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Background In 2005, Bangladesh, India and Nepal agreed to eliminate visceral leishmaniasis (VL) as a public health problem. The approach to this was through improved case detection and treatment, and controlling transmission by the sand fly vector Phlebotomus argentipes, with indoor residual spraying (IRS) of insecticide. Initially, India applied DDT with stirrup pumps for IRS, however, this did not reduce transmission. After 2015 onwards, the pyrethroid alpha-cypermethrin was applied with compression pumps, and entomological surveillance was initiated in 2016. Methods Eight sentinel sites were established in the Indian states of Bihar, Jharkhand and West Bengal. IRS coverage was monitored by household survey, quality of insecticide application was measured by HPLC, presence and abundance of the VL vector was monitored by CDC light traps, insecticide resistance was measured with WHO diagnostic assays and case incidence was determined from the VL case register KAMIS. Results Complete treatment of houses with IRS increased across all sites from 57% in 2016 to 70% of houses in 2019, rising to >80% if partial house IRS coverage is included (except West Bengal). The quality of insecticide application has improved compared to previous studies, average doses of insecticide on filters papers ranged from 1.52 times the target dose of 25mg/m2 alpha-cypermethrin in 2019 to 1.67 times in 2018. Resistance to DDT has continued to increase, but the vector was not resistant to carbamates, organophosphates or pyrethroids. The annual and seasonal abundance of P. argentipes declined between 2016 to 2019 with an overall infection rate of 0.03%. This was associated with a decline in VL incidence for the blocks represented by the sentinel sites from 1.16 per 10,000 population in 2016 to 0.51 per 10,000 in 2019. Conclusion Through effective case detection and management reducing the infection reservoirs for P. argentipes in the human population combined with IRS keeping P. argentipes abundance and infectivity low has reduced VL transmission. This combination of effective case management and vector control has now brought India within reach of the VL elimination targets., Author summary Visceral Leishmaniasis (VL), also known as kala-azar, is a major parasitic disease in South Asia (Indian subcontinent), with 85% of the disease incidence in India. Historically VL had been controlled and almost eliminated with Indoor Residual Spraying (IRS) using dichlorodiphenyltrichloroethane (DDT). However, reinitiating this approach in 2015 failed due to high insecticide resistance in the sand fly vector and poor IRS quality, meaning that VL elimination targets were not met. To improve this the National Vector Borne Disease Control Programme changed to an effective insecticide, alpha-cypermethrin and altered the mode of application to compression pumps. Sentinel sites were established to monitor the entomological indicators, these showed the positive impact of these changes from 2016 to 2019. During this period the overall incidence of disease has decreased, and India is now on track to reach it’s target incidence for VL of less than 1/1000 people at the sub-district (block) level.

Background Work to control the gambiense form of human African trypanosomiasis (gHAT), or sleeping sickness, is now directed towards ending transmission of the parasite by 2030. In order to supplement gHAT case-finding and treatment, since 2011 tsetse control has been implemented using Tiny Targets in a number of gHAT foci. As this intervention is extended to new foci, it is vital to understand the costs involved. Costs have already been analysed for the foci of Arua in Uganda and Mandoul in Chad. This paper examines the costs of controlling Glossina palpalis palpalis in the focus of Bonon in Côte d’Ivoire from 2016 to 2017. Methodology/Principal findings Some 2000 targets were placed throughout the main gHAT transmission area of 130 km2 at a density of 14.9 per km2. The average annual cost was USD 0.5 per person protected, USD 31.6 per target deployed of which 12% was the cost of the target itself, or USD 471.2 per km2 protected. Broken down by activity, 54% was for deployment and maintenance of targets, 34% for tsetse surveys/monitoring and 12% for sensitising populations. Conclusions/Significance The cost of tsetse control per km2 of the gHAT focus protected in Bonon was more expensive than in Chad or Uganda, while the cost per km2 treated, that is the area where the targets were actually deployed, was cheaper. Per person protected, the Bonon cost fell between the two, with Uganda cheaper and Chad more expensive. In Bonon, targets were deployed throughout the protected area, because G. p. palpalis was present everywhere, whereas in Chad and Uganda G. fuscipes fuscipes was found only the riverine fringing vegetation. Thus, differences between gHAT foci, in terms of tsetse ecology and human geography, impact on the cost-effectiveness of tsetse control. It also demonstrates the need to take into account both the area treated and protected alongside other impact indicators, such as the cost per person protected., Author summary Sleeping sickness is a fatal disease in Africa caused by trypanosomes transmitted by the bite of infected tsetse flies. The World Health Organization has set the absence of new infections as a goal for 2030. To achieve this, screening and treatment of patients is supplemented by tsetse control. Tiny Targets are small insecticide-impregnated panels of blue cloth and black netting which attract and kill tsetse. To maintain the momentum in these last stages of eliminating the disease, it is important to understand the costs of vector control. This paper presents the results of two years’ cost monitoring in Bonon, an area covering 130 km2, home to 120,000 people. Since 2016, ~2,000 Tiny Targets have been deployed annually at a cost of USD 471 per km2 per year. Bonon is a degraded forested area and a relatively high number of targets was required as tsetse are present throughout. Nevertheless, the cost comes to only USD 0.5 per person protected per year. Compared to operations using Tiny Targets in Uganda and Chad, the cost was higher per km2 protected, reflecting the need to place targets throughout the area, but low per person protected compared to Chad, highlighting the need to use a range of comparators.

Background Medicine quality screening devices hold great promise for post-market surveillance (PMS). However, there is little independent evidence on their field utility and usability to inform policy decisions. This pilot study in the Lao PDR tested six devices’ utility and usability in detecting substandard and falsified (SF) medicines. Methodology/principal findings Observational time and motion studies of the inspections by 16 Lao medicine inspectors of 1) the stock of an Evaluation Pharmacy (EP), constructed to resemble a Lao pharmacy, and 2) a sample set of medicines (SSM); were conducted without and with six devices: four handheld spectrometers (two near infrared: MicroPHAZIR RX, NIR-S-G1 & two Raman: Progeny, Truscan RM); one portable mid-infrared spectrometer (4500a), and single-use paper analytical devices (PAD). User experiences were documented by interviews and focus group discussions. Significantly more samples were wrongly categorised as pass/fail with the PAD compared to the other devices in EP inspections (p, Author summary Substandard and falsified (SF) medicines threaten the lives of millions of people, especially where pharmaceutical legislation and regulation are limited. Screening for SF medicines in supply chains (‘post-market surveillance’) by medicine inspectors is crucial but currently relies only on subjective visual inspection of medicines in most countries. Many innovative portable screening technologies now exist and could be key additional assets to the current practice, but none have been extensively evaluated for medicine quality post-market surveillance. We assessed the utility and usability of six screening devices in the hands of Lao medicines inspectors in a pharmacy constructed to resemble a Lao pharmacy. Five spectrometers showed promising accuracies to identify falsified medicines, but difficulties to correctly set them up before running tests were observed. Reading and interpreting colour barcodes of the ‘paper analytical cards’–a lab-on-a-chip test by inspectors were difficult, leading to lower accuracy than with spectrometers. The study suggests that overconfidence in devices may cause harm by reducing inspectors’ investment in visual inspection—a crucial step to identify falsified medicines. Advantages/limitations of the devices are also documented to inform policy.

Hemorrhagic fever with renal syndrome (HFRS) is a zoonosis characterized by clinical features of high fever, hemorrhage, and renal damage. China has the largest number of HFRS cases worldwide, accounting for over 90% of the total reported cases. In this paper, we used surveyed HFRS data and satellite imagery to conduct geostatistical analysis for investigating the associations of rapid urbanization, water bodies, and other factors on the spatiotemporal dynamics of HFRS from year 2005 to 2018 in Xi’an City, Northwest China. The results revealed an evident epidemic aggregation in the incidence of HFRS within Xi’an City with a phenomenal fluctuation in periodic time series. Rapid urbanization was found to greatly affect the HFRS incidence in two different time phases. HFRS caused by urbanization influences farmers to a lesser extent than it does to non-farmers. The association of water bodies with the HFRS incidence rate was found to be higher within the radii of 696.15 m and 1575.39 m, which represented significant thresholds. The results also showed that geomatics approaches can be used for spatiotemporally investigating the HFRS dynamic characteristics and supporting effective allocations of resources to formulate strategies for preventing epidemics., Author summary Hemorrhagic fever with renal syndrome (HFRS) is an infectious disease transmitted by the infected reservoir hosts, which chiefly include rodents, shrews, and moles. The mechanism of HFRS infection is determined by a complex interplay of various natural and socioeconomic factors. Previous studies have identified a close relationship between urbanization processes and HFRS transmission dynamics. However, the relationship involves a dual response and has not yet been quantitatively identified. This research aimed to spatiotemporally characterize how rapid urbanization affects the dynamics of HFRS. In addition, the role of water bodies, vegetation, rainfall, and occupation types in epidemic transmissions has also not been adequately investigated at the interurban scale over a long time period. Therefore, we analyzed the spatiotemporal association between the distributions of water bodies and HFRS infections and also investigated the interactions between urbanization, water body, vegetation, rainfall, and different occupation types by using multi-source data through both traditional statistical and geospatial techniques. Our work revealed biphasic associations among HFRS infection with both rapid urbanization and distribution of water bodies. Hence, it can provide useful information to formulate effective strategies for the prevention and control of HFRS.

West Nile virus (WNV) is a globally distributed mosquito-borne virus of great public health concern. The number of WNV human cases and mosquito infection patterns vary in space and time. Many statistical models have been developed to understand and predict WNV geographic and temporal dynamics. However, these modeling efforts have been disjointed with little model comparison and inconsistent validation. In this paper, we describe a framework to unify and standardize WNV modeling efforts nationwide. WNV risk, detection, or warning models for this review were solicited from active research groups working in different regions of the United States. A total of 13 models were selected and described. The spatial and temporal scales of each model were compared to guide the timing and the locations for mosquito and virus surveillance, to support mosquito vector control decisions, and to assist in conducting public health outreach campaigns at multiple scales of decision-making. Our overarching goal is to bridge the existing gap between model development, which is usually conducted as an academic exercise, and practical model applications, which occur at state, tribal, local, or territorial public health and mosquito control agency levels. The proposed model assessment and comparison framework helps clarify the value of individual models for decision-making and identifies the appropriate temporal and spatial scope of each model. This qualitative evaluation clearly identifies gaps in linking models to applied decisions and sets the stage for a quantitative comparison of models. Specifically, whereas many coarse-grained models (county resolution or greater) have been developed, the greatest need is for fine-grained, short-term planning models (m–km, days–weeks) that remain scarce. We further recommend quantifying the value of information for each decision to identify decisions that would benefit most from model input.

Substandard and falsified (SF) antimalarials have devastating consequences including increased morbidity, mortality and economic losses. Portable medicine quality screening devices are increasingly available, but whether their use for the detection of SF antimalarials is cost-effective is not known. We evaluated the cost-effectiveness of introducing such devices in post-market surveillance in pharmacies in Laos, conservatively focusing on their outcome in detecting SF artemisinin-based combination therapies (ACTs). We simulated the deployment of six portable screening devices: two handheld near-infrared [MicroPHAZIR RX, NIR-S-G1], two handheld Raman [Progeny, TruScan RM]; one portable mid-infrared [4500a FTIR] spectrometers, and single-use disposable paper analytical devices [PADs]. We considered two scenarios with high and low levels of SF ACTs. Different sampling strategies in which medicine inspectors would test 1, 2, or 3 sample(s) of each brand of ACT were evaluated. Costs of inspection including device procurement, inspector time, reagents, reference testing, and replacement with genuine ACTs were estimated. Outcomes were measured as disability adjusted life years (DALYs) and incremental cost-effectiveness ratios were estimated for each device compared with a baseline of visual inspections alone. In the scenario with high levels of SF ACTs, all devices were cost-effective with a 1-sample strategy. In the scenario of low levels of SF ACTs, only four devices (MicroPHAZIR RX, 4500a FTIR, NIR-S-G1, and PADs) were cost-effective with a 1-sample strategy. In the multi-way comparative analysis, in both scenarios the NIR-S-G1 testing 2 samples was the most cost-effective option. Routine inspection of ACT quality using portable screening devices is likely to be cost-effective in the Laos context. This work should encourage policy-makers or regulators to further investigate investment in portable screening devices to detect SF medicines and reduce their associated undesired health and economic burdens., Author summary Distribution of poor quality medicines are an increasing global concern, especially in low- and middle-income countries (LMICs) where the effectiveness of antimicrobials can be a matter of life-or-death for patients with malaria and other potentially fatal infectious diseases. Substandard and falsified antimalarial drugs, including artemisinin-based combination therapies are widely distributed across LMICs. This endangers patients and in the longer term threatens malaria control and elimination campaigns by promoting the development of drug resistance. New field detection devices are increasingly available and could enhance the inspection process with prompt and actionable, real-time results. We conducted a cost-effectiveness analysis of the implementation of six portable devices for medicine quality screening during pharmacy post-market surveillances in Laos. This analysis conservatively focused only on the benefits of these devices in detecting substandard and falsified artemisinin-based combination therapies (ACTs), measured in terms of health outcomes for malaria patients obtaining treatment from pharmacies. Our findings suggest that using these portable devices for routine surveillance of ACT quality is likely to be cost-effective. Policy-makers and regulators might therefore consider investment in these field detection devices to minimise undesired health and economic burdens associated with substandard and falsified medicines.

Background As China is moving onto schistosomiasis elimination/eradication, diagnostic methods with both high sensitivity and specificity for Schistosoma japonicum infections in humans are urgently needed. Microscopic identification of eggs in stool is proven to have poor sensitivity in low endemic regions, and antibody tests are unable to distinguish between current and previous infections. Polymerase chain reaction (PCR) technologies for the detection of parasite DNA have been theoretically assumed to show high diagnostic sensitivity and specificity. However, the reported performance of PCR for detecting S. japonicum infection varied greatly among studies. Therefore, we performed a meta-analysis to evaluate the overall diagnostic performance of variable-temperature PCR technologies, based on stool or blood, for detecting S. japonicum infections in humans from endemic areas. Methods We searched literatures in eight electronic databases, published up to 20 January 2021. The heterogeneity and publication bias of included studies were assessed statistically. The risk of bias and applicability of each eligible study were assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 tool (QUADAS-2). The bivariate mixed-effects model was applied to obtain the summary estimates of diagnostic performance. The hierarchical summary receiver operating characteristic (HSROC) curve was applied to visually display the results. Subgroup analyses and multivariate regression were performed to explore the source of heterogeneity. This research was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and was registered prospectively in PROSPERO (CRD42021233165). Results A total of 2791 papers were retrieved. After assessing for duplications and eligilibity a total of thirteen publications were retained for inclusion. These included eligible data from 4268 participants across sixteen studies. High heterogeneity existed among studies, but no publication bias was found. The pooled analyses of PCR data from all included studies resulted in a sensitivity of 0.91 (95% CI: 0.83 to 0.96), specificity of 0.85 (95% CI: 0.65 to 0.94), positive likelihood ratio of 5.90 (95% CI: 2.40 to 14.60), negative likelihood ratio of 0.10 (95% CI: 0.05 to 0.20) and a diagnostics odds ratio of 58 (95% CI: 19 to 179). Case-control studies showed significantly better performances for PCR diagnostics than cross-sectional studies. This was further evidenced by multivariate analyses. The four types of PCR approaches identified (conventional PCR, qPCR, Droplet digital PCR and nested PCR) differed significantly, with nested PCRs showing the best performance. Conclusions Variable-temperature PCR has a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas. More high quality studies on S. japonicum diagnostic techniques, especially in low endemic areas and for the detection of dual-sex and single-sex infections are required. These will likely need to optimise a nested PCR alongside a highly sensitive gene target. They will contribute to successfully monitoring endemic areas as they move towards the WHO 2030 targets, as well as ultimately helping areas to achieve these goals., Author summary Schistosoma japonicum is a parasite that can cause serious intestinal schistosomiasis. The infection is mainly diagnosed by parasitological and immunological methods, such as Kato-Katz test and indirect hemagglutination assay. However, both of these are not sensitive enough to accurately assess schistosomiasis elimination/eradication. PCR assays, detecting parasite DNA, are theoretically a highly suitable, sensitive and specific, alternative. However, reported performance varies greatly among studies. Therefore, we performed this meta-analysis (PROSPERO, registered No. CRD42021233165) to analyze and summarize the data from relevant studies of variable-temperature PCR for the diagnosis of S. japonicum infections, using stool or blood samples from humans in endemic areas. We retrieved a total of 13 eligible articles including data from 4268 participants across 16 studies. There was high heterogeneity among studies, but no publication bias was found. Analyses revealed that PCR techniques had a satisfactory performance for diagnosing S. japonicum infections in humans in endemic areas, with both high sensitivity and specificity. Further research on S. japonicum diagnostic techniques, especially in low endemicity areas and for detection of dual-sex and single-sex infections are required. These may be best using highly sensitive gene targets in nested PCR reactions.

Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease characterized by a wide geographical distribution in the Mediterranean basin and is endemic in several of its countries. In addition, the vector Phlebotomus sergenti is abundantly present all around the basin. Its transmission cycle is still subject to debate. In some countries, the presence of an animal reservoir has been confirmed. In Morocco, CL due to L. tropica has risen since the 1980s and has spread widely to become the most abundant form of leishmaniasis in the territory. However, the anthroponotic transmission is so far the only recognized mode, despite recordings of L. tropica infection in animal hosts. In this review article, we assess the situation of CL due to L. tropica in the Mediterranean basin with a focus on Morocco and gather knowledge about any potential zoonotic transmission in the country. A concomitant zoonotic transmission could explain the persistence of the disease in areas where human protective measures combined with vector management did not help reduce the disease burden., Author summary Cutaneous leishmaniasis (CL) due to Leishmania tropica is a neglected tropical disease still considered to be anthroponotic in Morocco despite evidence of zoonotic transmission in other endemic countries of the Mediterranean basin. Its high incidence in the country makes it necessary to investigate whether or not a potential concomitant zoonotic transmission exists alongside the anthroponotic one. Moreover, several reports of natural animal infection have been noted in the country. In this paper, we review how CL due to L. tropica is present around the Mediterranean basin, with a particular focus on the Moroccan foci, and try to unveil the existence of a zoonotic transmission in the area. A deep understanding of the transmission patterns of L. tropica in the region is necessary for the implementation of effective control measures and a better assessment of the disease burden. In addition, the complexity of this neglected disease requires more fundamental and applied research to unveil potential factors involved in its spread.

Background Sustainability within neglected tropical disease (NTD) programs is a complex and challenging issue. The need for a shared understanding about what sustainability means for NTD programs is more important than ever as stakeholders are currently realigning for the next decade of NTD programming with the launch of WHO’s new NTD roadmap for 2012–2030. The aim of this paper is to assess different perspectives to generate a working definition of sustainability for NTD programs. Methodology/Principal findings This study surveyed affiliates of the NTD NGO Network (NNN) about their definitions of sustainability and then analyzed the data using an inductive and deductive process. The research team drafted a sustainability statement based on the survey findings and then solicited and incorporated feedback on the statement from a diverse group of expert reviewers. The final statement includes a working definition of sustainability for NTD programs that highlights three key essential components to sustainability: domestic commitment, responsive resource mobilization, and accountability. Conclusions/Significance This research resulted in a sustainability statement, based on a survey and extensive consultation with stakeholders, that represents a starting point for shared understanding around the concept of sustainability for NTD programs. Future collaborative work should build off this definition and seek to incorporate indicators for sustainability into programmatic decision-making., Author summary The question of whether a global public health program can be sustainable is as important as whether that program is effective. While neglected tropical disease (NTD) programs have achieved tangible success in reducing the burden of NTDs over the past decade through a massive collaboration between global and local stakeholders, the achievement of global NTD control and elimination goals will depend in large part on whether these efforts are sustained. This study seeks to encourage more and better dialogue around NTD program sustainability by incorporating a wide variety of expert perspectives to create and propose a shared definition of sustainability upon which future NTD programming decisions can be made. The sustainability statement based on the findings from this study suggests that three essential components to NTD program sustainability are commitment from decision-makers within NTD-endemic countries, resource mobilization that is responsive to local needs, and enhanced mechanisms for accountability.

Background The number of new leprosy cases is declining globally, but the disability caused by leprosy remains an important disease burden. The chance of disability is increased by delayed case detection. This review focusses on the individual and community determinants of delayed leprosy case detection. Methods This study was conducted according to the PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analysis). The study protocol is registered in PROSPERO (code: CRD42020189274). To identify determinants of delayed detection, data was collected from five electronic databases: Embase.com, Medline All Ovid, Web of Science, Cochrane CENTRAL, and the WHO Global Health Library. Results We included 27 papers from 4315 records assessed. They originated in twelve countries, had been published between January 1, 2000, and January 31, 2021, and described the factors related to delayed leprosy case detection, the duration of the delayed case, and the percentage of Grade 2 Disability (G2D). The median delay in detection ranged from 12 to 36 months, the mean delay ranged from 11.5 to 64.1 months, and the percentage of G2D ranged from 5.6 to 43.2%. Health-service-seeking behavior was the most common factor associated with delayed detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor. Conclusions Delayed leprosy case detection is clearly correlated with increased disability and should therefore be a priority of leprosy programs. Interventions should focus on determinants of delayed case detection such as health-service-seeking behavior, and should consider relevant individual, socioeconomic, and community factors, including stigmatization. Further study is required of the health service-related factors contributing to delay., Author summary Leprosy remains an important public health problem with many new leprosy patients diagnosed with visible physical deformities, indicating a long delay in the detection of cases. For effective prevention programs, it is important to know the factors at the level of the individual and the community that contribute to the delay. We reviewed all published studies that reported individual and community factors related to delayed case detection in leprosy and included 27 studies in our analysis, published between January 1, 2000, and January 31, 2021. Health-service-seeking behavior was the most common factor associated with delay in case detection. The most common individual factors were older age, being male, having a lower disease-symptom perception, having multibacillary leprosy, and lack of knowledge about leprosy. The most common socioeconomic factors were living in a rural area, performing agricultural labor, and being unemployed. Stigma was the most common social and community factor associated with detection delay. The presence of physical disability in newly diagnosed leprosy patients is clearly related to the delay in detecting these patients. Leprosy control interventions should take factors related to detection delay into account more comprehensively. Also, there is a need to study health service-related factors that contribute to detection delay of leprosy patients.