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.

Strengthening Indonesia's Field Epidemiology Training Programme to address International Health Regulations requirements.

PROBLEM: According to the International Health Regulations (IHR), countries need to strengthen core capacity for disease surveillance and response systems. Many countries are establishing or enhancing their field epidemiology training programmes (FETPs) to meet human resource needs but face challenges in sustainability and training quality. Indonesia is facing these challenges, which include limited resources for field training and limited coordination in a newly decentralized health system. APPROACH: A national FETP workplan was developed based on an evaluation of the existing programme and projected human resource needs. A Ministry of Health Secretariat linking universities, national and international partners was established to oversee revision and implementation of the FETP. LOCAL SETTING: The FETP is integrated into the curriculum of Indonesian universities and field training is conducted in district and provincial health offices under the coordination of the universities and the FETP Secretariat. RELEVANT CHANGES: The FETP was included in the Ministry of Health workforce development strategy through governmental decree. Curricula have been enhanced and field placements strengthened to provide trainees with better learning experiences. To improve sustainability of the FETP, links were established with the Indonesian Epidemiologists' Association, local governments and donors to cultivate future FETP champions and maintain funding. Courses, competitions and discussion forums were established for field supervisors and alumni. These changes have increased the geographic distribution of students, intersectoral and international participation and the quality of student performance. LESSONS LEARNT: The main lesson learnt is that linkages with universities, ministries and international agencies such as the World Health Organization are critical for building a sustainable high-quality programme. The most critical factors were development of trusting relationships and clear definitions of the responsibilities of each stakeholder.

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.