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Background: Human African trypanosomiasis (HAT) is a neglected tropical disease that usually occurs in rural areas in sub-Saharan Africa. It caused devastating epidemics during the 20th century. Sustained, coordinated efforts by different stakeholders working with national sleeping sickness control programmes (NSSCPs) succeeded in controlling the disease and reducing the number of cases to historically low levels. In 2012, WHO targeted the elimination of the disease as a public health problem by 2020. This goal has been reached and a new ambitious target was stated in the WHO road map for NTDs 2021–2030 and endorsed by the 73rd World Health Assembly: the elimination of gambiense HAT transmission (i.e. reducing the number of reported cases to zero). The interruption of transmission was not considered as an achievable goal for rhodesiense HAT, as it would require vast veterinary interventions rather than actions at the public health level. Methodology/principal findings: Data reported to WHO by NSSCPs were harmonized, verified, georeferenced and included in the atlas of HAT. A total of 802 cases were reported in 2021 and 837 in 2022. This is below the target for elimination as a public health problem at the global level (< 2000 HAT cases/year); 94% of the cases were caused by infection with T. b. gambiense. The areas reporting ≥ 1 HAT case/10 000 inhabitants/year in 2018–2022 cover a surface of 73 134 km2, with only 3013 km2 at very high or high risk. This represents a reduction of 90% from the baseline figure for 2000–2004, the target set for the elimination of HAT as a public health problem. For the surveillance of the disease, 4.5 million people were screened for gambiense HAT with serological tests in 2021–2022, 3.6 million through active screening and 0.9 million by passive screening. In 2021 and 2022 the elimination of HAT as a public health problem was validated in Benin, Uganda, Equatorial Guinea and Ghana for gambiense HAT and in Rwanda for rhodesiense HAT. To reach the next goal of elimination of transmission of gambiense HAT, countries have to report zero cases of human infection with T. b. gambiense for a period of at least 5 consecutive years. The criteria and procedures to verify elimination of transmission have been recently published by WHO. Conclusions/significance: HAT elimination as a public health problem has been reached at global level, with seven countries already validated as having reached this goal. This achievement was made possible by the work of NSSCPs, supported by different public and private partners, and coordinated by WHO. The new challenging goal now is to reach zero cases by 2030. To reach this goal is crucial to maintain the engagement and support of donors and stakeholders and to keep the involvement and coordination of all partners. Along with the focus on elimination of transmission of gambiense HAT, it is important not to neglect rhodesiense HAT, which is targeted for elimination as a public health problem in the WHO road map for NTDs 2021–2030. Author summary: Human African trypanosomiasis (HAT), also known as "sleeping sickness, is a neglected tropical disease (NTD) transmitted by the bite of infected tsetse flies mainly affecting rural areas in sub-Saharan Africa. During the 20th century it caused enormous suffering in the endemic areas with a last reported peak in the late 1990s. This situation triggered a successful coordinated control effort that allowed, in 2012, the targeting of elimination of the disease as a public health problem by 2020. This paper follows previous papers to present the achievements towards HAT elimination. Annually reported cases have been kept below 1000 cases per year. HAT surveillance is maintained through active screening in endemic areas but also within a network of health facilities able to detect the disease. The World Health Organization (WHO), as defined in its 2021–2030 road map for NTDs, is now targeting the elimination of transmission of gambiense HAT and the elimination of rhodesiense HAT as a public health problem. The commitment of national health authorities and the international community will be essential to achieve these ambitious targets. [ABSTRACT FROM AUTHOR]

Background: Chagas disease or American trypanosomiasis, a neglected tropical disease, is a persistent Public Health problem in Latin America and other, non-endemic, countries. Point-of-care (POC) sensitive methods are still needed to improve and extend early diagnosis in acute infections such as congenital Chagas disease. The objective of this study was to analytically evaluate in the lab the performance of a qualitative POC molecular test (Loop-mediated isothermal amplification (LAMP), Eiken, Japan) for rapid diagnosis of congenital Chagas disease employing FTA cards or Whatman 903 filter paper as solid supports for small-scale volumes of human blood. Methodology/principal findings: We used human blood samples artificially infected with cultured T. cruzi strains to assess the analytical performance of the test in comparison with liquid blood anticoagulated with heparin. The DNA extraction process was evaluated using the ultrarapid purification system PURE manufactured by Eiken Chemical Company (Tokio, Japan) over artificially infected liquid blood or different amounts of dried blood spot (DBS) 3- and 6-mm pieces of FTA and Whatman 903 paper. LAMP was performed on a AccuBlock (LabNet, USA) heater or in the Loopamp LF-160 incubator (Eiken, Japan), and visualization of results was either done at naked eye, using the LF-160 device or P51 Molecular Fluorescence Viewer (minipcr bio, USA). Best conditions tested showed a limit of detection (LoD) with 95% accuracy (19/20 replicates) of 5 and 20 parasites/mL, respectively for heparinized fluid blood or DBS samples. FTA cards showed better specificity than Whatman 903 filter paper. Conclusions/significance: Procedures to operate LAMP reactions from small volumes of fluid blood or DBS in FTA were standardized for LAMP detection of T. cruzi DNA. Our results encourage prospective studies in neonates born to seropositive women or oral Chagas disease outbreaks to operationally evaluate the method in the field. Author summary: Chagas disease is a global health problem in endemic and non-endemic regions due to migration. Early diagnosis of newborns to seropositive mothers is of utmost importance to Public Health, enabling prompt access to highly effective anti-parasitic treatment. For this, it is essential to develop rapid and sensitive methods at point-of-care (POC). The aim of this work was to estimate the analytical performance of the molecular amplification technique named Loop-mediated isothermal amplification (LAMP) as POC strategy to detect Trypanosoma cruzi in small volumes of blood collected in dried blood spots. The procedure was carried out in human blood samples spiked with T. cruzi strains on Whatman 903 or FTA commercial filter papers in comparison with fluid blood in heparin as anticoagulant. We used an ultra-rapid DNA extraction method, tested the LAMP reaction in two different heaters and visualized the results either by the naked eye or using fluorescence viewers. FTA cards showed excellent sensitivity and specificity; LAMP could be performed in a simple heater and results easily visualized with fluorescence viewers. The entire process entails handling basic laboratory devices that will enable POC diagnosis of congenital infection and other acute cases of Chagas disease such as those derived from oral outbreaks. [ABSTRACT FROM AUTHOR]

Critical scientific questions remain regarding infection with Mycobacterium ulcerans, the organism responsible for the neglected tropical disease, Buruli ulcer (BU). A controlled human infection model has the potential to accelerate our knowledge of the immunological correlates of disease, to test prophylactic interventions and novel therapeutics. Here we present microbiological evidence supporting M. ulcerans JKD8049 as a suitable human challenge strain. This non-genetically modified Australian isolate is susceptible to clinically relevant antibiotics, can be cultured in animal-free and surfactant-free media, can be enumerated for precise dosing, and has stable viability following cryopreservation. Infectious challenge of humans with JKD8049 is anticipated to imitate natural infection, as M. ulcerans JKD8049 is genetically stable following in vitro passage and produces the key virulence factor, mycolactone. Also reported are considerations for the manufacture, storage, and administration of M. ulcerans JKD8049 for controlled human infection. Non-technical author summary: In this paper, we progress our research towards establishing a controlled human infection model (CHIM) of Buruli ulcer, caused by Mycobacterium ulcerans. It is crucial that the challenge agent used for such experiments is thoroughly characterised; not only is this important to ensure standardisation between participants, but also to reinforce their safety. Using established criteria, we systematically demonstrate why the isolate M. ulcerans JKD8049 may be a suitable challenge strain. This strain is non-genetically modified, susceptible to antibiotics, can be cultured in relatively simple media, and can be filtered and preserved as individual bacteria to ensure accurate dosing of participants. Even after repeatedly culturing the organism for months, it remains genetically stable, so significant mutations are not expected to develop during manufacture. After preserving the isolate at -80°C, it can be revived and diluted for human inoculation at very low doses. Importantly, it produces the toxin mycolactone, so it is expected to recreate typical Buruli ulcer disease in participants, which will be important to properly test vaccines and other therapeutics. We also demonstrate a set of principles to ensure the produced batch is free from contamination. [ABSTRACT FROM AUTHOR]

On 8 June 2022, the World Health Organization (WHO) released pivotal guidance, "Ending the neglect to attain the Sustainable Development Goals: A strategic framework for integrated control and management of skin-related neglected tropical diseases." Skin-related neglected tropical diseases, or skin NTDs, comprise a group of NTDs that produce signs and symptoms on the skin and include at least 9 diseases or disease groups. Moving away from disease-specific approaches, it is anticipated that synergies will be identified and integrated building on this shared feature, where possible, to achieve a greater health impact. This paper intends to draw attention to the prospects created by this scheme. The framework is a key basis for a proposal produced by WHO dedicated to skin NTD integration and describes the practical opportunities for this evolving strategy. It underlines the wider health benefits that will follow, thus working towards Universal Health Coverage and skin health for all. [ABSTRACT FROM AUTHOR]

Visceral leishmaniasis (VL) is a neglected tropical disease that is globally distributed and has the potential to cause very serious illness. Prior literature highlights the emergence and spread of VL is influenced by multiple factors, such as socioeconomic status, sanitation levels or animal and human reservoirs. The study aimed to retrospectively investigate the presence and infectiousness of VL in Rio Grande do Norte (RN), Brazil between 2007 and 2020. We applied a hierarchical Bayesian approach to estimate municipality-specific relative risk of VL across space and time. The results show evidence that lower socioeconomic status is connected to higher municipality-specific VL risk. Overall, estimates reveal spatially heterogeneous VL risks in RN, with a high probability that VL risk for municipalities within the West Potiguar mesoregion are more than double the expected VL risk. Additionally, given the data available, results indicate there is a high probability of increasing VL risk in the municipalities of Natal, Patu and Pau dos Ferros. These findings demonstrate opportunities for municipality-specific public health policy interventions and warrant future research on identifying epidemiological drivers in at-risk regions. Author summary: As a neglected tropical disease (NTD), Leishmaniasis contributes to poor health outcomes, suffering, and death of vulnerable populations. Leishmania infantum or Leishmania donovani is transmitted from animals to humans through the sandfly vector and can be fatal in 5% of the cases even with treatment. Visceral leishmaniasis is a severe form of Leishmaniasis. The purpose of this study was to estimate regions of high Visceral leishmaniasis risk in Rio Grande do Norte, Brazil between 2007 and 2020 to help inform public health initiatives and potential health policy interventions for this disease. Visceral leishmaniasis is a reportable disease and therefore VL cases are documented to the Brazilian Ministry of Health database through passive surveillance. Passive surveillance data can suffer from missing information; individuals may be asymptomatic, or may not seek medical care allowing for diagnosis. When modeling disease risk from passive surveillance data, assuming there is an absence of disease in regions without documented cases can underestimate disease risk. In this paper we estimate disease risk and identify areas with high-risk and increasing infection trends over time while considering data characteristics such as missing information and high correlation of risk factors. [ABSTRACT FROM AUTHOR]

T cells recognize their ligand, the peptide major histocompatibility complex (MHC), via the T-cell receptor (TCR), which is composed of covalently linked α and β or γ and δ chains. This recognition is critical for T-cell ontogeny and controls the selection, activation, and function of T lymphocytes. Specific TCR αβ variable regions have been associated with immunopathogenesis of Chagas disease. Here, we present a systematic review that compiles experimental in vivo and human data regarding the preferential expression of variable alpha (Vα) and variable beta (Vβ) chain regions in Trypanosoma cruzi infection. The original studies indexed in PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. The analysis showed that expression of TCR Vα subfamilies were evaluated in one human study, and, unlike TCR Vβ, TCR Vα presented a more restricted usage. Despite the great variability in the usage of TCR Vβ regions in human Chagas disease, a down-regulation of TCR Vβ5 expression by T cells from patients in the acute phase of the disease was shown. Opposingly, this TCR region was found overly expressed in CD4+ T cells from chronic Chagas patients. It was also demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs of T. cruzi-infected animals had a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they display the same TCR Vβ region usage, these cells are functionally distinct. Despite the limitations of few papers and year of publication of the studies, compiling the data derived from them reveals that further investigation of TCR usage will point to their potential role in protective or pathogenic responses, as biomarkers of disease progression, and in the search for dominant peptides potentially useful for the development of vaccines or therapies. Author summary: Chagas disease is a neglected tropical disease, caused by infection with Trypanosoma cruzi. Differential expression of certain T-cell receptor (TCR) variable regions has been associated with the immunopathogenesis of Chagas disease. Here, we present a systematic review that compiled experimental in vivo and human data regarding the preferential expression of TCR alpha and beta chain variable regions in Chagas disease. The original studies indexed in the PubMed/Medline, Scopus, and Web of Science databases were screened according to the PRISMA strategy. Despite the great variability in the use of TCR Vβ in T. cruzi infection, the outcomes indicate that there is a down-regulation of TCR Vβ5 expression in T cells from patients in the acute phase of Chagas disease. However, this region is preferentially expressed by CD4+ T cells from chronic Chagas patients. Additionally, it has been demonstrated that murine Vβ9+ T cells derived from nonlymphoid organs displayed a modulatory profile, while splenic Vβ9+ T cells produced inflammatory cytokines, indicating that although they express the same TCR Vβ region, these cells are functionally distinct. Information on TCR expression, specificity and function have critical impact on vaccine design. [ABSTRACT FROM AUTHOR]

Background: Mycetoma is an important neglected tropical disease associated with debilitation, disfigurement and death if not diagnosed and treated adequately. In Pakistan, mycetoma cases have frequently been diagnosed in histopathology and microbiology laboratories. However, there is scarcity of published data from this country. Therefore, the objectives of this study were to evaluate the frequency and type of mycetoma reported in skin and soft tissue biopsies from a single center over 10 years and review of published literature from Pakistan. Method: This descriptive observational retrospective study was conducted at the Aga Khan University Hospital laboratory, Karachi, Pakistan. Laboratory data from 2009–2018 of skin and soft tissue biopsies with positive findings of mycetoma were retrieved from hospital information system. The variables for statistical analysis were age and gender of patient, anatomical site of lesion, residence of patient (geographical location) in the country, etiologic agents of mycetoma and significant gross and microscopic histopathological findings. The data was entered, and descriptive epidemiologic assessment was carried out using MS excel 2013. Geographical information system was used for mapping the location. Literature review of mycetoma cases reported from Pakistan was done on PubMed, Google search and PakMediNet from 1980 till April 2019. Result: During ten years of study period, 89 skin and soft tissue biopsies were reported as mycetoma, majority were eumycetoma [n = 66/89 (74%)] followed by actinomycetoma [n = 23/89 (26%)]. Involvement of lower limb was predominantly observed [n = 74/89 (83%)] in which foot had significant contribution [n = 65/74 (88%)]. Only 18 specimens were submitted for microbiological assessment and six grew agents of mycetoma, with Madurella mycetomatis reported in only three. Well-formed granuloma formation was observed in only 26%[n = 23/89] of cases. Specific geographical location was not identified, and cases were reported from across the country. From Pakistan, only two original papers and 7 case reports were available in published literature. Conclusion: This single center study reports a handful of cases of mycetoma from Pakistan. We conclude that the index of suspicion should remain high among treating surgeons and physicians and clinical laboratories should improve their diagnostic capacity and skills. This will have a great impact on disease outcome and patient's life. Author summary: World Health Organization (WHO) has included Mycetoma in the neglected tropical diseases. Epidemiological data of mycetoma cases from Pakistan is not available. Although physicians and surgeons frequently see cases of mycetoma in their clinical practice, but poor socioeconomic conditions of patients restrict laboratory diagnosis such as histopathological and microbiological confirmation of disease. This leads to disability, disfigurement and at times limb loss or mortality. Through this study we are documenting the diagnosed cases of mycetoma from specimens submitted to our laboratory. The diagnosis was mainly made by histopathological examination of samples. It is disappointing to note that mycetoma was not included in the differential diagnosis list of clinicians. Probably, that is the reason that very few samples were submitted to the microbiology laboratory for the culture to find out etiologic agents of eumycetoma and actinomycetoma. Overall, this study has highlighted the gaps in the clinical as well as laboratory diagnosis of this disease and case management. [ABSTRACT FROM AUTHOR]

Background: Lymphatic filariasis (LF) is a neglected tropical disease caused by the filarial nematodes Wuchereria bancrofti, Brugia malayi and Brugia timori. The Global Program to Eliminate LF uses mass drug administration (MDA) of anti-filarial drugs that clear microfilariae (Mf) from blood to interrupt transmission by mosquitos. New diagnostic tools are needed to assess the impact of MDA on bancroftian filariasis, because available serologic tests can remain positive after successful treatment. Methodology/Principal findings: We identified Wb-bhp-1, which encodes a W. bancrofti homologue of BmR1, the B. malayi protein used in the Brugia Rapid antibody test for brugian filariasis. Wb-bhp-1 has a single exon that encodes a 16.3 kD protein (Wb-Bhp-1) with 45% amino acid identity to BmR1. Immunohistology shows that anti-Wb-Bhp-1 antibodies primarily bind to Mf. Plasma from 124 of 224 (55%) microfilaremic individuals had IgG4 antibodies to Wb-Bhp-1 by ELISA. Serologic reactivity to Wb-Bhp-1 varied widely with samples from different regions (sensitivity range 32–92%), with 77% sensitivity for 116 samples collected from microfilaremic individuals outside of sub-Saharan Africa. This variable sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. Individuals with higher Mf counts were more likely to have anti-Wb-Bhp-1 antibodies. Cross-reactivity was observed with a minority of plasma samples from people with onchocerciasis (17%) or loiasis (10%). We also identified, cloned and characterized BmR1 homologues from O. volvulus and L. loa that have 41% and 38% identity to BmR1, respectively. However, antibody assays with these antigens were not sensitive for onchocerciasis or loiasis. Conclusions: Wb-Bhp-1 is a novel antigen that is useful for serologic diagnosis of bancroftian filariasis. Additional studies are needed to assess the value of this antigen for monitoring the success of filariasis elimination programs. Author summary: Lymphatic filariasis (LF) is a highly disabling and stigmatizing disease caused by parasitic worms that are transmitted by mosquitoes. There is a coordinated global effort to eliminate LF based on mass drug administration (MDA) of donated anti-filarial medications. Improved methods are needed to determine when transmission of the infection has been interrupted in previously endemic areas so that MDA can be safely stopped. This paper reports the discovery and characterization of a novel W. bancrofti antigen, Wb-Bhp-1, which is a homologue of the Brugia malayi protein used in antibody tests to monitor filariasis elimination in areas of Asia where LF is caused by Brugia species. We show that a test for IgG4 antibodies to Wb-Bhp-1 was fairly specific for W. bancrofti infection. However, the sensitivity of this test varied by the geographic origin of the samples. Sensitivity was highest for samples collected in the Indo-Pacific region and lowest for samples collected in Côte d'Ivoire. Geographic differences in the parasite or the human immune responses to infection may account for this variability. This range in sensitivity highlights the importance of validating new diagnostic tests for parasitic diseases with samples from different geographical regions. [ABSTRACT FROM AUTHOR]

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., Competing Interests: The authors have declared that no competing interests exist.

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. [ABSTRACT FROM AUTHOR]

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 (p<0.05), increased with age (0.20, 8.17, 21.04, and 29.49 for the 0–14, 15–44, 45–64 and over 65-year-old age groups, respectively; p<0.05) and showed a downward trend (negative values) of estimated slopes for the whole province and each Department. Bermejo Department showed the highest (T:-1.02, 95%CI: [-1.42, -0.66]) and Patiño the lowest decreasing trend (T:-0.45, 95%CI: [-0.74, -0.11]). The NCDR trend for both sexes was similar (T:-0.55, 95%CI: [-0.64, -0.46]), and age groups showed a decreasing trend (S15-44:-103, S45-64:-81, S>65:-61, p<0.05), except for the 0–14 age group (S:-3, p>0.05), 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. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer [BU] is a chronic and debilitating neglected tropical skin disease caused by Mycobacterium ulcerans. The treatment of moderate to severe BU affects the well-being of entire households and places a strain on both gender relations within households and social relations with kin asked for various types of support. In this paper, we employ the conceptual lenses provided by the Household Production of Health approach to understanding the impact of illness on the household as a unit of analysis, gender studies, and social support related research to better understand BU health care decision making and the psychosocial experience of BU hospitalization., Methods: An ethnography attentive to circumstance and the nested contexts within which stakeholders respond to BU was conducted employing semi-structured interviews, illness narratives, and case studies. An iterative process of data collection with preliminary analyses and reflection shaped subsequent interviews. Interviews were conducted with 45 women in households having a member afflicted with BU in two communes of Benin with high prevalence rates for BU. The first commune [ZE] has a well-established decentralized BU treatment program and a well-functioning referral network linked to the Allada reference hospital specializing in the care of BU and other chronic ulcers. The second commune [Ouinhi] is one of the last regions of the country to introduce a decentralized BU treatment program. A maximum variation purposeful sample was selected to identify information-rich health care decision cases for in-depth study., Principal Findings: Study results demonstrated that although men are the primary decision makers for healthcare decisions outside the home, women are largely responsible for arranging care for the afflicted in hospital in addition to managing their own households. A woman's agency and ability to influence the decision-making process is largely based on whatever social support and substitute labor she can mobilize from her own network of kin relations. When support wanes, women are placed in a vulnerable position and often end up destitute. Decentralized BU treatment is preferred because it enables a woman to remain in her own household as a patient or caretaker of an ill family member while engaging in child care and petty revenue earing activities. Remaining in the hospital (a liminal space) as either patient or caretaker also renders a woman vulnerable to rumor and innuendo about sexual liaisons and constitutes a form of social risk. Social risk in some cases eclipses the physical risk of the disease in what we would describe as a hierarchy of risks., Conclusion: This study illustrates the importance of decentralized treatment programs for NTDs such as BU. Such programs enable patients to remain in their homes while being treated, and do not displace women responsible for the welfare of the entire household. When women are displaced the well-being of the entire household is placed in jeopardy., Competing Interests: The authors have declared that no competing interests exist.

Background: In 2012 human African trypanosomiasis (HAT), also known as sleeping sickness, was targeted for elimination as a public health problem, set to be achieved by 2020. The World Health Organization (WHO) provides here the 2018 update on the progress made toward that objective. Global indicators are reviewed, in particular the number of reported cases and the areas at risk. Recently developed indicators for the validation of HAT elimination at the national level are also presented. Methodology/Principal Findings: With 977 cases reported in 2018, down from 2,164 in 2016, the main global indicator of elimination is already well within the 2020 target (i.e. 2,000 cases). Areas at moderate or higher risk (i.e. ≥ 1 case/10,000 people/year) are also steadily shrinking (less than 200,000 km2 in the period 2014–2018), thus nearing the 2020 target [i.e. 90% reduction (638,000 km2) from the 2000–2004 baseline (709,000 km2)]. Health facilities providing diagnosis and treatment of gambiense HAT continued to increase (+7% since the previous survey), with a better coverage of at-risk populations. By contrast, rhodesiense HAT health facilities decreased in number (-10.5%) and coverage. At the national level, eight countries meet the requirements to request validation of gambiense HAT elimination as a public health problem (i.e. Benin, Burkina Faso, Cameroon, Côte d'Ivoire, Ghana, Mali, Rwanda, and Togo), while for other endemic countries more efforts are needed in surveillance, control, or both. Conclusions/Significance: The 2020 goal of HAT elimination as a public health problem is within grasp, and eligible countries are encouraged to request validation of their elimination status. Beyond 2020, the HAT community must gear up for the elimination of gambiense HAT transmission (2030 goal), by preparing for both the expected challenges (e.g. funding, coordination, integration of HAT control into regular health systems, development of more adapted tools, cryptic trypanosome reservoirs, etc.) and the unexpected ones. Author summary: Human African trypanosomiasis (HAT), a lethal disease transmitted by tsetse flies, wreaked havoc in Africa at different times in the 20th century. Over the past twenty years, huge efforts made by a broad coalition of stakeholders curbed the last epidemic and brought the disease to the brink of elimination. In this paper, the latest figures on disease occurrence, geographical distribution and control activities are presented. Strong evidence indicates that the elimination of sleeping sickness 'as a public health problem' by 2020 is well within reach. In particular, fewer than one thousand new cases were reported in 2018, and the area where the risk of infection is estimated as moderate, high or very high has shrunk to less than 200,000 km2. More than half of this area is in the Democratic Republic of the Congo. The interruption of transmission of the gambiense form, targeted by the World Health Organization (WHO) for 2030, will require renewed efforts to tackle a range of expected and unexpected challenges. The rhodesiense form of the disease represents a small part of the overall HAT burden. For this form, the problem of under detection is on the rise and, because of an important animal reservoir, the elimination of disease transmission is not envisioned at this stage. [ABSTRACT FROM AUTHOR]

Diagnosing Buruli ulcer (BU) is complicated by limited access to the sensitive IS2404 qPCR. Experienced clinicians report a distinct odour of Buruli ulcers. We explored the potential of headspace analysis by thermal desorption-gas chromatography-mass spectrometry to detect volatile organic compounds (VOCs) from Mycobacterium ulcerans both in vitro and clinically. This study was conducted in two phases: a discovery and validation phase. During the discovery phase, VOCs that enable identification of M. ulcerans cultures were determined. During the validation phase, these VOCs were evaluated in clinical samples for which we used gauzes from patients with skin ulcerations in the Democratic Republic of Congo. Seven M. ulcerans headspace samples were compared with four from sterile growth medium and laboratory environmental air. The univariate analysis resulted in the selection of 24 retained VOC fragments and a perfect differentiation between cultures and controls. Sixteen of 24 fragments were identified, resulting in eleven unique compounds, mainly alkanes. Methylcyclohexane was the best performing compound. Based on these 24 fragments, headspace samples originating from gauzes of 50 open skin lesions (12 qPCR positive and 38 negative) were analysed and an AUC of 0.740 (95%-CI 0.583–0.897) was obtained. As this is an experimental study, future research has to confirm whether the identified compounds can serve as novel biomarkers. Author summary: In this study the odour of bacteria that cause Buruli ulcer was examined. First, the air of bacteria cultured in the lab was analysed and compared with controls. Next, air was sampled from gauzes worn by people in the Kongo Central province, the Democratic Republic of Congo. Their lesions were compatible with Buruli ulcer disease but only 12 out of 50 were infected with the Buruli bacterium. In the odour of the Buruli bacteria and in gauzes from people with Buruli ulcer, several chemicals were present more abundantly than in gauzes from people with wounds caused by other diseases. Future research has to determine whether these chemicals can become part of a new test for Buruli ulcer disease. [ABSTRACT FROM AUTHOR]

Introduction: Buruli ulcer (BU) caused by Mycobacterium ulcerans (MU) is a devastating necrotic skin disease. PCR, recommended for confirmation of BU by WHO, requires an adequately equipped laboratory, therefore often delaying timely diagnosis and treatment of BU patients in remote settings. Loop-mediated isothermal amplification (LAMP) is a PCR-based protocol for isothermal amplification of DNA that has been suggested for diagnosis of BU in low-resource settings. Study aims and methods: This is an exploratory diagnostic test evaluation study, with an embedded qualitative sub-study. Its aims are two-fold: First, to evaluate a simple rapid syringe-based DNA extraction method (SM) in comparison with a more elaborate conventional DNA extraction method (CM), followed by a LAMP assay targeting IS2404 for the detection of MU, either using a commercially available pocket warmer (pw) or a heat block (hb) for incubation. Second, to complement this by exploring the diagnostic workflow for BU at a community-based health centre in an endemic area in rural Ghana as an example of a potential target setting, using interviews with researchers and health care workers (HCWs). Diagnostic test evaluation results are discussed in relation to the requirements of a target product profile (TPP) for BU diagnosis and the target setting. Results: A protocol using SM for DNA extraction followed by IS2404 PCR (IS2404 PCRSM) was able to identify MU DNA in 73 out of 83 BU clinical specimens submitted for diagnosis. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of IS2404 PCRSM were 90.12%, 100%, 100% and 65.21% respectively, as compared to the reference standard IS2404 PCR in combination with a standard extraction protocol for mycobacterial DNA. Evaluation of the LAMP assay on 64 SM DNA extracts showed a sensitivity, specificity, PPV and NPV of 83.6%, 100%, 100% and 50%, respectively, using either pocket warmer (pwLAMPSM) or heat block (hbLAMPSM) for incubation of the reaction, as compared to the same reference standard. The limit of detection of pwLAMPSM was found to be 30 copies of the IS2404 target. Interview findings explored barriers to BU diagnosis and treatment, including perceptions of the disease, costs, and availability of transport. Participants confirmed that a diagnosis at the PoC, in addition to screening based on clinical criteria, would be advantageous in order to prevent delays and loss to follow-up. Discussion and conclusions: The high diagnostic and analytic accuracy of the pwLAMP, evaluated by us in combination with a syringe-based DNA extraction method, supports its potential use for the rapid detection of MU in suspected BU samples at the community or primary health care level without reliable electricity supply. Further optimization needs include a lysis buffer, evaluation directly at the PoC and/or other sites, assessing staff training requirements and quality control. Author summary: Buruli ulcer (BU) is a severe bacterial skin disease. Molecular diagnostic methods, as recommended by the World Health Organization (WHO), require a well-equipped laboratory with reliable electricity supply, which is challenging in low-resource settings. We aimed to evaluate a protocol for loop-mediated isothermal amplification (LAMP), independent of power supply, as an alternative DNA-detection based diagnostic tool for peripheral health care facilities at the point-of-care (PoC). Our protocol included a rapid syringe-based DNA extraction method, followed by a LAMP assay using a commercial pocket warmer for incubation. It showed promising results, with around 84% sensitivity and 100% specificity, as compared to standard molecular methods. Through interviews and discussions with researchers, healthcare workers and community members, we characterized the diagnostic and treatment workflow at a potential target site in an endemic area in Ghana's Eastern Region. Reported barriers to treatment seeking included perceptions of BU and price and availability of transport, and confirmed potential advantages of diagnosis at the PoC in preventing delays and loss to follow-up. Our study suggests that this LAMP protocol could hold promise for rapid and accurate diagnosis of BU in settings with unreliable electricity; further research will need to include further optimization and evaluation. [ABSTRACT FROM AUTHOR]

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.

Background: American Cutaneous Leishmaniasis (ACL) shows variable response to therapy, but data on species-specific treatment efficacy is scarce. We describe the clinical characteristics and outcome of patients with ACL imported to a tertiary centre in Germany and determine whether species-specific therapy according to the 2014 "LeishMan" group recommendations is associated with cure. Methods: A retrospective chart review was conducted at the Charité Institute of International Health in Berlin. We analysed data on PCR-confirmed ACL cases collected between 2000 and 2023. Systemic therapy included liposomal amphotericin B, miltefosine, pentavalent antimony, ketoconazole or itraconazole. Localized therapy included perilesional pentavalent antimony or paromomycin ointment. Cure was defined as re-epithelialization of ulcers or disappearance of papular-nodular lesions after 3 months of treatment. Logistic regression models were used to quantify the effect of species-specific systemic therapy on the outcome. Results: 75 cases were analysed. Most patients were male (62%), median age was 35 years, no patient had a history of immunosuppression. The most common reason for travel was tourism (60%), the most common destination was Costa Rica (28%), the median duration of illness was 8 weeks, and most patients presented with ulcers (87%). Lesions were complex in 43%. The most common Leishmania (L.) species was L. braziliensis (28%), followed by L. panamensis (21%). 51/73 (70%) patients were cured after initial therapy and 17/21 (81%) after secondary therapy. Cure after systemic therapy was more frequent when species-specific treatment recommendations were followed (33/45; 73%), compared to when not followed, (6/17; 35%, P = 0.008). This association was independent of age, sex, previous therapy, complex lesions, and Leishmania species (adjusted OR, 5.06; 95% CI, 1.22–24.16). Conclusions: ACL is a rare, imported disease in Germany. Complex lesions were common, challenging successful therapy. This study highlights the importance of identifying the parasite species and suggests that a species-specific approach to treatment leads to better outcomes. Author summary: American cutaneous leishmaniasis is a skin disease caused by parasites that are transmitted through the bite of sandflies. It is considered as a neglected tropical disease. In non-endemic countries like Germany, this disease is rarely seen and is imported by migrants or travellers who have been infected in tropical or subtropical areas of the Americas. Experts suggest that the treatment should be given depending on the specific parasite species found in the affected skin, but there is still a scarcity of information on the optimal management strategy. We analysed 75 American cutaneous leishmaniasis cases seen between 2000 and 2023 at our German medical centre. Most patients were men, around 35 years of age, who most commonly travelled to the Americas for tourism. We found that when using systemic medications (i.e., given by mouth, injection or drip into a vein), that were recommended for the specific parasite type, patients were more likely to be cured, with a 73% success rate, compared to a mere 35% success rate when those recommendations were not followed. This highlights the importance of identifying the species that is causing the disease, and suggests that tailoring treatment to the specific parasite species increases the chances of cure. [ABSTRACT FROM AUTHOR]

Introduction: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. Methods: We searched PubMed, EMBASE, EconLit, OpenGrey, and EBSCO Open Dissertations, for articles reporting financial hardship caused by NTDs from database inception to January 1, 2023. We summarized the study findings and methodological characteristics. Meta-analyses were performed to pool the prevalence of CHS. Heterogeneity was evaluated using the I2 statistic. Results: Ten out of 1,768 studies were included, assessing CHS (n = 10) and impoverishment (n = 1) among 2,761 patients with six NTDs (Buruli ulcer, chikungunya, dengue, visceral leishmaniasis, leprosy, and lymphatic filariasis). CHS was defined differently across studies. Prevalence of CHS due to OOP costs was relatively low among patients with leprosy (0.0–11.0%), dengue (12.5%), and lymphatic filariasis (0.0–23.0%), and relatively high among patients with Buruli ulcers (45.6%). Prevalence of CHS varied widely among patients with chikungunya (11.9–99.3%) and visceral leishmaniasis (24.6–91.8%). Meta-analysis showed that the pooled prevalence of CHS due to OOP costs of visceral leishmaniasis was 73% (95% CI; 65–80%, n = 2, I2 = 0.00%). Costs of visceral leishmaniasis impoverished 20–26% of the 61 households investigated, depending on the costs captured. The reported costs did not capture the financial burden hidden by the abandonment of seeking healthcare. Conclusion: NTDs lead to a substantial number of households facing financial hardship. However, financial hardship caused by NTDs was not comprehensively evaluated in the literature. To develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors. Author summary: Neglected tropical diseases (NTDs) mainly affect underprivileged populations, potentially resulting in catastrophic health spending (CHS) and impoverishment from out-of-pocket (OOP) costs. This systematic review aimed to summarize the financial hardship caused by NTDs. We found that NTDs lead to a substantial number of households facing financial hardship. CHS risk due to direct OOP costs was relatively low among patients with leprosy (0.0–11.0%), dengue (12.5%), and lymphatic filariasis (0.0–23.0%), and relatively high among patients with Buruli ulcers (45.6%). CHS risk varied widely among patients with chikungunya (11.9–99.3%) and visceral leishmaniasis (24.6–91.8%). Costs of visceral leishmaniasis impoverished 20–26% of 61 households, depending on the costs captured. Nevertheless, financial hardship caused by NTDs was not comprehensively evaluated in the literature. Therefore, to develop evidence-informed strategies to minimize the financial hardship caused by NTDs, studies should evaluate the factors contributing to financial hardship across household characteristics, disease stages, and treatment-seeking behaviors. [ABSTRACT FROM AUTHOR]

Background: Stigma related to skin neglected tropical diseases like Buruli ulcer (BU) and yaws has remained underexplored and existing studies are limited to individual diseases despite the WHO call for integration in disease management. Within two districts in central Ghana, we explored stigma associated with BU and yaws to understand overlaps and disease-specific nuances to help guide integrated interventions. Methodology/Principal findings: In-depth interviews were conducted with 31 current or formerly affected individuals to assess the experiences, effects and coping strategies adopted to manage disease related stigma. Data were analysed along broad themes based on the sociological construct of macro and micro interaction and Goffman's treatise on stigma. Disapproving community labels fueled by misconceptions were noted among BU participants which contributed to macro stigma experiences, including exclusion, discrimination and avoidance. In contrast, a high level of social acceptance was reported among yaws participants although some micro-level stigma (anticipated, felt and self-stigma) were noted by individuals with both diseases. While younger participants experienced name-calling and use of derogatory words to address affected body parts, older participants and caregivers discussed the pain of public staring. Stigma experiences had negative consequences on psychosocial well-being, schooling, and social relations, particularly for BU affected people. Problem-focused strategies including confrontation, selective disclosure and concealment as well as emotion-focused strategies (religious coping and self-isolation) were noted. Conclusions and significance: The types and levels of stigma varied for BU and yaws. Stigma experiences also differed for adults and children in this setting and these differences should be accounted for in integrated interventions for these skin NTDs. School health programs need to prioritize educating school teachers about skin NTDs and the negative impact of stigma on the wellbeing of children. Author summary: Stigma related to Neglected Tropical Diseases (NTDs) constitutes a burden on the social and economic life of affected people, their caregivers and communities. Current evidence on stigma has been limited to a small number of NTDs. The WHO recommends integration approaches to NTDs are therefore understanding stigma and its differential impact is important. We explored stigma experiences, effects and coping strategies simultaneously in BU and yaws in two districts in central Ghana. Findings showed nuances for macro-level stigma associated with BU; individuals were stigmatized by community members; interestingly, this was not noted for yaws. Negative effects of stigma found included psychosocial burden, effects on academic work and straining of social relationships. Some affected individuals dealt with the source of stigma actively avoiding disclosure, selective disclosure, concealment with clothing and confrontation. Emotion-focused strategies such as religious coping and self-isolation were reported; these were noted to aggravate psychosocial problems being experienced by affected people. We propose that, the differences in stigma among people affected by BU and yaws, and the role of age in determining types of stigma identified in this study should be considered in integrated interventions for skin NTDs. School health programs are encouraged to educate teachers about skin NTDs and the negative effects of stigma on students. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and clarithromycin (CLA) with wound care. Treatment compliance may be challenging due to socioeconomic determinants. Previous minimum Inhibitory Concentration and checkerboard assays showed that amoxicillin/clavulanate (AMX/CLV) combined with RIF+CLA were synergistic against M. ulcerans. However, in vitro time kill assays (TKA) are a better approach to understand the antimicrobial activity of a drug over time. Colony forming units (CFU) enumeration is the in vitro reference method to measure bacterial load, although this is a time-consuming method due to the slow growth of M. ulcerans. The aim of this study was to assess the in vitro activity of RIF, CLA and AMX/CLV combinations against M. ulcerans clinical isolates by TKA, while comparing four methodologies: CFU enumeration, luminescence by relative light unit (RLU) and optical density (at 600 nm) measurements, and 16S rRNA/IS2404 genes quantification. Methodology/Principal findings: TKA of RIF, CLA and AMX/CLV alone and in combination were performed against different M. ulcerans clinical isolates. Bacterial loads were quantified with different methodologies after 1, 3, 7, 10, 14, 21 and 28 days of treatment. RIF+AMX/CLV and the triple RIF+CLA+AMX/CLV combinations were bactericidal and more effective in vitro than the currently used RIF+CLA combination to treat BU. All methodologies except IS2404 quantitative PCR provided similar results with a good correlation with CFU enumeration. Measuring luminescence (RLU) was the most cost-effective methodology to quantify M. ulcerans bacterial loads in in vitro TKA. Conclusions/Significance: Our study suggests that alternative and faster TKA methodologies can be used in BU research instead of the cumbersome CFU quantification method. These results provide an in vitro microbiological support to of the BLMs4BU clinical trial (NCT05169554, PACTR202209521256638) to shorten BU treatment. Author summary: Since 2004, when only surgery was available, Buruli ulcer (BU) treatment has improved reaching to the efficient 8-weeks all oral antibiotic course of rifampicin and clarithromycin together with wound care and, sometimes, tissue grafting and surgery. This skin neglected tropical disease caused by Mycobacterium ulcerans mainly affects people living in rural areas in under-resourced countries with limited access to health services and medicines, thus compromising patients' treatment adherence. The inclusion of amoxicillin/clavulanate in BU therapy was previously described in vitro with the potential to shorten BU treatment. In this study, we confirmed the high bactericidal activity over time of rifampicin and amoxicillin/clavulanate-containing combinations against M. ulcerans, being even more effective in vitro than the antibiotic combination currently used to treat BU. A comparison of different methodologies that are applied in the laboratory and in the clinic showed good correlation between them, leading to a wide variety of biomarkers for BU research and giving the opportunity for clinical translation; the choice of the most suitable one being driven by the purpose and the context of the study. These in vitro data provide further support to the ongoing clinical trial in West Africa to evaluate if BU treatment can be shortened from 8 to 4 weeks (BLMs4BU trial: NCT05169554, PACTR202209521256638). [ABSTRACT FROM AUTHOR]

Background: Reducing social distance between hospital staff and patients and establishing clear lines of communication is a major challenge when providing in-patient care for people afflicted by Buruli ulcer (BU) and chronic ulcers. Research on hospitals as therapeutic communities is virtually non-existent in Africa and is currently being called for by medical anthropologists working in the field of health service and policy planning. This paper describes a pioneering attempt to establish a therapeutic community for patients suffering from BU and other chronic ulcers requiring long term hospital care in Benin. Methods: A six-month pilot project was undertaken with the objectives of establishing a therapeutic community and evaluating its impact on practitioner and patient relations. The project was designed and implemented by a team of social scientists working in concert with the current and previous director of a hospital serving patients suffering from advanced stage BU and other chronic ulcers. Qualitative research initially investigated patients’ understanding of their illness and its treatment, identified questions patients had about their hospitalization, and ascertained their level of social support. Newly designed question–answer health education sessions were developed. Following these hospital wide education sessions, open forums were held each week to provide an opportunity for patients and hospital staff to express concerns and render sources of discontent transparent. Patient group representatives then met with hospital staff to problem solve issues in a non-confrontational manner. Psychosocial support for individual patients was provided in a second intervention which took the form of drop-in counseling sessions with social scientists trained to serve as therapy facilitators and culture brokers. Results: Interviews with patients revealed that most patients had very little information about the identity of their illness and the duration of their treatment. This knowledge gap surprised clinic staff members, who assumed someone had provided this information. Individual counseling and weekly education sessions corrected this information gap and reduced patient concerns about their treatment and the status of their healing process. This led to positive changes in staff–patient interactions. There was widespread consensus among both patients and staff that the quality of communication had increased significantly. Open forums providing an opportunity for patients and staff to air grievances were likewise popular and patient representative meetings resulted in productive problem solving supported by the hospital administration. Some systemic problems, however, remained persistent challenges. Patients with ulcers unrelated to BU questioned why BU patients were receiving preferential treatment, given special medicines, and charged less for their care. The idea of subsidized treatment for one disease and not another was hard to justify, especially given that BU is not contagious. Conclusion: This pilot project illustrates the basic principles necessary for transforming long term residential hospitals into therapeutic communities. Although the focus of this case study was patients suffering from chronic ulcers, the model presented is relevant for other types of patients with cultural adaptation. [ABSTRACT FROM AUTHOR]

Background: The lymphatic filariasis (LF) elimination program in all sixty-three endemic districts of Nepal was based on annual mass drug administration (MDA) using a combination of diethylcarbamazine (DEC) and albendazole for at least 5 years. The MDA program was started in the Parsa district of the Terai region and at least six rounds of MDA were completed between 2003 and 2017 in all filariasis endemic districts of Central Nepal. Transmission Assessment Survey (TAS) report indicated that circulating filarial antigen (CFA) prevalence was below the critical value i.e., ≤ 2% in selected LF endemic districts of Central Nepal. Based on the TAS report, antigen-positive cases were found clustered in the foci of those districts which were considered as "hotspots". Hence the present study was designed to assess microfilaremia in hotspots of four endemic districts of Central Nepal after the MDA program. Methodology and principal findings: The present study assessed microfilaremia in hotspots of four endemic districts i.e. Lalitpur and Dhading from the hilly region and Bara and Mahottari from the Terai region of Central Nepal. Night blood samples (n = 1722) were collected by finger prick method from the eligible sample population irrespective of age and sex. Community people's participation in the MDA program was ensured using a structured questionnaire and chronic clinical manifestation of LF was assessed using standard case definition. Two districts one each from the hilly region (Lalitpur district) and Terai region (Bara district) showed improved microfilaria (MF) prevalence i.e. below the critical level (<1%) while the other two districts are still over the critical level. There was a significantly high prevalence of MF in male (p = <0.05) and ≥41 years of age group (p = <0.05) community people in the hotspots of four endemic districts. People who participated in the previous rounds of the MDA program have significantly low MF prevalence. The upper confidence limit of MF prevalence in all hotspots of four districts was above the critical level (>1%). Chronic clinical manifestation of LF showed significant association with the older age group (≥41 years) but not with sex. Conclusions: The study revealed LF transmission improved in hotspots of two districts while continued in others but the risk of LF resurgence cannot be ignored since the upper confidence level of MF prevalence is over 1% in all the hotspots studied districts. High MF prevalence is well correlated with the number of MDA rounds but not with the MDA coverage. Community people involved in MDA drug uptake in any previous and last rounds have significantly less MF infection. Hence it is recommended that before deciding to stop the MDA rounds it is essential to conduct the MF survey at the hotspots of the sentinel sites. Author summary: Lymphatic filariasis is a neglected tropical disease that causes disability to human beings and is caused by a group of filarial nematodes such as W. bancrofti, Brugia malayi, and Brugia timori while these parasites are transmitted by different species of vector mosquitoes. Nepal government started the MDA program in 2003 and has completed 6–11 rounds of anti-filarial medicine with DEC and albendazole between 2007 and 2022 in selected endemic districts of Central Nepal. TAS report showed a low level of infection (<2%) in all study districts. Interestingly we found that the antigen-positive cases were clustered in foci. We defined those circulating filarial antigen (CFA) positive clustered areas as hotspots and assessed MF infection among the adult community people after the MDA program. The result revealed evidence of MF prevalence above threshold in the hotspots of two districts one each from the hilly region (Dhading district) and Terai region (Mahottari district) even after the completion of the MDA program. In those areas, alternative treatment strategies should be employed to reduce the active infection which can serve as reservoirs for recrudescence transmission. Hence it is urgently needed to identify and screen MF infection among community individuals of hotspots after completion of the MDA program even in other districts. [ABSTRACT FROM AUTHOR]

Background: Cystic echinococcosis (CE) is a neglected zoonotic disease that is caused by Echinococcus granulosus sensu lato (s.l.), the life cycle of which involves multiple hosts. We conducted a systematic review (SR) on E. granulosus s.l. in the Greater Horn of Africa (GHA), to provide a picture of its recent epidemiology across all hosts. Methods: For this SR, conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, five electronic databases, as well experts in the region were consulted to retrieve records published between 2000 and 2022, reporting the presence of E. granulosus s.l. infections in any natural host in the GHA (Djibouti, Eritrea, Ethiopia, Kenya, Sudan, Somalia, South Sudan, Tanzania and Uganda). Principal findings: A total of 247 records were retained, describing the presence of E. granulosus s.l. throughout the GHA, except for Djibouti. Only few population surveys on human CE were conducted in the area, with the prevalence ranging between 0.3 and 11.3%. In animals, the reported prevalence ranged up to 61.6% in camels, 88.4% in cattle; 65.2% in goats, 9.9% in pigs, 67.8% in sheep and 94.5% in dogs. In addition, E. granulosus s.l. was also reported in wildlife. A total of five species were reported in the different hosts, namely E. granulosus sensu stricto (G1, G3, GOmo), E. canadensis (G6/7), E. ortleppi (G5), E. felidis, and E. equinus (G4). Conclusions: We confirm that E. granulosus s.l. is prevalent throughout the GHA. Nevertheless, despite our efforts to screen grey literature, an accurate assessment of the epidemiology in GHA remains challenging, due to the lack of combined host, in-depth risk factor and behavioural studies, as well as the wide diversity in subpopulations studied and diagnostic tools used. Interdisciplinary and transboundary partnerships would be essential for the design of effective control strategies, tuned to the GHA setting. Author summary: Cystic echinococcosis (CE) is a disease caused by the tapeworm Echinococcus granulosus that affects both humans and animals. In the Greater Horn of Africa (GHA), the livelihoods of millions of people depend on livestock and herding dogs. At the same time, poor animal slaughter practices still exist in the area. Therefore, the GHA is considered a textbook example for the transmission of E. granulosus. Nevertheless, although the World Health Organization (WHO) prioritized CE as one of the seven neglected zoonotic tropical diseases, a recent summary on the true extent to which the tapeworm occurs across the different host species in the GHA, and the factors that contribute to its transmission is missing. Our systematic review of the literature on the topic confirms that the tapeworm is widely spread in the GHA. At the same time, it remains difficult to accurately assess the occurrence of the worm and how exactly it spreads between the hosts, in absence of well-designed surveys. Based on the nature of the disease (involving both animals and humans) and the disease being highly prevalent in pastoralist communities that move across national borders, a firm response to control CE will require both interdisciplinary and transboundary partnerships. [ABSTRACT FROM AUTHOR]

Epidemics of yaws-like cutaneous ulcers are regularly documented in children in the tropics. They occur mainly in poor and remote communities without access to health facilities. The integration of molecular tools into yaws control efforts has made it possible to describe Haemophilus ducreyi (HD) as a major cause of cutaneous ulcers. The objective of this study was to determine the prevalence of HD as cause of cutaneous ulcers, investigate its presence in asymptomatic individuals and identify associated risk factors. A cross-sectional study was conducted in yaws endemic districts of Cameroon. Participants included people presenting yaws-like ulcers and asymptomatic individuals. Swab samples were collected from each participant and tested for HD and Treponema pallidum (TP) using an established qPCR method. Additionally, demographic, habitat, proximity, and hygiene characteristics were collected using a structured questionnaire. A total of 443 individuals participated in the study, including 271 ulcer cases and 172 asymptomatic contacts. The prevalence of HD in ulcers was 30.3% (Confidence Interval (CI) 95% [24.8–35.7]) and the prevalence of asymptomatic HD carriage was 8.6% (CI95% [4.5–12.9]). TP was also detected in our sample among ulcer cases but in lower proportion (5.2% CI95% [2.5–7.8]) compared to HD. The adjusted logistic regression model showed that women were as much at risk of having HD cutaneous ulcer as men regardless of age. Physical proximity to a confirmed ulcer case was the major factor identified favouring HD transmission. HD ulcers were more likely to be present on Bantu individuals compared to Baka as well as HD colonization. These findings highlight HD as the most common cause of cutaneous ulcers in yaws-endemic communities in Cameroon. The exact implications of detecting HD on intact skin are not yet clear. Further studies are needed to understand the significance of this carriage in the spread dynamics of the disease. Author summary: Cutaneous ulcers are commonly found affecting children in low-income countries of Africa and the South Pacific. In rural and remote communities of Cameroon the limited access to health care and shortage of sanitation is associated with a high morbidity of cutaneous ulcers. The latter represent an important cause of suffering and stigmatization in children. HD is commonly known as the causative agent of the sexually transmitted infection chancroid and has been recently described as a leading cause of cutaneous ulcers in yaws-endemic regions. In this study, we investigated the presence of HD and the associated risk factors. Our findings indicate a prevalence of HD associated with cutaneous ulcers of 30.3% and a prevalence of asymptomatic HD carriage of 5.2%. Physical proximity to a confirmed ulcer case, Bantu ethnicity, and the use of traditional latrines were the main risk factors associated with HD ulcers. TP DNA was detected in some cutaneous ulcer samples but in lower proportion compared to HD. This study confirms that HD is a leading cause of cutaneous ulcer in yaws endemic areas in Cameroon. National control programmes in endemic countries should therefore consider this pathogen in their strategies for controlling and eliminating skin neglected tropical diseases (NTDs). [ABSTRACT FROM AUTHOR]

Background: Chronic tropical cutaneous ulcers remain a neglected medical condition in West Africa, particularly Buruli ulcer, which is caused by mycolactone cytotoxin-secreting Mycobacterium ulcerans (M. ulcerans). Medical management of this highly debilitating and necrotising skin infection may be modified by colonisation and co-infection of the ulcer by opportunistic and pathogenic microorganisms, which considerably delays and increases the cost of treatment. Methodology/principal finding: We diagnosed chronic tropical cutaneous ulcers in nine patients in Côte d'Ivoire using M. ulcerans-specific PCRs and culturomics. This revealed M. ulcerans in 7/9 ulcer swabs and 5/9 control swabs as well as an additional 122 bacterial species, 32 of which were specific to ulcers, 61 specifics to the controls, and 29 which were shared, adding 40 bacterial species to those previously reported. Whole genome sequencing of four Bordetella trematum (B. trematum) isolates in four Buruli ulcer swabs and no controls indicated cytolethal distending toxins, as confirmed by cytotoxic assay. Conclusions/significance: In four cases of Buruli ulcer in Côte d'Ivoire, B. trematum was a co-pathogen which was resistant to rifampicin and clarithromycin, unmatching M. ulcerans antibiotic susceptibility profile and counteracting the current treatment of Buruli ulcer in West Africa and Australia. Thus, we report here chronic mixed M. ulcerans-B. trematum chronic tropical ulcer as a specific form of Buruli ulcer in West Africa. Author summary: Buruli ulcer, a severe necrotising skin infection caused by M. ulcerans, remains a neglected health problem in some rural communities in West Africa. Although it can be successfully treated with an antibiotic combination of rifampicin and streptomycin or clarithromycin, the presence of other pathogens or opportunistic agents complicates its management. These co-infections or superinfections make treatment more complex and expensive. In this study, we highlight the association of M. ulcerans, a cytotoxin producer, with B. trematum, another toxin producer associated with chronic ulcers in Buruli ulcer patients. B. trematum shows resistance to the antibiotics used in the Buruli ulcer treatment regimen. Therefore, it is essential to conduct further research to understand the magnitude of its contribution to the illness. [ABSTRACT FROM AUTHOR]

Background: Buruli ulcer (BU), caused by Mycobacterium ulcerans infection, is a debilitating disease of the skin and underlying tissue. The first phase of a BU prevention and treatment programme (BUPaT) was initiated from 2005-2008, in the Ga-West and Ga-South municipalities in Ghana to increase access to BU treatment and to improve early case detection and case management. This paper assesses achievements of the BUPaT programme and lessons learnt. It also considers the impact of the programme on broader interests of the health system., Methods: A mixed-methods approach included patients' records review, review of programme reports, a stakeholder forum, key informant interviews, focus group discussions, clinic visits and observations., Principal Findings: Extensive collaboration existed across all levels, (national, municipality, and community), thus strengthening the health system. The programme enhanced capacities of all stakeholders in various aspects of health services delivery and demonstrated the importance of health education and community-based surveillance to create awareness and encourage early treatment. A patient database was also created using recommended World Health Organisation (WHO) forms which showed that 297 patients were treated from 2005-2008. The proportion of patients requiring only antibiotic treatment, introduced in the course of the programme, was highest in the last year (35.4% in the first, 23.5% in the second and 42.5% in the third year). Early antibiotic treatment prevented recurrences which was consistent with programme aims., Conclusions: To improve early case management of BU, strengthening existing clinics to increase access to antibiotic therapy is critical. Intensifying health education and surveillance would ultimately increase early reporting and treatment for all cases. Further research is needed to explain the role of environmental factors for BU contagion. Programme strategies reported in our study: collaboration among stakeholders, health education, community surveillance and regular antibiotic treatment can be adopted for any BU-endemic area in Ghana.

There is no effective vaccine against Buruli ulcer. In experimental footpad infection of C57BL/6 mice with M. ulcerans, a prime-boost vaccination protocol using plasmid DNA encoding mycolyltransferase Ag85A of M. ulcerans and a homologous protein boost has shown significant, albeit transient protection, comparable to the one induced by M. bovis BCG. The mycolactone toxin is an obvious candidate for a vaccine, but by virtue of its chemical structure, this toxin is not immunogenic in itself. However, antibodies against some of the polyketide synthase domains involved in mycolactone synthesis, were found in Buruli ulcer patients and healthy controls from the same endemic region, suggesting that these domains are indeed immunogenic. Here we have analyzed the vaccine potential of nine polyketide synthase domains using a DNA prime/protein boost strategy. C57BL/6 mice were vaccinated against the following domains: acyl carrier protein 1, 2, and 3, acyltransferase (acetate) 1 and 2, acyltransferase (propionate), enoylreductase, ketoreductase A, and ketosynthase load module. As positive controls, mice were vaccinated with DNA encoding Ag85A or with M. bovis BCG. Strongest antigen specific antibodies could be detected in response to acyltransferase (propionate) and enoylreductase. Antigen-specific Th1 type cytokine responses (IL-2 or IFN-γ) were induced by vaccination against all antigens, and were strongest against acyltransferase (propionate). Finally, vaccination against acyltransferase (propionate) and enoylreductase conferred some protection against challenge with virulent M. ulcerans 1615. However, protection was weaker than the one conferred by vaccination with Ag85A or M. bovis BCG. Combinations of these polyketide synthase domains with the vaccine targeting Ag85A, of which the latter is involved in the integrity of the cell wall of the pathogen, and/or with live attenuated M. bovis BCG or mycolactone negative M. ulcerans may eventually lead to the development of an efficacious BU vaccine. Author Summary: Buruli ulcer (BU) is an infectious disease, characterized by deep, ulcerating skin lesions, particularly on arms and legs, which are provoked by a toxin. BU is caused by a microbe of the genus that also cause tuberculosis and leprosy. The 33 countries where Buruli ulcer has been detected, especially in West Africa, have mainly tropical and subtropical climates, although the disease is also present in temperate areas of Australia and Japan. There is no effective vaccine against BU and it is still not fully understood which immune defence mechanisms (antibodies and/or T cells) are needed to control the infection. The identification of microbial components that are involved in immune control is an essential step in the development of an effective vaccine. In this paper, we used an experimental mouse model to demonstrate the immunogenicity and the vaccine potential of enzymes involved in the toxin synthesis. Combinations with other vaccine candidates, such as a subunit vaccine against Ag85A targeting cell wall synthesis or with live, attenuated M. bovis BCG or mycolactone negative Mycobacterium ulcerans remain to be tested. [ABSTRACT FROM AUTHOR]

Background: Visceral leishmaniasis belongs to the list of neglected tropical diseases and is considered a public health problem worldwide. Spatial correlation between the occurrence of the disease in humans and high rates of canine infection suggests that in the presence of the vector, canine visceral leishmaniasis is the key factor for triggering transmission to humans. Despite the control strategies implemented, such as the sacrifice of infected dogs being put down, the incidence of American visceral leishmaniasis remains high in many Latin American countries. Methodology/Principal Findings: Mathematical models were developed to describe the transmission dynamics of canine leishmaniasis and its control by culling. Using these models, imperfect control scenarios were implemented to verify the possible factors which alter the effectiveness of controlling this disease in practice. Conclusions/Significance: A long-term continuous program targeting both asymptomatic and symptomatic dogs should be effective in controlling canine leishmaniasis in areas of low to moderate transmission (R0 up to 1.4). However, the indiscriminate sacrifice of asymptomatic dogs with positive diagnosis may jeopardize the effectiveness of the control program, if tests with low specificity are used, increasing the chance of generating outrage in the population, and leading to lower adherence to the program. Therefore, culling must be planned accurately and implemented responsibly and never as a mechanical measure in large scale. In areas with higher transmission, culling alone is not an effective control strategy. Author Summary: Visceral leishmaniasis is listed as a neglected tropical disease and is considered a public health problem worldwide. The disease has been documented since 1885, the first case being reported in India. After over 120 years, the incidence of the disease remains high despite control strategies implemented. In areas where the disease is zoonotic, such as in Brazil, identification as well as removal of infected dogs is recommended in highly endemic areas for they are considered to be the reservoir of the Leishmania chagasi parasite. The theoretical basis that supports the culling of infected dogs is the assumption that the incidence of human infection is directly related to the number of infectious dogs. However, there is no consensus among researchers on the effectiveness of this strategy for controlling either human or canine visceral leishmaniasis. In this context, mathematical models can provide a basis for determining the strategies with the greatest potential for success. This paper aims to contribute to this discussion by introducing further complexities into the problem, in particular, the imperfect diagnosis of this infection and the time gap between laboratory diagnosis and culling and the presence of asymptomatic infections. [ABSTRACT FROM AUTHOR]

Background: The reservoir and mode of transmission of Mycobacterium ulcerans, the causative agent of Buruli ulcer, remain unknown. Ecological, genetic and epidemiological information nonetheless suggests that M. ulcerans may reside in aquatic protozoa. Methodology/Principal Findings: We experimentally infected Acanthamoeba polyphaga with M. ulcerans and found that the bacilli were phagocytised, not digested and remained viable for the duration of the experiment. Furthermore, we collected 13 water, 90 biofilm and 45 detritus samples in both Buruli ulcer endemic and non-endemic communities in Ghana, from which we cultivated amoeboid protozoa and mycobacteria. M. ulcerans was not isolated, but other mycobacteria were as frequently isolated from intracellular as from extracellular sources, suggesting that they commonly infect amoebae in nature. We screened the samples as well as the amoeba cultures for the M. ulcerans markers IS2404, IS2606 and KR-B. IS2404 was detected in 2% of the environmental samples and in 4% of the amoeba cultures. The IS2404 positive amoeba cultures included up to 5 different protozoan species, and originated both from Buruli ulcer endemic and non-endemic communities. Conclusions/Significance: This is the first report of experimental infection of amoebae with M. ulcerans and of the detection of the marker IS2404 in amoeba cultures isolated from the environment. We conclude that amoeba are potential natural hosts for M. ulcerans, yet remain sceptical about their implication in the transmission of M. ulcerans to humans and their importance in the epidemiology of Buruli ulcer. Author Summary: Buruli ulcer (BU) is a devastating skin disease caused by Mycobacterium ulcerans, an environmental bacterium that is probably linked to slow-running water. It is unlikely to occur free-living, but even though M. ulcerans DNA has been detected in quite a few different organisms (with most studies focusing on insects), it is still not clear what its real reservoir is. Amoeboid protozoa, inhabitants of biofilms in slow flowing water, are good candidates since all previously tested mycobacteria are resistant to the digestion by these macrophage-like organisms. In this paper we demonstrate that M. ulcerans can indeed infect Acanthamoeba polyphaga in the lab, and remain viable intracellularly. We also collected water, biofilm and detritus samples in BU endemic and non-endemic regions in Ghana. We found that several mycobacteria species commonly occur intracellularly in protozoa in these environments. Amoebae were isolated from almost all samples, and an M. ulcerans marker (IS2404) was detected in 4% of the amoeba cultures. We conclude that amoebae are potential hosts for M. ulcerans. However, because these IS2404 positive amoebae originated from both BU endemic and non-endemic areas, we remain sceptical about their implication in the transmission of M. ulcerans to humans. [ABSTRACT FROM AUTHOR]

Background: The increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni. Methodology/Principal Findings: Here we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass) and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths), and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets. Conclusions/Significance: Using the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest novel target candidates that may merit further study, the lists can easily be modified in a user-specific manner, either by adjusting the weights for chosen criteria or by changing the criteria that are included. Author Summary: In cell-based drug development, researchers attempt to create drugs that kill a pathogen without necessarily understanding the details of how the drugs work. In contrast, target-based drug development entails the search for compounds that act on a specific intracellular target—often a protein known or suspected to be required for survival of the pathogen. The latter approach to drug development has been facilitated greatly by the sequencing of many pathogen genomes and the incorporation of genome data into user-friendly databases. The present paper shows how the database TDRtargets.org can identify proteins that might be considered good drug targets for diseases such as African sleeping sickness, Chagas disease, parasitic worm infections, tuberculosis, and malaria. These proteins may score highly in searches of the database because they are dissimilar to human proteins, are structurally similar to other "druggable" proteins, have functions that are easy to measure, and/or fulfill other criteria. Researchers can use the lists of high-scoring proteins as a basis for deciding which potential drug targets to pursue experimentally. [ABSTRACT FROM AUTHOR]

Background: Female Genital Schistosomiasis (FGS) is a neglected disease of the genital tract due to the inflammatory response to the presence of Schistosoma haematobium eggs in the genital tract. The WHO has prioritized the improvement of diagnostics for FGS and previous studies have explored the PCR-based detection of Schistosoma DNA on genital specimens, with encouraging results. This study aimed to determine the prevalence of FGS among women living in an endemic district in North-western Tanzania, using PCR on samples collected though cervical-vaginal swabs, and to compare the performance of self-collected and healthcare worker–collected (operator-collected) samples, and the acceptability of the different sampling methods. Methods/Principal findings: A cross-sectional study was conducted involving 211 women living in 2 villages in the Maswa district of North-western Tanzania. Urine, self-collected and operator-collected cervical-vaginal swabs were obtained from participants. A questionnaire was administered, focusing on the comfortability in undergoing different diagnostic procedures. Prevalence of urinary schistosomiasis, as assessed by eggs in urine, was 8.5% (95%CI 5.1–13.1). DNA was pre-isolated from genital swabs and transported at room temperature to Italy for molecular analysis. Prevalence of active schistosomiasis, urinary schistosomiasis, and FGS were 10.0% (95% CI 6.3–14.8), 8.5% (95%CI 5.1–13.1), and 4.7% (95%CI 2.3–8.5), respectively. When real-time PCR was performed after a pre-amplification step, the prevalence of active schistosomiasis increased to 10.4% (95%CI 6.7–15.4), and FGS to 5.2% (95%CI 2.6–9.1). Of note, more cases were detected by self-collected than operator-collected swabs. The vast majority of participants (95.3%) declared that they were comfortable/very comfortable about genital self-sampling, which was indicated as the preferred sampling method by 40.3% of participants. Conclusions/Significance: The results of this study show that genital self-sampling followed by pre-amplified PCR on room temperature-stored DNA is a useful method from both technical and acceptability point of views. This encourages further studies to optimize samples processing, and identify the best operational flow to allow integration of FGS screening into women health programmes, such as HPV screening. Author summary: Female Genital Schistosomiasis (FGS) is a severe debilitating disease of the female genital tract, caused by infection with Schistosoma haematobium, the agent of urogenital schistosomiasis. It is estimated that FGS affects 20–56 million girls and women, especially in sub-Saharan Africa. The diagnosis of FGS is currently difficult, and this disease often remains undiagnosed or is misdiagnosed as sexually transmitted diseases or genital cancer, with dramatic health and social consequences for the affected women. The WHO has prioritized the improvement of diagnostics for FGS. In this study, we applied and compared the performance of two genital sampling methods (self-collected and healthcare worker (operator)-collected cervical-vaginal swab) followed by molecular analysis, and assessed their comparative acceptability among 211 women living in a S. haematobium endemic district in North-western Tanzania. We found that not only self-collection by genital swab was well accepted, and actually the preferred sampling method for a high proportion of participants, but that PCR had higher sensitivity when applied to self-collected samples as compared to operator-collected swabs. Furthermore, we used room temperature-stored DNA, which offered greater ease of sample preservation and transportation after extraction. This encourages further studies to optimize samples processing and identify the best operational flow to allow integration of FGS screening into women health programmes, such as HPV screening. [ABSTRACT FROM AUTHOR]

Critical knowledge gaps regarding infection with Mycobacterium ulcerans, the cause of Buruli ulcer (BU), have impeded development of new therapeutic approaches and vaccines for prevention of this neglected tropical disease. Here, we review the current understanding of host–pathogen interactions and correlates of immune protection to explore the case for establishing a controlled human infection model of M. ulcerans infection. We also summarise the overarching safety considerations and present a rationale for selecting a suitable challenge strain. [ABSTRACT FROM AUTHOR]

Background: The leishmaniases are a group of four vector-borne neglected tropical diseases caused by 20 species of protozoan parasites of the genus Leishmania and transmitted through a bite of infected female phlebotomine sandflies. Endemic in over 100 countries, the four types of leishmaniasis–visceral leishmaniasis (VL) (known as kala-azar), cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL), and post-kala-azar dermal leishmaniasis (PKDL)–put 1.6 billion people at risk. In Kenya, the extent of leishmaniasis research has not yet been systematically described. This knowledge is instrumental in identifying existing research gaps and designing appropriate interventions for diagnosis, treatment, and elimination. Methodology/Principal findings: This study used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology to determine the state of leishmaniases research in Kenya and identify research gaps. We searched seven online databases to identify articles published until January 2022 covering VL, CL, MCL, and/or PKDL in Kenya. A total of 7,486 articles were found, of which 479 underwent full-text screening, and 269 met our eligibility criteria. Most articles covered VL only (n = 141, 52%), were published between 1980 and 1994 (n = 108, 39%), and focused on the theme of "vectors" (n = 92, 34%). The most prevalent study types were "epidemiological research" (n = 88, 33%) tied with "clinical research" (n = 88, 33%), then "basic science research" (n = 49, 18%) and "secondary research" (n = 44, 16%). Conclusion/Significance: While some studies still provide useful guidance today, most leishmaniasis research in Kenya needs to be updated and focused on prevention, co-infections, health systems/policy, and general topics, as these themes combined comprised less than 4% of published articles. Our findings also indicate minimal research on MCL (n = 1, <1%) and PKDL (n = 2, 1%). We urge researchers to renew and expand their focus on these neglected diseases in Kenya. Author summary: The leishmaniases are a group of four vector-borne neglected tropical diseases (NTDs) that are endemic in over 100 countries, putting over 1.6 billion people at risk. In Kenya, the extent of research on leishmaniasis remains unclear. Therefore, this scoping review aims to uncover and classify the body of literature on leishmaniasis in Kenya to elucidate gaps in knowledge and inform future research, related health policies, and interventions in Kenya. Through a database search, we identified 269 articles that met our eligibility criteria, which were included in our final analysis. Our analysis revealed that the majority of articles discussed VL. Most articles were published between 1980 and 1994. There was uneven distribution between the themes of published articles, with vector-related research dominating the list, followed by treatment, diagnostics, general epidemiology, and pathophysiology. The most prevalent type of study was a tie between epidemiological and clinical research, followed by basic science research and then secondary research. There is minimal research coverage on MCL and PKDL, which is as expected given the low prevalence of these diseases in Kenya. Furthermore, little research spans prevention, co-infections, health systems/policy, and general topics. [ABSTRACT FROM AUTHOR]

Background: Onchocerciasis ("river blindness") has been targeted for elimination. New treatments that kill or permanently sterilize female worms could accelerate this process. Prior studies have shown that triple drug treatment with ivermectin plus diethylcarbamazine and albendazole (IDA) leads to prolonged clearance of microfilaremia in persons with lymphatic filariasis. We now report results from a randomized clinical trial that compared the tolerability and efficacy of IDA vs. a comparator treatment (ivermectin plus albendazole, IA) in persons with onchocerciasis. Methods and findings: The study was performed in the Volta region of Ghana. Persons with microfiladermia and palpable subcutaneous nodules were pre-treated with two oral doses of ivermectin (150 μg/kg) separated by at least 6 months prior to treatment with either a single oral dose of ivermectin 150 μg/kg plus albendazole 400 mg (IA), a single oral dose of IDA (IDA1, IA plus diethylcarbamazine (DEC. 6 mg/kg) or three consecutive daily doses of IDA (IDA3). These treatments were tolerated equally well. While adverse events were common (approximately 30% overall), no severe or serious treatment-emergent adverse events were observed. Skin microfilariae were absent or present with very low densities after all three treatments through 18 months, at which time nodules were excised for histological assessment. Nodule histology was evaluated by two independent assessors who were masked regarding participant infection status or treatment assignment. Significantly lower percentages of female worms were alive and fertile in nodules recovered from study participants after IDA1 (40/261, 15.3%) and IDA3 (34/281, 12.1%) than after IA (41/180, 22.8%). This corresponds to a 40% reduction in the percentage of female worms that were alive and fertile after IDA treatments relative to results observed after the IA comparator treatment (P = 0.004). Percentages of female worms that were alive (a secondary outcome of the study) were also lower after IDA treatments (301/574, 52.4%) than after IA (127/198, 64.1%) (P = 0.004). Importantly, some comparisons (including the reduced % of fertile female worms after IDA1 vs IA treatment, which was the primary endpoint for the study) were not statistically significant when results were adjusted for intraclass correlation of worm fertility and viability for worms recovered from individual study participants. Conclusions: Results from this pilot study suggest that IDA was well tolerated after ivermectin pretreatment. They also suggest that IDA was more effective than the comparator treatment IA for killing or sterilizing female O. volvulus worms. No other short-course oral treatment for onchocerciasis has been demonstrated to have macrofilaricidal activity. However, this first study was too small to provide conclusive results. Therefore, additional studies will be needed to confirm these promising findings. Trial registration: The study is registered at Cinicaltrials.gov under the number NCT04188301. Author summary: Why was this study done?: Onchocerciasis is a neglected tropical disease caused by parasitic round worms. The infective worm larvae are transmitted by black flies that breed near rivers in sub-Saharan Africa. The parasites cause severe skin disease with itching and ocular disease; the common name for the infection is "river blindness". WHO has targeted onchocerciasis for elimination and mass drug administration is the key intervention strategy. There is an urgent need for improved treatments to kill or permanently sterilize the adult parasites. This study tested a combination drug treatment that is quite effective for treating other related worm infections. What did the researchers do and find?: We performed a randomized clinical trial that compared a triple drug combination with a standard of care two-drug treatment that is widely used in Africa. We found that the new treatment was as safe as the standard treatment. More importantly, analysis of adult female worms surgically removed from study participants suggested that the new treatment might be more effective than the standard treatment for killing or permanently sterilizing the parasites. However, this first study was too small to provide conclusive results. What do these findings mean?: An improved treatment could improve chances for eliminating onchocerciasis in Africa. Results from this study can be used to better plan follow-up studies to explore the value of this and other new combination treatments for onchocerciasis. [ABSTRACT FROM AUTHOR]

Background: Mycetoma is a chronic, progressively destructive disease of subcutaneous tissues and bones caused by certain species of bacteria or fungi. We conducted a cross-sectional community-based study alongside mapping of mycetoma in five administrative units with high mycetoma endemicity in the Eastern Sennar Locality, Sennar State, Sudan. Methods: A household survey was administered which included questions about the household members, household characteristics, economic activity and history of mycetoma. A clinical examination was conducted on all members of the household. If mycetoma was suspected, an individual questionnaire was completed collecting demographic, clinical and epidemiological data as well as information on the use of health care and associated costs. Geographical coordinates and photos of the lesions were taken, and the affected persons were referred to the medical centre for confirmation of the diagnosis and treatment. We compared the characteristics of households with confirmed cases of mycetoma with those without confirmed cases, and individuals with confirmed mycetoma with those in whom mycetoma was not confirmed. Results: In total 7,798 households in 60 villages were surveyed; 515 suspected cases were identified and 359 cases of mycetoma were confirmed. Approximately 15% of households with mycetoma had more than one household member affected by this disease. Households with mycetoma were worse off with respect to water supply, toilet facilities, electricity and electrical appliances compared to the survey households. Only 23% of study participants with mycetoma had sought professional help. Of these, 77% of patients travelled an average of six hours to visit a medical facility. More than half of patients had to pay towards their treatment. The estimated average cost of treatment was 26,957 Sudanese pounds per year (566 US dollars, exchange rate 2018). Conclusions: Results of this survey suggest that agricultural practices and reduced access to sanitation and clean water can be risk factors in developing mycetoma. Poor access to health care and substantial financial costs were barriers to seeking treatment for mycetoma. Author summary: Mycetoma is a neglected tropical disease caused by certain species of bacteria or fungi. The pathogens enter the body through a break in the skin and infect underlying soft tissues, leading to tissue destruction, loss of function, amputations and disability. Early diagnosis of mycetoma requires a clear understanding of disease prevalence, distribution and the contributing risk factors. In this study, we describe the results from a cross-sectional community-based study conducted in five administrative units with high mycetoma endemicity in the Eastern Sennar Locality, Sennar State, Sudan. 7,798 households in 60 villages were randomly selected across the entire locality. A household survey was administered and household members underwent clinical examination. In case of suspected mycetoma, geographical coordinates and photos of the lesions were taken, further demographic and clinical data were collected as was information on the use of health care and associated costs, and the individual was referred to the medical centre for confirmation of the diagnosis and treatment. This study aimed to identify socioeconomic risk factors contributing to mycetoma. We compared the characteristics of the households with confirmed cases of mycetoma with those without cases and individuals with confirmed mycetoma with those in whom mycetoma was not confirmed. Our results suggest that agricultural practices and reduced access to clean water and sanitation may be risk factors in developing mycetoma. Poor access to health care and substantial financial costs may be barriers to seeking treatment for mycetoma. [ABSTRACT FROM AUTHOR]

Background: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. Methods: We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified with wounds received free care and were invited to participate in the wound management study simultaneously carried out in the survey area. The data were analysed for wound prevalence, stratified by wound and patient characteristics. Results: 3842 HDSS-registered persons were surveyed. Overall wound prevalence derived from combined active and passive case finding was 13.0%. 74.1% (403/544) of patients were below the age of 15 years. Most frequent aetiologies were mechanical trauma (85.3%), furuncles (5.1%), burns (2.9%) and Buruli ulcer (2.2%). Most wounds were acute and smaller than 5 cm2 in size. 22.0% (176/799) of wounds showed evidence of secondary bacterial infection. 35.5% (22/62) of chronic wounds had persisted entirely neglected for years. Buruli ulcer prevalence was 2.3 per 1000 individuals and considerably higher than expected from an annual incidence of 0.01 per 1000 individuals as reported by WHO for Côte d'Ivoire at the time of the study. Conclusions: Skin wounds are highly prevalent in rural West Africa, where they represent a widely neglected problem. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. Trial registration: Registration at ClinicalTrials.gov NCT03957447. Author summary: Data on the burden and clinical epidemiology of skin wounds in rural sub-Saharan Africa is scant. The scale of the problem including preventable progression to chronic wounds, disability and systemic complications is largely unaddressed. We conducted a cross-sectional study combining active (household-based survey) and passive case finding (health services-based survey) to determine the burden and clinical epidemiology of wounds within the Taabo Health and Demographic Surveillance System (HDSS) in rural Côte d'Ivoire. Patients identified were invited to participate in the wound management study simultaneously carried out in the survey area. We surveyed approximately 4000 HDSS-registered persons and found a high overall wound prevalence (13.0%), predominately in children. Mechanical trauma was the leading cause, followed by furuncles, burns and Buruli ulcer. Most wounds were acute and had a size of less than 5 cm2, but a substantial proportion was large, complicated, or chronic, some of the latter persisting neglected for years. The HDSS-based survey with combined active and passive case finding adopted in this study provides a better estimate than school- and health institution-based surveys which underestimate the frequency of skin wounds and, particularly, of neglected tropical diseases of the skin, such as Buruli ulcer and yaws. A comparison with country-specific WHO data suggests underreporting of Buruli ulcer cases. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis (CL) is generally caused by Leishmania aethiopica in Ethiopia, and is relatively hard to treat. Sodium stibogluconate (SSG) is the only routinely and widely available antileishmanial treatment, and can be used systemically for severe lesions and locally for smaller lesions. There is limited data on the effectiveness of intralesional (IL) SSG for localized CL in Ethiopia and therefore good data is necessary to improve our understanding of the effectiveness of the treatment. Methodology/Principal findings: A pragmatic (before and after Quazi experimental) study was done to assess the effectiveness of intralesional SSG among localized CL patients at Boru Meda general hospital, Northeast Ethiopia. Patients who were assigned to intralesional SSG by the treating physician were eligible for this study. Study subjects were recruited between January and August 2021. Infiltration of intralesional SSG was given weekly to a maximum of six doses. However, when a patient's lesions were already cured before getting 6 doses, treatment was not conintued, and patient were only asked to come for lesion assessment. Skin slit smears (SSS) were taken each week until they became negative. Outcomes were assessed at day 90, with patients who had 100% reepithelization (for ulcerative lesions) and/or flattening (for indurated lesions) defined as cured. Multi-level logistic regression was done to assess factors associated with cure. A total of 83 patients were enrolled, and final outcomes were available for 72 (86.75%). From these 72, 43 (59.7%, 95% confidence interval 0.44–0.69) were cured at day 90. Adverse effects were common with 69/72 patients (95.8%) reporting injection site pain. Factors associated with cure were age (OR 1.07 95% CI: 1.07–1.27), being male (OR 1.79, 95% CI: 1.10–2.25), size of the lesion (OR 0.79, 95% CI: 0.078–0.94) and skin slit smear (SSS) result +1 grading (OR 1.53, 95% CI: 1.24–1.73) and +2 grading (OR 1.51, 95% CI: 1.41–3.89) compared to the SSS grade +6. Conclusion: Our findings revealed that intralesional sodium stibogluconate resulted in a cure rate of around 60%, with almost all patients experiencing injection site pain. This emphasizes the need for local treatment options which are more patient-friendly and have better cure rates. Author summary: Cutaneous leishmaniasis (CL) is a neglected tropical disease that is quite common in Ethiopia. This is caused by Leishmania aethiopica, which results in severe lesions that do not seem to respond well to treatment. In Ethiopia, sodium stibogluconate is the most widely used treatment for leishmaniasis, but data on the effectiveness of intralesional sodium stibogluconate for localized CL is scarce. We recorded treatment outcomes and adverse events of patients with localized CL lesions who were treated with intralesional SSG up to six times with one injection administered every week. Patients were followed for 90 days, after which the cure rate was assessed. Among 83 patients enrolled, 72 were seen for outcome assessment. Less than 60% of patients were cured, despite having received at least 5 doses of treatment. Almost all patients reported injection site pain as a side-effect. The low cure rate and a high proportion of patients reporting pain indicate that intralesional sodium stibogluconate is not ideal as a treatment regimen. Cryotherapy or thermo therapy could be a better alternative, but a comparative clinical trial is needed to provide concrete evidence as to which treatment should be recommended. [ABSTRACT FROM AUTHOR]

Background: Mucosal Leishmaniasis (ML), a neglected tropical disease caused by Leishmania parasites, impairs the quality of life of under-resourced populations in South America. If not treated promptly, this disease progresses to facial deformities and death. The low sensitivity of microscopy results and the unavailability of other accurate tests hamper the diagnosis. As clinical criteria are readily available in any setting, these may be combined in a syndromic algorithm, which in turn can be used as a diagnostic tool. We explore potential clinical criteria for a syndromic diagnostic algorithm for ML in rural healthcare settings in South America. Methodology/Principal findings: The protocol for this systematic review was pre-registered in PROSPERO with the number: CRD42017074148. In patients with ML, described in case series identified through a systematic retrieval process, we explored the cumulative ML detection rates of clinical criteria. Participants: all patients with active mucosal disease from an endemic area in South America. Any original, non-treatment study was eligible, and case reports were excluded. PUBMED, EMBASE, Web of Science, SCIELO, and LILACS databases were searched without restrictions. The risk of bias was assessed with the JBI checklist for case series. We included 10 full texts describing 192 ML patients. Male gender had the highest detection rate (88%), followed by ulcer of the nasal mucosa (77%), age >15 (69%), and symptom duration >4 months (63%). Significance: Within this selection of patients, we found that the male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to the highest detection rates. However, higher detection comes -naturally- with a higher rate of false positives as well. As we only included ML patients, this could not be verified. Therefore, the criteria that we found to be most promising should be validated in a well-designed prospective study. Author summary: Mucosal leishmaniasis, a disease caused by Leishmania parasites, is transmitted from animals to humans by sandflies. It is a forgotten disease that affects under-resourced populations in South America. Without treatment, this disease mutilates the face and can even be fatal. Diagnosing mucosal leishmaniasis is challenging. The only available testing in rural areas is the use of either a lesion smear or biopsy for light microscopy, however, this is unreliable. Many patients suffer for years before receiving treatment. Syndromic algorithms use patient characteristics, such as age, gender, and symptoms to identify patients for treatment. This method has been promoted to manage infectious diseases, such as tuberculosis and sexually transmitted diseases, in low resource settings. We explore clinical criteria for a new algorithm to diagnose mucosal leishmaniasis in patients described in the medical literature. We searched the literature for reports written in any language and identified 10 studies describing 192 patients with mucosal leishmaniasis. We found that male gender, ulcer of the nasal mucosa, age >15, and symptom duration >4 months lead to acceptable detection rates. Therefore, diagnostic algorithms might improve the detection of patients with mucosal leishmaniasis but need prospective studies in clinical practice to prove their true potential. [ABSTRACT FROM AUTHOR]

Buruli ulcer is a chronic skin disease caused by a toxic lipid mycolactone produced by Mycobacterium ulcerans, which induces local skin tissue destruction and analgesia. However, the cytotoxicity pathway induced by mycolactone remains largely unknown. Here we investigated the mycolactone-induced cell death pathway by screening host factors using a genome-scale lenti-CRISPR mutagenesis assay in human premonocytic THP-1 cells. As a result, 884 genes were identified as candidates causing mycolactone-induced cell death, among which SEC61A1, the α-subunit of the Sec61 translocon complex, was the highest scoring. CRISPR/Cas9 genome editing of SEC61A1 in THP-1 cells suppressed mycolactone-induced endoplasmic reticulum stress, especially eIF2α phosphorylation, and caspase-dependent apoptosis. Although previous studies have reported that mycolactone targets SEC61A1 based on mutation screening and structural analysis in several cell lines, we have reconfirmed that SEC61A1 is a mycolactone target by genome-wide screening in THP-1 cells. These results shed light on the cytotoxicity of mycolactone and suggest that the inhibition of mycolactone activity or SEC61A1 downstream cascades will be a novel therapeutic modality to eliminate the harmful effects of mycolactone in addition to the 8-week antibiotic regimen of rifampicin and clarithromycin. Author summary: Buruli ulcer is a chronic skin disease caused by the bacterium Mycobacterium ulcerans. The disease mainly affects children in West Africa, and the skin ulcers are induced by mycolactone, a toxin produced by the bacteria. The mycolactone diffuses through the skin, killing cells, creating irreversible ulceration, and weakening host immune defenses. However, the cytotoxic pathway induced by mycolactone remains largely unknown. We evaluated the mycolactone-induced cell death pathway by screening host factors using a genome-scale knockout assay in human premonocytic THP-1 cells. We identified 884 genes that are potentially involved in mycolactone-induced cell death, of which SEC61A1, the α-subunit of the Sec61 translocon complex, was the highest ranking. Knockout of SEC61A1 in THP-1 cells resulted in suppression of endoplasmic reticulum stress and caspase-dependent apoptosis induced by mycolactone. These results suggest that SEC61A1 is an essential mediator of mycolactone-induced cell death. [ABSTRACT FROM AUTHOR]

Background: The prevalence of Strongyloides stercoralis infection is estimated to be 30–100 million worldwide, although this an underestimate. Most cases remain undiagnosed due to the asymptomatic nature of the infection. We wanted to estimate the seroprevalence of S. stercoralis infection in a South Indian adult population. Methods: To this end, we performed community-based screening of 2351 individuals (aged 18–65) in Kanchipuram District of Tamil Nadu between 2013 and 2020. Serological testing for S. stercoralis was performed using the NIE ELISA. Results: Our data shows a seroprevalence of 33% (768/2351) for S. stercoralis infection which had a higher prevalence among males 36% (386/1069) than among females 29.8% (382/1282). Adults aged ≥55 (aOR = 1.65, 95% CI: 1.25–2.18) showed higher adjusted odds of association compared with other age groups. Eosinophil levels (39%) (aOR = 1.43, 95% CI: 1.19–1.74) and hemoglobin levels (24%) (aOR = 1.25, 95% CI: 1.11–1.53) were significantly associated with S. stercoralis infection. In contrast, low BMI (aOR = 1.15, 95% CI: 0.82–1.61) or the presence of diabetes mellitus (OR = 1.18, 95% CI: 0.83–1.69) was not associated with S. stercoralis seropositivity. Conclusions: Our study provides evidence for a very high baseline prevalence of S. stercoralis infection in South Indian communities and this information could provide realistic and concrete planning of control measures. Author summary: Strongyloidiasis is a neglected tropical disease caused by a parasite which is endemic to parts of Latin America, Asia and Africa. Due to its characteristic life cycle, individuals can carry the infection lifelong with few or no symptoms. With the aim of knowing the prevalence of S. stercoralis at the community level, a population in the rural area of South India was studied using serologic assessments. There was a seroprevalence of S. stercoralis infection in this study of 33%. This suggests a need to revise control programs in order to avoid continued transmission. [ABSTRACT FROM AUTHOR]

Background: The estimated five million snakebites per year are an important health problem that mainly affect rural poor populations. The global goal is to halve both mortality and morbidity from this neglected tropical disease by 2030. Data on snakebite morbidity are sparse and mainly obtained from hospital records. Methods: This community-based study was conducted among 379 rural residents with or without a history of snakebite in the Ashanti and Upper West regions of Ghana. All participants in the snakebite group were bitten at least six months before the day of survey. The World Health Organisation Disability Assessment Schedule 2.0 (WHODAS 2.0) and the Buruli Ulcer Functional Limitation Score were used to obtain patient-reported measure of functioning and disability. Long-term consequences were evaluated based on the severity of the symptoms at the time of the snakebite. Findings: The median (IQR) time since the snakebite was 8.0 (3.5–16.5) years. The relative risk of disability was 1.54 (95% CI, 1.17–2.03) in the snakebite group compared to the community controls. Among patients with clinical symptoms suggesting envenoming at the time of bite, 35% had mild/moderate disabilities compared to 20% in the control group. The disability domains mainly affected by snakebite envenoming were cognition level, mobility, life activities and participation in society. A combination of the severity of symptoms at the time of the bite, age, gender and region of residence most accurately predicted the odds of having functional limitations and disabilities. Conclusion: The burden of snakebite in the community includes long-term disabilities of mild to moderate severity, which need to be considered when designing appropriate public health interventions. Estimating the total burden of snakebite is complicated by geographic differences in types of snakes and their clinical manifestations. Author summary: Snakebite is a neglected tropical disease of public health concern. The majority of cases occur in tropical rural regions where access to adequate medical interventions is limited. The outcome of these bites may cause a range of manifestations, varying from local lesions to life threatening effects and death. Available estimates of snakebite burden are often based on severe complications such as death and amputations and are limited to health facility-based evaluations. We conducted a community-based study to identify the long-term consequences of snakebite by comparing participants with or without a history of snakebite in two regions in Ghana. A history of snakebite was associated with the chance of having disabilities. Combining community estimates of mild to moderate complications with data on severe complications from the health system level provides a more comprehensive overview of the overall snakebite burden. The incorporation of mental health and rehabilitation interventions into integrated neglected tropical diseases (NTD) programmes can reduce the risk of disabilities and improve the wellbeing of snakebite and other NTD patients. [ABSTRACT FROM AUTHOR]

Background: Schistosomiasis is one of the widely distributed neglected tropical diseases. It is a serious public health problem in sub-Saharan Africa. The disease is highly prevalent and widely distributed in Ethiopia due to suitable environmental factors and human activities. The prevalence and infection intensity varied from locality to locality in the country. This study aimed to assess the prevalence and intensity of S. mansoni infection and associated risk factors among schoolchildren around Lake Tana. Methods: A school-based cross-sectional study was conducted among 710 schoolchildren from February to April 2021 in eight selected primary schools around Lake Tana. A questionnaire was used to collect data on socio-demographic information and potential risk factors of S. mansoni infection. After collecting socio-demographic information, students were requested to bring about 2grams of stool specimens for parasitological examination. The collected stool samples were processed using a single Kato-Katz and Ritchie's concentration techniques. The data were analyzed using SPSS software version 23 and factors with a p-value < 0.05 were considered as statistically significant. Results: The overall prevalence of S. mansoni was 34.9% (95% CI: 31.4–38.7) among schoolchildren in the study area. The eggs per gram (EPG) of stool ranged from 24 to 1659 with arithmetic and geometric mean values of 138.1 EPG and 85.1 EPG, respectively. The majority of S. mansoni infections (61.4%) were classified as low infection intensity. Among the different determinant factors being male (AOR = 1.74; 95%CI = 1.233–2.457; P-value = 0.002), bathing habits (AOR = 1.494; 95%CI = 1.013–2.199; P-value = 0.043) and students attending at Qunzela primary school (AOR = 10.545; 95%CI = 3.264–34.067; P-value = 0.001), Alabo primary school (AOR = 3.386; 95%CI = 1.084–10.572; P-value = 0.036) were significantly associated with S. mansoni infection. Conclusion: This study revealed that more than one-third of schoolchildren were infected by S. mansoni in the study area. The majority of the infections were classified as low infection intensity. Being male, bathing habits and schools in which students attended were independent explanatory factors for S. mansoni infection. Therefore, integrated control strategies are needed to improve the health conditions of schoolchildren in the study area. Author summary: We conducted a school-based cross-sectional study to assess the prevalence and intensity of Schistosoma mansoni infection and associated risk factors. Stool samples were collected from 681 schoolchildren and processed using Kato-Katz and Ritchie's concentration techniques. Among those students, 238 (34.9%) were infected with S. mansoni. Kato-Katz and Ritchie's concentration detect 220 (92.4%) and 165 (69.3%) of the total positive cases, respectively. Most of the S. mansoni infections were categorized as low infection intensity based on egg per gram of stool. Among the potential risk factors assessed; being male, bathing habits in open water and schools in which students attended were independent predictors for S. mansoni infection. [ABSTRACT FROM AUTHOR]

Background: Chronic wounds pose a significant healthcare burden in low- and middle-income countries. Buruli ulcer (BU), caused by Mycobacterium ulcerans infection, causes wounds with high morbidity and financial burden. Although highly endemic in West and Central Africa, the presence of BU in Sierra Leone is not well described. This study aimed to confirm or exclude BU in suspected cases of chronic wounds presenting to Masanga Hospital, Sierra Leone. Methodology: Demographics, baseline clinical data, and quality of life scores were collected from patients with wounds suspected to be BU. Wound tissue samples were acquired and transported to the Swiss Tropical and Public Health Institute, Switzerland, for analysis to detect Mycobacterium ulcerans using qPCR, microscopic smear examination, and histopathology, as per World Health Organization (WHO) recommendations. Findings: Twenty-one participants with wounds suspected to be BU were enrolled over 4-weeks (Feb-March 2019). Participants were predominantly young working males (62% male, 38% female, mean 35yrs, 90% employed in an occupation or as a student) with large, single, ulcerating wounds (mean diameter 9.4cm, 86% single wound) exclusively of the lower limbs (60% foot, 40% lower leg) present for a mean 15 months. The majority reported frequent exposure to water outdoors (76%). Self-reports of over-the-counter antibiotic use prior to presentation was high (81%), as was history of trauma (38%) and surgical interventions prior to enrolment (48%). Regarding laboratory investigation, all samples were negative for BU by microscopy, histopathology, and qPCR. Histopathology analysis revealed heavy bacterial load in many of the samples. The study had excellent participant recruitment, however follow-up proved difficult. Conclusions: BU was not confirmed as a cause of chronic ulceration in our cohort of suspected cases, as judged by laboratory analysis according to WHO standards. This does not exclude the presence of BU in the region, and the definitive cause of these treatment-resistance chronic wounds is uncertain. Author summary: Chronic wounds constitute a significant surgical burden to low- and middle-income countries; however, their aetiology often remains poorly understood. This study improves our understanding of wound aetiology through tissue analysis of chronic leg wounds suspected to be caused by Buruli ulcer (BU). BU is a neglected tropical disease caused by infection with Mycobacterium ulcerans, and remains severely under-researched. There is a lack of testing facilities in regions surrounding endemic countries which makes prevalence difficult to determine, with a particular paucity of data from Sierra Leone (SL). This study identified twenty-one patients with wounds suspected to be caused by BU who presented to Masanga Hospital (Tonkonili District, Sierra Leone) between February and March 2019. Tissue samples were acquired from the wounds and transported to a European tropical health laboratory for analysis. Significant bacterial loads were demonstrated in the samples. However, the gold-standard molecular tests recommended by World Health Organisation (WHO) revealed no cases of BU. These results suggest that BU is not a major cause of chronic wounds in the Northern Province of Sierra Leone. Our conclusions cannot necessarily be generalised to other regions of Sierra Leone, therefore further studies in other geographical districts are required. [ABSTRACT FROM AUTHOR]

Mycobacterium ulcerans is the causative agent of Buruli ulcer, a rare but chronic debilitating skin and soft tissue disease found predominantly in West Africa and Southeast Australia. While a moderate body of research has examined the distribution of M. ulcerans, the specific route(s) of transmission of this bacterium remain unknown, hindering control efforts. M. ulcerans is considered an environmental pathogen given it is associated with lentic ecosystems and human-to-human spread is negligible. However, the pathogen is also carried by various mammals and invertebrates, which may serve as key reservoirs and mechanical vectors, respectively. Here, we examine and review recent evidence from these endemic regions on potential transmission pathways, noting differences in findings between Africa and Australia, and summarising the risk and protective factors associated with Buruli ulcer transmission. We also discuss evidence suggesting that environmental disturbance and human population changes precede outbreaks. We note five key research priorities, including adoption of One Health frameworks, to resolve transmission pathways and inform control strategies to reduce the spread of Buruli ulcer. Author summary: Buruli ulcer is a debilitating skin and soft tissue disease characterised by large ulcerative wounds that are treated with antibiotics or with adjunctive surgery for advanced cases. Found predominantly in West Africa and Southeast Australia, the causative agent is the environmental bacterial pathogen Mycobacterium ulcerans. Lack of understanding of transmission pathways, combined with the absence of a vaccine, has hindered efforts to control the spread of M. ulcerans. Here, in order to identify probable transmission pathways and inform future studies, we review literature linking M. ulcerans to environmental reservoirs, mammalian hosts, and potential invertebrate vectors. We also summarise factors and behaviours that reduce the risk of developing Buruli ulcer, to inform effective prevention strategies and further shed light on transmission pathways. [ABSTRACT FROM AUTHOR]

Chagas disease (CD) is a human disease caused by Trypanosoma cruzi. Whilst endemic in Latin America, the disease is spread around the world due to migration flows, being estimated that 8 million people are infected worldwide and over 10,000 people die yearly of complications linked to CD. Current chemotherapeutics is restricted to only two drugs, i.e. benznidazole (BNZ) and nifurtimox (NIF), both being nitroaromatic compounds sharing mechanism of action and exerting suboptimal efficacy and serious adverse effects. Recent clinical trials conducted to reposition antifungal azoles have turned out disappointing due to poor efficacy outcomes despite their promising preclinical profile. This apparent lack of translation from bench models to the clinic raises the question of whether we are using the right in vitro tools for compound selection. We propose that speed of action and cidality, rather than potency, are properties that can differentiate those compounds with better prospect of success to show efficacy in animal models of CD. Here we investigate the use of in vitro assays looking at the kinetics of parasite kill as a valuable surrogate to tell apart slow- (i.e. azoles targeting CYP51) and fast-acting (i.e. nitroaromatic) compounds. Data analysis and experimental design have been optimised to make it amenable for high-throughput compound profiling. Automated data reduction of experimental kinetic points to tabulated curve descriptors in conjunction with PCA, k-means and hierarchical clustering provide drug discoverers with a roadmap to guide navigation from hit qualification of a screening campaign to compound optimisation programs and assessment of combo therapy potential. As an example, we have studied compounds belonging to the GSK Chagas Box stemmed from the HTS campaign run against the full GSK 1.8 million compounds collection [1]. Author summary: One of the challenges in early drug discovery of small molecules is the improvement of the poor success rate in the translation from in vitro biological profile into efficacy in disease models, and ultimately in the clinic. Reductionist in vitro models on the bench may not properly recapitulate disease biology, thus overlooking critical properties of candidate compounds. Chagas Disease is a neglected tropical disease caused by Trypanosoma cruzi, a protozoan parasite with a complex life cycle. Despite the promising prospect based on in vitro and in vivo preclinical studies, efforts to reposition antifungal azoles turned out to be disappointing in clinical trials, with treatment failure in Chagas patients. This raises the question of whether we are using the right preclinical tools for decision-making about moving compounds forward for the treatment of this disease. We hypothesise that in vitro potency and efficacy values alone might be distorting the translational power of preclinical compounds, and we propose the use of rate-of-kill (RoK) assays in high-throughput mode. Herewith we disclose a simple, systematic, and automated methodology of analysis of the otherwise complex kinetic patterns, which provides drug discoverers with a navigation guide along a compound optimisation program or prioritisation of best exemplars across different chemical series. [ABSTRACT FROM AUTHOR]

This article explores the lack of scientific interest in neglected tropical diseases (NTDs) and the challenges in accurately measuring their impact. NTDs primarily affect people in the poorest countries and are not economically lucrative for drug development. The World Health Organization uses the disability-adjusted life year (DALY) statistic to assess the morbidity and mortality of diseases, but it is argued that DALYs for NTDs are consistently underestimated. Despite potential improvements in calculating DALYs, governments and policymakers still rely on them to prioritize prevention and healthcare efforts. The article highlights the neglect of NTDs by the scientific community, with NTDs receiving significantly less research attention compared to non-NTD conditions with similar DALYs. However, there are signs of increased interest in NTDs in recent years, which may help bridge the research gap. The authors stress the importance of more research on NTDs to gain a more accurate understanding of their burden and address the lack of attention they currently receive. [Extracted from the article]

Gambiense Human African Trypanosomiasis (g-HAT) is a neglected tropical disease caused by trypanosomes transmitted by tsetse flies. 70% of cases in 2019 (604/863) occurred in the Democratic Republic of Congo (DRC). The national programme for g-HAT elimination in DRC includes a large-scale deployment of Tiny Targets which attract and kill tsetse. This intervention is directed by vector-control specialists with small teams, moving in canoes, deploying Tiny Targets along riverbanks where tsetse concentrate. While the targets are deployed in communal areas, and the method is cheap and easy-to-use, local people have little involvement. This study aimed to evaluate if a community-led vector control programme was feasible in the context of DRC's g-HAT elimination programme. In 2017, a community-led intervention was implemented in three villages in the Kwilu province of DRC. This intervention was evaluated through an Action Research with qualitative data collected through 21 focus group discussions and 289 hours of observation. Also the geographical location and quality of each Tiny Targets were collected (total number deployed = 2429). This research revealed that community-based approach largely worked: people were motivated and proactive, showed a good application of the acquired knowledge resulting in an effective deployment of Tiny Targets. In addition, our study provided evidence that acceptability of the targets by the community can improve deployment quality by reducing target loss and damage. The approach was feasible in places where canoe-based teams could not reach. Against these advantages, a community-based approach was time-consuming and had to adapt to the seasonal and daily rhythms of the community. A community-based approach for tsetse control is technically feasible and recommended but limits to the speed and scale of the approach restraints its application as a standalone strategy in a large-scale national programme aiming to eliminate g-HAT in a short timeframe. Author summary: Sleeping sickness (Human African Trypanosomiasis, HAT) is a neglected disease caused by Trypanosoma brucei gambiense or T.b.rhodesiense both transmitted by tsetse flies. Currently 70% of the global cases of Gambiense HAT (g-HAT) occur in Democratic Republic of Congo (DRC). Over the last 20 years, a national programme of screening and treating humans has driven down the number of cases of g-HAT from >30,000 to <2,000 cases/year. However, epidemiological models suggest that the complete elimination of g-HAT across DRC requires the addition of vector control. Accordingly, in 2016 large-scale deployment of Tiny Targets which attract and kill tsetse, was adopted as part of the national strategy to eliminate g-HAT. Targets are deployed by canoe-based teams directed and managed by vector control specialists. Using an Action-Research approach and qualitative methods, we assessed whether local communities in three villages could play a greater role. We found that Tiny Targets were well accepted by local people who deployed targets effectively, but the speed and scale of the deployment was limited by the underlying movement of local people and the rhythms of their life. We conclude that a community-based approach is feasible but not as a standalone large-scale programme in DRC. [ABSTRACT FROM AUTHOR]

Background: Cutaneous leishmaniasis is one of the most neglected tropical diseases increasing in its public health importance. In Ethiopia over 28 million people are living at risk of infection. Method: Institution based cross-sectional study was conducted at Borumeda Hospital from February to May 2019. A total 205 leishmaniasis suspected patients were included by systematic random sampling technique. Socio demographic characteristics were collected using pre-tested questionnaires. Parasitological investigation was done from skin slit sample by using Geimsa staining method. Species identification was done by PCR-RFLP. Data were entered in to EpiData version 3.1 and analyzed using SPSS version 20 software. P-value of ≤ 0.05 was considered as statistically significant. Result: A total of 205 participants consisting 59% male and 41% female included in this study. The mean age (±SD) of the study participants was 31.9 (±14.29). The overall prevalence of cutaneous leishmaniasis was 22.4% (46/205). The prevalence in males (13.7%) was higher than in females (8.8%). It was more prevalent in the age group 16-45years old (15.6%). Clinically, 60% of patients' hade single lesion with 1.55 average number of lesions. About 30.7% of patients' had indurated plaque type of lesion. Most of the lesions were found on head and face (59%). House near to farmland, presence of hyrax in the village and presence of other cutaneous leishmaniasis cases in the neighborhood were independent predicator of cutaneous leishmaniasis prevalence. L.aethopica was found to be the etiologic agent of cutaneous leishmaniasis in the study participants. Conclusion: The prevalence of cutaneous leishmaniasis was 22.4%, this alerts the need of intervention. It is statistically associated with house near to farm land, presence of other cutaneous leishmaniasis cases in the neighborhood and presence of hyrax in village. Head and face were the most common sites of lesion. Author summary: Cutaneous leishmaniasis (CL) is vector-born intracellular protozoan infection of human. It is the most common form of leishmaniasis. Cutaneous leishmaniasis imposes a major public health problem to human being. Cutaneous leishmaniasis is associated with a wide spectrum of clinical presentation like nodular, Papular, nodulo-Papular, diffuse induration, nodulo-ulcerative and indurated plaque. Its clinical manifestation usually begins with an erythematous papule seen at the site of inoculation, then papule enlarges and breaks, forming a painless ulcer with a well-demarcated raised border with different centimeters in diameter, finally this will end up with depressed scar after healing. The lesions usually occur in the face and exposed extremities. Even though CL is not fatal, it can lead to disfigurement and lifelong scar leading to social exclusion and stigmatization. The number of cases and epidemiological foci of CL in Ethiopia is increasing. Here we confirm endemicity of CL in Kutaber district. We also showed as CL is associated with the presence of hyrax, working in and near to farm land and the existence of CL lesion in the neighbor. [ABSTRACT FROM AUTHOR]

Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar pathologic conditions. They primarily target the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease, being endemic in specific locations within countries of the Americas, Asia, and Africa, while in Europe it is only rarely reported. The reason for a spatial inequality in the prevalence of leprosy in so-called endemic pockets within a country is still largely unexplained. A systematic review was conducted targeting leprosy transmission research data, using PubMed and Scopus as sources. Publications between January 1, 1945 and July 1, 2019 were included. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. The transmission of this disease is probably much more complicated than was thought before. In the Americas, the nine-banded armadillo (Dasypus novemcinctus) has been established as another natural host and reservoir of M. leprae. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. More recently, in red squirrels (Sciurus vulgaris) with leprosy-like lesions in the British Isles M. leprae and M. lepromatosis DNA was detected. This finding was unexpected, because leprosy is considered a disease of humans (with the exception of the armadillo), and because it was thought that leprosy (and M. leprae) had disappeared from the United Kingdom. Furthermore, animals can be affected by other leprosy-like diseases, caused by pathogens phylogenetically closely related to M. leprae. These mycobacteria have been proposed to be grouped as a M. leprae-complex. We argue that insights from the transmission and reservoirs of members of the M. leprae-complex might be relevant for leprosy research. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. A reduction in transmission cannot be expected to be accomplished by actions or interventions from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, to increase our understanding of the intricate picture of leprosy transmission, we propose a One Health transdisciplinary research approach. Author summary: Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) and the more recently discovered Mycobacterium lepromatosis (M. lepromatosis). The two leprosy bacilli cause similar stigmatizing pathologic conditions. M. leprae primarily targets the skin and the peripheral nervous system. Currently it is considered a Neglected Tropical Disease. The transmission pathways of M. leprae are not fully understood. Solid evidence exists of an increased risk for individuals living in close contact with leprosy patients, most likely through infectious aerosols, created by coughing and sneezing, but possibly also through direct contact. However, this systematic review underscores that human-to-human transmission is not the only way leprosy can be acquired. Anthroponotic and zoonotic transmission have both been proposed as modes of contracting the disease, based on data showing identical M. leprae strains shared between humans and armadillos. A better understanding of possible animal or environmental reservoirs is needed, because transmission from such reservoirs may partly explain the steady global incidence of leprosy despite effective and widespread multidrug therapy. Reducing transmission cannot be expected from the human healthcare domain alone, as the mechanisms involved are complex. Therefore, we propose a One Health transdisciplinary research approach. [ABSTRACT FROM AUTHOR]