James W. Rudge

Emerging infectious diseases in southeast Asia: regional challenges to control

Summary Southeast Asia is a hotspot for emerging infectious diseases, including those with pandemic potential. Emerging infectious diseases have exacted heavy public health and economic tolls. Severe acute respiratory syndrome rapidly decimated the regions tourist industry. Influenza A H5N1 has had a profound effect on the poultry industry. The reasons why southeast Asia is at risk from emerging infectious diseases are complex. The region is home to dynamic systems in which biological, social, ecological, and technological processes interconnect in ways that enable microbes to exploit new ecological niches. These processes include population growth and movement, urbanisation, changes in food production, agriculture and land use, water and sanitation, and the effect of health systems through generation of drug resistance. Southeast Asia is home to about 600 million people residing in countries as diverse as Singapore, a city state with a gross domestic product (GDP) of US

Parasite genetic differentiation by habitat type and host species: molecular epidemiology of Schistosoma japonicum in hilly and marshland areas of Anhui Province, China

37 500 per head, and Laos, until recently an overwhelmingly rural economy, with a GDP of US

Population Genetics of Schistosoma japonicum within the Philippines Suggest High Levels of Transmission between Humans and Dogs

890 per head. The regional challenges in control of emerging infectious diseases are formidable and range from influencing the factors that drive disease emergence, to making surveillance systems fit for purpose, and ensuring that regional governance mechanisms work effectively to improve control interventions.

Contrasting reservoirs for Schistosoma japonicum between marshland and hilly regions in Anhui, China – a two-year longitudinal parasitological survey

Schistosoma japonicum, a parasite of significant public health importance in parts of China and Southeast Asia, is a true generalist pathogen with over 40 species of mammals suspected as definitive host reservoirs. In order to characterize levels of parasite gene flow across host species and identify the most important zoonotic reservoirs, S. japonicum larvae (miracidia) were sampled from a range of definitive host species in two contrasting habitat types within Anhui Province, China: a low‐lying marshland region, and a hilly region, where animal reservoir populations may be predicted to differ substantially. Miracidia samples were genotyped using seven multiplexed microsatellite markers. Hierarchical F‐statistics and clustering analyses revealed substantial geographical structuring of S. japonicum populations within Anhui, with strong parasite genetic differentiation between habitat types. Within most villages, there was very little or no parasite genetic differentiation among host species, suggesting frequent S. japonicum gene flow, and thus also transmission, across species. Moreover, the data provide novel molecular evidence that rodents and dogs are potentially very important infection reservoirs in hilly regions, in contrast to bovines in the marshland regions. The parasite genetic differentiation between habitat types might therefore be associated with contrasting host reservoirs. The high levels of parasite gene flow observed across host species in sympatric areas have important implications for S. japonicum control, particularly in hilly regions where control of infection among wild rodent populations could be challenging.

Identifying host species driving transmission of schistosomiasis japonica, a multihost parasite system, in China

Background Schistosoma japonicum, which remains a major public health problem in the Philippines and mainland China, is the only schistosome species for which zoonotic transmission is considered important. While bovines are suspected as the main zoonotic reservoir in parts of China, the relative contributions of various non-human mammals to S. japonicum transmission in the Philippines remain to be determined. We examined the population genetics of S. japonicum in the Philippines in order to elucidate transmission patterns across host species and geographic areas. Methodology/Principal Findings S. japonicum miracidia (hatched from eggs within fecal samples) from humans, dogs, pigs and rats, and cercariae shed from snail-intermediate hosts, were collected across two geographic areas of Samar Province. Individual isolates were then genotyped using seven multiplexed microsatellite loci. Wrights FST values and phylogenetic trees calculated for parasite populations suggest a high frequency of parasite gene-flow across definitive host species, particularly between dogs and humans. Parasite genetic differentiation between areas was not evident at the definitive host level, possibly suggesting frequent import and export of infections between villages, although there was some evidence of geographic structuring at the snail–intermediate host level. Conclusions/Significance These results suggest very high levels of transmission across host species, and indicate that the role of dogs should be considered when planning control programs. Furthermore, a regional approach to treatment programs is recommended where human migration is extensive.

Transmission of Schistosoma japonicum in Marshland and Hilly Regions of China: Parasite Population Genetic and Sibship Structure

Schistosoma japonicum remains highly endemic in many counties in China and has recently re-emerged, to a large extent, in previously controlled areas. To test the hypothesis that small rodents and less agriculturally important domestic animals such as dogs and cats may play an important role in the transmission and potential re-emergence of this disease, an annual investigation of S. japonicum among humans, domestic animals and rodents, combined with detailed surveys of the snail intermediate host, was performed across 3 marshland villages and 3 hilly villages in Anhui province of China over 2 consecutive years. The highest infection prevalence and intensity observed across all mammals was in rodents in the hilly region; while in the marshland, bovines were suspected as the main reservoirs. However, relatively high infection prevalence levels were also found in dogs and cats in both regions. Such results may have implications for the current human- and bovine-oriented control policy for this medically and veterinarily important disease, particularly within the hilly regions of mainland China.

Health System Resource Gaps and Associated Mortality from Pandemic Influenza across Six Asian Territories

Understanding disease transmission dynamics in multihost parasite systems is a research priority for control and potential elimination of many infectious diseases. In China, despite decades of multifaceted control efforts against schistosomiasis, the indirectly transmitted helminth Schistosoma japonicum remains endemic, partly because of the presence of zoonotic reservoirs. We used mathematical modeling and conceptual frameworks of multihost transmission ecology to assess the relative importance of various definitive host species for S. japonicum transmission in contrasting hilly and marshland areas of China. We examine whether directing control interventions against zoonotic reservoirs could further reduce incidence of infection in humans or even eliminate transmission. Results suggest that, under current control programs, infections in humans result from spillover of transmission among zoonotic reservoirs. Estimates of the basic reproduction number within each species suggest that bovines (water buffalo and cattle) maintained transmission in the marshland area and that the recent removal of bovines from this area could achieve local elimination of transmission. However, the sole use of antifecundity S. japonicum vaccines for bovines, at least at current efficacies, may not achieve elimination in areas of comparable endemicity where removal of bovines is not a feasible option. The results also suggest that rodents drive transmission in the hilly area. Therefore, although targeting bovines could further reduce and potentially interrupt transmission in marshland regions of China, elimination of S. japonicum could prove more challenging in areas where rodents might maintain transmission. In conclusion, we show how mathematical modeling can give important insights into multihost transmission of indirectly transmitted pathogens.

Critical interactions between Global Fund-supported programmes and health systems: a case study in Indonesia

The transmission dynamics of Schistosoma japonicum remain poorly understood, as over forty species of mammals are suspected of serving as reservoir hosts. However, knowledge of the population genetic structure and of the full-sibship structuring of parasites at two larval stages will be useful in defining and tracking the transmission pattern between intermediate and definitive hosts. S. japonicum larvae were therefore collected in three marshland and three hilly villages in Anhui Province of China across three time points: April and September-October 2006, and April 2007, and then genotyped with six microsatellite markers. Results from the population genetic and sibling relationship analyses of the parasites across two larval stages demonstrated that, within the marshland, parasites from cattle showed higher genetic diversity than from other species; whereas within the hilly region, parasites from dogs and humans displayed higher genetic diversity than those from rodents. Both the extent of gene flow and the estimated proportion of full-sib relationships of parasites between two larval stages indicated that the cercariae identified within intermediate hosts in the marshlands mostly came from cattle, whereas in the hilly areas, they were varied between villages, coming primarily from rodents, dogs or humans. Such results suggest a different transmission process within the hilly region from within the marshlands. Moreover, this is the first time that the sibling relationship analysis was applied to the transmission dynamics for S. japonicum.

Critical interactions between Global Fund-supported programmes and health systems: a case study in Lao People's Democratic Republic

Background Southeast Asia has been the focus of considerable investment in pandemic influenza preparedness. Given the wide variation in socio-economic conditions, health system capacity across the region is likely to impact to varying degrees on pandemic mitigation operations. We aimed to estimate and compare the resource gaps, and potential mortalities associated with those gaps, for responding to pandemic influenza within and between six territories in Asia. Methods and Findings We collected health system resource data from Cambodia, Indonesia (Jakarta and Bali), Lao PDR, Taiwan, Thailand and Vietnam. We applied a mathematical transmission model to simulate a “mild-to-moderate” pandemic influenza scenario to estimate resource needs, gaps, and attributable mortalities at province level within each territory. The results show that wide variations exist in resource capacities between and within the six territories, with substantial mortalities predicted as a result of resource gaps (referred to here as “avoidable” mortalities), particularly in poorer areas. Severe nationwide shortages of mechanical ventilators were estimated to be a major cause of avoidable mortalities in all territories except Taiwan. Other resources (oseltamivir, hospital beds and human resources) are inequitably distributed within countries. Estimates of resource gaps and avoidable mortalities were highly sensitive to model parameters defining the transmissibility and clinical severity of the pandemic scenario. However, geographic patterns observed within and across territories remained similar for the range of parameter values explored. Conclusions The findings have important implications for where (both geographically and in terms of which resource types) investment is most needed, and the potential impact of resource mobilization for mitigating the disease burden of an influenza pandemic. Effective mobilization of resources across administrative boundaries could go some way towards minimizing avoidable deaths.

Critical interactions between Global Fund-supported programmes and health systems: a case study in Papua New Guinea

The Global Fund to Fight AIDS, Tuberculosis and Malaria has played an important role in financing the response to HIV/AIDS and tuberculosis (TB) in Indonesia. As part of a series of case studies, we assessed the nature and extent of integration of Global Fund portfolios into the national HIV and TB programmes, integration of the HIV and TB programmes within the general health system, and system-wide effects of Global Fund support on the health care system in Indonesia. The study relied on a literature review and interviews with 22 key informants using the Systemic Rapid Assessment Toolkit and thematic analysis. Global Fund programmes in Indonesia are highly vertical and centralized, in contrast with the decentralized nature of the Indonesian health system. Consequently, there is more integration of all functions at local levels than centrally. There is a high level of integration of planning of Global Fund HIV and TB portfolios into the National AIDS and TB programmes and some limited integration of these programmes with other disease programmes, through joint working groups. Other synergies include strengthening of stewardship and governance and increased staff recruitment encouraged by incentive payments and training. Monitoring and evaluation functions of the Global Fund programmes are not integrated with the disease programmes, with parallel indicators and reporting systems. System-wide effects include greater awareness of governance and stewardship in response to the temporary suspension of Global Fund funding in 2008, and increased awareness of the need to integrate programme planning, financing and service delivery. Global Fund investment has freed up resources for other programmes, particularly at local levels. However, this may hinder a robust exit strategy from Global Fund funding. Furthermore, Global Fund monetary incentives may result in staff shifting into HIV and TB programmes.