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Human cases of avian influenza A(H5N1) in North-West Frontier Province, Pakistan, October?November 2007 [WHO, WER]
Weekly epidemiological record - Relev? ?pid?miologique hebdomadaire - 3 OCTOBER 2008, 83rd YEAR / 3 OCTOBRE 2008, 83e ANN?E - No. 40, 2008, 83, 357?364 - http://www.who.int/wer (http://www.who.int/wer/2008/wer8340.pdf)
Human cases of avian influenza A(H5N1) in North-West Frontier Province, Pakistan, October?November 2007
On 21 October 2007, an outbreak of highly pathogenic avian influenza A(H5N1) was identified at a poultry farm near Abbottabad, in the North-West Frontier Province of Pakistan.
On 26 November 2007, the Pakistan National Institute of Health was informed that people with suspected H5N1 virus infection had been hospitalized at a tertiary care hospital in Peshawar; at the same time, the Institute received clinical specimens for diagnostic testing.
A team from the National Institute of Health, joined by staff from WHO?s country offi ce, conducted the initial case investigation.
Based on the findings of the investigation and the results of preliminary tests conducted by the National Institute of Health, the Ministry of Health officially reported the possible occurrence of human cases of H5N1 virus infection to WHO on 12 December 2007.
Health authorities in Pakistan asked WHO to provide technical support to enable investigation of several suspected human cases of A(H5N1) virus infection.
This report describes the findings of the investigation into the family cluster that included 3 laboratory-confirmed cases.
Background
Pakistan is a country of 160 million people that shares borders with Afghanistan, China, India and the Islamic Republic of Iran.
H5N1 virus has been circulating in China since 2004 and has been detected in other neighbouring countries among poultry or birds since 2006.
In addition, China has detected human cases of H5N1 virus infection.
Since 2006, sporadic outbreaks of H5N1 infection among poultry have been reported in Pakistan; infections have also been documented in wild birds. Many of the outbreaks have been reported in the ?poultry belt? of the North-West Frontier Province, including the Abbottabad and Mansehra areas.
This region of the province has a high density of poultrybreeding farms, accounting for 70% of all such farms in the country.
National surveillance for avian influenza in poultry was initiated approximately 10 years ago, and there is now a network of regional laboratories and a reference laboratory in Islamabad. Culling and ring vaccination are conducted in response to outbreaks in poultry.
Field activities
WHO?s international investigation team was composed of staff members from Pakistan?s National Institute of Health, the United States Naval Medical Research Unit Number 3, the United States Centers for Disease Control and Prevention and WHO. During 17?27 December 2007, the team made field visits to the affected areas, including hospitals where patients suspected of being infected with the H5N1 virus were being treated, family homes in Peshawar and Charsada, and poultry farms near Abbottabad (Map 1).
To corroborate information, the team reviewed preliminary reports from previous investigations and interviewed WHO officers in the field; clinicians, nurses and hospital management in 2 hospitals; affected family members; local health authorities; members of the mobile investigation teams; and officials from UNICEF, the United Nations High Commissioner for Refugees, and the Office of the United Nations Food and Agriculture Organization of the United Nations.
Laboratory testing by a WHO reference laboratory for diagnosis of influenza A/H5 infection1 was conducted on specimens from suspected cases and their contacts to confirm the initial test results obtained by the National Institute of Health.
The Peshawar family cluster
* Case 1
In late October 2007, a laboratory-confirmed outbreak of highly pathogenic avian influenza A(H5N1) among poultry occurred at a breeding farm located near Abbottabad in the North-West Frontier Province. A culling operation was carried out during 22?23 October.
One of the 13 people performing the culling was a 25-year-old livestock production officer (Case 1).
During this operation, Case 1 handled dead, sick and healthy chickens without using personal protective equipment.
During culling, both live and dead poultry were collected and put into large bags until each bag was full; each bag was then tied and placed in a deep pit for burial. Case 1 gathered chickens and placed them in the bag and also held the bag open while others put chickens inside.
On 29 October, Case 1 developed a fever and sought treatment at a clinic in Abbottabad. His symptoms progressed over the next several days to include cough and dyspnoea.
On 2 November, Case 1 travelled to his family?s home in Peshawar (a 4-hour journey) by public transportation.
Living in his family?s household were members of his extended family including 5 brothers and 2 sisters.
Case 1 continued to have symptoms and was seen as an outpatient at a hospital in Peshawar on 4 November, where he received treatment with antibiotics and antimalarials.
By the next day, his dyspnoea had worsened and he was admitted to hospital. Chest radiography was performed; it showed bilateral infiltrates. On 6 November, he was transferred to the intensive care unit where he spent 9 days; he was transferred back to the general ward on 14 November. On 16 November, he was discharged home. Blood samples taken on 29 November and analysed by microneutralization assays demonstrated antibody titres against influenza A(H5N1) virus of 1:2560; samples from 8 December showed titres of 1:1280. Western blot assay was also positive for influenza A(H5N1) virus.
* Case 2
On 12 November, a 22-year-old university student, a brother of Case 1, became ill with fever and headache. Symptoms progressed to include cough and dyspnoea; he was admitted to hospital on 14 November. His chest X-ray showed a right-middle lung infiltrate. The next day, his condition worsened, and he was transferred to the intensive care unit where his condition continued to deteriorate; on 19 November, he required mechanical ventilation. He died later the same day. Laboratory testing was not performed.
Case 2 had had close prolonged contact with Case 1.
They ate meals together and slept 2 nights in the same bedroom at the family?s Peshawar home starting on 2 November. Case 2 had had prolonged visits on 5 November and 7 November with Case 1 during Case 1?s hospitalization. Case 2 had no history of exposure to sick or dead poultry.
* Case 3
On 21 November, a 27-year-old water management officer, also a brother of Case 1, developed fever. On 23 November, he developed dyspnoea and was admitted to hospital in an isolation room. His chest X-ray showed a right lung infiltrate. Oseltamivir treatment was started on 27 November. On 28 November, his condition deteriorated. He was transferred to the intensive care unit and started on mechanical ventilation. He died later the same day. Throat and blood samples had been collected on 26 November. The throat swab was positive for H5 by real-time reverse transcriptase?polymerase chain reaction (RT?PCR); influenza A(H5N1) virus was isolated from the specimen at a WHO influenza A/H5 reference laboratory.
Case 3 had had close prolonged contact with both Case 2 and Case 1. He was the primary caregiver for Case 2 during his hospitalization for severe acute respiratory infection during 14?19 November. Case 3 had also shared a bedroom with Case 1 during 2?4 November and had visited Case 1 during his hospitalization. Case 3 had no history of exposure to sick or dead poultry.
* Case 4
On 21 November, a 32-year-old brother of Case 1 developed fever. Oseltamivir treatment was started the next day. However, fever persisted, and on 23 November he was admitted to hospital with dyspnoea and an abnormal chest X-ray. The patient remained in an isolation ward in stable condition. He fully recovered from his illness. Both throat swab and blood samples were collected on
29 November; blood sample collection was repeated on 8 December. Although the throat swab was negative for H5 by RT?PCR, subsequent serology tests were positive and showed that seroconversion had occurred between the time of the first and second serum sample. The initial specimen yielded a microneutralization H5 antibody titre of 1:10; a later specimen yielded a positive microneutralization test with an antibody titre of 1:320 and a positive western blot assay.
* Case 5
Case 5 was a 33-year-old brother of Case 1. He was asymptomatic but clinical specimens were collected from him owing to the close and prolonged contact with his ill brothers. Initial testing at the National Institute of Health yielded positive results for H5 RT?PCR on a throat swab collected on 29 November. When serum specimens were tested by microneutralization assay, a specimen collected on 8 December yielded an H5 antibody titre of 1:320 and a positive western blot assay.
Discussion
After thorough epidemiological investigation by the international investigation team and confirmatory testing of clinical specimens by WHO influenza A/H5 reference laboratories, 3 cases were confirmed as avian influenza A(H5N1) infection.2 The 3 confirmed cases were brothers aged between 25 and 32 years. One of the cases died within 7 days of onset of illness; the other 2 cases
recovered.
In addition, the investigation detected 1 probable case of H5N1 infection and 1 asymptomatic seropositive case within the same family. These are the first human cases of influenza A(H5N1) virus infection documented in Pakistan.
Case 1 is also the first person to have documented influenza A(H5N1) disease following occupational exposure during poultry culling.
With respect to the chain of transmission, evidence gathered during the investigation supports the theory of initial transmission from poultry to humans followed by human-to-human transmission involving a third generation.
Only 1 of the brothers (the first to become ill) had a clear history of contact with sick or dead poultry (the poultry had been laboratory-confi rmed as being infected with H5N1 virus); the other brothers who became ill had not been working in occupations related to the poultry industry or farming.
The brothers resided in the city of Peshawar, where there had been no reported poultry outbreaks of infl uenza A(H5N1) since March 2007. Environmental sampling in the Peshawar and Charsada homes of the affected brothers, in addition to sampling of healthy poultry at the Peshawar home, were all negative for influenza A(H5N1) virus.
The relatively long period of time between the dates of onset of illness of the 4 brothers (24 days between first date of onset and last date of onset) supports a chain of transmission among humans rather than a common source of infection from poultry.
Case 1, the index case, was most likely infected during the culling carried out during 22?23 October. Infection during 22?23 October and onset of fever on 29 October reflects an incubation time of 6?7 days, which is within the expected range.3 Case 1 had no other known exposures to a source of influenza A(H5N1) virus, and this particular culling exercise was the first in which he had
ever participated. The most likely next link in the chain would be human-to-human transmission of the virus from Case 1 to his younger brother, Case 2. This brother had had prolonged close contact with Case 1, sharing meals and a bedroom with him during 2?5 November and visiting Case 1 in hospital on 5 and 7 November.
Case 2 was a university student and had had no known exposure to sick or dead birds or poultry. If we assume his source of infection was his brother, his incubation time is in the range of 5?10 days and is similar to that of previously reported cases.2 The clinical course of illness in Case 2 and his epidemiological link to Case 1, a confirmed case of H5N1 infection, strongly support
the inference that his illness and death were caused by infection with H5N1. Since there was no laboratory confirmation of disease in Case 2, he is classified as a probable case of H5N1 infection.
The next most likely link in the chain of transmission would be human-to-human transmission from Case 2 to Case 3. Case 3 had had prolonged close contact with Case 2 during 12?19 November, when he acted as the primary caregiver for Case 2 during his illness. The date of fever onset for Case 3 was 21 November. If Case 3 was infected by Case 2, the incubation range would be 2?10 days, and this incubation period is consistent with that seen in previous outbreaks.2
Case 4 most likely acquired his infection from Case 2. This older brother had an exposure history similar to Case 3, which included sharing meals and a sleeping room with his brothers. This exposure to potential sources of infection started on 2 November and continued until 19 November as he visited Case 1 and Case 2 in hospital and attended to them. Considering the incubation period, Case 4 was most likely to have been infected by Case 2, since that would result in an incubation period in the range of 2?10 days. Case 5 was asymptomatic but had laboratory tests indicating infection with influenza A(H5N1).
Case 5 had had frequent close contact with all 4 of his brothers when they were ill, and infection may have occurred after exposure to any of them. Case 5 had no known contact with sick or dead poultry. Asymptomatic seroconversion in household contacts has been documented previously in a study in Hong Kong SAR conducted after the 1997 outbreak of influenza A(H5N1).4
Other sources of infection could be considered, including the possibility of poultry-to-human transmission in all cases. However, only Case 1 had an occupation that brought him into contact with poultry or wild birds. Household poultry and several environmental samples from the homes of the affected family were tested for the presence of the virus, but all tests were negative. There
were no reported outbreaks of H5N1 infection in poultry in Peshawar or Charsada in the latter part of 2007. Indirect transmission from poultry to humans through fomites seems unlikely. Case 1 denied removing or transporting anything (including equipment or poultry) from the infected farm after the culling. Case 1 stated that immediately after the culling, he had washed the clothing
he wore during culling. Therefore, contaminated clothing was not transported to Peshawar, the site of the other infections. Case 1 continued to wear the shoes he had worn during the culling (which took place on 22?23 October), but he did not travel to Peshawar until 2 November.
It seems unlikely that shoes worn daily for 1 week would remain sufficiently soiled that they could cause infection in human contacts >10 days later.
Conclusion
The illnesses of the 4 brothers are consistent with influenza A(H5N1) virus infection. After considering the information gathered during investigation of this cluster of cases, evidence supports a chain of transmission beginning with poultry-to-human transmission followed by human-to-human transmission for 3 generations of transmission. Despite thorough investigation and active
surveillance, there was no evidence of sustained transmission in the community. Contacts in the immediate and extended family and health-care workers received follow-up clinical and laboratory testing, but there was no evidence of further influenza A(H5N1) infection. Evidence gathered during the investigation supports the hypothesis that this outbreak of influenza A(H5N1) infection was limited to a family cluster and was not sustained in the community. Human-to-human transmission probably occurred, but only after prolonged and intimate contact among family members.
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1 The reference laboratories involved included the United States Naval Medical Research Unit Number 3, the National Institute for Medical Research, London, United Kingdom and the United States Centers for Disease Control and Prevention, Atlanta, GA, United States. For a complete list of all influenza A/H5 reference laboratories, see http://www.who.int/csr/disease/avian_infl uenza/guidelines/referencelabs/en/
2 WHO?s case definitions for human infection with infl uenza A(H5N1) can be found at http://www.who.int/csr/disease/avian...n2006_08_29/en
3 WHO Writing Committee. Update on avian infl uenza A(H5N1) virus infection in humans. New England Journal of Medicine, 2008, 358:261?273.
4 Katz JM et al. Antibody response in individuals infected with avian infl uenza A(H5N1) viruses and detection of anti-H5 antibody among household and social contacts. Journal of Infectious Diseases, 1999, 180:1763?1770.
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Weekly epidemiological record - Relev? ?pid?miologique hebdomadaire - 3 OCTOBER 2008, 83rd YEAR / 3 OCTOBRE 2008, 83e ANN?E - No. 40, 2008, 83, 357?364 - http://www.who.int/wer (http://www.who.int/wer/2008/wer8340.pdf)
Human cases of avian influenza A(H5N1) in North-West Frontier Province, Pakistan, October?November 2007
On 21 October 2007, an outbreak of highly pathogenic avian influenza A(H5N1) was identified at a poultry farm near Abbottabad, in the North-West Frontier Province of Pakistan.
On 26 November 2007, the Pakistan National Institute of Health was informed that people with suspected H5N1 virus infection had been hospitalized at a tertiary care hospital in Peshawar; at the same time, the Institute received clinical specimens for diagnostic testing.
A team from the National Institute of Health, joined by staff from WHO?s country offi ce, conducted the initial case investigation.
Based on the findings of the investigation and the results of preliminary tests conducted by the National Institute of Health, the Ministry of Health officially reported the possible occurrence of human cases of H5N1 virus infection to WHO on 12 December 2007.
Health authorities in Pakistan asked WHO to provide technical support to enable investigation of several suspected human cases of A(H5N1) virus infection.
This report describes the findings of the investigation into the family cluster that included 3 laboratory-confirmed cases.
Background
Pakistan is a country of 160 million people that shares borders with Afghanistan, China, India and the Islamic Republic of Iran.
H5N1 virus has been circulating in China since 2004 and has been detected in other neighbouring countries among poultry or birds since 2006.
In addition, China has detected human cases of H5N1 virus infection.
Since 2006, sporadic outbreaks of H5N1 infection among poultry have been reported in Pakistan; infections have also been documented in wild birds. Many of the outbreaks have been reported in the ?poultry belt? of the North-West Frontier Province, including the Abbottabad and Mansehra areas.
This region of the province has a high density of poultrybreeding farms, accounting for 70% of all such farms in the country.
National surveillance for avian influenza in poultry was initiated approximately 10 years ago, and there is now a network of regional laboratories and a reference laboratory in Islamabad. Culling and ring vaccination are conducted in response to outbreaks in poultry.
Field activities
WHO?s international investigation team was composed of staff members from Pakistan?s National Institute of Health, the United States Naval Medical Research Unit Number 3, the United States Centers for Disease Control and Prevention and WHO. During 17?27 December 2007, the team made field visits to the affected areas, including hospitals where patients suspected of being infected with the H5N1 virus were being treated, family homes in Peshawar and Charsada, and poultry farms near Abbottabad (Map 1).
To corroborate information, the team reviewed preliminary reports from previous investigations and interviewed WHO officers in the field; clinicians, nurses and hospital management in 2 hospitals; affected family members; local health authorities; members of the mobile investigation teams; and officials from UNICEF, the United Nations High Commissioner for Refugees, and the Office of the United Nations Food and Agriculture Organization of the United Nations.
Laboratory testing by a WHO reference laboratory for diagnosis of influenza A/H5 infection1 was conducted on specimens from suspected cases and their contacts to confirm the initial test results obtained by the National Institute of Health.
The Peshawar family cluster
* Case 1
In late October 2007, a laboratory-confirmed outbreak of highly pathogenic avian influenza A(H5N1) among poultry occurred at a breeding farm located near Abbottabad in the North-West Frontier Province. A culling operation was carried out during 22?23 October.
One of the 13 people performing the culling was a 25-year-old livestock production officer (Case 1).
During this operation, Case 1 handled dead, sick and healthy chickens without using personal protective equipment.
During culling, both live and dead poultry were collected and put into large bags until each bag was full; each bag was then tied and placed in a deep pit for burial. Case 1 gathered chickens and placed them in the bag and also held the bag open while others put chickens inside.
On 29 October, Case 1 developed a fever and sought treatment at a clinic in Abbottabad. His symptoms progressed over the next several days to include cough and dyspnoea.
On 2 November, Case 1 travelled to his family?s home in Peshawar (a 4-hour journey) by public transportation.
Living in his family?s household were members of his extended family including 5 brothers and 2 sisters.
Case 1 continued to have symptoms and was seen as an outpatient at a hospital in Peshawar on 4 November, where he received treatment with antibiotics and antimalarials.
By the next day, his dyspnoea had worsened and he was admitted to hospital. Chest radiography was performed; it showed bilateral infiltrates. On 6 November, he was transferred to the intensive care unit where he spent 9 days; he was transferred back to the general ward on 14 November. On 16 November, he was discharged home. Blood samples taken on 29 November and analysed by microneutralization assays demonstrated antibody titres against influenza A(H5N1) virus of 1:2560; samples from 8 December showed titres of 1:1280. Western blot assay was also positive for influenza A(H5N1) virus.
* Case 2
On 12 November, a 22-year-old university student, a brother of Case 1, became ill with fever and headache. Symptoms progressed to include cough and dyspnoea; he was admitted to hospital on 14 November. His chest X-ray showed a right-middle lung infiltrate. The next day, his condition worsened, and he was transferred to the intensive care unit where his condition continued to deteriorate; on 19 November, he required mechanical ventilation. He died later the same day. Laboratory testing was not performed.
Case 2 had had close prolonged contact with Case 1.
They ate meals together and slept 2 nights in the same bedroom at the family?s Peshawar home starting on 2 November. Case 2 had had prolonged visits on 5 November and 7 November with Case 1 during Case 1?s hospitalization. Case 2 had no history of exposure to sick or dead poultry.
* Case 3
On 21 November, a 27-year-old water management officer, also a brother of Case 1, developed fever. On 23 November, he developed dyspnoea and was admitted to hospital in an isolation room. His chest X-ray showed a right lung infiltrate. Oseltamivir treatment was started on 27 November. On 28 November, his condition deteriorated. He was transferred to the intensive care unit and started on mechanical ventilation. He died later the same day. Throat and blood samples had been collected on 26 November. The throat swab was positive for H5 by real-time reverse transcriptase?polymerase chain reaction (RT?PCR); influenza A(H5N1) virus was isolated from the specimen at a WHO influenza A/H5 reference laboratory.
Case 3 had had close prolonged contact with both Case 2 and Case 1. He was the primary caregiver for Case 2 during his hospitalization for severe acute respiratory infection during 14?19 November. Case 3 had also shared a bedroom with Case 1 during 2?4 November and had visited Case 1 during his hospitalization. Case 3 had no history of exposure to sick or dead poultry.
* Case 4
On 21 November, a 32-year-old brother of Case 1 developed fever. Oseltamivir treatment was started the next day. However, fever persisted, and on 23 November he was admitted to hospital with dyspnoea and an abnormal chest X-ray. The patient remained in an isolation ward in stable condition. He fully recovered from his illness. Both throat swab and blood samples were collected on
29 November; blood sample collection was repeated on 8 December. Although the throat swab was negative for H5 by RT?PCR, subsequent serology tests were positive and showed that seroconversion had occurred between the time of the first and second serum sample. The initial specimen yielded a microneutralization H5 antibody titre of 1:10; a later specimen yielded a positive microneutralization test with an antibody titre of 1:320 and a positive western blot assay.
* Case 5
Case 5 was a 33-year-old brother of Case 1. He was asymptomatic but clinical specimens were collected from him owing to the close and prolonged contact with his ill brothers. Initial testing at the National Institute of Health yielded positive results for H5 RT?PCR on a throat swab collected on 29 November. When serum specimens were tested by microneutralization assay, a specimen collected on 8 December yielded an H5 antibody titre of 1:320 and a positive western blot assay.
Discussion
After thorough epidemiological investigation by the international investigation team and confirmatory testing of clinical specimens by WHO influenza A/H5 reference laboratories, 3 cases were confirmed as avian influenza A(H5N1) infection.2 The 3 confirmed cases were brothers aged between 25 and 32 years. One of the cases died within 7 days of onset of illness; the other 2 cases
recovered.
In addition, the investigation detected 1 probable case of H5N1 infection and 1 asymptomatic seropositive case within the same family. These are the first human cases of influenza A(H5N1) virus infection documented in Pakistan.
Case 1 is also the first person to have documented influenza A(H5N1) disease following occupational exposure during poultry culling.
With respect to the chain of transmission, evidence gathered during the investigation supports the theory of initial transmission from poultry to humans followed by human-to-human transmission involving a third generation.
Only 1 of the brothers (the first to become ill) had a clear history of contact with sick or dead poultry (the poultry had been laboratory-confi rmed as being infected with H5N1 virus); the other brothers who became ill had not been working in occupations related to the poultry industry or farming.
The brothers resided in the city of Peshawar, where there had been no reported poultry outbreaks of infl uenza A(H5N1) since March 2007. Environmental sampling in the Peshawar and Charsada homes of the affected brothers, in addition to sampling of healthy poultry at the Peshawar home, were all negative for influenza A(H5N1) virus.
The relatively long period of time between the dates of onset of illness of the 4 brothers (24 days between first date of onset and last date of onset) supports a chain of transmission among humans rather than a common source of infection from poultry.
Case 1, the index case, was most likely infected during the culling carried out during 22?23 October. Infection during 22?23 October and onset of fever on 29 October reflects an incubation time of 6?7 days, which is within the expected range.3 Case 1 had no other known exposures to a source of influenza A(H5N1) virus, and this particular culling exercise was the first in which he had
ever participated. The most likely next link in the chain would be human-to-human transmission of the virus from Case 1 to his younger brother, Case 2. This brother had had prolonged close contact with Case 1, sharing meals and a bedroom with him during 2?5 November and visiting Case 1 in hospital on 5 and 7 November.
Case 2 was a university student and had had no known exposure to sick or dead birds or poultry. If we assume his source of infection was his brother, his incubation time is in the range of 5?10 days and is similar to that of previously reported cases.2 The clinical course of illness in Case 2 and his epidemiological link to Case 1, a confirmed case of H5N1 infection, strongly support
the inference that his illness and death were caused by infection with H5N1. Since there was no laboratory confirmation of disease in Case 2, he is classified as a probable case of H5N1 infection.
The next most likely link in the chain of transmission would be human-to-human transmission from Case 2 to Case 3. Case 3 had had prolonged close contact with Case 2 during 12?19 November, when he acted as the primary caregiver for Case 2 during his illness. The date of fever onset for Case 3 was 21 November. If Case 3 was infected by Case 2, the incubation range would be 2?10 days, and this incubation period is consistent with that seen in previous outbreaks.2
Case 4 most likely acquired his infection from Case 2. This older brother had an exposure history similar to Case 3, which included sharing meals and a sleeping room with his brothers. This exposure to potential sources of infection started on 2 November and continued until 19 November as he visited Case 1 and Case 2 in hospital and attended to them. Considering the incubation period, Case 4 was most likely to have been infected by Case 2, since that would result in an incubation period in the range of 2?10 days. Case 5 was asymptomatic but had laboratory tests indicating infection with influenza A(H5N1).
Case 5 had had frequent close contact with all 4 of his brothers when they were ill, and infection may have occurred after exposure to any of them. Case 5 had no known contact with sick or dead poultry. Asymptomatic seroconversion in household contacts has been documented previously in a study in Hong Kong SAR conducted after the 1997 outbreak of influenza A(H5N1).4
Other sources of infection could be considered, including the possibility of poultry-to-human transmission in all cases. However, only Case 1 had an occupation that brought him into contact with poultry or wild birds. Household poultry and several environmental samples from the homes of the affected family were tested for the presence of the virus, but all tests were negative. There
were no reported outbreaks of H5N1 infection in poultry in Peshawar or Charsada in the latter part of 2007. Indirect transmission from poultry to humans through fomites seems unlikely. Case 1 denied removing or transporting anything (including equipment or poultry) from the infected farm after the culling. Case 1 stated that immediately after the culling, he had washed the clothing
he wore during culling. Therefore, contaminated clothing was not transported to Peshawar, the site of the other infections. Case 1 continued to wear the shoes he had worn during the culling (which took place on 22?23 October), but he did not travel to Peshawar until 2 November.
It seems unlikely that shoes worn daily for 1 week would remain sufficiently soiled that they could cause infection in human contacts >10 days later.
Conclusion
The illnesses of the 4 brothers are consistent with influenza A(H5N1) virus infection. After considering the information gathered during investigation of this cluster of cases, evidence supports a chain of transmission beginning with poultry-to-human transmission followed by human-to-human transmission for 3 generations of transmission. Despite thorough investigation and active
surveillance, there was no evidence of sustained transmission in the community. Contacts in the immediate and extended family and health-care workers received follow-up clinical and laboratory testing, but there was no evidence of further influenza A(H5N1) infection. Evidence gathered during the investigation supports the hypothesis that this outbreak of influenza A(H5N1) infection was limited to a family cluster and was not sustained in the community. Human-to-human transmission probably occurred, but only after prolonged and intimate contact among family members.
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1 The reference laboratories involved included the United States Naval Medical Research Unit Number 3, the National Institute for Medical Research, London, United Kingdom and the United States Centers for Disease Control and Prevention, Atlanta, GA, United States. For a complete list of all influenza A/H5 reference laboratories, see http://www.who.int/csr/disease/avian_infl uenza/guidelines/referencelabs/en/
2 WHO?s case definitions for human infection with infl uenza A(H5N1) can be found at http://www.who.int/csr/disease/avian...n2006_08_29/en
3 WHO Writing Committee. Update on avian infl uenza A(H5N1) virus infection in humans. New England Journal of Medicine, 2008, 358:261?273.
4 Katz JM et al. Antibody response in individuals infected with avian infl uenza A(H5N1) viruses and detection of anti-H5 antibody among household and social contacts. Journal of Infectious Diseases, 1999, 180:1763?1770.
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(Click on image to open a larger view.)
<table style="width: auto;"><tbody><tr><td>
</td></tr><tr><td style="font-family: arial,sans-serif; font-size: 11px; text-align: right;">From MAPS</td></tr></tbody></table>------
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