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Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.

Background Podoconiosis is a chronic non-infectious preventable disease. Though not fatal, it may cause social, economic and physical disability. Ethiopia is projected to bear one-fourth (25%) of the global burden of podoconiosis. Despite its huge economic impact and chronic morbidity and disability, podoconiosis seems to be neglected. Therefore, the aim of this study was to assess the prevalence of podoconiosis and its associated factors in Gamo zone, Southern Ethiopia. Methods A community based cross sectional study was conducted among 683 household members. A multistage sampling method was used to select study participants. Binary logistic regression model was fitted to identify factors associated with podoconiosis. Odds ratio with 95% confidence interval was computed to determine the level of significance; in multivariable analysis, variables with a P value less than 0.05 were considered as statistically significant. Results The prevalence of podoconiosis was 6.2% (95%CI: 4.3–8%). The significantly contributed factors for the prevalence of podoconiosis were wealth index (AOR = 0.249, 95%CI = 0.073–0.845), number of shoes owned (AOR = 6.199, 95% CI = 1.281–29.98), times when individual do not wear shoes (AOR = 2.448, 95%CI = 1.041–5.754), soap utilization during foot washing (AOR = 2.773, 95%CI = 1.210–6.355) and family history of leg swelling (AOR = 4.69, 95%CI = 2.215–9.935). Conclusions This study showed that there was significant burden of podoconiosis in the study area. Wealth index, times when individual do not wear shoes, number of shoes owned, soap utilization during foot washing, and family history of leg swelling were significantly associated with podoconiosis. It is recommended to practice secondary prevention which includes regular foot hygiene and wearing shoes, and the use of antiseptic soaks.

The major soil-transmitted helminths that infect humans are the roundworms, whipworms and hookworms. Soil-transmitted helminth infections rank among the most important neglected tropical diseases in terms of morbidity, and almost one billion people are still infected with at least one species. While anthelmintic drugs are available, they do not offer long term protection against reinfection, precipitating the need for vaccines that provide long-term immunologic defense. Vaccine discovery and development is in advanced clinical development for hookworm infection, with a bivalent human hookworm vaccine in clinical trials in Brazil and Africa, but is in its infancy for both roundworm (ascariasis) and whipworm (trichuriasis) infections. One of the greatest hurdles to developing soil-transmitted helminth vaccines is the potent immunoregulatory properties of these helminths, creating a barrier to the induction of meaningful long-term protective immunity. While challenging for vaccinologists, this phenomenon presents unique opportunities to develop an entirely new class of anti-inflammatory drugs that capitalise on these immunomodulatory strategies. Epidemiologic studies and clinical trials employing experimental soil-transmitted helminth challenge models, when coupled with findings from animal models, show that at least some soil-transmitted helminth-derived molecules can protect against the onset of autoimmune, allergic and metabolic disorders, and several natural products with the desired bioactivity have been isolated and tested in pre-clinical settings. The yin and yang of soil-transmitted helminth infections reflect both the urgency for effective vaccines and the potential for new immunoregulatory molecules from parasite products.

Background: Ivermectin is widely used for the treatment of neglected tropical diseases associated with adverse maternal and fetal outcomes when the infection complicates the pregnancy. However, the United States FDA classification and current distribution protocols limit ivermectin treatment in pregnant women because antepartum safety has not been well-established. Objective: We conducted a scoping review to address the question of what is known from both human and vertebrate animal studies about the safety of systemic ivermectin exposure during pregnancy. Methods: We searched PubMed for adverse outcomes related to systemic ivermectin exposure in human and vertebrate animal pregnancies, including English-language primary articles from 1900 - 2019. Results: We identified 23 primary articles for evaluation, including 10 human studies and 13 vertebrate animal studies of interest. One prospective randomized, controlled trial investigating the safety of systemic ivermectin exposure during pregnancy and four retrospective human studies did not identify a significant association with adverse birth outcome metrics. Out of the three human case reports, two reported uncomplicated prenatal courses and one reported stillbirth and maternal death. A retrospective cross-sectional study concluded a positive association between onchocerciasis and spontaneous abortion, mitigated by ivermectin mass drug administration. While adverse pregnancy outcomes were observed at high doses in mice, rats, and rabbits, there was overall a lack of evidence to support concerns that therapeutic doses of ivermectin (0.2 mg/kg) cause adverse pregnancy outcomes. Conclusion: Further research is warranted to address safety concerns regarding the use of ivermectin in pregnant women in treating and preventing neglected helminth infections that threaten maternal-child health.

Vertebrate-parasitic nematodes cause debilitating, chronic infections in millions of people worldwide. The burden of these so-called ‘neglected tropical diseases’ is often carried by poorer socioeconomic communities in part because research on parasitic nematodes and their vertebrate hosts is challenging and costly. However, complex biological and pathological processes can be modeled in simpler organisms. Here, we consider how insight into the interactions between entomopathogenic nematodes (EPN), their insect hosts and bacterial symbionts may reveal novel treatment targets for parasitic nematode infections. We argue that a combination of approaches that target nematodes, as well as the interaction of pathogens with insect vectors and bacterial symbionts, offer potentially effective, but underexplored opportunities.

Neglected tropical disease (NTD) is a set of 20 deadliest endemic diseases which shows its presence in most of the developing countries worldwide. Nearly 1 billion of the population are affected by it and suffered from poverty yearly. These diseases offer their own unique challenges and limitations towards effective prevention and treatment methods. Neglected tropical diseases are severe infections they may not kill the patient but debilitate the patient by causing severe skin deformities, disfigurement and horrible risks for several infections. Existing therapies for neglected diseases suffer from the loopholes like high degree of toxicity, side effects, low bioavailability, improper targeting and problematic application for affected populations. Progress in the field of nanotechnology in last decades suggested the intervention of nanocarriers to take over and drive the research and development to the next level by incorporating established drugs into the nanocarriers rather than discovering the newer drugs which is an expensive affair. These nanocarriers are believed to be a sure shot technique to fight infections at root level by virtue of its nanosize and ability to reach at cellular level. This article highlights the recent advances, rationale, targets and the challenges that are being faced to fight against NTDs and how the novel therapy tactics are able to contribute to its importance in prevention and treatment of NTDs.

Background During the 2014–15 Ebola Virus Disease (EVD) epidemic, thousands of people in Sierra Leone were infected with the devastating virus and survived. Years after the epidemic was declared over, stigma toward EVD survivors and others affected by the virus is still a major concern, but little is known about the factors that influence stigma toward survivors. This study examines how key personal and ecological factors predicted EVD-related stigma at the height of the 2014–2015 epidemic in Sierra Leone, and the personal and ecological factors that shaped changes in stigma over time. Methods Using three waves of survey data from a representative sample in the Western Urban and Western Rural districts of Sierra Leone, this study examines factors associated with self-reported personal stigma toward Ebola survivors (11 items, α = 0.77) among 1008 adults (74.6% retention rate) from 63 census enumeration areas of the Western Rural and Western Urban districts of Sierra Leone. Participants were randomly sampled at the height of the EVD epidemic and followed up as the epidemic was waning and once the epidemic had been declared over by the WHO. Three-level mixed effects models were fit using Stata 16 SE to examine cross-sectional associations as well as predictors of longitudinal changes in stigma toward EVD survivors. Results At the height of the EVD epidemic, female sex, household wealth, post-traumatic stress, EVD-related fear and perceived infection risk are a few of the factors which predicted higher levels of stigma toward survivors. On average, stigma toward EVD survivors decreased significantly as the epidemic declined in Sierra Leone, but female sex, EVD fear, and risk perceptions predicted a slower rate of change. Conclusion This study identified key individual and psychosocial characteristics which may predict higher levels of stigma toward infectious disease survivors. Future studies should pursue a better understanding of how personal characteristics and perceptions, including psychosocial distress, fear, and perceived infection risk serve as pathways for stigma in communities affected by infectious disease.

Human African and American trypanosomiasis are the vector-borne parasitic diseases that have killed millions of people early, and many people are yet suffering from these neglected diseases. The causative agents of these infections are parasitic protozoans of the genus Trypanosoma. Current treatment regimens against these endemic diseases have several limitations in terms of safety, efficacy, route of administration, and some of them have lost efficacy due to the emergence of resistance in their respective parasites. In this review, the most promising compounds identified by different strategies of drug development against these neglected diseases including target-based approach, the phenotypic high-throughput screening, the drug repurposing approach and combination therapy are emphasized. The potent heterocyclic compounds currently undergoing pre-clinical or clinical studies have also been assessed to ascertain an effective class of organic compounds having significant therapeutic potential against these tropical diseases. The molecular hybridization of outlined motifs may result in more active compounds and circumvent the development of resistance by specific targets in future.

INTRODUCTION Lymphatic filariasis (LF), also known as elephantiasis, has been recognized by the world health organization and the centers for disease control and prevention as one of the neglected tropical diseases. The huge prevalence and risk of manifestation to date reflect the poor management of this disease. The disease poses vast public health and socio-economic burdens and generates a dire need for the development of a prophylactic solution for mass administration. AREAS COVERED Vaccination has been a sought-out strategy for dealing with ever-evolving infectious diseases and can be duly tuned to become a cost effective means of disease control and eventual eradication. In this review, we highlight the epidemiology of LF with the current diagnosis and treatment modules. The need for the development of a potential vaccine candidates, and challenges are discussed. The evidence presented in this review aims to enlighten the readers regarding the essential factors governing LF and its management using prophylactic measures. EXPERT OPINION The complex nature of filarial parasites is evident from the absence of a single vaccine for LF. The development and selection of an appropriate preclinical model and its translation into clinical practice is deemed to be a major task needing in-depth evaluation to formulate an effective vaccine. Explorations of the existing vaccine platforms would serve to be an apt strategy in this direction.

Twenty diseases are recognized as neglected tropical diseases (NTDs) by World Health Assembly resolutions, including human filarial diseases. The end of NTDs is embedded within the Sustainable Development Goals for 2030, under target 3.3. Onchocerciasis afflicts approximately 20.9 million people worldwide with > 90% of those infected residing in Africa. Control programs have made tremendous efforts in the management of onchocerciasis by mass drug administration and aerial larviciding; however, disease elimination is not yet achieved. In the new WHO roadmap, it is recognized that new drugs or drug regimens that kill or permanently sterilize adult filarial worms would significantly improve elimination timelines and accelerate the achievement of the program goal of disease elimination. Drug development is, however, handicapped by high attrition rates, and many promising molecules fail in preclinical development or in subsequent toxicological, safety and efficacy testing; thus, research and development (R&D) costs are, in aggregate, very high. Drug discovery and development for NTDs is largely driven by unmet medical needs put forward by the global health community; the area is underfunded and since no high return on investment is possible, there is no dedicated drug development pipeline for human filariasis. Repurposing existing drugs is one approach to filling the drug development pipeline for human filariasis. The high cost and slow pace of discovery and development of new drugs has led to the repurposing of “old” drugs, as this is more cost-effective and allows development timelines to be shortened. However, even if a drug is marketed for a human or veterinary indication, the safety margin and dosing regimen will need to be re-evaluated to determine the risk in humans. Drug repurposing is a promising approach to enlarging the pool of active molecules in the drug development pipeline. Another consideration when providing new treatment options is the use of combinations, which is not addressed in this review. We here summarize recent advances in the late preclinical or early clinical stage in the search for a potent macrofilaricide, including drugs against the nematode and against its endosymbiont, Wolbachia pipientis.

This publication addresses the limited use of qualitative methods in neglected tropical disease (NTD) programmes. It describes a scoping literature review conducted to inform the development of a guide to inform the use of rapid qualitative assessments to strengthen NTD mass drug administration (MDA) programmes. The review assessed how qualitative methods are currently used by NTD programmes and identified qualitative approaches from other health and development programmes with the potential to strengthen the design of MDA interventions. Systematic review articles were reviewed and searched using key terms conducted on Google Scholar and PubMed. Results show that methods used by NTD programmes rely heavily on focus group discussions and in-depth interviews, often with time-consuming analysis and limited information on how results are applied. Results from other fields offered insight into a wider range of methods, including participatory approaches, and on how to increase programmatic uptake of findings. Recommendations on how to apply these findings to NTD control are made. The topic of human resources for qualitative investigations is explored and a guide to improve MDAs using qualitative methods is introduced. This guide has direct applicability across the spectrum of NTDs as well as other public health programmes.

The complexity of Chagas disease is still a challenge in endemic regions and an emergent public health problem in non-endemic countries. The causative agent of this neglected tropical disease, Trypanosoma cruzi, is mainly transmitted by triatomine vectors and possesses multiple epidemiologically important strains. Current chemotherapeutics are outdated and their limited efficacy is one of the major reasons for treatment discontinuation. In this context, the development of novel, safe and economically accessible antichagasic drugs is required. Various classes of heterocycles and natural compounds have been described as potential antichagasic scaffolds, and coumarins are no exception. These versatile compounds have a wide spectrum of biological activities, and numerous natural and synthetic coumarins have been reported with antichagasic potential. This review aims to discuss the available literature between 2001 and 2020 regarding natural and synthetic coumarins with anti- Trypanosoma cruzi activity. Moreover, some of the studies herein comprised are dedicated to the potential of coumarins to inhibit promising targets in Trypanosoma cruzi.

INTRODUCTION Leishmaniasis is a major public health problem and the second most lethal parasitic disease in the world due to the lack of effective treatments and vaccines. Even when not lethal, leishmaniasis significantly affects individuals and communities through life-long disabilities, psycho-sociological trauma, poverty, and gender disparity in treatment. AREAS COVERED This review discusses the most relevant and recent research available on Pubmed and GoogleScholar highlighting leishmaniasis' global impact, pathogenesis, treatment options, and lack of effective control strategies. An effective vaccine is necessary to prevent morbidity and mortality, lower health care costs, and reduce the economic burden of leishmaniasis for endemic low- and middle-income countries. Since there are several forms of leishmaniasis, a pan-Leishmania vaccine without geographical restrictions is needed. This review also focuses on recent advances and common challenges in developing prophylactic strategies against leishmaniasis. EXPERT OPINION Despite advances in pre-clinical vaccine research, approval of a human leishmaniasis vaccine still faces major challenges - including manufacturing of candidate vaccines under Good Manufacturing Practices, developing well-designed clinical trials suitable in endemic countries, and defined correlates of protection. In addition, there is a need to explore Challenge Human Infection Model to avoid large trials because of fluctuating incidence and prevalence of leishmanasis.

International audience; We evaluated programmatic approaches for skin neglected tropical disease (NTD) surveillance and completed a robust estimation of the burden of skin NTDs endemic to West Africa (Buruli ulcer, leprosy, lymphatic filariasis morbidity, and yaws). In Maryland, Liberia, exhaustive case finding by community health workers of 56,285 persons across 92 clusters identified 3,241 suspected cases. A total of 236 skin NTDs (34.0 [95% CI 29.1-38.9]/10,000 persons) were confirmed by midlevel healthcare workers trained using a tailored program. Cases showed a focal and spatially heterogeneous distribution. This community health worker‒led approach showed a higher skin NTD burden than prevailing surveillance mechanisms, but also showed high (95.1%) and equitable population coverage. Specialized training and task-shifting of diagnoses to midlevel health workers led to reliable identification of skin NTDs, but reliability of individual diagnoses varied. This multifaceted evaluation of skin NTD surveillance strategies quantifies benefits and limitations of key approaches promoted by the 2030 NTD roadmap of the World Health Organization.

This article examines the impact of coronavirus disease 2019 (COVID-19) on dog-mediated rabies, a neglected tropical disease that remains endemic in >65 countries. A globally agreed strategy for rabies elimination is underpinned by a One Health approach, coordinating human and animal health sectors and engaging communities. We present data on the scale and nature of COVID-19 disruption to rabies control programmes and the wider learning for One Health implementation. We argue that the global shift in health priorities caused by the pandemic, and consequent side-lining of animal health, will have broader ramifications for One Health implementation and preparedness for future emergent zoonoses.

Schistosome infection is regarded as one of the most important and neglected tropical diseases associated with poor sanitation. Like other living organisms, schistosomes employ multiple biological processes, of which some are regulated by a post-translational modification called Adenosine Diphosphate-ribosylation (ADP-ribosylation), catalyzed by ADP-ribosyltransferases. ADP-ribosylation is the addition of ADP-ribose moieties from Nicotinamide Adenine Dinucleotide (NAD+) to various targets, which include proteins and nucleotides. It is crucial in biological processes such as DNA repair, apoptosis, carbohydrate metabolism and catabolism. In the absence of a vaccine against schistosomiasis, this becomes a promising pathway in the identification of drug targets against various forms of this infection. The tegument of the worm is an encouraging immunogenic target for anti-schistosomal vaccine development. Vaccinology, molecular modeling and target-based drug discovery strategies have been used for years in drug discovery and for vaccine development. In this paper, we outline ADP-ribosylation and other different approaches to drug discovery and vaccine development against schistosomiasis.

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent anti-trypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.

Background The World Health Organization previously set goals of controlling morbidity due to schistosomiasis by 2020 and attaining elimination as a public health problem (EPHP) by 2025 (now adjusted to 2030 in the new neglected tropical diseases roadmap). As these milestones are reached, it is important that programs reassess their treatment strategies to either maintain these goals or progress from morbidity control to EPHP and ultimately to interruption of transmission. In this study, we consider different mass drug administration (MDA) strategies to maintain the goals. Methods We used 2 independently developed, individual-based stochastic models of schistosomiasis transmission to assess the optimal treatment strategy of a multiyear program to maintain the morbidity control and the EPHP goals. Results We found that, in moderate-prevalence settings, once the morbidity control and EPHP goals are reached it may be possible to maintain the goals using less frequent MDAs than those that are required to achieve the goals. On the other hand, in some high-transmission settings, if control efforts are reduced after achieving the goals, particularly the morbidity control goal, there is a high chance of recrudescence. Conclusions To reduce the risk of recrudescence after the goals are achieved, programs have to re-evaluate their strategies and decide to either maintain these goals with reduced efforts where feasible or continue with at least the same efforts required to reach the goals.

As programs move closer toward the World Health Organization (WHO) goals of reduction in morbidity, elimination as a public health problem or elimination of transmission, countries will be faced with planning the next stages of surveillance and control in low prevalence settings. Mathematical models of neglected tropical diseases (NTDs) will need to go beyond predicting the effect of different treatment programs on these goals and on to predicting whether the gains can be sustained. One of the most important challenges will be identifying the policy goal and the right constraints on interventions and surveillance over the long term, as a single policy option will not achieve all aims—for example, minimizing morbidity and minimizing costs cannot both be achieved. As NTDs move toward 2030 and beyond, more nuanced intervention choices will be informed by quantitative analyses which are adapted to national context.

Successful achievement of global targets for elimination of trachoma as a public health problem and eradication of yaws will require control efforts to reach marginalized populations, including refugees. Testing for serologic evidence of transmission of trachoma and yaws in residents of registered camps and a Makeshift Settlement in Cox’s Bazar District, Bangladesh, was added to a serosurvey for vaccine-preventable diseases (VPDs) conducted April–May 2018. The survey was primarily designed to estimate remaining immunity gaps for VPDs, including diphtheria, measles, rubella, and polio. Blood specimens from 1- to 14-year-olds from selected households were collected and tested for antibody responses against antigens from Treponema pallidum and Chlamydia trachomatis using a multiplex bead assay to evaluate for serologic evidence of the neglected tropical diseases (NTDs) yaws and trachoma, respectively. The prevalence of antibodies against two C. trachomatis antigens in children ranged from 1.4% to 1.5% for Pgp3 and 2.8% to 7.0% for CT694. The prevalence of antibody responses against both of two treponemal antigens (recombinant protein17 and treponemal membrane protein A) tested was 0% to 0.15% in two camps. The data are suggestive of very low or no transmission of trachoma and yaws, currently or previously, in children resident in these communities. This study illustrates how integrated serologic testing can provide needed data to help NTD programs prioritize limited resources.

Coronavirus disease 2019 (COVID-19) protocols has reduced primary and secondary health care for other diseases, such as leishmaniasis, a parasitic, endemic, chronic and persistent disease in Brazil. To ascertain this, we compared the number of leishmaniasis cases diagnosed before and after the COVID-19 pandemic. In 5 regions of Brazil, there was an increase in the mean number of leishmaniasis clinic visits from 2020 pandemic period (over 57%) compared with 2017-2019 years. Interestingly, this increase was due to tegumentary leishmaniasis (TL) while visceral leishmaniasis consultations decreased considerably. The increase in clinic visits with a diagnosis of TL in all regions of Brazil during the pandemic period in 2020, shows that the epidemiological surveillance of neglected tropical diseases cannot slowdown in the country. Expanding information can minimize the negative impacts of COVID-19 on health promotion, prevention and monitoring of the most prevalent neglected diseases.

Disparities in control mechanisms to prevent the spread of Chagas disease in Switzerland raise questions about the process of its recognition as a public health problem, particularly as it concerns migrant populations. With a focus on congenital screening practices, I explore the way in which health care providers experience, problematize and respond to the disease, acting as key agents not only in the provision of care but also in the recognition of Chagas disease as a problem that needs to be addressed. Such an approach contributes to the understanding of processes of public health agenda creation around neglected tropical diseases in non-endemic countries.

The Ascend West and Central Africa programme, funded by the UK Foreign, Commonwealth and Development Office (FCDO) is supporting integrated preventative chemotherapy for up to five neglected tropical diseases (NTDs), including intestinal worms, lymphatic filariasis, river blindness, trachoma and schistosomiasis. The programme is implemented across 13 countries by a consortium of four leading international development partners: Sightsavers, Liverpool School of Tropical Medicine, Schistosomiasis Control Initiative Foundation and Mott Macdonald. This paper presents messages learnt from country assessments that took place prior to the global outbreak of coronavirus disease 2019 (COVID-19). These messages remain relevant post-COVID-19, with greater priority being given to the challenges for national NTD programmes in continuing to deliver mass drug administration (MDA) during the pandemic. Stakeholder coordination from the earliest stages of the pandemic has occurred at two levels: in the first mile with global partners of the NTD Supply Chain Forum and in the last mile with implementing partners in each country. This has been instrumental to manage delayed MDA, including the impact delays have on the shipment of NTD donated drugs and the distribution of stock held in country. The Ascend West and Central Africa programme is supporting countries with the resumption of MDA through a risk assessment and mitigation action (RAMA) process.

Background Strongyloidiasis is the most neglected of the neglected tropical diseases (NTDs). The aim of this commentary is to describe the possible reasons why strongyloidiasis is so overlooked in Ethiopia, and shed light on better ways of control and elimination of the disease. Main body This commentary highlights three points why strongyloidiasis is the most neglected of the NTDs in Ethiopia. Firstly, lack of clear category within the NTDs resulted in omission of the disease from reports, intervention programs, and preventive chemotherapy guidelines. Secondly, magnitude of the disease is underestimated due to paucity of studies and low sensitivity of diagnostic methods coupled with asymptomatic nature of most of the infections. Finally, ivermectin (the drug of choice for treatment of strongyloidiasis) is not in use for control of the other soil-transmitted helminthiasis, nor is there ivermectin mass drug administration for control of strongyloidiasis. This might have created gap in control and elimination of the disease in Ethiopia and possibly elsewhere. Conclusion Strongyloidiasis appears to be the most neglected of the NTDs mainly due to nature of the infection, low sensitivity of the routine diagnostic tools and it’s exclusion from strategic plans and intervention programs. Moreover, studies on strongyloidiasis should use sensitive diagnostic tools. Strongyloidiasis control and elimination programs should be based on reliable evidence of epidemiology of the disease in Ethiopia. Graphic Abstract

Trypanosomatid parasites are responsible for many Neglected Tropical Diseases (NTDs). NTDs are a group of illnesses that prevail in low-income populations, such as in tropical and subtropical areas of Africa, Asia, and the Americas. The three major human diseases caused by trypanosomatids are African trypanosomiasis, Chagas disease and leishmaniasis. There are known drugs for the treatment of these diseases that are used extensively and are affordable; however, the use of these medicines is limited by several drawbacks such as the development of chemo-resistance, side effects such as cardiotoxicity, low selectivity, and others. Therefore, there is a need to develop new chemotherapeutic against these tropical parasitic diseases. Metal-based drugs against NTDs have been discussed over the years as alternative ways to overcome the difficulties presented by approved antiparasitic agents. The study of late transition metal-based drugs as chemotherapeutics is an exciting research field in chemistry, biology, and medicine due to the ability to develop multitarget antiparasitic agents. The evaluation of the late transition metal complexes for the treatment of trypanosomatid diseases is provided here, as well as some insights about their mechanism of action.

Drug repurposing has increased in recent years as an attractive option for treating a number of diseases. Compared to those brought forward via traditional chemical development, drugs intended for repurposing can enter the market faster and with lower investment from pharmaceutical companies. However, a common trend is to focus on diseases that yield higher returns to the industry, such as cancer and common metabolic and inflammatory conditions, resulting in orphan illnesses and neglected tropical diseases having fewer repurposing options for affected patients. In addition, certain legal concerns, including limited patent coverage for the repurposed drugs and pharmacological challenges in performing clinical trials, reduce the likelihood of success. In this review, we discuss the most important concerns that affect the pathway of drug repurposing, with special emphasis on the economic revenues, government-industry associations, and legal considerations that together impact the pharmaceutical industry's decision-making on which compounds may be eligible for repurposing.

Chagas disease is the neglected tropical disease of greatest public health impact in the United States, where it affects over 300,000 people. Diverse barriers limit healthcare access for affected people; fewer than 1% have obtained testing or treatment. We interviewed 50 people with Chagas disease in Los Angeles, California, and administered a cultural consensus analysis questionnaire. Participants were asked about their experiences and perceptions of Chagas disease, access to healthcare, and strategies for coping with the disease. In participants' narratives, the physical and emotional impacts of the disease were closely interwoven. Participant explanatory models highlight difficulties in accessing care, despite a desire for biomedical treatment. Obtaining testing and treatment for Chagas disease poses substantial challenges for US patients.

Schistosomiasis, a neglected parasitic tropical disease that has plagued humans for centuries, remains a major public health burden. A primary challenge to understanding schistosomiasis is deciphering the most remarkable pathological feature of this disease, the granuloma - a highly dynamic and self-organized structure formed by both host and parasite components. Granulomas are considered a remarkable example of how parasites evolved with their hosts to establish complex and intimate associations. However, much remains unclear regarding life within the granuloma, and strategies to restrain its development are still lacking. Here we explore current information on the hepatic Schistosoma mansoni granuloma in the light of Ecology and propose that this intricate structure acts as a real ecosystem. The schistosomal granuloma is formed by cells (biotic component), protein scaffolds, fibres, and chemical compounds (abiotic components) with inputs/outputs of energy and matter, as complex as in classical ecosystems. We review the distinct cell populations ('species') within the granuloma and examine how they integrate with each other and interact with their microenvironment to form a multifaceted cell community in different space-time frames. The colonization of the hepatic tissue to form granulomas is explained from the point of view of an ecological succession whereby a community is able to modify its physical environment, creating conditions and resources for ecosystem construction. Remarkably, the granuloma represents a dynamic evolutionary system that undergoes progressive changes in the 'species' that compose its community over time. In line with ecological concepts, we examine the granuloma not only as a place where a community of cells is settled (spatial niche or habitat) but also as a site in which the functional activities of these combined populations occur in an orchestrated way in response to microenvironmental gradients such as cytokines and egg antigens. Finally, we assert how the levels of organization of cellular components in a granuloma as conventionally defined by Cell Biology can fit perfectly into a hierarchical structure of biological systems as defined by Ecology. By rethinking the granuloma as an integrating and evolving ecosystem, we draw attention to the inner workings of this structure that are central to the understanding of schistosomiasis and could guide its future treatment.

Background Leprosy is known to be unevenly distributed between and within countries. High risk areas or ‘hotspots’ are potential targets for preventive interventions, but the underlying epidemiologic mechanisms that enable hotspots to emerge, are not yet fully understood. In this study, we identified and characterized leprosy hotspots in Bangladesh, a country with one of the highest leprosy endemicity levels globally. Methods We used data from four high-endemic districts in northwest Bangladesh including 20 623 registered cases between January 2000 and April 2019 (among ~ 7 million population). Incidences per union (smallest administrative unit) were calculated using geospatial population density estimates. A geospatial Poisson model was used to detect incidence hotspots over three (overlapping) 10-year timeframes: 2000–2009, 2005–2014 and 2010–2019. Ordinal regression models were used to assess whether patient characteristics were significantly different for cases outside hotspots, as compared to cases within weak (i.e., relative risk (RR) of one to two), medium (i.e., RR of two to three), and strong (i.e., RR higher than three) hotspots. Results New case detection rates dropped from 44/100 000 in 2000 to 10/100 000 in 2019. Statistically significant hotspots were identified during all timeframes and were often located at areas with high population densities. The RR for leprosy was up to 12 times higher for inhabitants of hotspots than for people living outside hotspots. Within strong hotspots (1930 cases among less than 1% of the population), significantly more child cases (i.e., below 15 years of age) were detected, indicating recent transmission. Cases in hotspots were not significantly more likely to be detected actively. Conclusions Leprosy showed a heterogeneous distribution with clear hotspots in northwest Bangladesh throughout a 20-year period of decreasing incidence. Findings confirm that leprosy hotspots represent areas of higher transmission activity and are not solely the result of active case finding strategies.

Background Cutaneous leishmaniasis (CL), a neglected tropical disease, represents a significant public health problem in many endemic countries including Yemen. The ongoing armed conflict that started in March 2015 has had a negative impact on the entire healthcare system as well as on infectious disease control programmes. Therefore, this cross-sectional study aimed to assess knowledge and attitude towards CL among rural endemic communities in southwestern Yemen. Methods Five hundred households in five areas of Shara’b district of Taiz governorate were randomly selected to participate in a quantitative survey. A pretested structured questionnaire was used to collect data on the sociodemographic characteristics of the participants, their knowledge and attitude towards CL and their knowledge on the sand fly vector. Results The analysis was conducted on a final sample of 466 individuals (62.7% males and 37.3% females) aged between 18 and 70 years. Among the participants, 21.5% were non-educated while 39.7 and 20.8% had completed secondary school and tertiary education, respectively. Although the participants were aware of CL, about three quarters (77.7%) of them had poor overall knowledge about disease transmission, clinical presentation, treatment, and prevention. Interestingly, approximately half of the participants (49.1%) were able to differentiate sand flies from other flies and mosquitoes. However, only 14.8% of the participants knew about the role of the phlebotomine sand fly in the transmission of CL. Only 36.6% believed that CL can be prevented and 49.6% had a negative attitude towards the disease. Univariate and multivariate analyses showed that age and gender were the significant determinants of knowledge about CL and the sand fly vector among the studied population. Conclusion A poor level of knowledge about the different epidemiological aspects of CL was found among rural CL-endemic communities in Taiz. This factor, together with the major collapse of the healthcare infrastructure due to the ongoing civil war in Yemen, may be contributing to the continued endemicity of CL in the governorate. It is therefore recommended that health education on CL transmission and prevention should be provided to the targeted communities.

Background: Neglected Tropical Diseases (NTDs) affect a huge population of the world and the majority of the victims belong to the poor community of the developing countries. Until now, the World Health Organization (WHO) has identified 20 tropical diseases as NTDs that must be addressed with high priority. However, many heterocyclic scaffolds have demonstrated potent therapeutic activity against several NTDs. Objective: There are three major objectives: (1) To discuss the causes, symptoms, and current status of all the 20 NTDs; (2) To explore the available heterocyclic drugs, as well as their mechanisms of action (if known), that are being used to treat NTDs; (3) To develop general awareness on NTDs among the medicinal/health research community and beyond. Methods: The 20 NTDs have been discussed according to their alphabetic orders along with the possible heterocyclic remedies. The current status of treatment with an emphasis on the heterocyclic drugs (commercially available and investigational) has been outlined. In addition, a brief discussion of the impacts of NTDs on socio-economic conditions is included. Results: NTDs are often difficult to diagnose and the problem is worsened by the unhealthy hygiene, improper awareness, and inadequate healthcare in the developing countries where these diseases primarily affect poor people. The statistics include the duration of suffering, the number of individuals affected, and access to healthcare and medication. The mechanisms of action of various heterocyclic drugs, if reported, have been briefly summarized. Conclusion: Scientists and pharmaceutical corporations should allocate more resources to reveal the in-depth mechanism of action of many heterocyclic drugs that are currently being used for the treatment of NTDs. Analysis of current heterocyclic compounds and the development of new medications can help in the fight to reduce/remove the devastating effects of NTDs. An opinion-based concise review has been presented. Based on the available literature, this is the first attempt to present all the 20 NTDs and related heterocyclic compounds under the same umbrella.

Infection by Taenia solium poses a major burden across endemic countries. The World Health Organization (WHO) 2021–2030 Neglected Tropical Diseases roadmap has proposed that 30% of endemic countries achieve intensified T. solium control in hyperendemic areas by 2030. Understanding geographical variation in age-prevalence profiles and force-of-infection (FoI) estimates will inform intervention designs across settings.Human taeniasis (HTT) and human cysticercosis (HCC) age-prevalence data from 16 studies in Latin America, Africa and Asia were extracted through a systematic review. Catalytic models, incorporating diagnostic performance uncertainty, were fitted to the data using Bayesian methods, to estimate rates of antibody (Ab)-seroconversion, infection acquisition and Ab-seroreversion or infection loss. HCC FoI and Ab-seroreversion rates were also estimated across 23 departments in Colombia from 28,100 individuals.Across settings, there was extensive variation in all-ages seroprevalence. Evidence for Ab- seroreversion or infection loss was found in most settings for both HTT and HCC and for HCC Ab- seroreversion in Colombia. The average duration until humans became Ab-seropositive/infected decreased as all-age (sero)prevalence increased. There was no clear relationship between the average duration humans remain Ab-seropositive and all-age seroprevalence.Marked geographical heterogeneity in T. solium transmission rates indicate the need for setting- specific intervention strategies to achieve the WHO goals.

Background Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS) has become a widely used technique for the rapid and accurate identification of bacteria, mycobacteria and certain fungal pathogens in the clinical microbiology laboratory. Thus far, only few attempts have been made to apply the technique in clinical parasitology, particularly regarding helminth identification. Methods We systematically reviewed the scientific literature on studies pertaining to MALDI-TOF MS as a diagnostic technique for helminths (cestodes, nematodes and trematodes) of medical and veterinary importance. Readily available electronic databases (i.e. PubMed/MEDLINE, ScienceDirect, Cochrane Library, Web of Science and Google Scholar) were searched from inception to 10 October 2018, without restriction on year of publication or language. The titles and abstracts of studies were screened for eligibility by two independent reviewers. Relevant articles were read in full and included in the systematic review. Results A total of 84 peer-reviewed articles were considered for the final analysis. Most papers reported on the application of MALDI-TOF for the study of Caenorhabditis elegans, and the technique was primarily used for identification of specific proteins rather than entire pathogens. Since 2015, a small number of studies documented the successful use of MALDI-TOF MS for species-specific identification of nematodes of human and veterinary importance, such as Trichinella spp. and Dirofilaria spp. However, the quality of available data and the number of examined helminth samples was low. Conclusions Data on the use of MALDI-TOF MS for the diagnosis of helminths are scarce, but recent evidence suggests a potential role for a reliable identification of nematodes. Future research should explore the diagnostic accuracy of MALDI-TOF MS for identification of (i) adult helminths, larvae and eggs shed in faecal samples; and (ii) helminth-related proteins that are detectable in serum or body fluids of infected individuals. Electronic supplementary material The online version of this article (10.1186/s13071-019-3493-9) contains supplementary material, which is available to authorized users.

Strongyloides stercoralis is a parasitic worm that is of considerable clinical relevance. Indeed, it may persist asymptomatically for many years, but can lead to potentially fatal dissemination when the host's immune status is impaired. As commonly employed stool microscopy techniques (e.g. Kato-Katz thick smear) fail to detect S. stercoralis, the epidemiology is poorly understood. In 2013, we conducted a cross-sectional household survey in the district of Mimika in Papua, Indonesia. A total of 331 individuals, aged 1 month to 44 years, had a single stool sample subjected to real-time polymerase chain reaction (PCR) for S. stercoralis diagnosis. The prevalence of S. stercoralis infection was 32.0% (106/331 individuals); higher than any of the three main soil-transmitted helminths (Ascaris lumbricoides, 23.9%; Trichuris trichiura, 18.4%; and hookworm, 17.2%). Amongst the S. stercoralis-infected individuals, 73.6% were concurrently infected with another helminth, with hookworm being the most frequent co-infection (27.4%). Fourteen percent of the S. stercoralis infections had low cycle threshold values on real-time PCR, which may indicate a higher infection intensity. Multivariate logistic regression analysis revealed that age ≥5 years (adjusted odds ratio (OR) 5.8, 95% confidence interval (CI): 3.1-10.8) was significantly associated with S. stercoralis infection. There is a need for in-depth clinical and diagnostic studies to elucidate the public health impact of S. stercoralis infection in Indonesia.

The foremost concerns of COVID-19 vaccines are safety and efficacy, which becomes grave in countries with a high burden of Neglected Tropical Diseases. Studies proposed helminthic infections might alleviate the efficacy of COVID-19 vaccines. We share preliminary evidence on the association between filariasis and COVID-19 infection. We collated 2 ml of blood from 174 participants residing in filariasis endemic area. To determine filarial antigen, the Og4C3 test and for COVID-19 antibodies, tests through ELISA was performed. COVID-19 antibodies were present among 74/174 (42.5%), whereas filarial antigens were detected in 24/174 (13.8%) participants. An insignificant association [OR = 0.855 (0.36–2.034)] between two was observed. Hence, people in filarial endemic regions can continue taking vaccines without worrying about their efficacy due to the helminthic load in community.

The Community Dermatology Program established in the state of Guerrero, Mexico for almost 30 y provides an adaptable method of detecting and monitoring skin neglected tropical diseases such as mycetoma, which is endemic in the state. The program utilises general and thematic teaching elements combined with distance learning through teledermatology, direct patient consultations and close collaboration with community teams. Using this approach, a picture of mycetoma in Guerrero has emerged, with a focal hot spot located in the southern part of the state in the Costa Chica region. Although in much of Mexico Nocardia infections dominate, in this area there are also substantial numbers of cases of eumycetoma. This combined approach provides a means of early case detection and long-term surveillance through targeted use of a small specialist team.

Background Understanding how knowledge, attitudes and practices regarding leprosy differ in endemic countries can help us develop targeted educational and behavioural change interventions. This study aimed to examine the differences and commonalities in and determinants of knowledge, attitudes, practices and fears regarding leprosy in endemic districts in India and Indonesia. Principle findings A cross-sectional mixed-methods design was used. Persons affected by leprosy, their close contacts, community members and health workers were included. Through interview-administered questionnaires we assessed knowledge, attitudes, practices and fears with the KAP measure, EMIC-CSS and SDS. In addition, semi-structured interviews and focus group discussions were conducted. The quantitative data were analysed using stepwise multivariate regression. Determinants of knowledge and stigma that were examined included age, gender, participant type, education, occupation, knowing someone affected by leprosy and district. The qualitative data were analysed using open, inductive coding and content analysis. We administered questionnaires to 2344 participants (46% from India, 54% from Indonesia) as an interview. In addition, 110 participants were interviewed in-depth and 60 participants were included in focus group discussions. Knowledge levels were low in both countries: 88% of the participants in India and 90% of the participants in Indonesia had inadequate knowledge of leprosy. In both countries, cause, mode of transmission, early symptoms and contagiousness of leprosy was least known, and treatment and treatability of leprosy was best known. In both countries, health workers had the highest leprosy knowledge levels and community members the highest stigma levels (a mean score of up to 17.4 on the EMIC-CSS and 9.1 on the SDS). Data from the interviews indicated that people were afraid of being infected by leprosy. Local beliefs and misconceptions differed, for instance that leprosy is in the family for seven generations (Indonesia) or that leprosy is a result of karma (India). The determinants of leprosy knowledge and stigma explained 10–29% of the variability in level of knowledge and 3–10% of the variability in level of stigma. Conclusion Our findings show the importance of investigating the perceptions regarding leprosy prior to educational interventions in communities: even though knowledge levels were similar, local beliefs and misconceptions differed per setting. The potential determinants we included in our study explained very little of the variability in level of knowledge and stigma and should be explored further. Detailed knowledge of local knowledge gaps, beliefs and fears can help tailor health education to local circumstances., Author summary This study aimed to examine the differences and commonalities in and determinants of knowledge, attitudes, practices and fears regarding leprosy in endemic districts in India and Indonesia. Persons affected by leprosy, their close contacts, community members and health workers were included. We administered questionnaires (the KAP measure, EMIC-CSS and SDS) to 2344 participants. In addition, 110 participants were interviewed in-depth and 60 participants were included in focus group discussions. Knowledge levels were low. In both countries, cause, mode of transmission, early symptoms and contagiousness of leprosy was least known, and treatment and treatability of leprosy was best known. In both countries, health workers had the highest leprosy knowledge levels and community members the highest stigma levels. Data from the interviews indicated that people were afraid of being infected by leprosy. Local beliefs and misconceptions differed. The potential determinants we included in our study explained very little of the variability in level of knowledge and stigma and should be explored further. Our findings show the importance of investigating the perceptions regarding leprosy prior to educational interventions in communities: even though knowledge levels were similar, local beliefs and misconceptions differed per setting.

Background Malaria and neglected communicable protozoa parasitic diseases, such as leishmaniasis, and trypanosomiasis, are among the otherwise called diseases for neglected communities, which are habitual in underprivileged populations in developing tropical and subtropical regions of Africa, Asia, and the Americas. Some of the currently available therapeutic drugs have some limitations such as toxicity and questionable efficacy and long treatment period, which have encouraged resistance. These have prompted many researchers to focus on finding new drugs that are safe, effective, and affordable from marine environments. The aim of this review was to show the diversity, structural scaffolds, in-vitro or in-vivo efficacy, and recent progress made in the discovery/isolation of marine natural products (MNPs) with potent bioactivity against malaria, leishmaniasis, and trypanosomiasis. Main text We searched PubMed and Google scholar using Boolean Operators (AND, OR, and NOT) and the combination of related terms for articles on marine natural products (MNPs) discovery published only in English language from January 2016 to June 2020. Twenty nine articles reported the isolation, identification and antiparasitic activity of the isolated compounds from marine environment. A total of 125 compounds were reported to have been isolated, out of which 45 were newly isolated compounds. These compounds were all isolated from bacteria, a fungus, sponges, algae, a bryozoan, cnidarians and soft corals. In recent years, great progress is being made on anti-malarial drug discovery from marine organisms with the isolation of these potent compounds. Comparably, some of these promising antikinetoplastid MNPs have potency better or similar to conventional drugs and could be developed as both antileishmanial and antitrypanosomal drugs. However, very few of these MNPs have a pharmaceutical destiny due to lack of the following: sustainable production of the bioactive compounds, standard efficient screening methods, knowledge of the mechanism of action, partnerships between researchers and pharmaceutical industries. Conclusions It is crystal clear that marine organisms are a rich source of antiparasitic compounds, such as alkaloids, terpenoids, peptides, polyketides, terpene, coumarins, steroids, fatty acid derivatives, and lactones. The current and future technological innovation in natural products drug discovery will bolster the drug armamentarium for malaria and neglected tropical diseases.

Zoonotic taeniasis caused by the adult stage of Taenia solium, Taenia saginata or Taenia asiatica are considered neglected tropical diseases by the World Health Organization. The life cycle of these 3 metazoan species is very similar and includes an intermediate host: pigs in the case of T. solium and T. asiatica, and cattle in the case of T. saginata. By eating meat (pork/T. solium, T. asiatica; beef/T. saginata) containing live cysticerci, humans develop taeniasis, which is practically asymptomatic but is the main risk factor for intermediate hosts to become infected. T. saginata causes bovine cysticercosis, while T. solium and T. asiatica cause swine cysticercosis, of veterinary and economic importance. T. solium cysticerci cause neurological disease in humans: neurocysticercosis. Cysticerci develop after ingesting microscopic eggs released from a human tapeworm carrier. Here we describe the life stages of the parasites, diagnosis, pathogenesis, symptomatology of neurocysticercosis, and prevention and control measures. Highlighting the need to validate diagnostic tools, treatments and vaccination in endemic areas, with the challenge of addressing the most vulnerable populations that lack resources. If people understand the transmission route, avoid eating uncooked or insufficiently cooked meat and have adequate hygienic habits, the life cycle of the 3 zoonotic Taenia species may be interrupted. In addition, we describe the growing field of immune response and immunomodulation elicited by the parasites, which may provide essential tools for diagnosis, treatment, control of taeniasis/cysticercosis, as well as for identification of parasite-derived immunomodulators that could aid in the treatment of emerging inflammatory diseases worldwide.

Optimal control strategies for Taenia solium taeniasis and cysticercosis have not been determined. We conducted a 2-year cluster randomized trial in Peru by assigning 23 villages to 1 of 3 geographically targeted intervention approaches. For ring screening (RS), participants living near pigs with cysticercosis were screened for taeniasis; identified cases were treated with niclosamide. In ring treatment (RT), participants living near pigs with cysticercosis received presumptive treatment with niclosamide. In mass treatment (MT), participants received niclosamide treatment every 6 months regardless of location. In each approach, half the villages received targeted or mass oxfendazole for pigs (6 total study arms). We noted significant reductions in seroincidence among pigs in all approaches (67.1% decrease in RS, 69.3% in RT, 64.7% in MT; p