Edwin Michael

Burkholderia pseudomallei, the causative agent of melioidosis is an important cause of morbidity and mortality particularly among diabetics. We evaluated 228 isolates of B. pseudomallei for antimicrobial sensitivity during 2005-2010 using the disc diffusion technique, of which 144 were obtained from blood culture. More than 90% of the strains were susceptible to cefoperazone, ceftazidime, chloramphenicol and imipenem. Eighty-two percent of the isolates were susceptible to tetracycline and amoxicillin/clavulanate. The susceptibilities to ciprofloxacin was 78% and to trimethoprim-sulfamethoxezole was 47%. The susceptibilities to aminoglycoside antibiotics were low (21% to gentamicin and 6% to amikacin). The susceptibilities were similar between isolates from females and males, bacteremic and abacteremic cases, diabetics and non-diabetics, pneumonia and non-pneumonia cases and between those who died and those who survived. Our findings show antibiotic susceptibility patterns are not a major factor in determining outcomes of B. pseudomallei infection. Monitoring the drug susceptibilities among B. pseudomallei isolates needs to be conducted regularly to guide empiric therapy for melioidosis, as it causes high mortality, especially among diabetic cases.

The increasing proliferation of mobiles offers possibilities for improving health systems in developing countries. A case in point is Tanzania which has piloted a mobile phone-based Management Information System (MIS) for the control of neglected tropical diseases (NTDs) where village health workers (VHWs) were given mobile phones with web-based software to test the feasibility of using frontline health workers to capture data at point of source. Based on qualitative case study research carried out in 2011, we found that providing mobile phones to VHWs has helped to increase the efficiency of routine work boosting the motivation and self-esteem of VHWs. However, despite these advantages, the information generated from the mobile phone-based NTD MIS has yet to be used to support decentralised decision-making. Even with improved technology and political will, the biggest hindrance to local usage of information for health planning is the lack of synthesised and analysed health information from the district and national levels to the villages. Without inculcating a culture of providing health information feedback to frontline workers and community organisations, the benefits of the intervention will be limited. If not addressed, this will mean that mobiles have maintained the one-way upward flow of information for NTD control and simply made reporting more hi-tech.

Background: Melioidosis, a severe and fatal infectious disease caused by Burkholderia pseudomallei, is believed to an emerging global threat. However, data on the natural history, risk factors, and geographic epidemiology of the disease are still limited. Methods: We undertook a retrospective analysis of 145 confirmed cases extracted from a hospital-based Melioidosis Registry set up from 2005 in Hospital Sultanah Bahiyah, Alor Setar, Kedah state, Malaysia, in order to provide a first description of the contemporary incidence, risk factors, and clinical epidemiology of the disease in this putatively high risk region of the country. Results: The incidence of melioidosis in Alor Setar is remarkably high at 16.35 per 100,000 population per year. The mean age of patients was 50.40 years, with infection varying nonlinearly with age. Males (75.2%; P < 0.0001) predominated and the majority of cases were Malays (88.9%). The overall, crude mortality rate among the study patients was 33.8%. The proportions of cases and deaths were significantly greater among patients involved in farming, forestry and fishing and the unemployed (χ² = 30.57, P < 0.0001). A majority of cases (62.75%) were culture positive, with mortality in these patients being 45.05%. A large proportion (83.0%) of culture positives was also bacteremic. Pneumonia accounted for 42.06% of primary diagnoses followed in importance by soft tissue abscess. In patients with pneumonia and who were culture positive, the mortality rate was as high as 65.00%. Diabetes mellitus constituted the major underlying risk factor for developing and dying from melioidosis, occurring in 57% of all diagnosed cases. The age distribution of diabetes paralleled that of melioidosis cases. There were linear associations between cases and deaths with monthly rainfall. Conclusions: Melioidosis represents a complex socio-ecological public health problem in Kedah, being strongly related with age, occupation, rainfall and predisposing chronic diseases, such as diabetes mellitus. Among cases, bacteremic patients were associated with significantly high mortality despite provision of the recommended antibacterial therapy. The burden of this disease is likely to grow in this region unless better informed interventions targeted at high-risk groups and associated diseases are urgently implemented.

Large-scale intervention programmes to control or eliminate several infectious diseases are currently underway worldwide. However, a major unresolved question remains: what are reasonable stopping points for these programmes? Recent theoretical work has highlighted how the ecological complexity and heterogeneity inherent in the transmission dynamics of macroparasites can result in elimination thresholds that vary between local communities. Here, we examine the empirical evidence for this hypothesis and its implications for the global elimination of the major macroparasitic disease, lymphatic filariasis, by applying a novel Bayesian computer simulation procedure to fit a dynamic model of the transmission of this parasitic disease to field data from nine villages with different ecological and geographical characteristics. Baseline lymphatic filariasis microfilarial age-prevalence data from three geographically distinct endemic regions, across which the major vector populations implicated in parasite transmission also differed, were used to fit and calibrate the relevant vector-specific filariasis transmission models. Ensembles of parasite elimination thresholds, generated using the Bayesian fitting procedure, were then examined in order to evaluate site-specific heterogeneity in the values of these thresholds and investigate the ecological factors that may underlie such variability

Along-standing gap in lymphatic filariasis epidemiology is quantifying the potential effect that heterogeneous infection processes occurring in the major mosquito vector genera may have on parasite transmission and control. Although previous studies have focussed on examining the forms of the density dependent mechanisms regulating larval infection in various mosquito genera, there has been little work done thus far in investigating how such differential processes might interact with density-dependent processes occurring in other stages of the parasite life cycle to influence overall transmission dynamics between areas exposed to different transmitting vector populations. Here, we explore the impact that differences in vector genus-related larval infection dynamics may have on filariasis transmission and control using newly derived parasite transmission models incorporating the forms of the density-dependent processes regulating larval infection in the two major vectors transmitting filariasis, viz. culicine and anopheline mosquitoes. The key finding in this work is that filarial infection thresholds, system resilience, transmission dynamics and parasite response to control efforts, can all be influenced by the prevailing transmitting mosquito genus. In particular, we show that infection thresholds may be raised, system resilience to perturbations lowered and effects of repeated mass treatments in eliminating infection enhanced in anopheline filariasis compared to culicine filariasis, as a direct result of the occurrence and action of multiple positive density-dependent mechanisms influencing infection in this vector-parasite system, such as the “facilitation” function regulating larval infection dynamics in the vector and the inverse probability function governing adult worm mating in the host. These findings indicate that anopheline filariasis may be easier to eradicate than culicine filariasis for a given precontrol infection level, although the actual intensity of interventions required to achieve eradication may in fact be similar to that for culicine filariasis because of the higher infection levels generated as a result of the “facilitation” process in Anopheles transmission areas.

The planning and evaluation of parasitic control programmes are complicated by the many interacting population dynamic and programmatic factors that determine infection trends under different control options. A key need is quantification about the status of the parasite system state at any one given timepoint and the dynamic change brought upon that state as an intervention program proceeds. Here, we focus on the control and elimination of the vector-borne disease, lymphatic filariasis, to show how mathematical models of parasite transmission can provide a quantitative framework for aiding the design of parasite elimination and monitoring programs by their ability to support (1) conducting rational analysis and definition of endpoints for different programmatic aims or objectives, including transmission endpoints for disease elimination, (2) undertaking strategic analysis to aid the optimal design of intervention programs to meet set endpoints under different endemic settings and (3) providing support for performing informed evaluations of ongoing programs, including aiding the formation of timely adaptive management strategies to correct for any observed deficiencies in program effectiveness. The results also highlight how the use of a model-based framework will be critical to addressing the impacts of ecological complexities, heterogeneities and uncertainties on effective parasite management and thereby guiding the development of strategies to resolve and overcome such real-world complexities. In particular, we underscore how this approach can provide a link between ecological science and policy by revealing novel tools and measures to appraise and enhance the biological controllability or eradicability of parasitic diseases. We conclude by emphasizing an urgent need to develop and apply flexible adaptive management frameworks informed by mathematical models that are based on learning and reducing uncertainty using monitoring data, apply phased or sequential decision-making to address extant uncertainty and focus on developing ecologically resilient management strategies, in ongoing efforts to control or eliminate filariasis and other parasitic diseases in resource-poor communities.

The survival rate of infected vectors represents one of the fundamental components that influence the transmission dynamics of mosquito-borne diseases. Despite the occurrence of a number of studies investigating mosquito survival after infection with filarial worms, there remains conflicting evidence from both laboratory and field experiments as to the existence and mechanism for parasite-induced mortality among filarial mosquitoes. Here, we used a mixed effects meta-analytical framework to combine the data from all available vector-human host blood feeding experiments to evaluate the evidence for the impact of parasite load on the mortality rates of the three major lymphatic filariasis transmitting mosquito genera, Culex, Aedes, and Anopheles mosquitoes, over the extrinsic incubation period of parasitic infection. The results show that, despite the application of this approach, or in the case of Anopheles using a convention fixed effects logistic regression analysis supplemented with additional survival analysis of longitudinal data, no strong association between mortality rate and microfilariae (mf) uptake for either of the three mosquito genera is apparent in the combined data. Instead, a key finding is that study effects played a more crucial role in determining the levels of mortality observed in these experimental studies. This was most revealing in the case of Culex, given that the largest single study in terms of both the number of data points and range of mf intensities, in contrast to smaller studies, showed a significant positive association between mf intensity and mortality, indicating that in this genus at least, the detrimental effect of infection may be manifested only at the highest mf intakes. Although no density dependence in vector mortality was also observed for Aedes, possibly because of the use of restricted human mf intensity range in previous studies, an intriguing finding was that a significantly higher overall mortality was observed for this genus over mf intake ranges that produced much less corresponding mortality in Culex and Anopheles. The results also indicate that currently very little can be said about the survival rate of Anopheles mosquitoes infected with filarial worms because of the striking paucity of data for this genus. Further studies, using standardized methods and covering an appropriate range of mf uptake intensities and using study frameworks that allow the design and comparison of data from both experimental and field experiments, are clearly indicated if we are to reliably quantify the likely effect of filarial infection on vector survival.

The ultimate goal of the global programme against lymphatic filariasis is eradication through irrevocable cessation of transmission using 4 to 6 years of annual single dose mass drug administration. The costs of eradication, and logistical and managerial impediments to executing national and regional control programmes, and scientific uncertainty about transmission endpoints, are challenges to the success of this effort, especially in areas of high endemicity where financial resources are limited. We used a combined analysis of empirical community data describing the association between infection and chronic disease prevalence, mathematical modelling, and economic analyses to identify and evaluate the feasibility of setting an infection target level at which the chronic pathology attributable to lymphatic filariasis - lymphoedema of the extremities (elephantiasis) and hydroceles - becomes negligible in the face of continuing transmission as a first stage option in achieving the elimination of this parasitic disease. The results show that microfilaria prevalences below a threshold of 3.55% at a blood sampling volume of 1 ml could constitute readily achievable and sustainable targets to control disease due to lymphatic filariasis. They also show that as a result of the high marginal cost of curing the last few individuals to achieve elimination, maximal benefits can occur at the disease control threshold. Indeed, a key finding from our coupled economic and epidemiological analysis is that when initial uncertainty regarding eradication occurs and prospects for improving information to resolve such uncertainty over time exist, it is economically beneficial to adopt a flexible, sequential, eradication strategy based on controlling chronic disease initially. These results suggest that it may be optimal to set phased targets for the elimination of lymphatic filariasis, starting with disease control followed by intensified efforts to eradicate transmission as better knowledge regarding transmission dynamics and issues of implementation feasibility becomes evident. They also illustrate the importance of taking explicit accounts of uncertainties, multi-staged endpoints, and the value of embedding flexibility in the decision making process when determining optimal parasite eradication strategies.

Health is a serious development issue. The perceived link between health and development has been articulated in much of the policy and academic literature resulting in many initiatives to introduce integrated health information systems at the local level. Despite huge investments made in this direction, these systems have not made any radical impact on the delivery of healthcare for local communities. Drawing on empirical work in Tanzania, we argue that this has been because of the adoption of a narrow, managerialist perspective of “integration”. We propose instead an interpretation of integration from a variety of standpoints; development studies, management, and sociology. According to this approach, it is not just data that is integrated, but ways of working and the social relations which support the health information systems at global, national and local levels. In our discussion section, we broaden the scope of integrated health information systems to consider the integration of not just management information but also epidemiological data.

There is paucity of published data on the microfilarial infection among migrants from endemic countries entering Kuwait. The primary objectives of this study were to use routine health surveillance data to i) to estimate the prevalence of microfilarial infection in migrant workers to Kuwait and ii) to determine the occurrence of any time trends in the proportions of microfilaria positives among these workers over the recent past.