The elimination of human African trypanosomiasis: Monitoring progress towards the 2021-2030 WHO road map targets.

BACKGROUND: Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021-2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e. reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level. METHODOLOGY/PRINCIPAL FINDINGS: Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018-2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000-2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021-2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. CONCLUSIONS/SIGNIFICANCE: HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021-2030.

Accelerating Progress Towards the 2030 Neglected Tropical Diseases Targets: How Can Quantitative Modeling Support Programmatic Decisions?

Over the past decade, considerable progress has been made in the control, elimination, and eradication of neglected tropical diseases (NTDs). Despite these advances, most NTD programs have recently experienced important setbacks; for example, NTD interventions were some of the most frequently and severely impacted by service disruptions due to the coronavirus disease 2019 (COVID-19) pandemic. Mathematical modeling can help inform selection of interventions to meet the targets set out in the NTD road map 2021-2030, and such studies should prioritize questions that are relevant for decision-makers, especially those designing, implementing, and evaluating national and subnational programs. In September 2022, the World Health Organization hosted a stakeholder meeting to identify such priority modeling questions across a range of NTDs and to consider how modeling could inform local decision making. Here, we summarize the outputs of the meeting, highlight common themes in the questions being asked, and discuss how quantitative modeling can support programmatic decisions that may accelerate progress towards the 2030 targets.

Towards enhanced control of mycetoma: a roadmap to achieve the UN's sustainable development goals by 2030.

Mycetoma is a neglected tropical disease (NTD) with devastating morbidity and stigma. Despite increased awareness and international collaboration, the burden of mycetoma is largely unknown and diagnosis and treatment are difficult. Addressing mycetoma globally aligns with several United Nation's Sustainable Development Goals (SDGs). Little progress has been made since the WHO's NTD roadmap publication in 2020. The Global Mycetoma Working Group proposes an enhanced mycetoma-control roadmap to meet the SDGs, stimulate progress and improve the lives of patients experiencing mycetoma. By aligning mycetoma management with the goals and targets of this enhanced roadmap, it becomes possible to leverage existing resources, infrastructure and partnerships to improve the lives of affected individuals and communities. This updated assessment is designed for the benefit of health workers and providers in mycetoma-endemic areas, NTD government officials, civil society and funding and implementing agencies.

Social determinants of visceral leishmaniasis elimination in Eastern Africa.

Visceral leishmaniasis is a vector-borne, protozoan disease with severe public health implications. Following the successful implementation of an elimination programme in South Asia, there is now a concerted endeavour to replicate these efforts in Eastern Africa based on the five essential elimination pillars of case management, integrated vector management, effective surveillance, social mobilisation and operational research. This article highlights how key social determinants (SD) of health (poverty, sociocultural factors and gender, housing and clustering, migration and the healthcare system) operate at five different levels (socioeconomic context and position, differential exposure, differential vulnerability, differential outcomes and differential consequences). These SD should be considered within the context of increasing the success of the five-pillar elimination programme and reducing inequity in health.

Research priorities to support the development of integrated national strategies to control skin-neglected tropical diseases.

BACKGROUND: Skin-presenting neglected tropical diseases (skin-NTDs) impose large burdens on affected people, families and communities. The NTD Roadmap 2021-2030 presents a strategic plan to guide collaborative, multisectoral action to overcome these burdens, defining targets to control, eliminate and/or eradicate skin-NTDs by 2030. One of its targets is for 40 countries to adopt integrated skin-NTD strategies. Despite this high-level support for integration, only four countries were implementing integrated skin-NTD strategies in 2020. METHODS: We hosted workshops at the 2021 annual meeting of the Coalition for Operational Research on NTDs, to discuss the operationalisation of Roadmap goals into national strategies and interventions for skin-NTD control. Speakers included NTD Programme Managers from NTD-endemic countries, technical experts and researchers of different aspects of skin-NTDs. RESULTS: Challenges include community perceptions of interventions, demonstrating the cost-effectiveness of integrated care, availability and accessibility of community-based and primary healthcare services, the quality of data on skin-NTD morbidity and changes to operational structures required for integration. Research priorities included the identification of optimal case detection platforms, evaluation of integrated care, understanding the impacts of integration on community members and community health staff and development of point-of-care diagnostics. CONCLUSIONS: The operational research priorities are intended to support the scale-up of integrated skin-NTDs programmes.

Diagnostics to support mycetoma management-Development of two target product profiles.

OBJECTIVE: Mycetoma is a neglected tropical disease caused by more than 70 different microorganisms and identified by the WHO as one of the high-priority diseases for developing diagnostic tests. To ensure the production of diagnostic assays for use by clinical staff in endemic regions, target product profiles (TPPs) were designed. METHODS: We describe the development of two TPPs: one for a diagnostic test able to identify the causative agent of mycetoma and another that would determine when treatment could be stopped. The TPPs were developed by considering product use, design, performance, product configuration and costs. RESULTS: Version 1.0 TPPs for two uses were posted by WHO for a 1-month online public consultation on 25 October 2021, and the final TPP was posted online on 5 May 2022. CONCLUSION: A major difficulty encountered in developing both TPPs was the large number of agents able to cause mycetoma and the lack of specific biomarkers for most of them.

Landscape analysis of NTD diagnostics and considerations on the development of a strategy for regulatory pathways.

Access to quality-assured, accurate diagnostics is critical to ensure that the 2021-2030 neglected tropical disease (NTD) road map targets can be achieved. Currently, however, there is limited regulatory oversight and few quality assurance mechanisms for NTD diagnostic tools. In attempting to address such challenges and the changing environment in regulatory requirements for diagnostics, a landscape analysis was conducted, to better understand the availability of NTD diagnostics and inform future regulatory frameworks. The list of commercially available diagnostics was compiled from various sources, including WHO guidance, national guidelines for case detection and management, diagnostic target product profiles and the published literature. The inventory was analyzed according to diagnostic type, intended use, regulatory status, and risk classification. To estimate the global need and size of the market for each type of diagnostic, annual procurement data were collected from WHO, procurement agencies, NGOs and international organizations, where available and global disease prevalence. Expert interviews were also conducted to ensure a better understanding of how diagnostics are procured and used. Of 125 diagnostic tools included in this analysis, rapid diagnostic tools accounted for 33% of diagnostics used for NTDs and very few diagnostics had been subjected to regulatory assessment. The number of tests needed for each disease was less than 1 million units per annum, except in the case of two diseases, suggesting limited commercial value. Despite the nature of the market, and presumed insufficient return on commercial investment, acceptable levels of assurance on performance, quality and safety of diagnostics are still required. Priority actions include setting up an agile, interim, stepwise risk assessment mechanism, in particular for diagnostics of lower risk, in order to support national NTD programmes and their partners with the selection and procurement of the diagnostics needed to control, eliminate and eradicate NTDs.

The elimination of human African trypanosomiasis: Achievements in relation to WHO road map targets for 2020.

BACKGROUND: In the 20th century, epidemics of human African trypanosomiasis (HAT) ravaged communities in a number of African countries. The latest surge in disease transmission was recorded in the late 1990s, with more than 35,000 cases reported annually in 1997 and 1998. In 2013, after more than a decade of sustained control efforts and steady progress, the World Health Assembly resolved to target the elimination of HAT as a public health problem by 2020. We report here on recent progress towards this goal. METHODOLOGY/PRINCIPAL FINDINGS: With 992 and 663 cases reported in 2019 and 2020 respectively, the first global target was amply achieved (i.e. fewer than 2,000 HAT cases/year). Areas at moderate or higher risk of HAT, where more than 1 case/10,000 people/year are reported, shrunk to 120,000 km2 for the five-year period 2016-2020. This reduction of 83% from the 2000-2004 baseline (i.e. 709,000 km2) is slightly below the target (i.e. 90% reduction). As a result, the second global target for HAT elimination as a public health problem cannot be considered fully achieved yet. The number of health facilities able to diagnose and treat HAT expanded (+9.6% compared to a 2019 survey), thus reinforcing the capacity for passive detection and improving epidemiological knowledge of the disease. Active surveillance for gambiense HAT was sustained. In particular, 2.8 million people were actively screened in 2019 and 1.6 million in 2020, the decrease in 2020 being mainly caused by COVID-19-related restrictions. Togo and Côte d'Ivoire were the first countries to be validated for achieving elimination of HAT as a public health problem at the national level; applications from three additional countries are under review by the World Health Organization (WHO). CONCLUSIONS/SIGNIFICANCE: The steady progress towards the elimination of HAT is a testament to the power of multi-stakeholder commitment and coordination. At the end of 2020, the World Health Assembly endorsed a new road map for 2021-2030 that set new bold targets for neglected tropical diseases. While rhodesiense HAT remains among the diseases targeted for elimination as a public health problem, gambiense HAT is targeted for elimination of transmission. The goal for gambiense HAT is expected to be particularly arduous, as it might be hindered by cryptic reservoirs and a number of other challenges (e.g. further integration of HAT surveillance and control into national health systems, availability of skilled health care workers, development of more effective and adapted tools, and funding for and coordination of elimination efforts).

Modelling the spatial distribution of mycetoma in Sudan.

BACKGROUND: Mycetoma is a neglected tropical disease that is reported worldwide and Sudan has the highest reported number of mycetoma infections across the globe. The incidence, prevalence and burden of mycetoma globally are not precisely known and its risk factors remain largely unelucidated. METHODS: This study aimed to identify the environmental predictors of fungal and bacterial mycetoma in Sudan and to identify areas of the country where these niche predictors are met. Demographic and clinical data from confirmed mycetoma patients seen at the Mycetoma Research Centre from 1991 to 2018 were included in this study. Regression and machine learning techniques were used to model the relationships between mycetoma occurrence in Sudan and environmental predictors. RESULTS: The strongest predictors of mycetoma occurrence were aridity, proximity to water, low soil calcium and sodium concentrations and the distribution of various species of thorny trees. The models predicted the occurrence of eumycetoma and actinomycetoma in the central and southeastern states of Sudan and along the Nile river valley and its tributaries. CONCLUSION: Our results showed that the risk of mycetoma in Sudan varies geographically and is linked to identifiable environmental risk factors. Suitability maps are intended to guide health authorities, academic institutes and organisations involved in planning national scale surveys for early case detection and management, leading to better patient treatment, prevention and control of mycetoma.

Medicine donation programmes supporting the global drive to end the burden of neglected tropical diseases.

Neglected tropical diseases (NTDs) are targeted for global control or elimination. Recognising that the populations most in need of medicines to target NTDs are those least able to support and sustain them financially, the pharmaceutical industry created mechanisms for donating medicines and expertise to affected countries through partnerships with the WHO, development agencies, non-governmental organisations and philanthropic donors. In the last 30 y, companies have established programmes to donate 17 different medicines to overcome the burden of NTDs. Billions of tablets, capsules, intravenous and oral solutions have been donated, along with the manufacturing, supply chains and research necessary to support these efforts. Industry engagement has stimulated other donors to support NTDs with funds and oversight so that the 'heath benefit' return on investment in these programmes is truly a 'best value in public health'. Many current donations are 'open-ended', promising support as long as necessary to achieve defined health targets. Extraordinary global health advances have been made in filariasis, onchocerciasis, trachoma, trypanosomiasis, leishmaniasis, schistosomiasis, intestinal parasites and others; and these advances are taking place in the context of strengthening health systems and meeting the global development goals espoused by the WHO. The pharmaceutical manufacturers, already strong collaborators in initiating or supporting these disease-targeted programmes, have committed to continuing their partnership roles in striving to meet the targets of the WHO's new NTD roadmap to 2030.

Diagnostics and the neglected tropical diseases roadmap: setting the agenda for 2030.

Accurate and reliable diagnostic tools are an essential requirement for neglected tropical diseases (NTDs) programmes. However, the NTD community has historically underinvested in the development and improvement of diagnostic tools, potentially undermining the successes achieved over the last 2 decades. Recognizing this, the WHO, in its newly released draft roadmap for NTD 2021-2030, has identified diagnostics as one of four priority areas requiring concerted action to reach the 2030 targets. As a result, WHO established a Diagnostics Technical Advisory Group (DTAG) to serve as the collaborative mechanism to drive progress in this area. Here, the purpose and role of the DTAG are described in the context of the challenges facing NTD programmes.

Podoconiosis: key priorities for research and implementation.

Podoconiosis is a non-infectious tropical lymphoedema causing swelling of the lower legs. Podoconiosis is associated with stigma, depression and reduced productivity, resulting in significant socio-economic impacts for affected individuals, families and communities. It is caused by barefoot exposure to soils and affects disadvantaged populations. Evidence from the past 5 y suggests that podoconiosis is amenable to public health interventions, e.g. footwear and hygiene-based morbidity management, which reduce acute clinical episodes. Although much has been learned in recent years, advances in care for these patients and worldwide control requires further reliable and relevant research. To develop a comprehensive global control strategy, the following key research priorities are important: better understanding of the global burden of podoconiosis through extended worldwide mapping, development of new point-of-care diagnostic methods and approaches to define the presence of the environmental characteristics that contribute to the development of the condition, improving treatment through an increased understanding of the pathogenesis of dermal changes over time, improved understanding of optimal ways of providing patient care at the national level, including research to optimize behavioural change strategies, determine the optimum package of care and integrate approaches to deliver robust surveillance, monitoring and evaluation of control programmes.

Monitoring the elimination of human African trypanosomiasis at continental and country level: Update to 2018.

BACKGROUND: In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The World Health Organization (WHO) provides here the 2018 update on the progress made toward that objective. Global indicators are reviewed, in particular the number of reported cases and the areas at risk. Recently developed indicators for the validation of HAT elimination at the national level are also presented. METHODOLOGY/PRINCIPAL FINDINGS: With 977 cases reported in 2018, down from 2,164 in 2016, the main global indicator of elimination is already well within the 2020 target (i.e. 2,000 cases). Areas at moderate or higher risk (i.e. ≥ 1 case/10,000 people/year) are also steadily shrinking (less than 200,000 km2 in the period 2014-2018), thus nearing the 2020 target [i.e. 90% reduction (638,000 km2) from the 2000-2004 baseline (709,000 km2)]. Health facilities providing diagnosis and treatment of gambiense HAT continued to increase (+7% since the previous survey), with a better coverage of at-risk populations. By contrast, rhodesiense HAT health facilities decreased in number (-10.5%) and coverage. At the national level, eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem (i.e. Benin, Burkina Faso, Cameroon, Côte d'Ivoire, Ghana, Mali, Rwanda, and Togo), while for other endemic countries more efforts are needed in surveillance, control, or both. CONCLUSIONS/SIGNIFICANCE: The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones.

Mapping the global distribution of podoconiosis: Applying an evidence consensus approach.

BACKGROUND: Podoconiosis is a type of elephantiasis characterised by swelling of the lower legs. It is often confused with other causes of tropical lymphedema and its global distribution is uncertain. Here we synthesise the available information on the presence of podoconiosis to produce evidence consensus maps of its global geographical distribution. METHODS AND FINDINGS: We systematically searched available data on podoconiosis in SCOPUS and MEDLINE from inception, updated to 10 May, 2019, and identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used the number of cases reported in studies and prevalence data with geographical locations. We then developed an index to assess evidence quality and reliability, assigning each country an evidence consensus score. Using these summary scores, we then developed a contemporary global map of national-level podoconiosis status. There is evidence of podoconiosis in 17 countries (12 in Africa, three in Latin America, and two in Asia) and consensus on presence in six countries (all in Africa). We have identified countries where surveillance is required to further define the presence or absence of podoconiosis. We have highlighted areas where evidence is currently insufficient or conflicting, and from which more evidence is needed. CONCLUSION: The global distribution of podoconiosis is not clearly known; the disease extent and limits provided here inform the best contemporary map of the distribution of podoconiosis globally from available data. These results help identify surveillance needs, direct future mapping activities, and inform prevention plans and burden estimation of podoconiosis.

Premature deaths by visceral leishmaniasis in Brazil investigated through a cohort study: A challenging opportunity?

BACKGROUND: Visceral Leishmaniasis (VL) is the most severe form of leishmaniasis because it can lead to death. In the Americas, 96% of cases are in Brazil, and despite efforts, the fatality rate has increased in the past years. We analyzed deaths associated to VL in Brazil and investigated the factors that could influence on the timeliness of fatal outcome with emphasis on time (tStoD). METHODOLOGY: The registered deaths by VL were sourced from the Brazilian National Notification System from 2007-2014. Through a retrospective cohort study, univariate and multivariable Cox proportional hazards model analysis were performed and investigated the factors that could influence the time (tStoD). These factors were analyzed through survival models. RESULTS: Out of the 1,589 reported deaths, the median for onset of the symptoms and the case notification date (tStoN) is 25 days (10-61), and for date of case notification and death (tNotD) is 9 days (4-17). The time (tStoN) to event investigation for HIV non-infected individuals was 1.4 (1.16-1.68) greater than the HIV positive group. At the same time peri-urban and urban area were 0.83 (0.47-1.44) and 1.33 (1.16-1.52), respectively. The explorations revealed apparent differences between the time to event investigation (both for tStoN and tNotD) and the age at the onset of the symptoms. According to the tStoN the rate of notification is 1.73 times greater in patients under 5 years old at the onset of the clinical symptoms compared to older patients. CONCLUSION: VL patients under 5 years old were diagnosed earlier and had shorter survival. It could mean that in younger population, although properly diagnosed, the fatality pattern might be related to the severity of the disease. Main host characteristics were evaluated, and age and co-infections seem to have an impact in the disease progression.

Relationship of Serum Antileishmanial Antibody With Development of Visceral Leishmaniasis, Post-kala-azar Dermal Leishmaniasis and Visceral Leishmaniasis Relapse.

INTRODUCTION: To sustain the achievement of kala-azar elimination program (KEP), early detection and treatment of the visceral leishmaniasis (VL) cases and associated modalities such as treatment failure (TF), relapse VL (RVL), and Post-kala-azar dermal leishmaniasis (PKDL) is the cornerstone. A predictive biomarker for VL development and related complications could also play a crucial role in curtailing disease incidence and transmission. Investigations to find a biomarker with prospective capabilities are, however, scarce. Using samples and known clinical outcomes generated within two previous longitudinal cohort studies, we aimed to determine if fluctuations in serum anti-rK39 antibody levels could provide such predictive value. MATERIALS AND METHODS: Serum samples collected at four different time points (Baseline, 12, 18, and 24 months) from 16 patients who had developed VL within the monitoring period and 15 of their asymptomatic healthy controls counterparts were investigated. To investigate potential prediction of VL related complications, serum samples of 32 PKDL, 10 RVL, 07 TF, and 38 cured VL from a single dose AmBisome trial were analyzed. Of this second panel, all patients were monitored for 5 years and sera were collected at four time points (Baseline then 1, 6, and 12 months after treatment). The level of anti-rK39 antibodies in archived samples was measured by a semi-quantitative ELISA. RESULTS: The mean antibody level was significantly higher in VL patients compared to their asymptomatic healthy counterparts at each time point. Likewise, we observed a trend toward elevations in antibody levels for PKDL, RVL, TF relative to the reducing levels observed in cured VL. Receiver operating characteristic (ROC) analysis found a promising predictive power of rK39 antibody levels to reveal progression from asymptomatic Leishmania donovani infection stage to VL, defined as 87.5% sensitive and 95% specific. Following treatment, rk39 antibody notably showed 100% sensitivity and 95% specificity in predicting TF. CONCLUSION: Our data indicate that the relative quantity of serum anti-rK39 antibody has promise within either a predictive or prognostic algorithm for VL and VL-related modalities. These could enable VL control programs to implement more effective measures to eliminate the disease. Further research is, however, imperative to standardize the rK39 antibody ELISA between sites prior to broader use.

Monitoring the elimination of human African trypanosomiasis: Update to 2016.

BACKGROUND: Human African trypanosomiasis (HAT) is a neglected tropical disease targeted for elimination 'as a public health problem' by 2020. The indicators to monitor progress towards the target are based on the number of reported cases, the related areas and populations exposed at various levels of risk, and the coverage of surveillance activities. Based on data provided by the National Sleeping Sickness Control Programmes (NSSCP), Non-Governmental Organizations (NGOs) and research institutions-and assembled in the Atlas of HAT-the World Health Organization (WHO) provides here an update to 2016 for these indicators, as well as an analysis of the epidemiological situation. RESULTS: Trends for the two primary indicators of elimination are on track for the 2020 goal: 2,164 cases of HAT were reported in 2016 (as compared to the milestone of 4,000 cases), and for the period 2012-2016 280,000 km2 are estimated to be at moderate risk or higher (i.e. ≥ 1 case/10,000 people/year), as compared to the milestone of 230,000 km2. These figures correspond to reductions of 92% and 61% as compared to the respective baselines (i.e. 26,550 HAT cases in the year 2000, and 709,000 km2 exposed at various levels of risk for the period 2000-2004). Among the secondary indicators, an overall improvement in the coverage of at risk populations by surveillance activities was observed. Regarding passive surveillance, the number of fixed health facilities providing gambiense HAT diagnosis or treatment expanded, with 1,338 enumerated in endemic countries in 2017 (+52% as compared to the survey completed only sixteen months earlier). Concerning rhodesiense HAT, 124 health facilities currently provide diagnosis or treatment. The broadening of passive surveillance is occurring in a context of fairly stable intensity of active case finding, with between 1.8 million and 2.4 million people screened per year over the period 2012-2016. DISCUSSION: Elimination of HAT as a public health problem by 2020 seems within reach, as the epidemiological trends observed in previous years are confirmed in this latest 2016 monitoring update. However, looking beyond 2020, and in particular to the 2030 goal of elimination of transmission as zero cases for the gambiense form of the disease only, there is no room for complacency. Challenges still abound, including ensuring the effective integration of HAT control activities in the health system, sustaining the commitment of donors and HAT endemic countries, and clarifying the extent of the threat posed by cryptic reservoirs (e.g. human asymptomatic carriers and the possible animal reservoirs in gambiense HAT epidemiology). WHO provides through the network for HAT elimination the essential coordination of the wide range of stakeholders to ensure synergy of efforts.

Susceptibility of field-collected Phlebotomus argentipes (Diptera: Psychodidae) sand flies from Bangladesh and Nepal to different insecticides.

BACKGROUND: The sand fly Phlebotomus argentipes is the vector for visceral leishmaniasis (VL) in the Indian sub-continent. In Bangladesh since 2012, indoor residual spraying (IRS) was applied in VL endemic areas using deltamethrin. In Nepal, IRS was initiated in 1992 for VL vector control using lambda-cyhalothrin. Irrational use of insecticides may lead to vector resistance but very little information on this subject is available in both countries. The objective of this study was to generate information on the susceptibility of the vector sand fly, P. argentipes to insecticide, in support of the VL elimination initiative on the Indian sub-continent. METHODS: Susceptibility tests were performed using WHO test kits following the standard procedures regarding alpha cypermethrin (0.05%), deltamethrin (0.05%), lambda-cyhalothrin (0.05%), permethrin (0.75%), malathion (5%) and bendiocarb (0.1%) in six upazilas (sub-districts) in Bangladesh. In Nepal, the tests were performed for two insecticides: alpha cypermethrin (0.05%) and deltamethrin (0.05%). Adult P. argentipes sand flies were collected in Bangladesh from six VL endemic upazilas (sub-districts) and in Nepal from three endemic districts using manual aspirators. RESULTS: The results show that VL vectors were highly susceptible to all insecticides at 60 minutes of exposure in both countries. In Bangladesh, corrected mortality was 100% at 15 minutes as well as 30 minutes of exposure. The study sites in Nepal, however, showed some diverse results, with a mortality rate less than 90% for 15 minutes of exposure with alpha cypermethrin and deltamethrin in two districts but was above 95% after 30 minutes of exposure. CONCLUSIONS: These results suggest that the insecticides tested can still be used in the national programmes of Bangladesh and Nepal. However, insecticide rotation should be performed to mitigate the possible development of insecticide resistance. Periodic susceptibility tests should be performed by the countries to get timely alerts regarding insecticide resistance.

Control of Phlebotomus argentipes (Diptera: Psychodidae) sand fly in Bangladesh: A cluster randomized controlled trial.

BACKGROUND: A number of studies on visceral leishmaniasis (VL) vector control have been conducted during the past decade, sometimes came to very different conclusion. The present study on a large sample investigated different options which are partially unexplored including: (1) indoor residual spraying (IRS) with alpha cypermethrin 5WP; (2) long lasting insecticide impregnated bed-net (LLIN); (3) impregnation of local bed-nets with slow release insecticide K-O TAB 1-2-3 (KOTAB); (4) insecticide spraying in potential breeding sites outside of house using chlorpyrifos 20EC (OUT) and different combinations of the above. METHODS: The study was a cluster randomized controlled trial where 3089 houses from 11 villages were divided into 10 sections, each section with 6 clusters and each cluster having approximately 50 houses. Based on vector density (males plus females) during baseline survey, the 60 clusters were categorized into 3 groups: (1) high, (2) medium and (3) low. Each group had 20 clusters. From these three groups, 6 clusters (about 300 households) were randomly selected for each type of intervention and control arms. Vector density was measured before and 2, 4, 5, 7, 11, 14, 15, 18 and 22 months after intervention using CDC light traps. The impact of interventions was measured by using the difference-in-differences regression model. RESULTS: A total of 17,434 sand flies were collected at baseline and during the surveys conducted over 9 months following the baseline measurements. At baseline, the average P. argentipes density per household was 10.6 (SD = 11.5) in the control arm and 7.3 (SD = 8.46) to 11.5 (SD = 20.2) in intervention arms. The intervention results presented as the range of percent reductions of sand flies (males plus females) and rate ratios in 9 measurements over 22 months. Among single type interventions, the effect of IRS with 2 rounds of spraying (applied by the research team) ranged from 13% to 75% reduction of P. argentipes density compared to the control arm (rate-ratio [RR] ranged from 0.25 to 0.87). LLINs caused a vector reduction of 9% to 78% (RR, 0.22 to 0.91). KOTAB reduced vectors by 4% to 73% (RR, 0.27 to 0.96). The combination of LLIN and OUT led to a vector reduction of 26% to 86% (RR, 0.14 to 0.74). The reduction for the combination of IRS and OUT was 8% to 88% (RR, 0.12 to 0.92). IRS and LLIN combined resulted in a vector reduction of 13% to 85% (RR, 0.15 to 0.77). The IRS and KOTAB combination reduced vector densities by 16% to 86% (RR, 0.14 to 0.84). Some intermediate measurements for KOTAB alone and for IRS plus LLIN; and IRS plus KOTAB were not statistically significant. The bioassays on sprayed surfaces or netting materials showed favourable results (>80% mortality) for 22 months (IRS tested for 12 months). In the KOTAB, a gradual decline was observed after 6 months. CONCLUSIONS: LLIN and OUT was the best combination to reduce VL vector densities for 22 months or longer. Operationally, this is much easier to apply than IRS. A cost analysis of the preferred tools will follow. The relationship between vector density (males plus females) and leishmaniasis incidence should be investigated, and this will require estimates of the Entomological Inoculation Rate.