The report un-pdf'd
The report un-pdf'd
Human cases of influenza A(H5N1) infection in eastern Turkey, December 2005?January 2006
Background
On 3 January 2006, the National Influenza Centre at the Refik Saydam Hygiene Centre in Ankara, Turkey, informed WHO that 2 children with fulminant atypical pneumonia had been admitted to Y?z?nc? Yil University Hospital in the city of Van in eastern Turkey. Both were from a single family residing in Dogubeyazit District (Agri Province) and reported histories of recent contact with poultry. Nasal swabs, obtained from the patients 4?6 days after onset of llness, tested negative for influenza A(H5) infection by enzyme-linked immunosorbent assay rapid tests and realtime reverse-transcriptase polymerase chain reaction (rtRT-PCR) at the National Influenza Centre. Chickens had been dying in the Dogubeyazit District since the end of December 2005; influenza A(H5N1) virus activity in poultry was confirmed by laboratory testing in the neighbouring province of Igdir on 27 December 2005.
On 4 January 2006, the National Influenza Centre informed WHO that additional samples from the lower respiratory tracts of the 2 patients had tested positive for influenza A(H5N1) infection by rtRT-PCR. That same day, the Ministry of Health in Turkey publicly confirmed influenza A(H5N1) infection in 2 individuals, both of whom had died. On 5 January, at the request of the Ministry of Health, a 3-person international expert team led by WHO was deployed to assist national and local health authorities in investigation and control activities. National Intersectoral Crisis Committees, which included representatives from the Ministry of Health, the Ministry of Agriculture and Rural Affairs, academia and other concerned parties, were established in Ankara and in Van Province to coordinate outbreak response activities. On the same day, the culling of domestic birds in both Van Province and Agri Province commenced.
On 6 January 2006, the Ministry of Health circulated to health authorities in all provinces revised guidelines for the detection, investigation and treatment of patients suspected of having influenza A(H5N1) infection. On 7 January 2006, tests performed at the WHO Collaborating Centre for Reference and Research on Influenza at the National Institute for Medical Research in London, England, confirmed the positive test results obtained at the National Influenza Centre. On the same day, the WHO-coordinated Global Outbreak Alert and Response Network (GOARN) disseminated a request to partner institutions to mobilize additional international experts.
Between 5 January and 30 January 2006, WHO, through GOARN, the United Nations Food and Agriculture Organization, and the United Nations Children?s Fund (UNICEF) sent to Ankara and to Van Province more than 25 experts in infection control, clinical management, epidemiology, laboratory diagnosis, communication, social mobilization and animal health. Altogether, 10 institutions and organizations were represented in the WHO-led multidisciplinary international outbreak response team.1
This report describes the results of the epidemiological investigations conducted in Agri and Van provinces from where more than 80% of the laboratory-confirmed cases were reported.
Epidemiological description
A total of 10 cases of influenza A(H5N1) infection, including 4 fatal cases, with dates of onset from 25 December 2005 to 8 January 2006, were identified at health-care facilities in Agri Province (9 cases) and Van Province (1 case) (Fig. 1 and Table 1). In 9 cases, influenza A(H5N1) infection was confirmed by rtRT-PCR at the National Influenza Centre and the collaborating centre. In 1 case, influenza A(H5N1) virus infection was confirmed by rtRTPCR at the National Influenza Centre and by serology at the collaborating centre.
The median interval between the date of onset of illness and death was 8 days (mean, 8 days; range, 7?10 days). All cases occurred among children aged 3?15 years (median, 8.5 years; mean, 8.9 years). The median age among the 4 fatalities was 14 years (mean, 13.7 years; range, 12?15 years). Five of the cases occurred among females aged 8?15 years, 3 of whom died. The remaining cases occurred among males aged 4?14 years.
Altogether, 7 cases occurred in 3 different households in the Dogubeyazit District, representing 1 family cluster of 3 cases, and 2 family clusters of 2 cases each.
In addition to the 10 confirmed cases in Agri and Van provinces, between 1 January 2006 and 26 January 2006 more than 600 people from Van Province were investigated for influenza A(H5N1) infection. Altogether, 135 probable cases2 were hospitalized and received oseltamivir treatment in the Y?z?nc? Yil University Hospital. Influenza A(H5N1) infection was ruled out in all of them on the basis of rtRT-PCR analysis of nasopharyngeal swabs.
During the field investigation, information was collected from a variety of sources including surviving family members, local medical officers and epidemiologists.
Dogubeyazit District and Agri Province
Family A [Kocyigit family]
Family A, residing in the district capital, consisted of 6 members (4 children
[Muhammed Ali, Fatima, Hulya & Ali Hasan] and their parents
Zeki & Marifet]). Influenza A(H5N1) virus infection was confirmed in 3 of the children, all of whom died. The first case, a 14-year-old boy (Case 1)
[Muhammed Ali] developed symptoms on 26 December 2005. His 2 sisters, aged 15 years (Case 2)
[Fatima] and 12 years (Case 3)
[Hulya] became ill 2 days later. Case 1 attended the outpatient department of Dogubeyazit District Hospital on 27 December 2005 where he was provided with antibiotic treatment and discharged home. Owing to a worsening of his condition, he returned to Dogubeyazit District Hospital on 30 December 2005 together with his 2 sisters. Because the attending physician suspected avian influenza infection, all 3 children were transferred on the following day to Y?z?nc? Yil University Hospital, where they died.
Family A kept 8 chickens and 1 turkey. On 20 December 2005, 1 of the household?s chickens fell ill. On 25 December 2005, Case 1 and Case 2 slaughtered 1 of the chickens. Case 3 was reportedly not directly involved in the process but was present in the house.
The fourth child, a 6-year-old boy, presented with mild symptoms on 29 December 2005. He was admitted to Y?z?nc? Yil University Hospital for evaluation and treatment at the same time as his 3 siblings. Samples obtained from the 6-year-old tested negative for influenza A(H5N1) infection at both the National Influenza Centre and the collaborating centre. The children?s parents did not present with any clinical signs or symptoms.
Family B [Ozcan 1]
Family B, residing in a small village located on the outskirts of the district capital, consisted of 10 members (8 children
[Aysegul, Yusuf, Hakan, Hatice, Mehmet, Ahmet, Mustafa & Rumeysa] and their parents
[Samil & Refika]). The family kept 25 chickens and 2 domesticated pigeons that were being raised as pets. On 26 December 2005, the chickens became ill and were slaughtered over the next 3 days. Case 4, a 9-year-old girl
[Aysegul], helped her mother slaughter the sick chickens; she developed symptoms on 29 December 2005. On 30 December 2005, 1 of her brothers (Case 5), aged 3 years,
[Yusuf] became ill. The boy had not been present when the chickens were slaughtered but had played with the pet pigeons. Both children were administered a full course of oseltamivir treatment starting on the day of admission to hospital. Both children recovered.
On 4 January 2006, the mother and the remaining 6 siblings were admitted to Y?z?nc? Yil University Hospital, partly on clinical grounds (the mother had mild respiratory symptoms and 2 siblings had headache and malaise) and partly for social reasons. They each received a full course of oseltamivir treatment. Nasopharyngeal swabs obtained from them tested negative for influenza A(H5N1) infection by rtRT-PCR at both the National Influenza Centre and the collaborating centre.
Family C [Ozcan 2]
Family C, residing in the district capital, consisted of 8 members (6 children
[Fatma, Muhammet, ?] and their parents
[Mehmet Emin & ?]). The family kept 4 ducks and 4 pet pigeons. One duck became ill on 4 January 2006. On this date, Case 6, a 14-year-old girl,
[Fatma] helped her mother
[she is actually Fatma's step-mother] slaughter and prepare ducks for consumption. She and her younger brother (Case 7), aged 5 years,
[Muhammet] had onset of illness on 8 January 2006. Case 7 did not contribute to the preparation of the ducks but he had played with the family pigeons. Both children were transferred to Y?z?nc? Yil University Hospital 2 days later and were administered a full course of oseltamivir treatment. Case 6 died at the hospital on 15 January 2006; her brother recovered. The 6 remaining family members continued to be healthy.
The heads of family B and family C are brothers, but the 2 households are located about 2 kilometres apart. The 2 families had reportedly had no interactions during the period preceding the presentation of illness in the families. Therefore, these 2 family clusters should be regarded as epidemiologically unrelated. [Note, also that family A and family C are related -- Fatma Ozcan was reported as a cousin of the Kocyigits (see next post).]
Case 8
Case 8, a 5-year-old boy,
[Yusuf Tunc] residing in the same neighbourhood as family A and family C, presented with mild respiratory symptoms on 25 December 2005 and was admitted to Y?z?nc? Yil University Hospital on 1 January 2006. The boy?s family had a small flock of poultry; since December 2005, widespread death among free-ranging poultry had been reported in the immediate surroundings. Case 8 was administered a full course of oseltamivir treatment starting on the day of admission and he recovered.
Case 9
Case 9, a boy aged 4 years,
[Ferhat Tilaver] became ill on 6 January 2006. He was hospitalized in Erzincan Hospital on 9 January 2006 and, due to worsening of his condition, was transferred to Atat?rk University Aziziye Research Hospital in Erzurum on 13 January 2006. He resided in the village of ?etenli, near the district capital. The boy?s family did not raise poultry but widespread death among free-ranging poultry had been reported in the village, including among his neighbour?s poultry flock, since December 2005. Case 9 had no known contact with other cases. Case 9 was administered a full course of oseltamivir treatment starting on the day of admission and he recovered.
Van City, Van Province
Case 10
Case 10 was an 8-year-old girl
[Summeye Mamuk] from a suburb of the city of Van. Her family kept 22 hens; these had started dying around 26 December 2005 and were slaughtered by family members. The girl cared for a sick pet chicken and also helped her mother prepare the slaughtered poultry for consumption. She presented with conjunctivitis on 2 January 2006 and was admitted on the following day to Y?z?nc? Yil University Hospital, where she received a full course of treatment with oseltamivir. Because her respiratory symptoms were mild, she was discharged. The next day she was readmitted when local health workers noticed dead birds in the household. Case 10 recovered.
Discussion
The human cases of influenza A(H5N1) infection described here are the first cases documented in Turkey and the first to be diagnosed outside of south-east Asia. The investigations carried out by Turkey?s Ministry of Health, with the assistance of the international multidisciplinary team, supported the hypothesis that close exposure to infected poultry was the principal risk factor for human infections with this virus. This is corroborated by the fact that no new cases were detected after the Ministry of Agriculture and Rural Affairs implemented extensive culling of poultry in areas where suspected or confirmed outbreaks in poultry had been identified. Exposure to backyard poultry was common among all cases and, for at least 5 of them, close contact with sick or dead poultry could be documented. At least 2 cases also had direct contact with pet pigeons. However, the part played by pigeons in transmitting the virus could not be established because no samples were collected from pigeons in the area. Consequently, it is not known whether the pigeons could have been infected or perhaps had surface contamination of infectious excreta and transferred the virus to the children in this way.
Environmental factors might have contributed to the occurrence of human cases in Agri Province, which is located in the mountainous Anatolian Region. Poultry is usually kept and fed outside, but during the winter poultry is brought indoors at night to protect it from the cold. During the second half of December 2005, the average daily temperatures recorded in the area were unusually low, reaching ?30? C.3 Because of the severe cold spell, many families, among them families A, B and C, sheltered their poultry indoors. This, combined with the cramped living conditions of the rural population, considerably increased the opportunity for contact between humans and poultry.
Despite the fact that 8 cases, including 3 family clusters, were observed in a limited geographical area of approximately 2 km? and during a period of 2 weeks, field investigations provided no evidence of human-to-human transmission between households.
The affected families had had no interactions with one another during the period preceding the onset of illness; the children from the different families did not attend the same schools; and there were no reported community gatherings. Although the possibility of limited transmission within households cannot be excluded, the timing of the onset of illness (intervals of 0?2 days) within each of the 3 households, occurring in clusters, indicates that a common environmental source of exposure is the most likely explanation for infection. No additional cases were identified through the active followup of contacts of cases, including health-care personnel.
Factors influencing human susceptibility to influenza A(H5N1) infection and those associated with severe disease are poorly understood. Some behaviours are likely to increase the risk of becoming infected (for example, the slaughtering and defeathering of infected birds). However, among the families investigated in eastern Turkey, even though both children and parents had most likely been exposed to the same source, infection was documented only among children aged <16 years. To some extent, this reflects the same age distribution observed globally, where 50.5% of cases occurred among people aged <20 years, and it suggests that age-related factors may influence susceptibility to the disease. The 4 fatalities occurred in children aged 12?15 years, while the 4 children who recovered were aged 3?9 years. This reflects closely the global situation where the highest case?fatality rate (73%) has been observed in the 10?19-year age group.4
Footnotes:
1) 1 The international response team included members from the Swedish Central Field Epidemiology Group; the Israeli Medical Association; Institut de Veille Sanitaire, France; the United States Centers for Disease Control and Prevention; the European Centre for Disease Prevention and Control, Stockholm, Sweden; the European Union; the National Institute for Medical Research in London, England; the United Nations Food and Agriculture Organization; UNICEF; and WHO.
2) A probable case was defined as an individual presenting with fever and contact with birds or a with an individual with an illness compatible with influenza A(H5N1) infection.
3) 3 Giesecke J. Human cases of avian influenza in eastern Turkey: the weather factor. Eurosurveillance, 2006, 11: E060119 (available from
http://www.eurosurveillance. org/ew/2006/060119.asp).
4) 4 See No. 81, 2006, pp. 249?257.
http://www.who.int/wer/2006/wer8143.pdf
