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In most low-resource settings, microscopy still is the standard method for diagnosis of cutaneous leishmaniasis, despite its limited sensitivity. In Ethiopia, the more sensitive molecular methods are not yet routinely used. This study compared five PCR methods with microscopy on two sample types collected from patients with a suspected lesion to advise on optimal diagnosis of Leishmania aethiopica. Between May and July 2018, skin scrapings (SS) and blood exudate from the lesion spotted on filter paper (dry blood spot, DBS) were collected for PCR from 111 patients of four zones in Southern Ethiopia. DNA and RNA were simultaneously extracted from both sample types. DNA was evaluated by a conventional PCR targeting ITS-1 and three probe-based real-time PCRs: one targeting the SSU 18S rRNA and two targeting the kDNA minicircle sequence (the ‘Mary kDNA PCR’ and a newly designed ‘LC kDNA PCR’ for improved L. aethiopica detection). RNAs were tested with a SYBR Green-based RT-PCR targeting spliced leader (SL) RNA. Giemsa-stained SS smears were examined by microscopy. Of the 111 SS, 100 were positive with at least two methods. Sensitivity of microscopy, ITS PCR, SSU PCR, Mary kDNA PCR, LC kDNA PCR and SL RNA PCR were respectively 52%, 22%, 64%, 99%, 100% and 94%. Microscopy-based parasite load correlated well with real-time PCR Ct-values. Despite suboptimal sample storage for RNA detection, the SL RNA PCR resulted in congruent results with low Ct-values. DBS collected from the same lesion showed lower PCR positivity rates compared to SS. The kDNA PCRs showed excellent performance for diagnosis of L. aethiopica on SS. Lower-cost SL RNA detection can be a complementary high-throughput tool. DBS can be used for PCR in case microscopy is negative, the SS sample can be sent to the referral health facility where kDNA PCR method is available., Author summary Cutaneous leishmaniasis is a neglected tropical disease and causing a public health problem in Ethiopia. Microscopy is still the standard method for detection of the parasite in Ethiopia, and also in many other low resource settings. A more sensitive method is needed for timely diagnosis and treatment. In this study, we compared five molecular methods on samples collected from patients with a skin lesion suspected of cutaneous leishmaniasis to advice on optimal diagnosis of L. aethiopica. We collected two sample types from the same lesion (skin scrapings and lesion fluid on filter paper) and isolated both DNA and RNA of them. Majority (90.1%) of the samples from skin scrapings were positive in two or more methods and the molecular methods had a higher sensitivity than the conventional methods. Interestingly, we evaluated for the first time a new molecular method designed to improve L. aethiopica detection. Also, we showed that RNA detection performed well for samples that were collected under difficult field conditions. Samples collected on filter paper showed less positive results than skin scraped samples, but could still be the method of choice for easy sampling and transport in resource-limited settings as it performed better than microscopy.

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.

Neglected Tropical Diseases (NTDs) remain endemic to many regions of sub-Saharan Africa (SSA) left behind by socioeconomic progress. As such, these diseases are markers of extreme poverty and inequity that are propagated by the political, economic, social, and cultural systems that affect health and wellbeing. As countries embrace and work towards achieving the Sustainable Development Goals (SDGs), the needs of such vulnerable populations need to be addressed in local and global arenas. The research uses primary qualitative data collected from five NTD endemic counties of Kenya: interviews key informants (n = 21) involved in NTD implementation programs and focus groups (n = 5) of affected individuals. Informed by theories of political ecology of health, the research focuses on post-devolution Kenya and identifies the political, economic, social, and cultural factors that propagate NTDs and their effects on health and wellbeing. Our findings indicate that structural factors such as competing political interests, health worker strikes, inadequate budgetary allocations, economic opportunity, marginalization, illiteracy, entrenched cultural norms and practices, poor access to water, sanitation and housing, all serve to propagate NTD transmission and subsequently affect the health and wellbeing of populations. As such, we recommend that post-devolution Kenya ensures local political, economic and socio-cultural structures are equitable, sensitive and responsive to the needs of all people. We also propose poverty alleviation through capacity building and empowerment as a means of tackling NTDs for sustained economic opportunity and productivity at the local and national level., Author summary Wellbeing is currently seen as an avenue that shapes, happiness, productivity, environmental awareness, social inclusion, and justice; however, most countries presently adopting wellbeing measures are in the global north. Neglected Tropical Diseases (NTDs) significantly compromise populations’ health and well-being in the global south, causing undesirable effects on the personal, social, and economic capabilities of communities living in endemic regions. As countries work towards achieving the Sustainable Development Goals (SDGs), it is paramount that countries in the global south adopt wellbeing measures and, in doing so, capture the lived experiences of individuals experiencing inequities, particularly as these are shaped by NTDs. In sub-Saharan Africa (SSA), political and economic power manifests across different scales, determining human-environmental interaction, distribution of resources, and the transmission of infectious agents. This paper uses a political ecology of health approach to identify the political, economic, social and cultural factors that contribute to NTDs, which are among the world’s greatest global health problems. The vast majority of people bearing the burden of NTDs reside in low-income countries. Surprisingly, as the economies of the low-income countries improve to middle-income status, NTDs continue to thrive among sub-populations of low socioeconomic status because of the unequal distribution of economic gains. As a result, NTDs are found in environments characterized by poverty and income inequality, and other inequalities in access to health services, housing, safe water, and sanitation. This paper uses political ecology of health in the primarily biomedical field of NTDs to demonstrate that inequities are embedded within the broad political, socio-cultural, and economic systems that exacerbate NTD infection. The study recommends that NTD endemic countries in SSA formulate policies that enhance equity through capacity building and empowerment enhance population wellbeing.

Background Cryptosporidiosis is an emerging infectious disease of public health significance worldwide. The burden of disease caused by Cryptosporidium varies between and within countries/areas. To have a comprehensive understanding of epidemiological status and characteristics of human Cryptosporidium infection in China since the first report in 1987, a retrospective epidemiological analysis was conducted by presenting differences in the prevalence of Cryptosporidium by province, year, population, living environment and season and possible transmission routes and risk factors as well as genetic characteristics of Cryptosporidium in humans. Methodology/Principal findings A systematic search was conducted to obtain epidemiological papers of human Cryptosporidium infection/cryptosporidiosis from PubMed and Chinese databases. Finally, 164 papers were included in our analysis. At least 200,054 people from 27 provinces were involved in investigational studies of Cryptosporidium, with an average prevalence of 2.97%. The prevalence changed slightly over time. Variable prevalences were observed: 0.65–11.15% by province, 1.89–47.79% by population, 1.77–12.87% and 0–3.70% in rural and urban areas, respectively. The prevalence peak occurred in summer or autumn. Indirect person-to-person transmission was documented in one outbreak of cryptosporidiosis in a pediatric hospital. 263 Cryptosporidium isolates were obtained, and seven Cryptosporidium species were identified: C. hominis (48.3%), C. andersoni (22.43%), C. parvum (16.7%), C. meleagridis (8.36%), C. felis (3.04%), C. canis (0.76%) and C. suis (0.38%). Conclusions/Significances This systematic review reflects current epidemiological status and characteristics of Cryptosporidium in humans in China. These data will be helpful to develop efficient control strategies to intervene with and prevent occurrence of human Cryptosporidium infection/cryptosporidiosis in China as well as have a reference effect to other countries. Further studies should focus on addressing a high frequency of C. andersoni in humans and a new challenge with respect to cryptosporidiosis with an increasing population of elderly people and patients with immunosuppressive diseases., Author summary Cryptosporidium is a major cause of diarrheal disease in humans globally. Due to the lack of effective drug treatment and vaccine prevention against cryptosporidiosis, it is particularly important to develop efficient control strategies to intervene with and prevent Cryptosporidium infection in humans. The present review presented and analyzed epidemiological status and characteristics of Cryptosporidium infection in humans in China since the first report in 1987. To date, epidemiological investigations of Cryptosporidium infecion have been carried out in different populations in 27 provinces, autonomous regions, and municipalities. Average prevalence of Cryptosporidium was 2.97% (5,933/200,054). Like other infectious disease, due to poor sanitation conditions in rural areas, people living in rural areas had a significantly higher prevalence of Cryptosporidium (1.77–12.87%) than those living in urban areas (0–3.70%). Seven Cryptosporidium species were identified, including C. hominis, C. andersoni, C. parvum, C. meleagridis, C. felis, C. canis and C. suis. This retrospective epidemiological analysis indicates wide geographical distribution of human Cryptosporidium infection/cryptosporidiosis in China.

Domestic dogs are responsible for 99% of all cases of human rabies and thus, mass dog vaccination has been demonstrated to be the most effective approach towards the elimination of dog-mediated human rabies. Namibia demonstrated the feasibility of this approach by applying government-led strategic rabies vaccination campaigns to reduce both human and dog rabies incidences in the Northern Communal Areas of Namibia since 2016. The lessons learnt using paper-based form for data capturing and management of mass dog vaccination campaign during the pilot and roll out phase of the project (2016–2018) led to the implementation of a simple and accurate data collection tool in the second phase (2019–2022) of the rabies elimination program. In this paper, we describe the implementation of such custom-developed vaccination tracking device, i.e. the Global Alliance for Rabies Control (GARC) Data Logger (GDL), and the integration of the collected data into a website-based rabies surveillance system (Rabies Epidemiological Bulletin—REB) during 2019 and 2020 campaigns. A total of 10,037 dogs and 520 cats were vaccinated during the 2019 campaign and 13,219 dogs and 1,044 cats during the 2020 campaign. The vaccination data were recorded with the GDL and visualized via REB. Subsequent GIS-analysis using gridded population data revealed a suboptimal vaccination coverage in the great majority of grid cells (82%) with a vaccination coverage below 50%. Spatial regression analysis identified the number of schools, estimated human density, and adult dog population were associated with the vaccination performance. However, there was an inverse correlation to human densities. Nonetheless, the use of the GDL improved data capturing and monitoring capacity of the campaign, enabling the Namibian government to improve strategies for the vaccination of at-risk areas towards achieving adequate vaccination coverage which would effectively break the transmission of rabies., Author summary We used a custom-developed vaccination tracking device—the Global Alliance for Rabies Control (GARC) Data Logger—to capture dog rabies vaccination data during the 2019 and 2020 mass vaccination campaign in the Northern Communal Areas of Namibia, and then integrated the collected data into the web-based Rabies Epidemiological Bulletin, a rabies-specific disease surveillance platform for rabies-endemic countries. This approach allowed automatic collation, analysis and, visualization of data and drastically improved the data capturing and monitoring capacity of the Namibian government led campaign. Additionally, subsequent GIS analysis enabled a better estimation of vaccination coverage at a much higher spatial resolution, thus identifying areas where improvements in the vaccination strategy are needed to ensure long-term success of the project.

The estimated 50 million nomadic pastoralists in Africa are among the most “hard-to-reach” populations for health-service delivery. While data are limited, some studies have identified these communities as potential disease reservoirs relevant to neglected tropical disease programs, particularly those slated for elimination and eradication. Although previous literature has emphasized the role of these populations’ mobility, the full range of factors influencing health service utilization has not been examined systematically. We systematically reviewed empirical literature on health services uptake among African nomadic pastoralists from seven online journal databases. Papers meeting inclusion criteria were reviewed using STROBE- and PRISMA-derived guidelines. Study characteristics were summarized quantitatively, and 10 key themes were identified through inductive qualitative coding. One-hundred two papers published between 1974–2019 presenting data from 16 African countries met our inclusion criteria. Among the indicators of study-reporting quality, limitations (37%) and data analysis were most frequently omitted (18%). We identified supply- and demand-side influences on health services uptake that related to geographic access (79%); service quality (90%); disease-specific knowledge and awareness of health services (59%); patient costs (35%); contextual tailoring of interventions (75%); social structure and gender (50%); subjects’ beliefs, behaviors, and attitudes (43%); political will (14%); social, political, and armed conflict (30%); and community agency (10%). A range of context-specific factors beyond distance to facilities or population mobility affects health service uptake. Approaches tailored to the nomadic pastoralist lifeway, e.g., that integrated human and veterinary health service delivery (a.k.a., “One Health”) and initiatives that engaged communities in program design to address social structures were especially promising. Better causal theorization, transdisciplinary and participatory research methods, clearer operational definitions and improved measurement of nomadic pastoralism, and key factors influencing uptake, will improve our understanding of how to increase accessibility, acceptability, quality and equity of health services to nomadic pastoralist populations., Author summary There are approximately 50 million nomadic pastoralists in Africa for whom there is little data on healthcare access and utilization. This data scarcity presents a challenge to prevent, treat and control neglected tropical diseases and design the health service delivery mechanisms through which these objectives can be met. Examining a range of studies conducted over a 45-year period, we identified supply- and demand-side influences on health services uptake in ten thematic areas. These included physical proximity to, and quality of, health services; monetary and opportunity costs of accessing care; and societal and gender norms governing power dynamics within nomadic pastoralist groups as well as those between them and health care providers. The knowledge, attitudes and practices of health care providers and health seekers also played a role in utilization, as did hegemonic factors including “political will” and varying degrees of social conflict. NTD research topics included guinea worm, lymphatic filariasis, rabies, soil-transmitted helminths, tuberculosis (bovine and human), cholera, and rift valley fever. Studies pertaining to community-directed initiatives and “One Health” approaches offered promising solutions to increase service uptake. We recommend ways to strengthen future research on this subject to improve health service delivery to, and uptake among, nomadic pastoralist populations.

Background Onchocerciasis transmission across international borders is not uncommon, yet a coordinated cross border stops mass drug administration (MDA) decision has not been documented. Methods/Principle findings The Galabat-Metema focus involves neighboring districts on the border between Sudan and Ethiopia. Mass drug administration (MDA) was provided once and subsequently twice per year in this focus, with twice-per-year beginning in Ethiopia’s Metema subfocus in 2016 and in the Sudan’s Galabat subfocus in 2008. Ov16 ELISA-based serosurveys were conducted in 6072 children under 10 years of age in the Metema subfocus in 2014, and 3931 in the Galabat in 2015. Between 2014 and 2016, a total of 27,583 vector Simulium damnosum flies from Metema and 9,148 flies from Galabat were tested by pool screen PCR for Onchocerca volvulus O-150 DNA. Only 8 children were Ov16 seropositive (all in the Metema subfocus); all were negative by skin snip PCR. The upper limit of the 95% confidence interval (UCL) for Ov16 seropositive was, Author summary Onchocerciasis is a vector-borne tropical disease caused by the parasitc worm, Onchocerca volvulus. The vector is Simulium flies that breed in fast flowing rivers and streams. The infection can cause skin disease and loss of vision, giving risk to the common name of ‘river blindness’ for the condition. Ivermectin (Mectizan) mass drug administration (MDA) given at high coverage for many years can interrupt transmission such that MDA can eventually be stopped. The present paper provides highlights of onchocerciasis transmission interruption in the first known coordinated international cross border focus with ivermectin MDA program in Africa, where 99% of the global onchocerciasis burden exists. This focus known as Galabat-Metema is shared between Ethiopia and Sudan, both of which have established a nationwide policy for elimination of onchocerciasis. The paper provides the history of MDA in the border area and the results leading a coordinated end to MDA in the focus in 2017.

Background The Bangladesh Lymphatic Filariasis (LF) Elimination Programme has made significant progress in interrupting transmission through mass drug administration (MDA) and has now focussed its efforts on scaling up managing morbidity and preventing disability (MMDP) activities to deliver the minimum package of care to people affected by LF clinical conditions. This paper highlights the Bangladesh LF Programme’s success in conducting a large-scale cross-sectional survey to determine the number of people affected by lymphoedema and hydrocoele, which enabled clinical risk maps to be developed for targeted interventions across the 34 endemic districts (19 high endemic; 15 low endemic). Methodology/Principal findings In the 19 high endemic districts, 8,145 community clinic staff were trained to identify and report patients in their catchment area. In the 15 low endemic districts, a team of 10 trained field assistants conducted active case finding with cases reported via a SMS mHealth tool. Disease burden and prevalence maps were developed, with morbidity hotspots identified at sub-district level based on a combination of the highest prevalence rates per 100,000 and case-density rates per square kilometre (km2). The relationship between morbidity and baseline microfilaria (mf) prevalence was also examined. In total 43,678 cases were identified in the 19 high endemic districts; 30,616 limb lymphoedema (70.1%; female 55.3%), 12,824 hydrocoele (29.4%), and 238 breast/female genital swelling (0.5%). Rangpur Division reported the highest cases numbers and prevalence of lymphoedema (26,781 cases, 195 per 100,000) and hydrocoele (11661 cases, 169.6 per 100,000), with lymphoedema predominately affecting females (n = 21,652). Rangpur and Lalmonirhat Districts reported the highest case numbers (n = 11,199), and prevalence (569 per 100,000) respectively, with five overlapping lymphoedema and hydrocoele sub-district hotspots. In the 15 low endemic districts, 732 cases were identified; 661 lymphoedema (90.2%; female 39.6%), 56 hydrocoele (7.8%), and 15 both conditions (2.0%). Spearman’s correlation analysis found morbidity and mf prevalence significantly positively correlated (r = 0.904; p, Author summary The Global Programme to Eliminate Lymphatic Filariasis (GPELF) requires lymphatic filariasis (LF) endemic countries, such as Bangladesh, to estimate the number of lymphoedema and hydrocoele cases in order to deliver the minimum package of care required to control morbidity and reduce patient suffering. This paper highlights the Bangladesh LF Elimination Programme’s progress in training more than 8000 community health workers to identify more than 44,000 cases across 34 endemic districts where approximately 70 million people are at risk. The morbidity data collected enabled the creation of a national database and a series of risk maps of lymphoedema and hydrocoele to be developed, which highlighted the significant burden in northern Rangpur Division, especially of lymphoedema among female patients. The Bangladesh LF Elimination Programme’s efforts to identify LF cases across all endemic districts represents one of the most comprehensive national databases on LF clinical cases in the world. It provides an informative database for health workers to use in the delivery of the minimum package of care and a template for other countries to adopt and develop national strategies to manage morbidity and prevent disability as recommended by GPELF.

Background Over the last decade, implementation research and a science of global health delivery have emerged as important vehicles to improve the effectiveness of interventions. Efforts to control neglected tropical diseases (NTD) operate in challenging circumstances and with marginalized populations, making attention to context-specific details particularly relevant. Socio-anthropological insights have much to offer a science of NTD delivery. In this paper, an accessible and actionable framework for understanding NTD intervention effectiveness, based on socio-anthropological research, is presented and its utility for program planning and monitoring and evaluation is outlined. Methodology/Principal findings The framework was developed inductively by comparatively analyzing three rapid ethnographic studies undertaken in Eastern Africa (2010–2013) on three different large-scale NTD interventions: rabies elimination in Tanzania, sleeping sickness control in Uganda and the prevention of parasitic worms in Zambia. The framework includes five “intervention domains” where the effectiveness of these interventions was negotiated and determined at the local level. This involves: 1) the terrain of intervention (including seasonality and geographical variability); 2) community agency (including local knowledge, risk perceptions, behaviors, leadership and social pressure); 3) the strategies and incentives of field staff (skills, motivations, capabilities and support); 4) the socio-materiality of technology (characteristics of intervention tools and the adoption process itself); and 5) the governance of interventions (policy narratives, available expertise, bureaucracy, politics and the utilization of knowledge). The paper illustrates the importance of each of these domains by drawing on the case study research, presenting lessons learnt and practical recommendations for how such insights could improve intervention delivery. Conclusions/Significance To help close the gap between efficacy and effectiveness in NTD programs, it is important that field staff: 1) generate meaningful knowledge about contextual factors; 2) use this knowledge to tailor field strategies; and 3) create routine mechanisms to account for the dynamic process of implementation itself. The framework presented here offers a simple analytical tool to strengthen these knowledge-to-action relationships existing project planning tools, drawing on the insights of socio-anthropology., Author summary Many efficacious tools exist to control NTDs, but effectively moving these tools and approaches from the boardroom to the village is a complicated socio-political process. In the era of Sustainable Development Goals, global health has become more focused on improving the delivery of existing interventions. Greater attention to implementation research, including the value of social science perspectives, has followed in an effort to build a science of global health delivery. This paper presents an accessible and actionable socio-anthropological framework for understanding the effectiveness factors of NTD interventions. The framework was developed by comparatively analyzing three large-scale NTD interventions in Eastern Africa: rabies elimination in Tanzania, sleeping sickness control in Uganda and the prevention of parasitic worms in Zambia. The framework includes five “intervention domains” where the effectiveness of these interventions was determined: 1) the terrain of intervention; 2) community agency; 3) the strategies and incentives of field staff; 4) the socio-materiality of technology; and 5) the governance of interventions. The paper illustrates the importance of each of these domains, presenting lessons learnt and practical recommendations. As a flexible analytical tool, the framework could be integrated into the planning and implementation process itself, bringing the insights of socio-anthropological approaches into an emerging science of NTD delivery.

Background In the Cameroon, previous efforts to identify Buruli ulcer (BU) through the mobilization of community health workers (CHWs) yielded poor results. In this paper, we describe the successful creation of a BU community of practice (BUCOP) in Bankim, Cameroon composed of hospital staff, former patients, CHWs, and traditional healers. Methods and principle findings All seven stages of a well-defined formative research process were conducted during three phases of research carried out by a team of social scientists working closely with Bankim hospital staff. Phase one ethnographic research generated interventions tested in a phase two proof of concept study followed by a three- year pilot project. In phase three the pilot project was evaluated. An outcome evaluation documented a significant rise in BU detection, especially category I cases, and a shift in case referral. Trained CHW and traditional healers initially referred most suspected cases of BU to Bankim hospital. Over time, household members exposed to an innovative and culturally sensitive outreach education program referred the greatest number of suspected cases. Laboratory confirmation of suspected BU cases referred by community stakeholders was above 30%. An impact and process evaluation found that sustained collaboration between health staff, CHWs, and traditional healers had been achieved. CHWs came to play a more active role in organizing BU outreach activities, which increased their social status. Traditional healers found they gained more from collaboration than they lost from referral. Conclusion/ Significance Setting up lines of communication, and promoting collaboration and trust between community stakeholders and health staff is essential to the control of neglected tropical diseases. It is also essential to health system strengthening and emerging disease preparedness. The BUCOP model described in this paper holds great promise for bringing communities together to solve pressing health problems in a culturally sensitive manner., Author summary Buruli ulcer (BU) is a neglected tropical disease primarily found in West Africa largely effecting the rural poor. BU has a known cause and cure, but an unknown route of transmission and a poorly understood incubation period. If not treated early and in a timely manner, BU often progresses to an advanced state requiring surgery and prolonged wound care. In the Cameroon, previous efforts to mobilize community health workers and educate community members to identify cases of BU yielded poor results. In this paper, we describe steps undertaken to create a successful BU community of practice (BUCOP) composed of community stakeholders working in concert with clinic staff. The success of the BUCOP was measured in terms of numbers of suspected BU cases referred and confirmed, a decline in treatment drop out, and sustained collaboration among stakeholders both during and following the pilot project. Pilot project success is attributed to an innovative and culturally sensitive approach to BU outreach education, increased levels of patient assistance, and mutual respect among BUCOP members for what each stakeholder contributed to BU detection, treatment, psychosocial support, and spiritual protection.

Background How can we explain the uneven decline of syphilis around the world following the introduction of penicillin? In this paper we use antenatal syphilis prevalence (ASP) to investigate how syphilis prevalence varied worldwide in the past century, and what risk factors correlate with this variance. Methods 1) A systematic review using PubMed and Google Scholar was conducted to identify countries with published data relating to ASP estimates from before 1952 until the present. Eleven countries were identified (Canada, Denmark, Finland, India, Japan, Norway, Singapore, South Africa, United States of America (USA), United Kingdom (UK) and Zimbabwe). The ASP epidemic curve for each population was depicted graphically. In South Africa and the USA, results are reported separately for the black and white populations. 2) National antenatal syphilis prevalence estimates for 1990 to 1999 and 2008 were taken from an Institute for Health Metrics and Evaluation database on the prevalence of syphilis in low risk populations compiled for the Global Burden of Diseases study and from a recent review paper respectively. National ASPs were depicted graphically and regional median ASPs were calculated for both time periods. 3) Linear regression was used to test for an association between ASP in 1990–1999 and 2008 and four risk factors (efficacy of syphilis screening/treatment, health expenditure, GDP per capita and circumcision prevalence). WHO world regions were included as potential explanatory variables. Results In most populations, ASP dropped to under 1% before 1960. In Zimbabwe and black South Africans, ASP was high in the pre-penicillin period, dropped in the post-penicillin period, but then plateaued at around 6% until the end of the 20th century when ASP dropped to just above 1%. In black Americans, ASP declined in the post penicillin period, but plateaued at 3–5% thereafter. ASP was statistically significantly higher in sub-Saharan Africa in 1990–1999 and 2008 than in the other world regions (P < 0.001). On multivariate analysis in both time periods, ASP was only associated with residence in sub-Saharan Africa. Conclusions Further research is necessary to elucidate the reasons for the higher prevalence of syphilis in sub-Saharan Africa., Author Summary Syphilis rates have varied tremendously between different populations around the world. We conducted a systematic review of syphilis prevalence in pregnant women in 13 populations with available data for the last 100 years. Our findings were that in most populations syphilis prevalence dropped to under 1% before 1960. In the 2 populations from sub Saharan Africa, the syphilis prevalence remained around 6% until 50 years after the introduction of penicillin. Other systematic reviews were utilized to provide syphilis prevalence estimates for all countries with available data for the periods 1990–1999 and 2008. We assessed if there was a correlation between national syphilis prevalence in these periods and five explanatory factors. Only residence in sub-Saharan Africa was associated with syphilis prevalence in both time periods. These findings, considered in conjunction with other types of evidence we review, such as the strong correlations at population level between syphilis prevalence and those of Herpes Simplex Virus-2 prevalence and HIV prevalence, suggest that common risk factors may underpin the spread of all three of these sexually transmitted diseases. Establishing what these factors are is of great importance to improve the health of highly affected populations such as those in sub-Saharan Africa.

Rabies is a fatal zoonosis that still causes nearly 70, 000 human deaths every year. In Europe, the oral rabies vaccination (ORV) of red foxes (Vulpes vulpes) was developed in the late 1970s and has demonstrated its effectiveness in the eradication of the disease in Western and some Central European countries. Following the accession of the three Baltic countries—Estonia, Latvia and Lithuania—to the European Union in 2004, subsequent financial support has allowed the implementation of regular ORV campaigns since 2005–2006. This paper reviews ten years of surveillance efforts and ORV campaigns in these countries resulting in the near eradication of the disease. The various factors that may have influenced the results of vaccination monitoring were assessed using generalized linear models (GLMs) on bait uptake and on herd immunity. As shown in previous studies, juveniles had lower bait uptake level than adults. For the first time, raccoon dogs (Nyctereutes procyonoides) were shown to have significantly lower bait uptake proportion compared with red foxes. This result suggests potentially altered ORV effectiveness in this invasive species compared to the red foxes. An extensive phylogenetic analysis demonstrated that the North-East European (NEE) rabies phylogroup is endemic in all three Baltic countries. Although successive oral vaccination campaigns have substantially reduced the number of detected rabies cases, sporadic detection of the C lineage (European part of Russian phylogroup) underlines the risk of reintroduction via westward spread from bordering countries. Vaccine induced cases were also reported for the first time in non-target species (Martes martes and Meles meles)., Author Summary This paper reviews ten years of rabies epidemiology in the three Baltic countries. Both surveillance efforts and oral rabies vaccination campaigns have resulted in the near eradication of the disease. Multivariate analysis assessed with generalized linear models (GLM) suggested lower oral vaccination effectiveness in raccoon dogs compared with red foxes, highlighting the importance of adapting oral vaccination strategy to each vector of the disease. Although eradication of the disease is almost achieved, the detection of some cases belonging with the Russian rabies lineage emphasizes a risk of rabies reintroduction in the Baltic States due to westward spread from bordering countries. This study show also the first vaccine-induced cases detected in non-target species (Martes martes and Meles meles).

Background Schistosomiasis, also known as bilharzia, is a chronic parasitic blood fluke infection acquired through contact with contaminated surface water. The illness may be mild or can cause significant morbidity with potentially serious complications. Children and those living in rural areas with limited access to piped water and services for healthcare are the most commonly infected. To address the prevalence of the disease in parts of South Africa (SA) effective national control measures are planned, but have not yet been implemented. This study aimed to estimate the prevalence and trends of public sector laboratory-confirmed schistosomiasis cases in SA over an eight-year (2011–2018) period, to inform future control measures. Methodology & principal findings This is a descriptive analysis of secondary data from the National Health Laboratory Service (NHLS). The study included all records of patients for whom microscopic examination detected Schistosoma species eggs in urine or stool specimens from January 2011 to December 2018. Crude estimates of the prevalence were calculated using national census mid-year provincial population estimates as denominators, and simple linear regression was used to analyse prevalence trends. A test rate ratio was developed to describe variations in testing volumes among different groups and to adjust prevalence estimates for testing variations. A total number of 135 627 schistosomiasis cases was analysed with the highest prevalence observed among males and individuals aged 5–19 years. We describe ongoing endemicity in the Eastern Cape Province, and indicate important differences in the testing between population groups. Conclusion While there was no overall change in the prevalence of schistosomiasis during the analysis period, an average of 36 people per 100 000 was infected annually. As such, this represents an opportunity to control the disease and improve quality of life of affected people. Laboratory-based surveillance is a useful method for reporting occurrence and evaluating future intervention programs where resources to implement active surveillance are limited., Author summary This is the first paper to describe the prevalence of human schistosomiasis in South Africa using nationally representative data. The prevalence remained consistent during the eight-year period, independent of increasing annual testing volumes. Groups with the highest burden included males and individuals aged 5–19 years. The schistosomiasis-endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal emerged as the highest-burdened areas, and ongoing endemicity in Eastern Cape Province was demonstrated. Western Cape Province likely reported cases imported from endemic provinces rather than being acquired by local transmission. In summary, schistosomiasis remains an important public health problem in South Africa that needs long-term sustainable, effective standardised interventions to reduce the burden. Passive laboratory-based surveillance is a practical tool for reporting prevalence, and could be used to monitor and evaluate future intervention programs.

Background In Peru, the information regarding sand fly vectors of leishmaniasis and bartonellosis in the Amazon region is limited. In this study, we carried out sand fly collections in Peruvian lowland and highland jungle areas using different trap type configurations and screened them for Leishmania and Bartonella DNA. Methodology/Principal findings Phlebotomine sand flies were collected in Peruvian Amazon jungle and inter Andean regions using CDC light trap, UV and color LED traps, Mosquito Magnet trap, BG Sentinel trap, and a Shannon trap placed outside the houses. Leishmania spp. screening was performed by kDNA PCR and confirmed by a nested cytochrome B gene (cytB) PCR. Bartonella spp. screening was performed by ITS PCR and confirmed by citrate synthase gene (gltA). The PCR amplicons were sequenced to identify Leishmania and Bartonella species. UV and Blue LED traps collected the highest average number of sand flies per hour in low jungle; UV, Mosquito Magnet and Shannon traps in high jungle; and Mosquito Magnet in inter Andean region. Leishmania guyanensis in Lutzomyia carrerai carrerai and L. naiffi in Lu. hirsuta hirsuta were identified based on cytB sequencing. Bartonella spp. related to Bartonella bacilliformis in Lu. whitmani, Lu. nevesi, Lu. hirsuta hirsuta and Lu. sherlocki, and a Bartonella sp. related to Candidatus B. rondoniensis in Lu. nevesi and Lu. maranonensis were identified based on gltA gene sequencing. Conclusions/Significance UV, Blue LED, Mosquito Magnet and Shannon traps were more efficient than the BG-Sentinel, Green, and Red LED traps. This is the first report of L. naiffi and of two genotypes of Bartonella spp. related to B. bacilliformis and Candidatus B. rondoniensis infecting sand fly species from the Amazon region in Peru., Author summary Leishmaniasis and human bartonellosis, two neglected tropical diseases, are endemic in Peruvian Andean regions. However, no human bartonellosis cases has been reported in the Amazon jungle where leishmaniasis has high prevalence. The improvement of sand fly trapping methods and identification of putative Leishmania and Bartonella vectors across Andean and Amazonian regions are important steps towards the design of better control strategies and reducing the risk of transmission in endemic areas. In this paper the authors explored the effectiveness of different trap types, based in LED colors and odor attractants, for sand fly collections in endemic areas of leishmaniasis and bartonellosis. Also, we reported for the first time the detection of Bartonella DNA in sand fly species from the Peruvian Amazon jungle, and the first record in Peru of L. (V.) naiffi infecting Lu. hirsuta hirsuta. The information provided by this manuscript will serve as a baseline for future surveillance and intervention studies about sand fly species as potential vectors of Leishmania and Bartonella in highly endemic areas.

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.

Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia’s second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper., Author summary The early COVID-19 pandemic in Malaysia was driven mainly by transmission following a religious mass gathering held in Kuala Lumpur at the end of February 2020. To study the genetic epidemiology of SARS-CoV-2 in Malaysia, we analysed 57 available and 58 newly generated Malaysian whole genome virus sequences. We found that lineage B.6, rare (1.4%) globally, first appeared after the mass gathering, was linked to attendees, and became predominant (65.2%) in Malaysia. Increases in COVID-19 cases and locally acquired B.6 strains were temporally linked. Non-B.6 viruses were mainly associated with travel and showed limited spread. Increases in B.6 viruses in Asia Pacific countries were temporally linked to participants returning from this mass gathering. Altogether, 95% of global B.6 sequences originated in Asia Pacific countries. We also report a mutation in the virus nsp3 gene found in 47.3% of global B.6 sequences and associated with reduced detection by a commercial diagnostic test. In conclusion, the religious mass gathering in Kuala Lumpur was associated with the second wave of COVID-19 cases of predominantly B.6 lineage in Malaysia, and subsequent spread of B.6 viruses regionally. Genome sequence data provides valuable insight into virus spread and is important for monitoring continued accuracy of diagnostic kits.

An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100–242) and 2008 cases in the country as a whole (95% CI: 1170–2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies., Author summary Significant healthcare burdens arise from dengue and traditional vector control is the primary control strategy to reduce dengue transmission potential. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. This paper examines the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst accounting for temporal confounders. We found that social distancing is expected to lead to an increase in the number of cases in Thailand, with the largest increase arising from Bangkok province. Social distancing policy estimates for Thailand were also found to be robust in sensitivity analysis. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies.

Plasmodium vivax malaria is much less common in Africa than the rest of the world because the parasite relies primarily on the Duffy antigen/chemokine receptor (DARC) to invade human erythrocytes, and the majority of Africans are Duffy negative. Recently, there has been a dramatic increase in the reporting of P. vivax cases in Africa, with a high number of them being in Duffy negative individuals, potentially indicating P. vivax has evolved an alternative invasion mechanism that can overcome Duffy negativity. Here, we analyzed single nucleotide polymorphism (SNP) and copy number variation (CNV) in Whole Genome Sequence (WGS) data from 44 P. vivax samples isolated from symptomatic malaria patients in southwestern Ethiopia, where both Duffy positive and Duffy negative individuals are found. A total of 123,711 SNPs were detected, of which 22.7% were nonsynonymous and 77.3% were synonymous mutations. The largest number of SNPs were detected on chromosomes 9 (24,007 SNPs; 19.4% of total) and 10 (16,852 SNPs, 13.6% of total). There were particularly high levels of polymorphism in erythrocyte binding gene candidates including merozoite surface protein 1 (MSP1) and merozoite surface protein 3 (MSP3.5, MSP3.85 and MSP3.9). Two genes, MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. Variation in gene copy number was also concentrated in genes involved in host-parasite interactions, including the expansion of the Duffy binding protein gene (PvDBP) on chromosome 6 and MSP3.11 on chromosome 10. Based on the phylogeny constructed from the whole genome sequences, the expansion of these genes was an independent process among the P. vivax lineages in Ethiopia. We further inferred transmission patterns of P. vivax infections among study sites and showed various levels of gene flow at a small geographical scale. The genomic features of P. vivax provided baseline data for future comparison with those in Duffy-negative individuals and allowed us to develop a panel of informative Single Nucleotide Polymorphic markers diagnostic at a micro-geographical scale., Author summary Plasmodium vivax is the most geographically widespread parasite species that causes malaria in humans. Although it occurs in Africa as a member of a mix of Plasmodium species, P. vivax is dominant in other parts of the world outside of Africa (e.g., Brazil). It was previously thought that most African populations were immune to P. vivax infections due to the absence of Duffy antigen chemokine receptor (DARC) gene expression required for erythrocyte invasion. However, several recent reports have indicated the emergence and potential spread of P. vivax across human populations in Africa. Compared to Southeast Asia and South America where P. vivax is highly endemic, data on polymorphisms in erythrocyte binding gene candidates of P. vivax from Africa is limited. Filling this knowlege gap is critical for identifying functional genes in erythrocyte invasion, biomarkers for tracking the P. vivax isolates from Africa, as well as potential gene targets for vaccine development. This paper examined the level of genetic polymorphisms in a panel of 43 potential erythrocyte binding protein genes based on whole genome sequences and described transmission patterns of P. vivax infections from different study sites in Ethiopia based on the genetic variants. Our analyses showed that chromosomes 9 and 10 of the P. vivax genomes isolated in Ethiopia had the most high-quality genetic polymorphisms. Among all erythrocyte binding protein gene candidates, the merozoite surface proteins 1 and merozoite surface protein 3 showed high levels of polymorphism. MAEBL and MSP3.8 related to immunogenicity and erythrocyte binding function were detected with significant signals of positive selection. The expansion of the Duffy binding protein and merozoite surface protein 3 gene copies was an independent process among the P. vivax lineages in Ethiopia. Various levels of gene flow were observed even at a smaller geographical scale. Our study provided baseline data for future comparison with P. vivax in Duffy negative individuals and help develop a panel of genetic markers that are informative at a micro-geographical scale.

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.

Background Buruli ulcer disease (BUD) results in disabilities and deformities in the absence of early medical intervention. The extensive role of caregiving in BUD is widely acknowledged, however, associated caregiver burden is poorly understood. In this paper we assessed the burden which caregivers experience when supporting patients with BUD in Ghana. Method/ principal findings This qualitative study was conducted in 3 districts in Ghana between August and October 2019. 13 semi-structured interviews were conducted on caregivers of BUD patients in the local language of Twi. Data was translated into English, coded into broad themes, and direct content analysis approach was used to analyse results. The results show the caregivers face financial, psychological and health issues as a consequence of their caregiving role. Conclusion/ significance This study found significant caregiver burden on family members. It also highlighted the psychological burden caregivers experience and the limited knowledge of the disease within endemic communities. Further research is needed to quantify the caregiver burden of BUD at different economic levels in order to better understand the impact of possible caregiver interventions on patient outcomes., Author summary Buruli ulcer disease (BUD) is a stigmatizing skin condition caused by the bacteria, Mycobacterium ulcerans. The disease results in permanent functional limitations in the absence of early medical intervention. The disabling BUD conditions, financial constraints and frequent hospital visits support the role of caregiving for affected individuals. Caregiver burden is poorly understood although the role and need for caregiving is widely recognised in BUD. This study identified a previously unrecognized burden on the caregivers of BUD patients in 3 endemic districts in Ghana. Specifically, we identified significant financial and psychological pressure on affected families in meeting healthcare related costs and physical care while also providing for their own and other family members’ needs. We also highlight the emotional burden experienced by caregivers, their reduced work productivity, the barriers caregivers face in accessing healthcare with BUD patients and the limited support available for caregivers. Our study highlights the serious social consequences of BUD in Ghana. Further quantitative research within different economic regions affected by BUD is warranted to better understand the caregiver burden of BUD.

Background Domestic carnivores can introduce rabies into disease-free countries or areas if they are incubating the disease and transported during the pre-symptomatic period. For pets moved into the European Union, the European Commission decided to establish a system of community approval of laboratories willing to carry out the rabies serological controls to guarantee an effective control system. As the specific institute to coordinate the approval of the laboratories, designated by the European Commission in 2000, our laboratory organizes annual proficiency tests (PT) for laboratories already agreed or willing to be agreed to perform rabies serological controls (by detecting rabies virus neutralizing antibodies only) in the frame of international trade. Methodology/Principal findings The assessment criteria of this PT rely on the analysis of the specificity and the intra-laboratory consistency. The approach used to evaluate the degree of laboratory consistency is based on the use of compiled data obtained from previous PT campaigns, and is measured by the quality of a regression model. By using historical data for calculating assigned values and associated standard deviations, instead of values obtained from only one campaign, they became robust without any additional statistical treatment. In the present paper, more than 800 historical values were compiled for each of the regression parameters. Conclusions/Significance Since the beginning of these PT schemes in 1999, the overall percentage of failing laboratories remained stable over the years (4.1%) while the number of participants increased to 79 in 2018. This highlighted the robustness and the consistency of the statistical analyses used to assess the laboratory’s performance over the years. The improvements carried out and the consistency of our statistical analyses have resulted in the compliance of the rabies serology PT with the ISO/IEC 17043 and ISO 13528:2015 International Standards., Author summary Proficiency testing (PT) schemes also known as “external quality assessment schemes” are one means to assess the quality and validity of routine measurements. PT schemes are the most common, and perhaps the most important type of inter-laboratory comparisons. As the specific institute to coordinate the approval of the laboratories, designated by the European Commission in 2000, our laboratory organizes annual PT for laboratories already agreed or willing to be agreed to perform rabies serological controls in the frame of international trade. Our PT program is conducted in compliance with the requirements of the ISO/ IEC 17043 International Standards. To enhance the robustness of our statistical analyses, we used an original approach to assess the performance of participants consisting in comparing individual laboratory values with assigned values calculated from compiled PT historical data. Since the beginning of these PT schemes in 1999, the overall percentage of failing laboratories remained stable over the years. The improvements carried out and the consistency of our statistical analyses have resulted in the compliance of the rabies serology PT with the International Standards.

The Peruvian-Brazilian border is a highly endemic tegumentary leishmaniasis region in South America. The interoceanic highway is a commercial route that connects Peru and Brazil through Madre de Dios and has raised concerns about its impact on previously undisturbed areas. In order to assess leishmaniasis transmission risk along this highway, we conducted a surveillance study of the sand fly populations in this area. Sand flies were collected between 2009 and 2010 along transects at 200 m, 600 m and 1000 m from six study sites located along the highway (Iberia, La Novia, Alto Libertad, El Carmen, Florida Baja, Mazuko and Mavila) and an undisturbed area (Malinowski). Collected specimens were identified based on morphology and non-engorged females of each species were pooled and screened by kinetoplast PCR to detect natural Leishmania infections. A total of 9,023 specimens were collected belonging to 54 different Lutzomyia species including the first report of Lu. gantieri in Peru. Four species accounted for 50% of all specimens (Lutzomyia carrerai carrerai, Lu. davisi, Lu. shawi and Lu. richardwardi). El Carmen, Alto Libertad, Florida Baja and Malinowski presented higher Shannon diversity indexes (H = 2.36, 2.30, 2.17 and 2.13, respectively) than the most human disturbed sites of Mazuko and La Novia (H = 1.53 and 1.06, respectively). PCR detected 10 positive pools belonging to Lu. carrerai carrerai, Lu. yuilli yuilli, Lu. hirsuta hirsuta, Lu. (Trichophoromyia) spp., and Lu. (Lutzomyia) spp. Positive pools from 1,000 m transects had higher infectivity rates than those from 600 m and 200 m transects (9/169 = 5.3% vs 0/79 = 0% and 1/127 = 0.8%, p = 0.018). El Carmen, accounted for eight out of ten positives whereas one positive was collected in Florida Baja and Mazuko each. Our study has shown differences in sand fly diversity, abundance and species composition across and within sites. Multiple clustered Lutzomyia pools with natural Leishmania infection suggest a complex, diverse and spotty role in leishmaniasis transmission in Madre de Dios, with increased risk farther from the highway., Author summary Leishmaniasis is a neglected disease that is endemic in tropical and subtropical regions affecting up to 2 million people every year. Currently, there is concern about the effects of human-made environmental changes on the transmission of leishmaniasis due to increased exposure to the sand fly vector. In this paper, the authors explored changes in the distribution of sand flies and natural leishmania infection across communities located along the interoceanic highway that connects Peru and Brazil. The study found differences in sand fly species composition and abundance between and within sites as well as a lower sand fly diversity in communities with high human disturbance. Ten pools belonging to Lutzomyia shawi, Lu. carrerai carrerai, Lu. yuilli yuilli, Lu. hirsuta hirsuta, Lu. (Helcocyrtomyia) spp. and Lu. (Lutzomyia) spp. were found positive for Leishmania spp. The majority of these positive pools were collected from a single community and far from the highway. The information provided by this manuscript will serve as a baseline to assess the effects of human activities in the region and guide future surveillance and intervention strategies.

Background The province of Formosa, Argentina, is endemic for leprosy. In the present paper, we assessed the trend (T, 2002–2016 time series) and the forecast for 2022 of new case detection rate (NCDR) and determined the spatial distribution of new cases detected (NCD) of leprosy. Methodology/Principal findings This is a descriptive observational study of 713 NCD of leprosy from provincial medical records between January 2002 and December 2016. The whole dataset from the provincial medical record was used to independently estimate the NCDR trends of the general population, age groups, sexes and Departments. This same database was used to estimate the NCDR forecast of the general population for 2022, applying a dynamic linear model with a local linear trend, using the MCMC algorithm. The NCDR was higher in men (p65:-61, p0.05), which showed no trend. Forecasts predicted that leprosy will not be eliminated by 2022 (3.64, 95%CI: [1.22, 10.25]). Conclusions/Significance Our results highlight the status of leprosy in Formosa and provide information to the provincial public health authorities on high-risk populations, stressing the importance of timely detection of new cases for further elimination of the disease in the province., Author summary Leprosy, a neglected tropical disease, is a public health problem in northern Argentina, causing permanent damage, stigmatization and discrimination. The Program for the Control of Leishmaniasis and Leprosy in Formosa province (PCLyLF) is responsible for the diagnosis and treatment of the disease and the active search for household contacts. The present study aimed to determine the spatial distribution of new cases of leprosy and the status of the disease using new case detection rate (NCDR) as the main epidemiological indicator. We determined the NCDR trends (2002–2016 time series) of the general population, age groups, sexes and Departments, and the NCDR forecast for the province by 2022. Our results indicated that leprosy was spread throughout Formosa, with higher rates in men and in patients over 65 years old. The NCDR showed a downward trend in the whole province and in each Department. The Departments of Bermejo and Matacos had the highest decreasing trend and the Department of Patiño the lowest one. Future projections show that leprosy will not be eliminated by 2022.

Background Toxoplasma gondii is an obligate intracellular and neurotropic apicomplexan protozoan parasite infecting almost all warm-blooded vertebrates including humans. To date in Ethiopia, no systematic study has been investigated on the overall effects of potential risk factors associated with seropositivity for Toxoplasma gondii among pregnant women and HIV infected individuals. We intended to determine the potential risk factors (PRFs) associated with seropositivity for Toxoplasma gondii from published data among pregnant women and HIV infected individuals of Ethiopia. Methodology An systematic review of the previous reports was made. We searched PubMed, Science Direct, African Journals Online, and Google Scholar for studies with no restriction on the year of publication. All references were screened independently in duplicate and were included if they presented data on at least two risk factors. Meta-analysis using the random or fixed-effects model was made to calculate the overall effects for each exposure. Results Of the 216 records identified, twenty-four reports met our eligibility criteria, with a total of 6003 individuals (4356 pregnant women and 1647 HIV infected individuals). The pooled prevalences of anti-Toxoplasma gondii antibodies were found at 72.5% (95% CI: 58.7% - 83.1%) in pregnant women and 85.7% (95% CI: 76.3% - 91.8%) in HIV infected individuals. A significant overall effect of anti-Toxoplasma gondii seropositivity among pregnant women (p < 0.05) was witnessed with age, abortion history, contact with cats, cat ownership, having knowledge about toxoplasmosis, being a housewife and having unsafe water source. Age, cat ownership, and raw meat consumption were also shown a significant effect (p < 0.05) to anti-Toxoplasma gondii seropositivity among HIV infected individuals. Conclusions This review showed gaps and drawbacks in the earlier studies that are useful to keep in mind to design accurate investigations in the future. The pooled prevalence of anti-Toxoplasma gondii antibodies was found to be higher among pregnant women and HIV infected individuals. This suggests that thousands of immunocompromised individuals (pregnant women and HIV infected patients) are at risk of toxoplasmosis due to the sociocultural and living standards of the communities of Ethiopia. Appropriate preventive measures are needed to reduce the exposure to Toxoplasma gondii infection. Further studies to investigate important risk factors are recommended to support the development of more cost-effective preventive strategies., Author summary Toxoplasma gondii is a cosmopolitan food and water-borne zoonotic protozoan parasite that able to infect almost all warm blooded vertebrates. It causes a considerable public health impact with higher burden in developing countries. Estimating pooled prevalence of Toxoplasma infection in high risk groups can draw health policy makers’ attention in planning a screening program and control needs. Several risk factors determine the circulation of Toxoplasma gondii between intermediate and final hosts. In this comprehensive systematic review and meta-analysis, we intended to determine the prevalence and associated potential factors of Toxoplasma gondii infection in pregnant women and HIV infected individuals of Ethiopia. We searched English electronic databases (PubMed, Science Direct, African Journals Online, and Google Scholar) for studies. Our review resulted in a total of 24 papers meeting the inclusion criteria. The studies were performed from 2007 to 2019 using a cross-sectional study design and with overall samples of 6003 individuals (4356 pregnant women and 1647 HIV infected individuals). The estimated pooled seroprevalence of anti-Toxoplasma gondii antibodies using random-effect model was found to be 72.5% (95% CI: 58.7% - 83.1%) in pregnant women and 85.7% (95% CI: 76.3% - 91.8%) in HIV infected individuals. Risk factors: age, abortion history, contact with cats, cat ownership, having knowledge about toxoplasmosis, being a housewife and having unsafe water source were showed significant overall effect on Toxoplasma gondii infection rate in pregnant women. Age, cat ownership and raw meat consumption also showed significant overall effect on infection rate with Toxoplasma gondii in HIV infected individuals. The findings of this study are valuable to increase awareness among public health workers and educators regarding Toxoplasma gondii infection in high risk groups (pregnant women and HIV infected individuals) and risk factors that influence the occurrence of its infection. The findings also indicate a need for prenatal screening for early diagnosis and treatment.

This paper reports the prevalence and intensity of soil-transmitted helminth (STH) infections measured in Zimbabwe before and after a control intervention based on annual deworming of school-age children (SAC) conducted from 2012 to 2018. In 2010, epidemiological data were collected from 13 195 SAC in 255 randomly selected schools in all districts nationwide using, as diagnostic methods, the Kato–Katz and the formal ether stool concentration technique. At follow up, conducted in 2017, only Kato–Katz was performed; specimens were collected from 13 352 children in 336 schools. The data were evaluated using a geospatial approach. The national prevalence of STH infection in SAC was estimated at 5.8% at baseline, with 0.8% of infections of moderate and heavy intensity. Preventive chemotherapy (PC) targeted all 2.5 million children of school age enrolled in Zimbabwe, with coverage ranging from 49% to 85%. At follow up, national prevalence of STH in SAC was estimated at 0.8%; infections of moderate and heavy intensity almost disappeared (0.1% prevalence). As a result, Zimbabwe can suspend deworming activities in 54 districts and reduce the frequency of PC in the remaining six districts. The total amount of albendazole tablets needed will be approximately 100 000 a year., Author summary We analysed the impact of 6 years of preventive chemotherapy intervention by the Ministry of Health and Child Care of Zimbabwe (MoHCC) to control STH infections in Zimbabwe. We applied a geostatistical method to analyse the epidemiological data before and after the intervention. The results are interesting because they demonstrate a complete elimination of infection of moderate heavy intensity (that are considered the ones causing most of STH morbidity and a drastic reduction in prevalence that entails an estimated reduction of 90% in the need for anthelminthic medicines to maintain the situation and a consequent reduction in programme costs.

Since leishmaniases are zoonotic vector-borne diseases transmitted through the bites of infected female sand flies, identification of the sources of imbibed blood meals and the detection and identification of leishmanial DNA in them are important in discerning animal reservoirs, clarifying the epidemiology and facilitating control of local leishmaniases. CDC light traps, aspirators and sticky paper traps were used to collect sand flies in four Palestinian foci of both, CL and VL. Phlebotomine species identification was based on morphological keys. Female specimens were screened to detect and identify leishmanial infections, using kDNA-PCR and ITS1-PCR, and engorged female specimens were analyzed to identify the origin of their blood meals, using an RDB blood meal assay based on the amplification of the cytochrome b gene (cytb) of vertebrate mitochondrial DNA (mtDNA). Twenty sand fly species, 11 of the genus Phlebotomus and nine the genus Sergentomyia, were identified. The most abundant species was Ph. papatasi (33.7%), followed by Ph. sergenti (21%). Among the 691 female sand fly specimens, 18.5% (128/691) were positive for leishmanial DNA, using the kDNA-PCR and 6.4% (44/691) were positive using the ITS1-PCR. DNA from parasites of the genus Leishmania was identified in only 1.5% of the infected sand flies. That of Leishmania tropica parasites was detected in six female specimens of Ph. sergenti and that of L. major parasites in two female specimens of Ph. papatasi. Interestingly, two engorged females of the species Se. (Neophlebotomus) sp. were positive for L. tropica DNA. Ninety engorged female sand flies of Ph. papatasi and 104 of Ph. sergenti had fed on a large variety of vertebrate hosts such as humans, hyraxes, rats, cows, goats and birds. Regarding blood-meals showing a mixture from different species of animal host, hyrax and rat blood was revealed in 8/104 (7.7%) females of Ph. sergenti. Detection of hyrax blood in engorged female sand flies of the species Ph. sergenti supports the role of hyraxes being a potential reservoir of L. tropica in Palestinian regions. Rat blood meals might be significant since a few strains L. tropica and L. infantum were isolated from rats. Further studies must be undertaken before conclusions could be drawn., Author summary Leishmaniases are vector-borne tropical diseases caused by more than twenty species belonging to the protozoan genus Leishmania and transmitted to humans and some other mammalian species by the bites of female phlebotomine sand flies. In the Palestinian Authority, cutaneous leishmaniasis (CL) is the most common leishmaniasis. This study investigated the Palestinian sand fly fauna, their infection rates and feeding preference determined by applying a kDNA-PCR and an ITS1-PCR. Twenty phlebotomine species were shown to be circulating in the study area. The most abundant species was Ph. papatasi (33.7%), followed by Ph. sergenti (21%). Infection by parasites of L. tropica was confirmed in 6.4%, using an ITS1-PCR. Meals of human blood were the most abundant (78.1%) and those of hyrax blood were identified in the cases of six sand flies, five Ph. sergenti and one Ph. papatasi

Owing to the increased reports in Aedes-borne diseases in the Caribbean and Latin America, the United States Agency for International Development assisted the Jamaican Ministry of Health and Wellness in conducting insecticide susceptibility tests on Aedes aegypti populations. Sentinel sites were established in seven parishes of Jamaica (St. Catherine, Kingston and St. Andrew, St. Thomas, Portland, St. Mary and St. Ann) and Aedes aegypti eggs were collected, reared to adults per collected population and their susceptibility to varying pyrethroids and organophosphates were tested using the World Health Organization paper bioassays for these insecticides. The Centers for Disease Control and Prevention bottle bioassay was used to assess susceptibility to the carbamate, bendiocarb. The voltage gated sodium channel gene mutations V1016I and I1011V, normally associated with pyrethroid resistance, were also analysed. The results showed that Aedes aegypti collected from all parishes exhibited resistance to pyrethroids at the following concentrations, permethrin 0.25–2.5%; deltamethrin 0.03–0.15%; lambda-cyhalothrin 0.03–0.3%; and etofenprox 0.5–2.5%. The insecticide deltamethrin at concentration 0.3% was the only pyrethroid tested that resulted in high mortality, 94.9 ± 0.34% knockdown within 1 hour of exposure and 98.95 ± 0.01% mortality (p, Author summary The recent outbreaks of chikungunya, Zika and dengue viruses in the Caribbean and Latin America during 2013–2018, have motivated local health authorities in individual countries to seek international assistance from multiple agencies and adjust their vector management strategies in order to contain the transmission of Aedes-borne diseases. Countries within the region rely mainly on the use of commercially available insecticides to manage the mosquito populations and by extension, reduce the transmission of vector-borne diseases. However, this practice is stymied by the ability of these insects to develop resistance mechanisms to insecticides of frequent use. Many countries in the Caribbean and Latin America regions lack the facilities and supplies to conduct routine insecticide susceptibility testing. In an effort to ascertain knowledge on the presence of insecticide resistance in Aedes aegypti populations, and to determine which insecticide is more effective to reduce vector populations of Jamaica, we conducted an array of bioassays with three different types of insecticides (pyrethroid, organophosphate, carbamate) to use local evidence and inform public health authorities on vector control status and alternatives.

Introduction Individuals and communities affected by NTDs are often the poorest and most marginalised; ensuring a gender and equity lens is centre stage will be critical for the NTD community to reach elimination goals and inform Universal Health Coverage (UHC). NTDs amenable to preventive chemotherapy have been described as a ‘litmus test’ for UHC due to the high mass drug administration (MDA) coverage rates needed to be effective and their model of community engagement. However, until now highly aggregated coverage data may have masked inequities in availability, accessibility and acceptability of medicines, slowing down the equitable achievement of elimination goals. Methods We conducted qualitative programmatic analysis across different country contexts through the novel application of the Tanahashi Coverage Framework enhanced by gendered intersectional theory to interrogate different components of programme coverage: availability, accessibility, acceptability, contact and effective. Drawing on communities and health implementers perspectives (using focus groups, interviews, and participatory methods) from varying levels of the health system, across four African country contexts (Cameroon, Ghana, Liberia and Nigeria), we show who is left behind and provide recommendations for programmes to respond. Findings We have unmasked inequities in programme delivery that repeatedly leave vulnerable populations underserved in relation to the prevention and treatment of PC NTDs across all components of coverage explored within the Tanahashi framework. Inequities are influenced by health systems challenges and limitations, due to lack of consideration of gender, power and equity issues. Effective treatment for individuals and communities is shaped by individual identities and the intersecting axes of inequity that converge to shape these positions including gender, age, disability, and geography. Health systems are inherently social and gendered thus they become mediators in managing the impact that social and structural processes have on individual health outcomes. Significance To our knowledge this is the only paper which has combined a comprehensive equity framework with intersectional feminist theory, to establish a fuller understanding of who is left behind and why in MDA across countries and contexts. Ensuring the most vulnerable have continued access to future treatment options will contribute to the progressive realisation of UHC, allowing the NTD community to continue to support their vision of being a true ‘litmus test’., Author summary Individuals and communities affected by Neglected Tropical Diseases (NTDs) are often the poorest and most marginalised. Some NTDs (lymphatic filariasis, onchocerciasis, soil transmitted helminths, schistosomiasis and trachoma) have been given specific targets for control and elimination by the year 2020. Reaching these goals is important for the attainment of Universal Health Coverage (UHC) as well as the Sustainable Development Goals and has been described as a litmus test. However, few studies have considered how fair progress toward attainment of these goals has been to date. We used qualitative research methods to explore the equity of progress toward these targets across four countries (Ghana, Cameroon, Liberia and Ghana). We used a framework for assessing health services coverage (The Tanahashi Framework) and combined it with gendered intersectional theory (a theory that helps us think about how individuals position of power and privilege shape their experience) to understand who is left behind and why in NTD programme delivery. We found that health systems challenges and limitations due to lack of consideration of gender and equity issues have left vulnerable populations underserved in relation to the prevention and treatment of PC NTDs. Key steps need to be taken at different health system levels to ensure the most vulnerable have continued access to future treatment options. This will contribute to the attainment of UHC, allowing the NTD community to continue to support their vision of being a true ‘litmus test’.

This paper presents the development of an agent-based model (ABM) to investigate Trypanosoma brucei rhodesiense human African trypanosomiasis (rHAT) disease transmission. The ABM model, fitted at a fine spatial scale, was used to explore the impact of a growing host population on the spread of disease along a 75 km transect in the Luangwa Valley, Zambia. The model was used to gain a greater understanding of how increases in human and domestic animal population could impact the contact network between vector and host, the subsequent transmission patterns, and disease incidence outcomes in the region. Modelled incidence rates showed increases in rHAT transmission in both humans and cattle. The primary demographic attribution of infection switched dramatically from young children of both sexes attending school, to adult women performing activities with shorter but more frequent trips, such as water and firewood collection, with men more protected due to the presence of cattle in their routines. The interpretation of model output provides a plausible insight into both population development and disease transmission in the near future in the region and such techniques could aid well-targeted mitigation strategies in the future., Author summary African trypanosomiasis is a parasitic disease which affects humans and other animals in 36 sub-Saharan African countries. The disease is transmitted by the tsetse fly, and the human form of the disease is known as sleeping sickness. With human and animal populations growing across Africa, demand for space to settle is on the rise, and people are being forced to occupy increasingly marginal spaces. This behaviour has the potential to increase exposure to pre-existing biological hazards, including vector-borne diseases. This investigation utilises agent-based modelling techniques to investigate the implications of a growing and spreading human and animal population in a region affected by Rhodesian human African trypanosomiasis. The model incorporates previously developed spatial data for the Luangwa Valley case study in Zambia, along with demographic data for its current inhabitants, and a detailed, seasonally-driven tsetse lifecycle. Tsetse and potential human and animal hosts are modelled at the individual level, allowing each contact and infection to be recorded through time. By modelling at a fine-scale, we can incorporate detailed mechanisms for tsetse birth, feeding, reproduction and death, as well as a realistic theoretical human and domestic animal population increase, before considering the possible spatial and demographic impact.

Introduction Molecular xenomonitoring (MX)—pathogen detection in the mosquito rather than human—is a promising tool for lymphatic filariasis (LF) surveillance. In the Recife Metropolitan Region (RMR), the last LF focus in Brazil, Culex quinquefasciatus mosquitoes have been implicated in transmitting Wuchereria bancrofti parasites. This paper presents findings on the ideal mosquito collection method, mosquito dispersion, W. bancrofti infection in mosquitoes and W. bancrofti antigen in humans to aid MX development. Methods Experiments occurred within two densely populated urban areas of Olinda, RMR, in July and August 2015. U.S. Centers for Disease Control and Prevention (CDC) light traps were compared to battery-powered aspirators as collection methods, and mosquito dispersion was measured by mosquito mark release recapture (MMRR). Female Cx. quinquefasciatus were tested by PCR for W. bancrofti infection, and study area residents were screened by rapid tests for W. bancrofti antigen. Results Aspirators caught 2.6 times more total Cx. quinquefasciatus, including 38 times more blood-fed and 5 times more gravid stages, than CDC light traps. They also collected 123 times more Aedes aegypti. Of the 9,644 marked mosquitoes released, only ten (0.01%) were recaptured, nine of which were < 50m (34.8m median, 85.4m maximum) from the release point. Of 9,169 unmarked mosquitoes captured in the MMR, 38.3% were unfed, 48.8% blood-fed, 5.5% semi-gravid, and 7.3% gravid. PCR on 182 pools (1,556 mosquitoes) found no evidence of W. bancrofti infection in Cx. quinquefasciatus. Rapid tests on 110 of 111 eligible residents were all negative for W. bancrofti antigen. Conclusions Aspirators were more effective than CDC light traps at capturing Ae. aegypti and all but unfed stages of Cx. quinquefasciatus. Female Cx. quinquefasciatus traveled short (< 86m) distances in this urban area. Lack of evidence for W. bancrofti infection in mosquitoes and antigen in humans in these fine-scale studies does not indicate that LF transmission has ceased in the RMR. A MX surveillance system should consider vector-specific collection methods, mosquito dispersion, and spatial scale but also local context, environmental factors such as sanitation, and host factors such as infection prevalence and treatment history., Author summary Lymphatic filariasis (LF) is a parasitic disease transmitted by mosquitoes, and can cause elephantiasis. It is the world’s leading cause of disability due to infectious diseases, affects over 120 million people globally, and is scheduled for global elimination via mass drug administration (MDA) and mosquito control. Molecular xenomonitoring (MX) is a process of screening mosquitoes—not humans—for parasites to estimate whether they are circulating in human populations. MX is especially useful during and following MDA, when new case detection becomes difficult, but is challenging to design and conduct in cities. Using two study sites in the Recife Metropolitan Region, Brazil, we investigated two crucial questions for urban MX development—“What is the best operationally feasible tool to catch adult mosquitoes?” and “How far do mosquitoes disperse in cities?”—in order to determine placement of future surveillance sites. We also screened a proportion of mosquitoes and all eligible residents from the study sites for LF infection. We determined that handheld battery powered aspirators were the best mosquito collection tool; that mosquitoes flew no more than about 85m; and—in this small sample of mosquitoes and very small sample of humans—there was no evidence of LF infection in mosquitoes or study area residents.

Background Mycobacterium ulcerans infection, commonly known as Buruli ulcer (BU), is a debilitating neglected tropical disease. Its management remains complex and has three main components: antibiotic treatment combining rifampicin and streptomycin for 56 days, wound dressings and skin grafts for large ulcerations, and physical therapy to prevent functional limitations after care. In Benin, BU patient care is being integrated into the government health system. In this paper, we report on an innovative pilot program designed to introduce BU decentralization in Ouinhi district, one of Benin’s most endemic districts previously served by centralized hospital-based care. Methodology/Principal findings We conducted intervention-oriented research implemented in four steps: baseline study, training of health district clinical staff, outreach education, outcome and impact assessments. Study results demonstrated that early BU lesions (71% of all detected cases) could be treated in the community following outreach education, and that most of the afflicted were willing to accept decentralized treatment. Ninety-three percent were successfully treated with antibiotics alone. The impact evaluation found that community confidence in decentralized BU care was greatly enhanced by clinic staff who came to be seen as having expertise in the care of most chronic wounds. Conclusions/Significance This study documents a successful BU outreach and decentralized care program reaching early BU cases not previously treated by a proactive centralized BU program. The pilot program further demonstrates the added value of integrated wound management for NTD control., Author summary The management of Buruli ulcer (BU) is complex, resulting in high costs to families and health systems. Early detection and treatment heals lesions without functional limitations. Decentralization of the management of this disease into the peripheral health system remains a challenge for national control programs. We report here on an innovative pilot intervention of decentralization of the management of BU in one of the most BU-endemic districts in Benin. The intervention was preceded by a culturally sensitive outreach campaign, which explained the disease’s symptoms and treatment options, and increased self-referral. It also included the treatment of all chronic ulcers free of charge. While serious cases of BU were still referred to the reference hospital for treatment, study results showed that 71% of BU cases could be treated in decentralized care; of these, 93% were successfully treated without functional limitations with antibiotics alone. The decentralized treatment option brought in new cases not previously treated by a proactive centralized BU program, and maintained total patient adherence to treatment protocols, in part through the support of community volunteer groups. The model developed in this pilot study may serve as the foundation and proof of concept for a larger community-based decentralized wound care agenda.

Introduction The Global Strategy to Eliminate Lymphatic Filiariasis (GFELF) through Mass Drug Administration (MDA) has been implemented in Ghana since the year 2000 and transmission has been interrupted in 76 of 98 endemic districts. To improve the MDA in the remaining districts with microfilaria (MF) prevalence above the 1% threshold for the interruption of transmission, there is a need to identify and implement appropriate quality improvement (QI) strategies. This paper describes the use of intervention mapping to select QI strategies to improve an existing evidence-based MDA program in Northern Ghana. Methods Due to the complexities associated with implementing evidence-based programs (EBP) such as the lymphatic filariasis MDA and variability in the context, an initial assessment to identify implementation bottlenecks associated with the quality of implementation of lymphatic filariasis MDA in the Bole District of Ghana was conducted using a mixed methods approach. Based on the findings of the initial assessment, a context specific QI strategy was designed and operationalized using intervention mapping strategy in terms of seven domains: actor, the action, action targets, temporality, dose, implementation outcomes addressed, and theoretical justification. Results The initial needs assessment shows that the persistent transmission of lymphatic filariasis in the Bole District is characterized by high levels of refusal to ingest the drug, high levels of reported adverse drug reactions, low MDA coverage at community level, poor adherence to the MDA protocol and non-participants’ responsiveness. Conclusion This study has shown that it is feasible to develop a context specific QI strategy for an existing evidence-based intervention based on an initial needs assessment through stakeholder participation using the IM approach. However, working (towards) QI requires more time than is usually available in public health service. Sufficient theoretical knowledge of implementation research and experience with technical IM experts must be available., Author summary Lymphatic Filariasis is a significant health problem threatening 1.1 billion people in 55 countries globally. After 18 years of implementing MDA in Ghana, LF transmission still persist in some districts with microfilaria prevalence level high above the threshold needed for the interruption of transmission of the disease. For Ghana to meet the 2020 NTDs deadline, it is important to identify context specific need-based QI strategies to make the drug accessible to all eligible individuals in the endemic communities. Hence, this study has demonstrated the feasibility of using IM to develop and implement a context specific QI strategy for an existing evidence-based intervention (LF MDA) towards elimination of lymphatic filariasis as a public health challenge in Bole District of Northern Ghana.

Background Yaws is targeted for eradication by 2020 in the WHA66.12 resolution of the World Health Assembly. The objective of this study was to describe the occurrence of yaws in the Americas and to contribute to the compilation of evidence based on published data to undertake the certification of yaws eradication. Methodology A systematic review of the epidemiological situation of yaws in the Americas was performed by searching in MEDLINE, Embase, LILACS, SCOPUS, Web of Science, DARE and Cochrane Database of Systematic Reviews. Experts on the topic were consulted, and institutional WHO/PAHO library databases were reviewed. Principal findings Seventy-five full-text articles published between 1839 and 2012 met the inclusion criteria. Haiti and Jamaica were the two countries with the highest number of papers (14.7% and 12.0%, respectively). Three-quarters of the studies were conducted before 1970. Thirty-three countries reported yaws case count or prevalence data. The largest foci in the history were described in Brazil and Haiti. The most recent cases reported were recorded in eight countries: Suriname, Guyana, Colombia, Haiti, Martinique, Dominica, Trinidad and Tobago, and Brazil. Gaps in information and heterogeneity were detected in the methodologies used and outcome reporting, making cross-national and chronological comparisons difficult. Conclusions The lack of recent yaws publications may reflect, in the best-case scenario, the interruption of yaws transmission. It should be possible to reach the eradication goal in the region of the Americas, but it is necessary to collect more information. We suggest updating the epidemiological status of yaws, especially in two countries that need to assess ongoing transmission. Twenty-four countries need to demonstrate the interruption of transmission and declare its status of yaws endemicity, and sixteen countries should declare if they are yaws-free. It is necessary to formally verify the achievement of this goal in Ecuador., Author summary Yaws is a contagious non-venereal treponematosis caused by the bacterium Treponema pallidum subspecies pertenue, transmitted by skin contact. It is a poverty-related chronic disease characterized by primary and secondary skin lesions, with latent infection and a chronic stage, which could include a destructive process of bones and joints. Early detection and treatment can avoid gross disfigurement and the associated stigma. Currently, the treatment with a single dose of oral azithromycin has proven effective. This systematic review shows that in the Americas there is a need to update the epidemiological situation of yaws and if needed, to implement and optimize the best public health recommended interventions to interrupt transmission and then verify elimination of transmission. Current WHO guidelines define the methodology for monitoring and evaluating yaws control programs. Yearly surveys of pre-school children, though logistically complex, are needed in the post-zero case surveillance.

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., Author summary Human African trypanosomiasis (HAT), also known as sleeping sickness, is a rare disease today, but throughout the 20th century it has demonstrated its potential for devastating epidemics. Over the last twenty years, substantial efforts against HAT enabled to dramatically reduce its prevalence, and the disease is now targeted for elimination by the World Health Organization (WHO). In this paper we provide an update to 2016 of the epidemiological situation, focusing on the number of reported cases, the areas and populations exposed at various levels of risk, and the coverage and intensity of surveillance activities. The trends show that attaining the 2020 target of elimination as a public health problem is within reach, with 2,164 reported cases in 2016 (as compared to the targeted milestone for the same year of 4,000 cases), and with an improved coverage of at risk populations by surveillance activities. Beyond 2020, achieving elimination of transmission for the gambiense form of the disease (targeted for 2030) will be more challenging, and it will require the sustained commitment of HAT endemic countries and donors, the adoption of innovative disease control approaches, and the coordination of a broad range of stakeholders.

Introduction Assessment of attitudes of health care professionals is important as negative attitude could constitute a major deterrent to care-seeking by persons affected by neglected tropical diseases (NTDs) such as leprosy. Leprosy continues to pose a major disease burden in India with an annual new case detection rate of 10.17 per 100,000 population. This paper reports on the development and validation of a culturally appropriate scale to measure attitude of health care providers (HCPs) towards persons affected by leprosy in Tamil Nadu, India. Methodology/Principal findings The Affective, Behavioural and Cognitive (ABC) model of attitudes guided the development of the scale. Steps in scale development included qualitative interviews and focus group discussions with medical officers and paramedical staff selected from high prevalence districts in Tamil Nadu, India which informed the development of the draft scale. Reviews of existing attitude questionnaires in related areas further contributed to scale development and together helped to generate a large pool of items which was then subjected to Thurston’s scaling method for selection of items from this pool. Face and content validity were obtained, following which internal consistency and test, re-test reliability were assessed. Scaling exercise resulted in 11 items being discarded from an initial pool of 38, owing to the poor agreement among experts regarding relevance. Face and content validity were good with experts endorsing relevance and applicability of items. The intra-class correlation coefficient (ICC) for test re-test reliability of the 27 item scale was 0.6 (95% CI: 0.20–0.78) indicating marginal intra-class correlation. The overall Cronbach’s alpha was 0.85 while the alphas for each of the affective and behavioural components was good at 0.78 and 0.69 respectively indicating a good degree of consistency and homogeneity between items but the alpha for the cognitive component was low at 0.53. Conclusions The ABC model of attitudes guided the development of the scale, ensured a mix of 27 items tapping into the three domains of Affect, Behaviour and Cognition which best explained the attitude construct. With good validity and alphas for each of the affective, behavioural components and overall alpha estimates, this scale can be a valuable tool to provide accurate estimates of the true attitudes held by HCPs. This, in turn, would be useful to obtain insights for appropriate intervention programmes that would help change negative attitudes of HCPs towards persons affected by leprosy. With some adaptations, the scales can be validated for other NTDs as well., Author summary Leprosy is an infectious disease caused by the Mycobacterium leprae and is one of the major causes of preventable disability. Early diagnosis and prompt treatment of all new cases of leprosy remain the key strategies for leprosy control as it would prevent nerve damage, disability and reduce the transmission of the disease. People affected by leprosy often experience severe stigmatization because of an adverse social judgment about the disease or its disabling consequences. This neglected tropical disease continues to pose a major disease burden in India. Despite the availability of health facilities there continue to be barriers towards leprosy diagnosis and early treatment. Assessment of attitudes of health care professionals is important as negative attitude could constitute a major deterrent to care-seeking by persons affected by leprosy. Researchers developed and validated a culturally appropriate scale to measure attitudes of health care providers towards persons affected by leprosy in Tamil Nadu, India. The scale would be useful to obtain insights of attitudes of health care professionals to plan appropriate programmes that would help to promote positive attitudes of healthcare providers towards persons affected by leprosy.

Background Bangladesh had one of the highest burdens of lymphatic filariasis (LF) at the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) with an estimated 70 million people at risk of infection across 34 districts. In total 19 districts required mass drug administration (MDA) to interrupt transmission, and 15 districts were considered low endemic. Since 2001, the National LF Programme has implemented MDA, reduced prevalence, and been able to scale up the WHO standard Transmission Assessment Survey (TAS) across all endemic districts as part of its endgame surveillance strategy. This paper presents TAS results, highlighting the momentous geographical reduction in risk of LF and its contribution to the global elimination target of 2020. Methodology/Principal findings The TAS assessed primary school children for the presence of LF antigenaemia in each district (known as an evaluation unit—EU), using a defined critical cut-off threshold (or ‘pass’) that indicates interruption of transmission. Since 2011, a total of 59 TAS have been conducted in 26 EUs across the 19 endemic MDA districts (99,148 students tested from 1,801 schools), and 22 TAS in the 15 low endemic non-MDA districts (36,932 students tested from 663 schools). All endemic MDA districts passed TAS, except in Rangpur which required two further rounds of MDA. In total 112 students (male n = 59; female n = 53), predominately from the northern region of the country were found to be antigenaemia positive, indicating a recent or current infection. However, the distribution was geographically sparse, with only two small focal areas showing potential evidence of persistent transmission. Conclusions/Significance This is the largest scale up of TAS surveillance activities reported in any of the 73 LF endemic countries in the world. Bangladesh is now considered to have very low or no risk of LF infection after 15 years of programmatic activities, and is on track to meet elimination targets. However, it will be essential that the LF Programme continues to develop and maintain a comprehensive surveillance strategy that is integrated into the health infrastructure and ongoing programmes to ensure cost-effectiveness and sustainability., Author summary Lymphatic filariasis (LF) was highly endemic in Bangladesh at the start of the Global Programme to Eliminate Lymphatic Filariasis (GPELF) in 2000, with approximately 70 million people at risk. To address this burden, the National LF Programme implemented mass drug administration (MDA) in 19 highly endemic districts to interrupt transmission, and conducted sentinel site assessments in 15 low endemic districts. In 2011, as part of the LF Programme’s endgame surveillance strategy, the standard WHO Transmission Assessment Survey (TAS) was used to show the reduction below transmission thresholds in order to stop MDA in all 34 endemic districts by testing a total of 136,080 primary school-aged children in 2,464 schools using rapid diagnostic tests. The data show that LF transmission has been interrupted in all districts except one, with the latter requiring two further two rounds of MDA. Bangladesh can now be considered, after 15 years of LF programmatic activities, as having very low or no risk of LF infection and is therefore on track to meet National and Global elimination targets of 2020.

Background Rabies in China remains a public health problem. In 2014, nearly one thousand rabies-related deaths were reported while rabies geographic distribution has expanded for the recent years. This report used surveillance data to describe the epidemiological characteristics of human rabies in China including determining high-risk areas and seasonality to support national rabies prevention and control activities. Methods We analyzed the incidence and distribution of human rabies cases in mainland China using notifiable surveillance data from 1960–2014, which includes a detailed analysis of the recent years from 2004 to 2014. Results From 1960 to 2014, 120,913 human rabies cases were reported in mainland China. The highest number was recorded in 1981(0.7/100,000; 7037 cases), and in 2007(0.3/100,000; 3300 cases). A clear seasonal pattern has been observed with a peak in August (11.0% of total cases), Human rabies cases were reported in all provinces with a yearly average of 2198 from 1960 to 2014 in China, while the east and south regions were more seriously affected compared with other regions. From2004 to 2014, although the number of cases decreased by 65.2% since 2004 from 2651 to 924 cases, reported areas has paradoxically expanded from 162 prefectures to 200 prefectures and from southern to the central and northern provinces of China. Farmers accounted most of the cases (65.0%); 50–59 age group accounted for the highest proportion (20.5%), and cases are predominantly males with a male-to-female ratio of 2.4:1 on average. Conclusions Despite the overall steady decline of cases since the peak in 2007, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Further investigations and efforts are warranted in the areas have high rabies incidence to control rabies by interrupting transmission from dogs to humans and in the dog population. Furthermore, elimination of rabies should be eventually the ultimate goal for China., Author Summary China is a high-risk environment for rabies, with human rabies cases second only to India globally. This paper reviews 55 years of rabies epidemiology in mainland China, and detailed analysis of data in recent years. In this study, notifiable surveillance data were analyzed and found that rabies still remains a serious public health problem in China, the east and south regions were more seriously affected compared with other regions, however, the occurrence of cases in new areas and the spread trend were obvious in China in recent years. Moreover, males in rural areas had higher risk of infection than residents in urban areas, a clear seasonal pattern has been observed with a peak in August. These findings indicated a clear need to increase government and public consciousness with regard to the potential risk of rabies and the means of avoiding the disease. Further efforts should be strengthen specially in the high spot areas.

Together, the Hajj and Umrah rank among the leading global venues that host annual mass human migrations. The Hajj is an annual pilgrimage to the Islamic holy city of Makkah in Saudi Arabia (Fig 1). It is considered a religious obligation for all adult Muslims worldwide who have the physical and financial ability and draws an estimated 2–3 million people annually [1]. Umrah is an Islamic pilgrimage to Makkah, which occurs at times other than the period of the Hajj—the period of Ramadan (fasting month) is considered the peak period [2]. In 2018, the Hajj is scheduled to take place in August, while Ramadan will occur between May and June [2]. Open in a separate window Fig 1 Outline map of Saudi Arabia and surrounding countries. The capital Riyadh, the two holy cities Makkah and Medina, and other cities mentioned in this paper are shown. Original figure.

Background Conducting clinical trials to assess experimental treatments for potentially pandemic infectious diseases is challenging. Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. Outbreaks are sudden and unpredictable and so it is essential that as much planning as possible takes place in advance. Statistical aspects of such trial designs should be evaluated and discussed in readiness for implementation. Methodology/Principal findings This paper proposes a generic ordinal sequential trial design (GOST) for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The design is intended as an off-the-shelf, ready-to-use robust and flexible option. The primary endpoint is a categorisation of patient outcome according to an ordinal scale. A sequential approach is adopted, stopping as soon as it is clear that the experimental treatment has an advantage or that sufficient advantage is unlikely to be detected. The properties of the design are evaluated using large-sample theory and verified for moderate sized samples using simulation. The trial is powered to detect a generic clinically relevant difference: namely an odds ratio of 2 for better rather than worse outcomes. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, but the precise value depends on both the magnitude of the treatment advantage and the nature of the ordinal scale. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size. Conclusions/Significance It is important and feasible to pre-determine many of the statistical aspects of an efficient trial design in advance of a disease outbreak. The design can then be tailored to the specific disease under study once its nature is better understood., Author summary Since many outbreaks of infectious diseases last only six to eight weeks, there is a need for trial designs that can be implemented rapidly in the face of uncertainty. The Generic Ordinal Sequential Trial (GOST) is a flexible statistical design for a randomised clinical trial comparing an experimental treatment for an emerging infectious disease with standard care. The details of the design are derived to satisfy a generic power requirement using large sample theory. The accuracy of the approach for moderate sample sizes is then checked using million-fold simulations, and found to be very reliable under a wide range of circumstances. Total sample sizes (across both treatments) of between 150 and 300 patients prove to be adequate in many cases, although more patients may be needed if the majority of patients die or if the majority experience complete recovery, as there is then less evidence available to distinguish between treatments. An advantage of the approach is that any erroneous assumptions made at the design stage about the proportion of patients falling into each outcome category have little effect on the error probabilities of the study, although they can lead to inaccurate forecasts of sample size.

Background Arbovirus infections are a serious concern in tropical countries due to their high levels of transmission and morbidity. With the outbreaks of chikungunya (CHIKV) in surrounding regions in recent years and the fact that the environment in Vietnam is suitable for the vectors of CHIKV, the possibility of transmission of CHIKV in Vietnam is of great interest. However, information about CHIKV activity in Vietnam remains limited. Methodology In order to address this question, we performed a systematic review of CHIKV in Vietnam and a CHIKV seroprevalence survey. The seroprevalence survey tested for CHIKV IgG in population serum samples from individuals of all ages in 2015 from four locations in Vietnam. Principal findings The four locations were An Giang province (n = 137), Ho Chi Minh City (n = 136), Dak Lak province (n = 137), and Hue City (n = 136). The findings give us evidence of some CHIKV activity: 73/546 of overall samples were seropositive (13.4%). The age-adjusted seroprevalences were 12.30% (6.58–18.02), 13.42% (7.16–19.68), 7.97% (3.56–12.38), and 3.72% (1.75–5.69) in An Giang province, Ho Chi Minh City, Dak Lak province, and Hue City respectively. However, the age-stratified seroprevalence suggests that the last transmission ended around 30 years ago, consistent with results from the systematic review. We see no evidence for on-going transmission in three of the locations, though with some evidence of recent exposure in Dak Lak, most likely due to transmission in neighbouring countries. Before the 1980s, when transmission was occurring, we estimate on average 2–4% of the population were infected each year in HCMC and An Giang and Hue (though transmision ended earlier in Hue). We estimate lower transmission in Dak Lak, with around 1% of the population infected each year. Conclusion In conclusion, we find evidence of past CHIKV transmission in central and southern Vietnam, but no evidence of recent sustained transmission. When transmission of CHIKV did occur, it appeared to be widespread and affect a geographically diverse population. The estimated susceptibility of the population to chikungunya is continually increasing, therefore the possibility of future CHIKV transmission in Vietnam remains., Author summary In recent years, the reemergence of chikungunya has gained global attention and threatened to become a global outbreak. Although the epidemiology of chikungunya is known globally, the viral activity in Vietnam has not been thoroughly investigated. In this paper, we used information from a systematic review and serological survey to understand the past activity of chikungunya in Vietnam. In the serological survey, we tested age -stratified population serum samples in the central and southern parts of Vietnam from 2015 for chikungunya IgG, which is indicative of past exposure to chikungunya. Our results show almost no positive individuals below the age of 30 years old, indicating very low to no virus transmission for the last 30 years. In individuals over 30 years old, there were more positive individuals, and we estimate widespread transmission with an average of 2–4% of the population infected each year. Because of the lack of recent transmission in these locations, the susceptible population is increasing and is now high, suggesting Vietnam is vulnerable to future outbreaks if chikungunya is reintroduced. Hence, chikungunya surveillance along with surveillance for other arboviruses, such as dengue, should be conducted in Vietnam.

WOS: 000424022700022, PubMed ID: 29329311, Introduction Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL). Materials and methods Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings. Results Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized. Conclusions The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments., World Health OrganizationWorld Health Organization [001]

Rabies is an ancient viral disease that significantly impacts human and animal health throughout the world. In the developing parts of the world, dog bites represent the highest risk of rabies infection to people, livestock, and other animals. However, in North America, where several rabies virus variants currently circulate in wildlife, human contact with the raccoon rabies variant leads to the highest per capita population administration of post-exposure prophylaxis (PEP) annually. Previous rabies variant elimination in raccoons (Canada), foxes (Europe), and dogs and coyotes (United States) demonstrates that elimination of the raccoon variant from the eastern US is feasible, given an understanding of rabies control costs and benefits and the availability of proper tools. Also critical is a cooperatively produced strategic plan that emphasizes collaborative rabies management among agencies and organizations at the landscape scale. Common management strategies, alone or as part of an integrated approach, include the following: oral rabies vaccination (ORV), trap-vaccinate-release (TVR), and local population reduction. As a complement, mathematical and statistical modeling approaches can guide intervention planning, such as through contact networks, circuit theory, individual-based modeling, and others, which can be used to better understand and predict rabies dynamics through simulated interactions among the host, virus, environment, and control strategy. Strategies derived from this ecological lens can then be optimized to produce a management plan that balances the ecological needs and program financial resources. This paper discusses the management and modeling strategies that are currently used, or have been used in the past, and provides a platform of options for consideration while developing raccoon rabies virus elimination strategies in the US.

Modelling disease dynamics is most useful when data are limited. We present a spatial transmission model for the spread of canine rabies in the currently rabies-free wild dog population of Australia. The introduction of a sub-clinically infected dog from Indonesia is a distinct possibility, as is the spillover infection of wild dogs. Ranges for parameters were estimated from the literature and expert opinion, or set to span an order of magnitude. Rabies was judged to have spread spatially if a new infectious case appeared 120 km from the index case. We found 21% of initial value settings resulted in canine rabies spreading 120km, and on doing so at a median speed of 67 km/year. Parameters governing dog movements and behaviour, around which there is a paucity of knowledge, explained most of the variance in model outcomes. Dog density, especially when interactions with other parameters were included, explained some of the variance in whether rabies spread 120km, but dog demography (mean lifespan and mean replacement period) had minimal impact. These results provide a clear research direction if Australia is to improve its preparedness for rabies., Author Summary Canine rabies typically persists in developing countries where stray and unvaccinated, free-roaming domestic dogs account for a substantial proportion of the population. In this paper we investigate whether sustained canine rabies transmission can occur within the wild dog population of Australia, which comprises dingoes and their hybrids with domestic dogs. To do this we simulated the transmission of rabies between wild dogs across a sizeable landscape area. Whenever the disease spread 120 km we considered an epidemic as having occurred and recorded the length of time it took to do so. This allowed us to estimate the probability the sustained transmission of canine rabies will occur (21%) upon its introduction along with the speed at which it will spread (67 km/year). We also determined that wild dog movements and behaviour (for which there is the least amount of information available at present) together with wild dog density are the most important factors influencing these two outcomes, whereas wild dog demography (including average lifespan and average replacement period) had minimal impact. Future research should therefore focus on studying wild dog movements and behaviour to improve Australia’s readiness to control and prevent canine rabies transmission and establishment.

Background Flea-borne diseases have a wide distribution in the world. Studies on the identity, abundance, distribution and seasonality of the potential vectors of pathogenic agents (e.g. Yersinia pestis, Francisella tularensis, and Rickettsia felis) are necessary tools for controlling and preventing such diseases outbreaks. The improvements of diagnostic tools are partly responsible for an easier detection of otherwise unnoticed agents in the ectoparasitic fauna and as such a good taxonomical knowledge of the potential vectors is crucial. The aims of this study were to make an exhaustive inventory of the literature on the fleas (Siphonaptera) and range of associated hosts in Iran, present their known distribution, and discuss their medical importance. Methodology/Principal Findings The data were obtained by an extensive literature review related to medically significant fleas in Iran published before 31st August 2016. The flea-host specificity was then determined using a family and subfamily-oriented criteria to further realize and quantify the shared and exclusive vertebrate hosts of fleas among Iran fleas. The locations sampled and reported in the literature were primarily from human habitation, livestock farms, poultry, and rodents’ burrows of the 31 provinces of the country. The flea fauna were dominated by seven families, namely the Ceratophyllidae, Leptopsyllidae, Pulicidae, Ctenophthalmidae, Coptopsyllidae, Ischnopsyllidae and Vermipsyllidae. The hosts associated with Iran fleas ranged from the small and large mammals to the birds. Pulicidae were associated with 73% (56/77) of identified host species. Flea-host association analysis indicates that rodents are the common hosts of 5 flea families but some sampling bias results in the reduced number of bird host sampled. Analyses of flea-host relationships at the subfamily level showed that most vertebrates hosted fleas belgonging to 3 subfamilies namely Xenopsyllinae (n = 43), Ctenophthalminae (n = 20) and Amphipsyllinae (n = 17). Meriones persicus was infested by 11 flea subfamilies in the arid, rocky, mountainous regions and Xenopsyllinae were hosted by at least 43 mammal species. These findings place the Persian jird (M. persicus) and the Xenopsyllinae as the major vertebrate and vector hosts of flea-borne diseases in Iran including Yersinia pestis, the etiological agent of plague. We found records of at least seven vector-borne pathogenic agents that can potentially be transmitted by the 117 flea species (or subspecies) of Iran. Conclusions/Significance Herein, we performed a thorough inventary of the flea species and their associated hosts, their medical importance and geographic distribution throughout Iran. This exercise allowed assessing the diversity of flea species with the potential flea-borne agents transmission risk in the country by arranging published data on flea-host associations. This information is a first step for issuing public health policies and rodent-flea control campaigns in Iran as well as those interested in the ecology/epidemiology of flea-borne disease., Author Summary The data about flea-borne emerging or re-emerging infections throughout Iran are limited. This paper showed that the flea fauna of Iran were dominated by seven families. Moreover flea-host association analysis indicates that rodents are common hosts of flea families and most vertebrates hosted fleas belonging to the subfamilies Xenopsyllinae, Ctenophthalminae and Amphipsyllinae. We showed that the Persian jird (Merions persicus Blanford, 1875) and the Xenopsyllinae are respectively the major vertebrate and potential vectors of flea-borne diseases in Iran. Further efforts are needed to inventorize and screen molecularly wild and domestic mammals flea fauna (>3kg) in order to monitor the risk of and control flea-borne infections in Iran, especially in the ecoregions with high diversity of flea and host species and in the old endemic plague foci of the country.

Background Sri Lanka’s Anti Filariasis Campaign distributed 5 rounds of mass drug administration (MDA with DEC plus albendazole) to all endemic regions in the country from 2002–2006. Post-MDA surveillance results have generally been encouraging. However, recent studies have documented low level persistence of Wuchereria bancrofti in Galle district based on comprehensive surveys that include molecular xenomonitoring (MX, detection of filarial DNA in mosquitoes) results. The purposes of this study were to demonstrate the use of MX in large evaluation units (EUs) and to field test different mosquito sampling schemes. Methodology/Principal Findings Galle district (population 1.1 million) was divided into two EUs. These included a coastal EU with known persistent LF and an inland EU with little persistent LF. Mosquitoes were systematically sampled from ~300 trap locations in 30 randomly selected clusters (health administrative units) per EU. Approximately 28,000 Culex quinquefasciatus were collected with gravid traps and tested for filarial DNA by qPCR. 92/625 pools (14.7%) from the coastal EU and 8/583 pools (1.4%) from the inland EU were positive for filarial DNA. Maximum likelihood estimates (MLE) for filarial DNA rates were essentially the same when the same number of mosquito pools were collected and tested from 75, 150, or 300 trap sites (range 0.61–0.78% for the coastal EU and 0.04–0.07% for the inland EU). The ability to use a smaller number of trap sites reduces the cost and time required for mosquito sampling. Conclusions/Significance These results suggest there is widespread persistence of W. bancrofti infection in the coastal Galle EU 8 years after the last round of MDA in 2006, and this is consistent with other data from the district. This study has shown that MX can be used by national programs to assess and map the persistence of W. bancrofti at the level of large EUs in areas with Culex transmission., Author Summary Lymphatic filariasis (LF) is a disabling neglected tropical disease that affects millions of people in 73 countries. The Global Program to Eliminate Lymphatic Filariasis (GPELF) is using mass drug administration (MDA) to reduce infections in humans below levels required for sustained transmission by mosquitoes. Prior studies have shown that molecular xenomonitoring (MX, detection of filarial DNA in insect vectors) is useful for detecting low-level persistence of W. bancrofti infection following MDA, but technical challenges have prevented national programs from adopting this approach on a large scale. This paper reports the first use of MX for post-MDA surveillance in large evaluation units. CDC gravid traps were effective for collecting large numbers of Culex quinquefasciatus mosquitoes, and filarial DNA was detected by qPCR. We found that MX is more sensitive than other surveillance methods for detecting persistent W. bancrofti in communities and that there is widespread, low-level persistence of infection in coastal Galle district (Sri Lanka) 8 years after the last round of MDA. The systematic mosquito sampling protocol used in this study should be feasible for use by national filariasis elimination programs to assess and map the persistence of W. bancrofti in regions where the infection is transmitted by Culex mosquitoes.

Background The Philippines is one of the developing countries highly affected by rabies. Dog vaccination campaigns implemented through collaborative effort between the government and NGOs have played an important role in successfully reducing the burden of disease within the country. Nevertheless, rabies vaccination of the domestic animal population requires continuous commitment not only from governments and NGOs, but also from local communities that are directly affected by such efforts. To create such long-term sustained programs, the introduction of affordable dog vaccination and registration fees is essential and has been shown to be an important strategy in Bohol, Philippines. The aim of this study, therefore, was to estimate the average amount of money that individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. This study also investigated some of the determinants of individuals’ willingness to pay (WTP). Methods A cross-sectional questionnaire was administered to 300 households in 17 municipalities (out of a total of 21) selected through a multi-stage cluster survey technique. At the time of the survey, Ilocos Norte had a population of approximately 568,017 and was predominantly rural. The Contingent Valuation Method was used to elicit WTP for dog rabies vaccination and registration. A ‘bidding game’ elicitation strategy that aims to find the maximum amount of money individuals were willing to pay was also employed. Data were collected using paper-based questionnaires. Linear regression was used to examine factors influencing participants’ WTP for dog rabies vaccination and registration. Key Results On average, Ilocos Norte residents were willing to pay 69.65 Philippine Pesos (PHP) (equivalent to 1.67 USD in 2012) for dog vaccination and 29.13PHP (0.70 USD) for dog registration. Eighty-six per cent of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. This study also found that WTP was influenced by demographic and knowledge factors. Among these, we found that age, income, participants’ willingness to commit to pay each year, municipality of residency, knowledge of the signs of rabies in dogs, and number of dogs owed significantly predicted WTP., Author Summary Rabies is one of the most fatal viral diseases mostly transmitted through a bite of an infected mammal. In many parts of Africa and Asia, rabid dogs are the main transmitters of the disease to humans. In the Philippines, government enforced dog registration laws and government/NGO sponsored mass dog vaccination campaigns have so far been the cornerstone in successfully reducing the burden of disease in parts of the country. To further enhance the continuation of such programs, however, an introduction of affordable dog vaccination and registration fees to the public is vital and have shown to be an important strategy in other parts of the country. Our main objective here was to systematically assess how much money individuals were willing to pay for dog vaccination and registration in Ilocos Norte, Philippines. We also assessed whether the amount individuals were willing to pay was influenced by their demographic and knowledge characteristics. We conducted a cross-sectional study using a combination of cluster sampling, random sampling, and convenience sampling methods to identify study participants. We employed a specific elicitation strategy (bidding game) to elicit how much individual were willing to pay for such services. Our results indicate that Ilocos Norte residents, on average, were willing to pay 69.65 PHP (1.67 USD) for dog vaccination and 29.13 PHP (0.70 USD) for dog registration. The majority (86%) of respondents were willing to pay the stated amount to vaccinate each of their dogs, annually. We also found that willingness to pay was influences by age, income, municipality of residency, people’s willingness to commit to pay each year, number of dogs owned, and knowledge regarding rabies signs in dogs. This findings give policy makers some indication of how much people were willing to contribute financially towards dog vaccination and registration in particular and towards rabies elimination from Ilocos Norte, in general. Socio-economic and demographic factors, however, may need to be considered prior to the introduction of such fees to the public.

Background Strongyloides stercoralis infects human hosts mainly through skin contact with contaminated soil. The result is strongyloidiasis, a parasitic disease, with a unique cycle of auto-infection causing a variety of symptoms and signs, with possible fatality from hyper-infection. Australian Indigenous community members, often living in rural and remote settings, are exposed to and infected with S. stercoralis. The aim of this review is to determine barriers to control of strongyloidiasis. The purpose is to contribute to the development of initiatives for prevention, early detection and effective treatment of strongyloidiasis. Methodology/Principle Findings Systematic search reviewing research published 2012 and earlier was conducted. Research articles discussing aspects of strongyloidiasis, context of infection and overall health in Indigenous Australians were reviewed. Based on the PRISMA statement, the systematic search of health databases, Academic Search Premier, Informit, Medline, PubMed, AMED, CINAHL, Health Source Nursing and Academic was conducted. Key search terms included strongyloidiasis, Indigenous, Australia, health, and community. 340 articles were retrieved with 16 original research articles published between 1969 and 2006 meeting criteria. Review found barriers to control defined across three key themes, (1) health status, (2) socioeconomic status, and (3) health care literacy and procedures. Conclusions/Significance This study identifies five points of intervention: (1) develop reporting protocols between health care system and communities; (2) test all Indigenous Australian patients, immunocompromised patients and those exposed to areas with S. stercoralis; (3) health professionals require detailed information on strongyloidiasis and potential for exposure to Indigenous Australian people; (4) to establish testing and treatment initiatives within communities; and (5) to measure and report prevalence rates specific to communities and to act with initiatives based on these results. By defining barriers to control of strongyloidiasis in Australian Indigenous people, improved outcomes of prevention, treatment of strongyloidiasis and increased health overall are attainable., Author Summary Strongyloides stercoralis, a nematode parasite, has a well-documented history of infecting human hosts in tropic and subtropic regions mainly through skin contact with inhabited soil. The result is strongyloidiasis, a human parasitic disease, with a unique cycle of auto-infection contributing to a variety of symptoms, of which, hyper-infection causing fatality may occur. In Australia, Indigenous community members often located in rural and remote settings, are exposed to and infected with strongyloides. Previous researchers report strongyloidiasis as a recurrent health issue for Indigenous Australians. This is a systematic review to determine the barriers to control for this pernicious pathogen. Barriers to control can be defined across three key themes: (1) health status, (2) socioeconomic status, and (3) health care literacy and procedure. By conceptualizing these barriers and addressing steps to control as outlined in this study, there is potential for improvement in prevention and treatment outcomes of strongyloidiasis and subsequently, overall health for Australian Indigenous people. This study contributes to furthering prevention and treatment of strongyloidiasis, increasing exposure to the issue of strongyloidiasis in Australian Indigenous people. It is the intent of this paper to express the need to have continued research and further health policy directed specifically to eradicate strongyloidiasis in Australian Indigenous communities.