discussion
In Ontario, Canada, enhanced surveillance directives detected 863 laboratory-confirmed cases of pandemic (H1N1) 2009 virus as of 29 May 2009. More than half of all confirmed cases occurred among people aged <20 years. Epidemiological data from WHO?s Region of the Americas and the European Region also show that the highest rates of illness have occurred among children and young adults.5,6,7 In Ontario, the age distribution of confirmed cases largely reflected submission patterns of specimens; the mean age of patients for whom specimens were submitted decreased over time as outbreaks spread through schools. The age distribution of infection with pandemic (H1N1) 2009 virus differs from the population that is at risk for seasonal influenza. Possible explanations for this include crossprotection occurring among older age groups owing to their prior exposure to H1N1 strains circulating before 1957, or minimal contact by older age groups with young travellers and school-aged children who amplify transmission during the early stage of the spread of a new influenza virus.6 Institutional outbreaks are unlikely to be a contributing factor, since only 2 of 112 respiratory outbreaks (1 in a hospital and 1 in a long-term care facility) registered with the laboratories of the Ontario Agency for Health Protection and Promotion from 20 April?12 June 2009 were caused by pandemic (H1N1) 2009 virus.8
As with seasonal influenza, most cases with pandemic (H1N1) 2009 influenza experienced mild illness and did not require hospitalization. The duration of symptoms was estimated at 4 days, which is consistent with a meta-analysis of studies among healthy volunteers experimentally infected with human influenza A(H1N1).9 The most commonly reported symptoms included cough, fever and sore throat. Unlike seasonal influenza, approximately one quarter of all cases reported gastrointestinal symptoms. This finding is consistent with other regions.7
Less than 10% of all cases reported having a chronic or underlying medical condition. By comparison, 22.0% (95% CI, 21.4?22.6%) of the population in Ontario reported having had a chronic condition diagnosed by a health professional in 2005.10 Hospitalization was more likely if the case reported having a chronic or underlying medical condition; however, more than half of all cases hospitalized did not report having such conditions. The number of cases reported here represents an underestimation of the true number of individuals infected. The ability to detect cases depends on health-seeking behaviours, testing behaviours, the resources available to health-care providers, and the sensitivity and specificity of laboratory tests. The lag in time
between the onset of illness and severe outcomes (hospitalization or death) may also underrepresent these outcomes; data were extracted 10 days after the case-reported date of 29 May 2009 to minimize this bias. Other biases in surveillance data, such as missing data and recall bias, should be considered when interpreting these results.
In conclusion, this summary provides important descriptive data on early cases of influenza caused by pandemic (H1N1) 2009 virus occurring prior to initiation of restrictions on laboratory testing. Continued and expanded surveillance is necessary to further characterize the pandemic and to support public-health planning. Areas for further investigation include determining transmission dynamics, seroprevalence and risk factors for infection and hospitalization.
[References]
1 The Ontario Agency for Health Protection and Promotion and the Ontario Ministry of Health and Long-Term Care thank all 36 regional health authorities for collecting data and contributing to this report. Staff from these 2 agencies wrote this report.
2 Mahony JB et al. Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza. Journal of Clinical Virology, 2009, 45:200?202.
3 Influenza-like illness is defined as the acute onset of respiratory illness with fever and >1 of the following symptoms: cough, sore throat, arthralgia, myalgia, prostration or malaise. In cases aged <5 years or >65, fever may not be prominent.
4 RT-PCR was the primary method used to detect the virus since viral culture was performed in only a small proportion of cases and no serology test was available at the time of testing.
5 See No. 23, 2009, pp. 213?219.
6 Preliminary analysis of influenza A (H1N1) individual and aggregated case reports from EU and EFTA Countries. Eurosurveillance, 2009, 14(23):1?5 (also available at LINK).
7 Emergence of a novel swine-origin influenza A (H1N1) virus in humans. New England Journal of Medicine, 2009, 360:2605?2615 (also available at LINK).
8 Gubbay JB et al. Respiratory infection outbreaks in institutions during the novel influenza A H1N1 virus pandemic in Ontario. ProMED-mail, 2009, archive number: 20090627.2338 (LINK, accessed October 2009).
9 Carrat F et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. American Journal of Epidemiology, 2008, 167:775?785.
10 Statistics Canada. Canadian Community Health Survey: detailed information for 2008, Ottawa, Ontario, 2009 (LINK, accessed October 2009).
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[Full PDF Document: LINK. EDITED.]
Weekly epidemiological record - 20 november 2009, 84th year - No. 47, 2009, 84, 485?492 - http://www.who.int/wer
Epidemiological summary of pandemic influenza A (H1N1) 2009 virus ? Ontario, Canada, June 2009
Background
In March and April 2009, a novel strain of influenza A (H1N1) virus was detected in Mexico and the United States. The virus has since spread worldwide, and there have been >340 000 laboratory-confirmed cases and >4100 deaths reported to WHO as of 27 September 2009. Given the evidence of sustained community-level outbreaks of novel influenza A (H1N1) in >1 WHO region, WHO declared a global pandemic of influenza A (H1N1) on 11 June 2009, designating the virus ?pandemic influenza A (H1N1) 2009 virus?.
Canada was one of the first countries to detect imported cases of pandemic (H1N1) 2009 virus; 6 cases were reported on 26 April 2009 by the provinces of Nova Scotia (4 cases) and British Columbia (2 cases). Two days later, the province of Ontario confirmed 4 cases of infection with the pandemic (H1N1) 2009 virus.
This report describes the epidemiology of the first cases of pandemic (H1N1) 2009 virus in Ontario, Canada, during the early course of the pandemic to assist health officials in developing policies related to the identification, prevention and treatment of infection with this virus.1
Methods
Setting
Ontario is Canada?s largest province, with a population of 12.2 million. The province?s public health system consists of 36 local health authorities that are responsible for delivering local health-promotion and disease-prevention programmes, as well as 1 central and 11 regional public health laboratories.
Public health surveillance
On 21 April 2009, the Ontario Ministry of Health and Long-Term Care issued to local health authorities an enhanced surveillance directive for severe respiratory illness and febrile respiratory illness occurring in people with a history of travel to Mexico. Additionally, a notice was distributed to health-care professionals recommending that nasopharyngeal swabs be collected from patients presenting with severe respiratory illness or febrile respiratory illness in emergency departments and ambulatory care settings. Travel criteria were removed on 19 May 2009, once sustained community spread had been established.
The Toronto laboratory of the Ontario Agency for Health Protection and Promotion performed the majority of tests for the virus in Ontario. All respiratory specimens submitted to the agency?s laboratories were tested, although specimens from patients had been triaged, thus patients at higher risk were given greater priority for testing. Testing practices and triaging remained consistent for the duration of this report period. Specimens were initially tested using reverse transcriptase (RT) polymerase chain reaction (PCR) for the influenza A virus matrix gene and Sanger sequencing on the PCR product. Specimens submitted after 15 May 2009 were tested using more sensitive real-time RT-PCR for the pandemic (H1N1) 2009 influenza virus (H and N genes) developed at the Toronto laboratory. The Luminex Respiratory Viral Panel multiplex assay and viral culture (Luminex Corporation, Austin, TX) were used to test approximately 6% of specimens.2
All laboratory-confirmed cases of pandemic (H1N1) 2009 virus were reported to local public health officials, who performed detailed case investigations and entered case information into the integrated Public Health Information System. Detailed case follow-up by public health authorities ceased on 29 May 2009; thus, data were extracted from the integrated system as of this date. Data on specimens submitted to and tested at the laboratory were extracted from the laboratory information system (known as Labware) as of 9 June 2009; all pending and indeterminate results were excluded from analysis. Given the different time periods examined, dates are specified throughout.
Case definition
A confirmed case was defined as a person with influenza-like illness3 and laboratory confirmation of infection with pandemic (H1N1) 2009 virus by >1 of the following tests:4 RT-PCR with genotyping of H1 or N1 novel influenza virus, or both; viral culture with strain typing; or a 4-fold rise in pandemic (H1N1) 2009 virus specific antibodies by serological testing. In practice, any patient who tested positive for the virus was classified as a case, irrespective of symptomatology.
Results
Laboratory submission patterns and test results
From 22 April 2009 to 9 June 2009, 11 560 specimens from patients were tested for pandemic (H1N1) 2009 virus, of which 1820 (15.7%) were positive. Pending (992) results and indeterminate (44) results were excluded from further analysis, producing a test denominator of 10 524. The highest submission rates occurred in the most densely populated regions of the province, including the Greater Toronto Area and Ottawa. More than half (55% or 5730) of all patients tested were female; sex was unknown for 114 patients. Submissions of specimens from school-aged children (5?19 years) accounted for 24.6% (2572) of all submissions, while 40.2% (4202) were from adults aged 20?49 years. Specimens were least likely to come from people aged >65 years (10.3% or 1072). Age was unknown for 78 patients.
Early in the outbreak, seasonal influenza A strains (H1 and H3) were predominant; however, from 10 May onwards, pandemic (H1N1) 2009 virus was detected in higher proportions. During the week beginning 31 May, 38.1% (658/1727) of specimens submitted tested positive for pandemic (H1N1) 2009 virus, and 0.7% (12) tested positive for seasonal influenza A, compared with 2.8% (57/2033) testing positive for pandemic (H1N1) 2009 virus and 5.1% (103) testing positive for seasonal influenza A during the week beginning 26 April.
Summary of confirmed cases
During the reporting period 28 April?29 May 2009, a total of 863 cases were laboratory-confirmed; the earliest reported date of symptom onset was 13 April 2009. Despite higher rates of submission for samples from females, there was a slight male predominance in cases (448 males, 414 females, 1 unknown). Cases occurred in people ranging in age from 2 months to 80 years (median, 16 years), with 52.6% (454) of cases aged 5?19 years.
Among those aged 10?19 years, more cases were confirmed in males than in females. Only 2.7% (23) of cases were aged >55 years (Fig. 1).
Clinical characteristics and underlying conditions
A total of 805 (93.3%) confirmed cases reported symptoms. The most commonly reported symptoms were cough (92.2% or 742), fever (91.3% or 735) and sore throat (40.5% or 326). Gastrointestinal symptoms, including vomiting and diarrhoea, were present in
189 cases (23.5%). Pneumonia (0.9% or 7) and respiratory distress (1.7% or 14) were not commonly reported.
The duration of symptoms was reported for 165 cases; the mean duration of illness was 4.7 days (95% confidence interval [CI], 4.2?5.2 days; median, 4 days; range, 0?23 days).
Altogether, 72 cases (8.3%) reported chronic or underlying medical conditions, including pregnancy. The most commonly reported conditions were cardiac or pulmonary disorders (77.85% or 56 cases), followed by diabetes and other metabolic diseases (15.3% or 11 cases), and cancer or other diseases that suppress the immune system (12.5% or 9 cases). Two cases (2.8%) reported they were pregnant. Information on obesity was not systematically collected.
Morbidity and mortality
A total of 31 (3.6%) cases were hospitalized, resulting in a crude hospitalization rate of 0.24 hospitalizations/100 000 population (95% CI, 0.16?0.34). At the time of data extraction, 5 cases remained in hospital. The median length of hospital stay for cases who had been discharged was 4.0 days (range, <24 hours to 20 days). Almost one third (32.2%) of hospitalized cases were aged 0?4 years. Cases with a chronic or underlying medical condition were significantly more likely to be hospitalized than cases without such conditions (X2, 57.00; P< 0.001).
Two deaths were reported, resulting in a crude mortality rate of 0.02 deaths/100 000 population (95% CI, 0.00?0.06) and a case-fatality rate of 0.2%. Both deaths occurred in males aged >40 years who had underlying medical conditions.
Exposure
The place of acquisition was known for 633 cases (73.3%). The majority of these cases (568, 89.7%) acquired the virus in Ontario; only 8.5% (54) of cases with a known exposure reported having travelled to Mexico within 7 days of symptom onset. In the early stages of the outbreak, most cases reported having travelled to Mexico; however, after initial importations of the virus, the vast majority of cases acquired it in Ontario (Fig. 2).
Among cases who acquired the infection in Ontario, 334 (58.8%) did not have known contact with a case. A number of school-related clusters were detected. In total, 351 (40.7%) of all cases reported a known connection to a school, either as a site where exposure occurred or as a transmission location; 70.7% (133/188) of cases in primary school (aged 6?12 years) and 71.4% (162/227) of those in secondary school (aged 13?17 years) reported either exposure at school or attending school while infectious.
Seasonal vaccination status
The Ontario government funds a universal influenza immunization programme that provides free vaccination to all residents aged >6 months; vaccination status during 2008?2009 was available for 714 (82.7%) cases, of which 27.3% (195) reported they had received the vaccine.
Discussion
In Ontario, Canada, enhanced surveillance directives detected 863 laboratory-confirmed cases of pandemic (H1N1) 2009 virus as of 29 May 2009. More than half of all confirmed cases occurred among people aged <20 years. Epidemiological data from WHO?s Region of the Americas and the European Region also show that the highest rates of illness have occurred among children and young adults.5,6,7 In Ontario, the age distribution of confirmed cases largely reflected submission patterns of specimens; the mean age of patients for whom specimens were submitted decreased over time as outbreaks spread through schools. The age distribution of infection with pandemic (H1N1) 2009 virus differs from the population that is at risk for seasonal influenza. Possible explanations for this include crossprotection occurring among older age groups owing to their prior exposure to H1N1 strains circulating before 1957, or minimal contact by older age groups with young travellers and school-aged children who amplify transmission during the early stage of the spread of a new influenza virus.6 Institutional outbreaks are unlikely to be a contributing factor, since only 2 of 112 respiratory outbreaks (1 in a hospital and 1 in a long-term care facility) registered with the laboratories of the Ontario Agency for Health Protection and Promotion from 20 April?12 June 2009 were caused by pandemic (H1N1) 2009 virus.8
As with seasonal influenza, most cases with pandemic (H1N1) 2009 influenza experienced mild illness and did not require hospitalization. The duration of symptoms was estimated at 4 days, which is consistent with a meta-analysis of studies among healthy volunteers experimentally infected with human influenza A(H1N1).9 The most commonly reported symptoms included cough, fever and sore throat. Unlike seasonal influenza, approximately one quarter of all cases reported gastrointestinal symptoms. This finding is consistent with other regions.7
Less than 10% of all cases reported having a chronic or underlying medical condition. By comparison, 22.0% (95% CI, 21.4?22.6%) of the population in Ontario reported having had a chronic condition diagnosed by a health professional in 2005.10 Hospitalization was more likely if the case reported having a chronic or underlying medical condition; however, more than half of all cases hospitalized did not report having such conditions. The number of cases reported here represents an underestimation of the true number of individuals infected. The ability to detect cases depends on health-seeking behaviours, testing behaviours, the resources available to health-care providers, and the sensitivity and specificity of laboratory tests. The lag in time
between the onset of illness and severe outcomes (hospitalization or death) may also underrepresent these outcomes; data were extracted 10 days after the case-reported date of 29 May 2009 to minimize this bias. Other biases in surveillance data, such as missing data and recall bias, should be considered when interpreting these results.
In conclusion, this summary provides important descriptive data on early cases of influenza caused by pandemic (H1N1) 2009 virus occurring prior to initiation of restrictions on laboratory testing. Continued and expanded surveillance is necessary to further characterize the pandemic and to support public-health planning. Areas for further investigation include determining transmission dynamics, seroprevalence and risk factors for infection and hospitalization.
[References]
1 The Ontario Agency for Health Protection and Promotion and the Ontario Ministry of Health and Long-Term Care thank all 36 regional health authorities for collecting data and contributing to this report. Staff from these 2 agencies wrote this report.
2 Mahony JB et al. Multiplex PCR tests sentinel the appearance of pandemic influenza viruses including H1N1 swine influenza. Journal of Clinical Virology, 2009, 45:200?202.
3 Influenza-like illness is defined as the acute onset of respiratory illness with fever and >1 of the following symptoms: cough, sore throat, arthralgia, myalgia, prostration or malaise. In cases aged <5 years or >65, fever may not be prominent.
4 RT-PCR was the primary method used to detect the virus since viral culture was performed in only a small proportion of cases and no serology test was available at the time of testing.
5 See No. 23, 2009, pp. 213?219.
6 Preliminary analysis of influenza A (H1N1) individual and aggregated case reports from EU and EFTA Countries. Eurosurveillance, 2009, 14(23):1?5 (also available at LINK).
7 Emergence of a novel swine-origin influenza A (H1N1) virus in humans. New England Journal of Medicine, 2009, 360:2605?2615 (also available at LINK).
8 Gubbay JB et al. Respiratory infection outbreaks in institutions during the novel influenza A H1N1 virus pandemic in Ontario. ProMED-mail, 2009, archive number: 20090627.2338 (LINK, accessed October 2009).
9 Carrat F et al. Time lines of infection and disease in human influenza: a review of volunteer challenge studies. American Journal of Epidemiology, 2008, 167:775?785.
10 Statistics Canada. Canadian Community Health Survey: detailed information for 2008, Ottawa, Ontario, 2009 (LINK, accessed October 2009).
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