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BACKGROUND: In line with movement restrictions and physical distancing essential for the control of the COVID-19 pandemic, WHO recommended postponement of all neglected tropical disease (NTD) control activities that involve community-based surveys, active case finding, and mass drug administration in April, 2020. Following revised guidance later in 2020, and after interruptions to NTD programmes of varying lengths, NTD programmes gradually restarted in the context of an ongoing pandemic. However, ongoing challenges and service gaps have been reported. This study aimed to evaluate the potential effect of the programmatic interruptions and strategies to mitigate this effect. METHODS: For seven NTDs, namely soil-transmitted helminths, schistosomiasis, lymphatic filariasis, onchocerciasis, trachoma, visceral leishmaniasis, and human African trypanosomiasis, we used mathematical transmission models to simulate the effect of programme interruptions on the dynamics of each of these diseases in different endemic settings. We also explored the potential benefit of implementing mitigation strategies, primarily in terms of minimising the delays to control targets. FINDINGS: We show that the effect of the COVID-19-induced interruption in terms of delay to achieving elimination goals might in some cases be much longer than the duration of the interruption. For schistosomiasis, onchocerciasis, trachoma, and visceral leishmaniasis, a mean delay of 2-3 years for a 1-year interruption is predicted in areas of highest prevalence. We also show that these delays can largely be mitigated by measures such as additional mass drug administration or enhanced case-finding. INTERPRETATION: The COVID-19 pandemic has brought infectious disease control to the forefront of global consciousness. It is essential that the NTDs, so long neglected in terms of research and financial support, are not overlooked, and remain a priority in health service planning and funding. FUNDING: Bill & Melinda

Introduction: The leishmaniases represent a group of parasitic diseases caused by infection with one of several species of Leishmania parasites. Disease presentation varies because of differences in parasite and host genetics and may be influenced by additional factors such as host nutritional status or co-infection. Studies in experimental models of Leishmania infection, vaccination of companion animals and human epidemiological data suggest that many forms of leishmaniasis could be prevented by vaccination, but no vaccines are currently available for human use. Areas covered: We describe some of the existing roadblocks to the development and implementation of an effective leishmaniasis vaccine, based on a review of recent literature found on PubMed, BioRxiv and MedRxiv. In addition to discussing scientific unknowns that hinder vaccine candidate identification and selection, we explore gaps in knowledge regarding the commercial and public health value propositions underpinning vaccine development and provide a route map for future research and advocacy. Expert opinion: Despite significant progress, leishmaniasis vaccine development remains hindered by significant gaps in understanding that span the vaccine development pipeline. Increased coordination and adoption of a more holistic view to vaccine development will be required to ensure more rapid progress in the years ahead.

Background: In March 2020, India declared a nationwide lockdown to control the spread of coronavirus disease 2019. As a result, control efforts against visceral leishmaniasis (VL) were interrupted. Methods: Using an established age-structured deterministic VL transmission model, we predicted the impact of a 6-to 24-month programme interruption on the timeline towards achieving the VL elimination target as well as on the increase of VL cases. We also explored the potential impact of a mitigation strategy after the interruption. Results: Delays towards the elimination target are estimated to range between 0 and 9 y. Highly endemic settings where control efforts have been ongoing for 5-8 y are most affected by an interruption, for which we identified a mitigation strategy to be most relevant. However, more importantly, all settings can expect an increase in the number of VL cases. This increase is substantial even for settings with a limited expected delay in achieving the elimination target. Conclusions: Besides implementing mitigation strategies, it is of great importance to try and keep the duration of the interruption as short as possible to prevent new individuals from becoming infected with VL and continue the efforts towards VL elimination as a public health problem in India.

Locally tailored interventions for neglected tropical diseases (NTDs) are becoming increas-ingly important for ensuring that the World Health Organization (WHO) goals for control and elimination are reached. Mathematical models, such as those developed by the NTD Modelling Consortium, are able to offer recommendations on interventions but remain constrained by the data currently available. Data collection for NTDs needs to be strengthened as better data are required to indirectly inform transmission in an area. Addressing specific data needs will improve our modelling recommendations, enabling more accurate tailoring of interventions and assessment of their progress. In this collection, we discuss the data needs for several NTDs, specifically gambiense human African trypanosomiasis, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminths (STH), trachoma, and visceral leishmaniasis. Similarities in the data needs for these NTDs highlight the potential for integration across these diseases and where possible, a wider spectrum of diseases.

The development of vaccines against one or all forms of human leishmaniasis remains ham-pered by a paucity of investment, at least in part resulting from the lack of well-evidenced and agreed estimates of vaccine demand. Starting from the definition of 4 main use cases (prevention of visceral leishmaniasis, prevention of cutaneous leishmaniasis, prevention of post-kala-azar dermal leishmaniasis and treatment of post-kala-azar dermal leishmaniasis), we have estimated the size of each target population, focusing on those endemic countries where incidence levels are sufficiently high to justify decisions to adopt a vaccine. We assumed a dual vaccine delivery strategy, including a wide age-range catch-up campaign before the start of routine immunisation. Vaccine characteristics and delivery parameters reflective of a target product profile and the likely duration of the clinical development effort were considered in forecasting the demand for each of the four indications. Over a period of 10 years, this demand is forecasted to range from 300–830 million doses for a vaccine preventing visceral leishmaniasis and 557–1400 million doses for a vaccine preventing cutaneous leishmaniasis under the different scenarios we simulated. In a scenario with an effective prophylactic visceral leishmaniasis vaccine, demand for use to prevent or treat post-kala-azar dermal leishmaniasis would be more limited (over the 10 years ~160,000 doses for prevention and ~7,000 doses for treatment). Demand would rise to exceed 330,000 doses, however, in the absence of an effective vaccine for visceral leishmaniasis. Because of the sizeable demand and potential for public health impact, a single-indication prophylactic vaccine for visceral or cutaneous leishmaniasis, and even more so a cross-protective prophylactic vaccine could attract the interest of commercial developers. Continuous refinement of these first-of-their kind estimates and confirmation of country willingness and ability to pay wil

Leishmania infantum is transmitted by sand flies and causes visceral leishmaniasis (VL) in humans, as well as canine leishmaniosis (CanL) in dogs, the main reservoir of infection in Europe. The infection spread northwards in the last two decades, but case data are scarce, hindering monitoring and evaluation of incidence as is required by European WHO guidelines. We aim to identify the current geographical distribution of CanL incidence in Spain, which has been endemic for CanL, and France, where CanL is emerging. An online survey was conducted among veterinarians in Spain and France questioning CanL incidence in the years 2016—2017. These data were interpolated to estimate incidence in both countries using the geographical analysis ordinary kriging. Two hundred and seventy-three (273) veterinarians from 81 out of 148 French and Spanish districts completed the survey. The mean incidence in veterinary practices was 21 CanL cases per 1000 dogs during the past year, which was higher in Spain (31/1000 dogs/year) than in France (6/1000 dogs/year). Incidence rates were highest in south-eastern Spain, but sporadic cases were found up to the most northern regions of France. Our study confirms the northward spread of CanL in Spain and France, as the incidence rates were higher than reported in previous studies and cases were found in areas formerly considered non-endemic for L. infantum. Monitoring the reservoir of infection in dogs is essential for implementing timely and geographically-targeted interventions to prevent further spread of CanL and VL in Europe.

Human visceral leishmaniasis (VL) vaccines are currently under development and there is a need to understand their potential impact on population wide VL incidence. We implement four characteristics from different human VL vaccine candidates into two published VL transmission model variants to estimate the potential impact of these vaccine characteristics on population-wide anthroponotic VL incidence on the Indian subcontinent (ISC). The vaccines that are simulated in this study 1) reduce the infectiousness of infected individuals towards sand flies, 2) reduce risk of developing symptoms after infection, 3) reduce the risk of developing post-kala-azar dermal leishmaniasis (PKDL), or 4) lead to the development of transient immunity. We also compare and combine a vaccine strategy with current interventions to identify their potential role in elimination of VL as a public health problem. We show that the first two simulated vaccine characteristics can greatly reduce VL incidence. For these vaccines, an approximate 60% vaccine efficacy would lead to achieving the ISC elimination target (<1 VL case per 10,000 population per year) within 10 years’ time in a moderately endemic setting when vaccinating 100% of the population. Vaccinating VL cases to prevent the development of PKDL is a promising tool to sustain the low incidence elimination target after regular interventions are halted. Vaccines triggering the development of transient immunity protecting against infection lead to the biggest reduction in VL incidence, but booster doses are required to achieve perduring impact. Even though vaccines are not yet available for implementation, their development should be pursued as their potential impact on transmission can be substantial, both in decreasing incidence at the population level as well as in sustaining the ISC elimination target when other interventions are halted.

Post-kala-azar dermal leishmaniasis (PKDL) is a parasitic skin infection which can occur after visceral leishmaniasis (VL). Recent xenodiagnosis studies (Mondal et al., Clin. Infect. Dis., 2018) have uncovered the infectiousness of PKDL. When including this in a transmission model, PKDL cases appear as an important reservoir of infection, likely frustrating the VL elimination efforts on the Indian subcontinent.

Background. Visceral leishmaniasis (VL) has been targeted by the World Health Organization (WHO) and 5 countries in the Indian subcontinent for elimination as a public health problem. To achieve this target, the WHO has developed guidelines consisting of 4 phases of different levels of interventions, based on vector control through indoor residual spraying of insecticide (IRS) and active case detection (ACD). Mathematical transmission models of VL are increasingly used for planning and assessing the efficacy of interventions and evaluating the intensity and timescale required to achieve the elimination target. Methods. This paper draws together the key policy-relevant conclusions from recent transmission modeling of VL, and presents new predictions for VL incidence under the interventions recommended by the WHO using the latest transmission models. Results. The model predictions suggest that the current WHO guidelines should be sufficient to reach the elimination target in areas that had medium VL endemicities (up to 5 VL cases per 10 000 population per year) prior to the start of interventions. However, additional interventions, such as extending the WHO attack phase (intensive IRS and ACD), may be required to bring forward elimination in regions with high precontrol endemicities, depending on the relative infectiousness of different disease stages. Conclusions. The potential hurdle that asymptomatic and, in particular, post-kala-azar dermal leishmaniasis cases may pose to reaching and sustaining the target needs to be addressed. As VL incidence decreases, the pool of immunologically naive individuals will grow, creating the potential for new outbreaks.

We present three transmission models of visceral leishmaniasis (VL) in the Indian subcontinent (ISC) with structural differences regarding the disease stage that provides the main contribution to transmission, including models with a prominent role of asymptomatic infection, and fit them to recent case data from 8 endemic districts in Bihar, India. Following a geographical cross-validation of the models, we compare their predictions for achieving the WHO VL elimination targets with ongoing treatment and vector control strategies. All the transmission models suggest that the WHO elimination target (<1 new VL case per 10,000 capita per year at sub-district level) is likely to be met in Bihar, India, before or close to 2020 in sub-districts with a pre-control incidence of 10 VL cases per 10,000 people per year or less, when current intervention levels (60% coverage of indoor residual spraying (IRS) of insecticide and a delay of 40 days from onset of symptoms to treatment (OT)) are maintained, given the accuracy and generalizability of the existing data regarding incidence and IRS coverage. In settings with a pre-control endemicity level of 5/10,000, increasing the effective IRS coverage from 60 to 80% is predicted to lead to elimination of VL 1–3 years earlier (depending on the particular model), and decreasing OT from 40 to 20 days to bring elimination forward by approximately 1 year. However, in all instances the models suggest that L. donovani transmission will continue after 2020 and thus that surveillance and control measures need to remain in place until the longer-term aim of breaking transmission is achieved.

Background: Visceral leishmaniasis (VL) is a neglected tropical disease transmitted by sandflies. On the Indian subcontinent (ISC), VL is targeted for elimination as a public health problem by 2017. In the context of VL, the elimination target is defined as an annual VL incidence of <1 per 10,000 capita at (sub-)district level. Interventions focus on vector control, surveillance and on diagnosing and treating VL cases. Many endemic areas have not yet achieved optimal control due to logistical, biological as well as technical challenges. We used mathematical modelling to quantify VL transmission dynamics and predict the feasibility of achieving the VL elimination target with current control strategies under varying assumptions about the reservoir of infection in humans. Methods: We developed three deterministic age-structured transmission models with different main reservoirs of infection in humans: asymptomatic infections (model 1), reactivation of infection after initial infection (model 2), and post kala-azar dermal leishmaniasis (PKDL; model 3). For each model, we defined four sub-variants based on different assumptions about the duration of immunity and age-patterns in exposure to sandflies. All 12 model sub-variants were fitted to data from the KalaNet study in Bihar (India) and Nepal, and the best sub-variant was selected per model. Predictions were made for optimal and sub-optimal indoor residual spraying (IRS) effectiveness for three different levels of VL endemicity. Results: Structurally different models explained the KalaNet data equally well. However, the predicted impact of IRS varied substantially between models, such that a conclusion about reaching the VL elimination targets for the ISC heavily depends on assumptions about the main reservoir of infection in humans: asymptomatic cases, recovered (immune) individuals that reactivate, or PKDL cases. Conclusions: Available data on the impact of IRS so far suggest one model is probably closest to re