Risk factors for cluster outbreaks of avian influenza A H5N1 infection, Indonesia.

BACKGROUND: By 30 July 2009, Indonesia had reported 139 outbreaks of avian influenza (AI) H5N1 infection in humans. Risk factors for case clustering remain largely unknown. This study assesses risk factors for cluster outbreaks and for secondary case infection. METHODS: The 113 sporadic and 26 cluster outbreaks were compared on household and individual level variables. Variables assessed include those never reported previously, including household size and genealogical relationships between cases and their contacts. RESULTS: Cluster outbreaks had larger households and more blood-related contacts, especially first-degree relatives, compared with sporadic case outbreaks. Risk factors for cluster outbreaks were the number of first-degree blood-relatives to the index case (adjusted odds ratio [aOR], 1.50; 95% confidence interval [CI]: 1.20-1.86) and index cases having direct exposure to sources of AI H5N1 virus (aOR, 3.20; 95% CI: 1.15-8.90). Risk factors for secondary case infection were being aged between 5 and 17 years (aOR, 8.32; 95% CI: 1.72-40.25), or 18 and 30 years (aOR, 6.04; 95% CI: 1.21-30.08), having direct exposure to sources of AI H5N1 virus (aOR, 3.48; 95% CI: 1.28-9.46), and being a first-degree relative to an index case (aOR, 11.0; 95% CI: 1.43-84.66). Siblings to index cases were 5 times more likely to become secondary cases (OR, 4.72; 95% CI: 1.67-13.35). CONCLUSIONS: The type of exposure and the genealogical relationship between index cases and their contacts impacts the risk of clustering. The study adds evidence that AI H5N1 infection is influenced by, and may even depend on, host genetic susceptibility.

Factors associated with case fatality of human H5N1 virus infections in Indonesia: a case series.

BACKGROUND: Indonesia has had the most human cases of highly pathogenic avian influenza A (H5N1) and one of the highest case-fatality rates worldwide. We described the factors associated with H5N1 case-fatality in Indonesia. METHODS: Between June, 2005, and February, 2008, there were 127 confirmed H5N1 infections. Investigation teams were deployed to investigate and manage each confirmed case; they obtained epidemiological and clinical data from case-investigation reports when possible and through interviews with patients, family members, and key individuals. FINDINGS: Of the 127 patients with confirmed H5N1 infections, 103 (81%) died. Median time to hospitalisation was 6 days (range 1-16). Of the 122 hospitalised patients for whom data were available, 121 (99%) had fever, 107 (88%) cough, and 103 (84%) dyspnoea on reaching hospital. However, for the first 2 days after onset, most had non-specific symptoms; only 31 had both fever and cough, and nine had fever and dyspnoea. Median time from onset to oseltamivir treatment was 7 days (range 0-21 days); treatment started within 2 days for one patient who survived, four (36.4%) of 11 receiving treatment within 2-4 days survived, six (37.5%) of 16 receiving treatment within 5-6 days survived, and ten (18.5%) of 44 receiving treatment at 7 days or later survived (p=0.03). Initiation of treatment within 2 days was associated with significantly lower mortality than was initiation at 5-6 days or later than 7 days (p<0.0001). Mortality was lower in clustered than unclustered cases (odds ratio 33.3, 95% CI 3.13-273). Treatment started at a median of 5 days (range 0-13 days) from onset in secondary cases in clusters compared with 8 days (range 4-16) for primary cases (p=0.04). INTERPRETATION: Development of better diagnostic methods and improved case management might improve identification of patients with H5N1 influenza, which could decrease mortality by allowing for earlier treatment with oseltamivir.

Three Indonesian clusters of H5N1 virus infection in 2005.

BACKGROUND: Since 2003, the widespread ongoing epizootic of avian influenza A (H5N1) among poultry and birds has resulted in human H5N1 cases in 10 countries. The first case of H5N1 virus infection in Indonesia was identified in July 2005. METHODS: We investigated three clusters of Indonesian cases with at least two ill persons hospitalized with laboratory evidence of H5N1 virus infection from June through October 2005. Epidemiologic, clinical, and virologic data on these patients were collected and analyzed. RESULTS: Severe disease occurred among all three clusters, including deaths in two clusters. Mild illness in children was documented in two clusters. The median age of the eight patients was 8.5 years (range, 1 to 38). Four patients required mechanical ventilation, and four of the eight patients (50%) died. In each cluster, patients with H5N1 virus infection were members of the same family, and most lived in the same home. In two clusters, the source of H5N1 virus infection in the index patient was not determined. Virus isolates were available for one patient in each of two clusters, and molecular sequence analyses determined that the isolates were clade 2 H5N1 viruses of avian origin. CONCLUSIONS: In 2005 in Indonesia, clusters of human infection with clade 2 H5N1 viruses included mild, severe, and fatal cases among family members.

Avian influenza H5N1 transmission in households, Indonesia.

BACKGROUND: Disease transmission patterns are needed to inform public health interventions, but remain largely unknown for avian influenza H5N1 virus infections. A recent study on the 139 outbreaks detected in Indonesia between 2005 and 2009 found that the type of exposure to sources of H5N1 virus for both the index case and their household members impacted the risk of additional cases in the household. This study describes the disease transmission patterns in those outbreak households. METHODOLOGY/PRINCIPAL FINDINGS: We compared cases (n = 177) and contacts (n = 496) in the 113 sporadic and 26 cluster outbreaks detected between July 2005 and July 2009 to estimate attack rates and disease intervals. We used final size household models to fit transmission parameters to data on household size, cases and blood-related household contacts to assess the relative contribution of zoonotic and human-to-human transmission of the virus, as well as the reproduction number for human virus transmission. The overall household attack rate was 18.3% and secondary attack rate was 5.5%. Secondary attack rate remained stable as household size increased. The mean interval between onset of subsequent cases in outbreaks was 5.6 days. The transmission model found that human transmission was very rare, with a reproduction number between 0.1 and 0.25, and the upper confidence bounds below 0.4. Transmission model fit was best when the denominator population was restricted to blood-related household contacts of index cases. CONCLUSIONS/SIGNIFICANCE: The study only found strong support for human transmission of the virus when a single large cluster was included in the transmission model. The reproduction number was well below the threshold for sustained transmission. This study provides baseline information on the transmission dynamics for the current zoonotic virus and can be used to detect and define signatures of a virus with increasing capacity for human-to-human transmission.

Rabies awareness in eight Asian countries.

Rabies is a deadly zoonotic disease most often transmitted to humans through a dog bite. Human mortality from endemic canine rabies is estimated by WHO to be around 55,000 deaths annually, with over 31,000 deaths in Asia alone, mostly children. Most of these deaths could be prevented through post-exposure prophylaxis (PEP), including immediate wound washing, rabies immunoglobulin administration and vaccination. Unfortunately, at-risk populations are not well-informed of the risk of rabies and what to do in the event of an animal bite. In order to identify the main gaps in rabies information and better define the most urgent information actions to be undertaken, the Asian Rabies Expert Bureau (AREB) conducted a multicentre, multi-country survey of patients seeking rabies post-exposure prophylaxis in rabies prevention centres from 1 July 2007 to 31 January 2008, in Bangladesh, China, India, Indonesia, Pakistan, the Philippines, Sri Lanka, and Thailand. Questionnaires were completed for 4377 subjects in the eight countries. Data was collected regarding the patient, former rabies exposures, the present wound, rabies exposure management, and rabies awareness. Two major issues were identified where active information of the population could make a difference: the necessity to apply appropriate wound care and to consult the nearest rabies prevention centre as soon as possible.