Tropical Diseases Research Articles

A Mini-Review on Elisa-Based Diagnosis of Schistosomiasis.

Schistosomiasis is a neglected tropical parasitic disease caused by trematode worms of the genus schistosoma, which affects approximately 240 million people worldwide. the diagnosis of the disease can be performed by parasitological, molecular, and/or immunological methods, however, the development of new diagnostic methods still essential to guide policy decisions, monitor disease trends and assess the effectiveness of interventions. in this sense, the current work summarizes the findings of a systematic review regarding antigens applied in the enzyme-linked immunosorbent assay test, which were patented and published over the last ten years. the literature search strategy used medical subject heading (mesh) terms to define as descriptors. "schistosoma mansoni" was used in arrangement with the descriptors "immunoassay", "enzyme-linked immunosorbent assay", "elisa", and "antigens", using the "and" connector. the patent search was done using keywords, including diagnosis and schistosoma or schistosomiasis or schistosome. several databases were employed for the patent search, such as intellectual property national institute; european patent office; the united states patent and trademark office; patent scope, and google patents. forty-one articles were retrieved, of which only five met the eligibility criteria. seventeen patents were taken from the databases, and a brief description of the most relevant inventions is given here. schistosomiasis is considered the most important helminthic disease in worldwide. therefore, it is important to of searching for and develops diagnostic methods based on serology to reduce morbidity and mortality caused by the disease.

Epidemiological Trends of Dengue in One of the Western Hilly Areas of Himachal Pradesh.

Dengue is one of the neglected tropical diseases, with a wide spectrum of diseases, ranging from acute febrile illness dengue fever to life-threatening dengue hemorrhagic fever or dengue shock syndrome. In recent years, it has become a major public health concern in many nonendemic areas as well. A secondary data analysis of records available with district Integrated Disease Surveillance Programme cell was conducted to study distribution (time, place, and person) of dengue from 2017 to 2022 in Kangra, a sub-Himalayan district of Himachal Pradesh (HP). In the evaluated period (2017-2022), a total of 6008 cases suspected of dengue were tested and test positivity of 7% (441) with male gender predominance was found. Mean age of the diagnosed cases was 37.7 ± 16.8 years. A seasonal trend was observed starting from late August to November in all study years. Dengue is still a neglected disease, but it has shown its presence especially in this part of HP, indicating the need for better preparation and sensitization of vector-borne disease control program activities, especially in post-monsoon, to prevent future epidemics.

Therapeutic efficacy of candidate antischistosomal drugs in a murine model of schistosomiasis mansoni.

Schistosomiasis is a neglected tropical disease associated with considerable morbidity. Praziquantel (PZQ) is effective against adult schistosomes, yet, it has little effect on juvenile stages, and PZQ resistance is emerging. Adopting the drug repurposing strategy as well as assuming enhancing the efficacy and lessening the doses and side effects, the present study aimed to investigate the in vivo therapeutic efficacy of the widely used antiarrhythmic, amiodarone, and diuretic, spironolactone, and combinations of them compared to PZQ. Mice were infected by Schistosoma mansoni "S. mansoni" cercariae (Egyptian strain), then they were divided into two major groups: Early- [3weeks post-infection (wpi)] and late- [6 wpi] treated. Each group was subdivided into seven subgroups: positive control, PZQ, amiodarone, spironolactone, PZQ combined with amiodarone, PZQ combined with spironolactone, and amiodarone combined with spironolactone-treated groups. Among the early-treated groups, spironolactone had the best therapeutic impact indicated by a 69.4% reduction of total worm burden (TWB), 38.6% and 48.4% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 49%. Whereas, among the late-treated groups, amiodarone combined with PZQ was superior to PZQ alone evidenced by 96.1% reduction of TWB with the total disappearance of female and copula in the liver and intestine, 53.1% and 84.9% reduction of liver and intestine egg load, and a significant reduction of liver granuloma number by 67.6%. Comparatively, spironolactone was superior to PZQ and amiodarone in the early treatment phase targeting immature stages, while amiodarone had a more potent effect when combined with PZQ in the late treatment phase targeting mature schistosomes.

Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.

Trypanosomiasis, caused by protozoan parasites of the Trypanosoma genus, remains a significant health burden in several regions of the world. Cysteine proteases play a crucial role in the pathogenesis of Trypanosoma parasites and have emerged as potential therapeutic targets for the development of novel antiparasitic drugs. This review article aims to provide a comprehensive overview of the role of cysteine proteases in trypanosomiasis and their potential as therapeutic targets. We discuss the biological significance of cysteine proteases in Trypanosoma parasites and their involvement in essential processes, such as host immune evasion, cell invasion, and nutrient acquisition. A comprehensive literature search was conducted to identify relevant studies and research articles on the role of cysteine proteases and their inhibitors in trypanosomiasis. The selected studies were critically analyzed to extract key findings and provide a comprehensive overview of the topic. Cysteine proteases, such as cruzipain, TbCatB and TbCatL, have been identified as promising therapeutic targets due to their essential roles in Trypanosoma pathogenesis. Several small molecule inhibitors and peptidomimetics have been developed to target these proteases and have shown promising activity in preclinical studies. Targeting cysteine proteases and their inhibitors holds great potential for the development of novel antiparasitic drugs against trypanosomiasis. The identification of potent and selective cysteine protease inhibitors could significantly contribute to the combat against trypanosomiasis and improve the prospects for the treatment of this neglected tropical disease.

Host guanylate binding proteins participate in parasite control during Leishmania infection

Abstract Cutaneous leishmaniasis (CL) is a debilitating neglected tropical disease causing lesions ranging from self-healing to permanent disfigurations. A predominant Th1 response relying on IFNγ production leads to parasite control during CL. Although IFNγ is mainly responsible for activating macrophages to produce NO leading to parasite control, IFNγ can activate other downstream pathways involved in cell autonomous immunity including the activation of guanylate binding proteins (GBPs), a class of interferon-inducible GTPases. GBPs play a role in host defense against some intracellular pathogens, but minimal work has been done to understand the role of GBPs during Leishmania infection. Utilizing RNA-Seq we found several GBPs are upregulated in lesions during L. major infection in mice. Single-cell RNA-Sequencing revealed macrophages as the main cell type expressing Gbps, including Gbp2, Gbp5, and Gbp7 during infection. Additionally, Gbp expression was not unique to L. major infection; both L. amazonensis and L. mexicana infection in vivo resulted in elevated Gbp expression. Preliminary in vitro experiments show macrophages from GBPChr3 KO mice harbor increased numbers of parasites compared to control macrophages with and without IFNγ treatment. Consistent with in vitro findings, infected GBPChr3 KO mice exhibit increased pathology compared to control mice. Together these data suggest GBPs participate in the defense against Leishmania parasites.

Noma finally recognised as a neglected tropical disease.

In December 2023, after decades of tireless advocacy from stakeholders and partners, the World Health Organization (WHO) gave noma the long overdue recognition as a neglected tropical disease. The significance of this official recognition cannot be overstated, and it is hoped this will serve as a turning point in our battle against this devastating disease.

Apparent absence of Trypanosoma cruzi in Mexican free-tailed bats (Tadarida brasiliensis) from Texas, USA

The Mexican free-tailed bat (Tadarida brasiliensis) is one of the most abundant mammals in North America. Mexican free-tailed bats have a wide geographic range stretching from northern South America to the western United States. Bats are theorized to be the original hosts for Trypanosoma cruzi —the causative agent of Chagas disease— and can serve as a source of infection to triatomine insect vectors that feed upon them. Chagas disease is a neglected tropical disease across the Americas where triatomines are present, including the southern United States, where Texas reports this highest number of locally-acquired human cases. To learn more about the role of bats in the ecology of Chagas disease in Texas, we surveyed a colony of Mexican free-tailed bats from Brazos County, Texas, for T. cruzi using carcasses salvaged after an extreme weather event. A total of 283 Mexican free-tailed bats collected in February 2021 were dissected and DNA from the hearts and kidneys was used for T. cruzi detection via qPCR. None of the bat hearts or kidneys tested positive for T. cruzi; this sample size affords 95% confidence that the true prevalence of T. cruzi in this population does not exceed 1%. Future sampling of multiple bat species as well as migrant and resident colonies of Mexican free-tailed bats across different times of the year over a broader geographic range would be useful in learning more about the role of bats in the ecology of Chagas disease in Texas.

An overview of qualitative and quantitative platelet abnormalities in schistosomiasis.

Schistosomiasis is a neglected tropical disease referring to the infection with blood parasitic trematodes of the genus Schistosoma. It impacts millions of people worldwide, primarily in low-to-middle-income countries. Patients infected with schistosomiasis often exhibit a distinct hematological profile, including anemia, eosinophilia, thrombocytopenia, and coagulopathy. Platelets, essential components of the hemostatic system, play a crucial role in the pathogenesis of schistosomiasis. Schistosomes secrete serine proteases and express ectoenzymes, such as calpain protease, alkaline phosphatase (SmAP), phosphodiesterase (SmNPP5), ATP diphosphohydrolase (SmATPDase1), serine protease Sk1, SmSP2, and Sm22.6, which can interfere with platelet normal functioning. This report provides comprehensive, up-to-date information on platelet abnormalities observed in patients with schistosomiasis, highlighting their importance in the disease progression and complications. It delves into the interactions between platelets and schistosomes, including the impact of platelet dysfunction on hemostasis and immune responses, immune-mediated platelet destruction, and the potential mechanisms by which schistosome tegumental ectoenzymes affect platelets. Furthermore, the report clarifies the relationship between platelet abnormalities and clinical manifestations such as thrombocytopenia, coagulation disorders, and the emergence of portal hypertension and gastrointestinal bleeding. Understanding the complex interplay between platelets and schistosomes is crucial for improving patient management and outcomes in schistosomiasis, particularly for those with platelet alterations. This knowledge contributes to improved diagnostic methods, innovative treatment strategies, and global efforts to control and eliminate schistosomiasis.

Drug Discovery Efforts to Identify Novel Treatments for Neglected Tropical Diseases - Cysteine Protease Inhibitors.

Neglected tropical diseases are a severe burden for mankind, affecting an increasing number of people around the globe. Many of those diseases are caused by protozoan parasites in which cysteine proteases play a key role in the parasite's pathogenesis. In this review article, we summarize the drug discovery efforts of the research community from 2017 - 2022 with a special focus on the optimization of small molecule cysteine protease inhibitors in terms of selectivity profiles or drug-like properties as well as in vivo studies. The cysteine proteases evaluated by this methodology include Cathepsin B1 from Schistosoma mansoni, papain, cruzain, falcipain, and rhodesain. Exhaustive literature searches were performed using the keywords "Cysteine Proteases" and "Neglected Tropical Diseases" including the years 2017 - 2022. Overall, approximately 3'000 scientific papers were retrieved, which were filtered using specific keywords enabling the focus on drug discovery efforts. Potent and selective cysteine protease inhibitors to treat neglected tropical diseases were identified, which progressed to pharmacokinetic and in vivo efficacy studies. As far as the authors are aware of, none of those inhibitors reached the stage of active clinical development. Either the inhibitor's potency or pharmacokinetic properties or safety profile or a combination thereof prevented further development of the compounds. More efforts with particular emphasis on optimizing pharmacokinetic and safety properties are needed, potentially by collaborations of academic and industrial research groups with complementary expertise. Furthermore, new warheads reacting with the catalytic cysteine should be exploited to advance the research field in order to make a meaningful impact on society.

Unveiling the anti-echinococcal efficacy of amide-based compounds: An in-silico and in-vitro study

Cystic echinococcosis (CE) is a significant global public health concern, particularly in regions where livestock rearing is prevalent. Despite its impact on morbidity and mortality, CE has received insufficient attention compared to other neglected tropical diseases. The complexities in CE management arise from challenges in early detection, effective treatment, and parasite eradication. The present study addresses this gap by exploring innovative therapeutic approaches using amide-based compounds. In recent years, computational approaches and in-vitro studies have become prominent in neglected tropical disease drug discovery. Leveraging insights from previous studies on amide-based compounds with anti-parasitic potential, this study systematically designed, synthesized, and characterized a library of 30 amide compounds. The research integrated in-silico screening, molecular docking, and in-vitro experimentation to assess the anti-echinococcal potential of these compounds. The study identified five promising amide compounds, namely 3,5-dinitro-N-p-tolylbenzamide, N-p-tolyl-1-naphthamide, N-p-tolyl-4-(trifluoromethoxy)benzamide, 4-pentyl-N-p-tolylbenzamide, and 2,3,4,5,6-pentafluoro-N-p-tolylbenzamide, based on their docking scores. These compounds were synthesized and characterized through various spectroscopic techniques, confirming their structural integrity. The in-vitro cytotoxicity assay on HepG2 cell lines revealed varying degrees of cytotoxicity for the synthesized compounds. Notably, 4-pentyl-N-p-tolylbenzamide demonstrated the least cytotoxicity. Subsequent scolicidal activity assessments on E. granulosus protoscoleces demonstrated the potent protoscolicidal activity of N-p-tolyl-1-naphthamide, indicating its potential as an effective anti-echinococcal agent. Overall, this study presents a comprehensive exploration of amide-based compounds as potential therapeutic agents against CE. The findings contribute to the development of innovative strategies for CE treatment, addressing the urgent need for effective and safe drugs in managing this neglected tropical disease.

Community Conversations: A Tool in Improving Health Outcomes and Reducing the Burden of Visceral Leishmaniasis (Kala-azar) in Isiolo County, Kenya

Visceral Leishmaniasis (Kala-azar) is a neglected tropical disease (NTD) caused by Leishmania species that affects human. Transmission is through the bite of Phlebotomus sandflies. Globally, WHO ranks Kala-azar as the second largest parasitic killer after Malaria. The disease poses a threat to more than a billion people on almost every continent. Approximately 90% of Kala-azar global burden is found in Africa. Major endemicity is documented in Eastern Africa (Kenya, South Sudan, Sudan, Ethiopia, and Somalia). Accurate burden of the disease in Kenya is unknown attributable to inadequate information on disease prevalence, diagnostic challenges, and spatial distribution. Additionally, morbidity and mortality levels from the disease in the Country are unknown ascribable to a low index of suspicion by healthcare workers, diagnostic challenges, and case management. An example of diagnostic challenges is a reported outbreak of ‘unknown disease’ akin to Kala-azar in Marsabit County in May 2023 where nine people were confirmed dead and over 80 hospitalized. This study aimed to analyze community’s prioritization of causes of Kalaazar as well as community awareness of disease prevention and control. Quantitative data were collected using Participatory Epidemiology methods in purposively selected study villages. Qualitative data were collected through semi-structured interviews. Study findings indicated that 97.2% of respondents had heard about Kala-azar. Despite the awareness, a broad gap between knowledge and practice of prevention and control strategies of the disease was evident. Kala-azar was associated with human behaviour like preferences for traditional and alternative treatment approaches (45.2%), evening outdoor practices before going to bed (99.6%), sleeping outdoors (60.1%), occasional bed nets use (69.2%), and availability of domestic animals and wild animals within house yards (54.6%). Cultural beliefs and practices were noted to play a key role in augmenting the disease burden, where most cases had burn scars from traditional healers’ therapeutic burns. As a consequence, they sought medical help after onset of complications, which ranged from increased severity to fatalities. Community engagement was minimal in prevention and control. In this participatory research, we propose behaviour change communication activities for the elimination of Kala-azar as a public health problem. This article serves as a base for future studies aimed at giving voice to communities while enhancing their understanding of causes of diseases, the possibility of enhanced early diagnostic techniques, and options for prevention, control, and surveillance which in turn is translated to action.

Dermonecrosis caused by a spitting cobra snakebite results from toxin potentiation and is prevented by the repurposed drug varespladib

Snakebite envenoming is a neglected tropical disease that causes substantial mortality and morbidity globally. The venom of African spitting cobras often causes permanent injury via tissue-destructive dermonecrosis at the bite site, which is ineffectively treated by current antivenoms. To address this therapeutic gap, we identified the etiological venom toxins in Naja nigricollis venom responsible for causing local dermonecrosis. While cytotoxic three-finger toxins were primarily responsible for causing spitting cobra cytotoxicity in cultured keratinocytes, their potentiation by phospholipases A2 toxins was essential to cause dermonecrosis in vivo. This evidence of probable toxin synergism suggests that a single toxin-family inhibiting drug could prevent local envenoming. We show that local injection with the repurposed phospholipase A2-inhibiting drug varespladib significantly prevents local tissue damage caused by several spitting cobra venoms in murine models of envenoming. Our findings therefore provide a therapeutic strategy that may effectively prevent life-changing morbidity caused by snakebite in rural Africa.

Evaluating the World Health Organization's SkinNTDs App as a Training Tool for Skin Neglected Tropical Diseases in Ghana and Kenya: Cross-Sectional Study.

Neglected tropical diseases (NTDs) affect over 1.5 billion people worldwide, primarily impoverished populations in low- and middle-income countries. Skin NTDs, a significant subgroup, manifest primarily as skin lesions and require extensive diagnosis and treatment resources, including trained personnel and financial backing. The World Health Organization has introduced the SkinNTDs app, a mobile health tool designed to train and be used as a decision support tool for frontline health care workers. As most digital health guidelines prioritize the thorough evaluation of mobile health interventions, it is essential to conduct a rigorous and validated assessment of this app. This study aims to assess the usability and user experience of World Health Organization SkinNTDs app (version 3) as a capacity-building tool and decision-support tool for frontline health care workers. A cross-sectional study was conducted in Ghana and Kenya. Frontline health care workers dealing with skin NTDs were recruited through snowball sampling. They used the SkinNTDs app for at least 5 days before completing a web-based survey containing demographic variables and the user version of the Mobile Application Rating Scale (uMARS), a validated scale for assessing health apps. A smaller group of participants took part in semistructured interviews and one focus group. Quantitative data were analyzed using SPSS with a 95% CI and P≤.05 for statistical significance and qualitative data using ATLAS.ti to identify attributes, cluster themes, and code various dimensions that were explored. Overall, 60 participants participated in the quantitative phase and 17 in the qualitative phase. The SkinNTDs app scored highly on the uMARS questionnaire, with an app quality mean score of 4.02 (SD 0.47) of 5, a subjective quality score of 3.82 (SD 0.61) of 5, and a perceived impact of 4.47 (SD 0.56) of 5. There was no significant association between the app quality mean score and any of the categorical variables examined, according to Pearson correlation analysis; app quality mean score vs age (P=.37), sex (P=.70), type of health worker (P=.35), country (P=.94), work context (P=.17), frequency of dealing with skin NTDs (P=.09), and dermatology experience (P=.63). Qualitative results echoed the quantitative outcomes, highlighting the ease of use, the offline functionality, and the potential utility for frontline health care workers in remote and resource-constrained settings. Areas for improvement were identified, such as enhancing the signs and symptoms section. The SkinNTDs app demonstrates notable usability and user-friendliness. The results indicate that the app could play a crucial role in improving capacity building of frontline health care workers dealing with skin NTDs. It could be improved in the future by including new features such as epidemiological context and direct contact with experts. The possibility of using the app as a diagnostic tool should be considered. RR2-10.2196/39393.

Severity Assessment and IL-5 Evaluation after Immunotherapy in Atopic Dermatitis Mice

Background: The effectiveness of immunotherapy in atopic dermatitis (AD) has been debated for many years. Immunotherapy suppresses Th2 cytokines, such as IL-5, which play a crucial role in the pathogenesis of AD. This study assessed the effect of immunotherapy on severity and IL-5 expression in AD mice.Methods: Male BALB/c mice were separated into three groups. The mice were sensitized with Dermatophagoides pteronyssinus allergen for seven days, except the mice in control group. The house dust mite (HDM) immunotherapy was injected subcutaneously every 3 days for 1.5 months with increasing doses (0.1, 1, 10, 100 μg in 100 μL PBS) every 4 injections. The mice in AD model and control group received placebo injections. Following immunotherapy, the mice were exposed to HDM allergen patch two times with 2 weeks interval in between. The mice were evaluated for severity score as the clinical marker and IL-5 expression with semiquantitative method as the histological marker.Results: The evaluation of severity score from two independent researchers showed a substantial agreement (Cohen’s kappa 0.613, p <0.001). The severity score of the immunotherapy group was significantly lower than the AD model group, while both immunotherapy and AD model group had significantly higher score than control group. IL-5 expression in the immunotherapy group was lower than the AD model group and slightly higher than control group. The mean difference between groups was not significant.Conclusion: The severity of skin lesion and IL-5 expression in AD mice receiving immunotherapy were lower than AD model group.Keywords: Atopic dermatitis; BALB/c mice; House dust mites; IL-5, Skin severity score; Tropical disease

A comprehensive study of prophage islands in Burkholderia pseudomallei complex

IntroductionBacteriophages are known as predators of bacteria and key biological factors influencing genetic recombination through phage transduction in bacteria. Phage transduction is known as one of the most common genetic recombination events found in Burkholderia pseudomallei, a diverse bacterial species and the causative agent of a deadly tropical disease melioidosis. The main objective of this study was to catalog prophages or prophage islands that are common in B. pseudomallei genomes.MethodsVarious bioinformatic tools were used to identify prophages in 106 complete B. pseudomallei genomes, and complete and incomplete genomes in other species within the B. pseudomallei Complex (BPC). Temperate phages were spontaneously induced from selected B. pseudomallei and B. thailandensis strains, and further characterized by transmission electron microscopy and whole genome sequencing.ResultsNine phage integration hotspots were identified in B. pseudomallei pan-genomes, eight of which were associated with tRNA gene-mediated site-specific recombination (tRNA-SSR) events. These genetic events occurred at various tRNA-genes including tRNA- Phenylalanine (anticodon GAA), - Methionine (CAU), - Proline (UGG), - Arginine (UCU), - Cysteine (GCA), - Arginine (CCG), - Serine (GGA), and – Selenocysteine (UCA) genes. Some of these events were also found in other related species within the B. pseudomallei Complex (BPC). We have demonstrated that lysogenic phages from select BPC strains could use B. pseudomallei strain Bp82 or 576mn as a host. These phages were classified into one of the two major groups, myoviruses or siphoviruses, based on their morphology and genomic composition.DiscussionWe have demonstrated that most B. pseudomallei strains are lysogenic, many containing at least one functional prophage in their genomes. Further investigation of the interactions between B. pseudomallei, bacteriophages, and other environmental and biological factors would provide a bigger picture of genomic diversity, potentially influence on survival of B. pseudomallei in the environment and its pathogenic specialization in hosts.

Snake Bite Health Education on Community and Pre Hospital Handling

Background: Snake bites are one of the most common health problems in tropical and subtropical countries. WHO has included snakebite in the list of neglected tropical diseases. The majority of Indonesians work in agriculture and are at high risk of being bitten by snakes. Pre-hospital handling of snakebites according to WHO recommendations by immobilizing using bandages and splints on the part affected by the snakebite then immediately refer to the nearest health service center.Purpose: This study aims to determine the effect of snakebite health education on people's knowledge and behavior about handling snakebites before going to the hospital in Wungu Village, Wungu District, Madiun Regency.Method: The research design is quasi-experimental with a one-group pre-test and post-test design. The population is the entire community of Wungu Village, Wungu District, Madiun Regency with a sample of 100 respondents by random sampling. Collecting data using a questionnaire analyzed with the Wilcoxon test.Results: The results of the research on community knowledge and behavior before being given health education were 44 people (88%) less knowledgeable and 39 people (78%), after being given health education, more than half of the respondents had good knowledge, namely 26 people (52% ) and many changes from good behavior as many as 29 people (58%).Conclusion: There is an effect of health education on people's knowledge and behavior about handling snake bites before going to the hospital with p = 0.000 <0.05.

Efficacy of monthly treatment with oral fluralaner (Bravecto® 1-Month) against Tunga penetrans in dogs in Brazil: a randomized, double-blind, controlled field study.

Tungiasis is a neglected tropical disease caused by the adult female sand flea (Tunga penetrans). Dogs are considered important reservoirs of T.penetrans in Brazil. The aim of this study was to determine the monthly insecticidal efficacy of a single oral administration of fluralaner at a dose of 10-18mg/kg (Bravecto® 1-Month, also registered as Defenza® in some countries; MSD Animal Health) in dogs naturally infested with T. penetrans. This clinical trial was conducted in a rural community located in Ilhéus, Bahia, Brazil. A total of 64 dogs were selected and distributed in a completely randomized design between a treated group (TG) that received one single dose of Bravecto® 1-Month (Defenza®) and a negative control group (CG) that received no treatment. Each group was composed of 32 dogs. The evaluations took place on days 0, 7 ± 2, 14 ± 2, 21 ± 2, 28 ± 2, 35 ± 2, and 42 ± 2 post treatment, in which the dogs were inspected to evaluate the infestation stage and classify lesions associated with tungiasis. The primary efficacy was determined from the percentage of treated dogs free of fleas (stage II and III lesions) after administration of the formulation at each evaluation time. Secondary efficacy was based on the number of active lesions (stages II and III) in each group at each evaluation time. The clinical condition of the animals was defined based on the Severity Score for Acute Dog Tungiasis (SCADT), which is related to the number and severity of lesions. The primary efficacy of the product was greater than 95.0% from days 7 to 21 and reached 100.0% between days 28 and 42, with a significant association between treatment and infestation decline (P < 0.025) between days 7 and 42. Secondary drug efficacy was greater than 99.9% from days 7 to 21, reaching 100.0% between days 28 and 42 (P < 0.05). The treated dogs also scored lower on the SCADT than the control animals did during the entire clinical evaluation period (P < 0.05). A single administration of Bravecto® 1-Month (Defenza®) was effective in eliminating Tunga penetrans infestations, as well as in preventing parasitism for at least 42days after treatment.

Stigma experiences, effects and coping among individuals affected by Buruli ulcer and yaws in Ghana.

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. 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. 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.

Detection of Asymptomatic Sickle Cell Hemoglobin Carriers and Fetal Hemoglobin Regulating Genetic Variants in African Descendants from Oaxaca, Mexico.

Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the β-globin mutation detection assay (β-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

Comparison of 2 Days versus 5 Days of Octreotide after Endoscopic Therapy in Preventing Early Esophageal Varices Rebleed: A Randomized Controlled Study

In esophageal varices bleeding, following the initial endoscopic hemostasis, it is recommended to administer vasoactive medications for a period of 2-5 days in order to avoid early rebleeding. Octreotide is the preferred vasoactive medication for treating variceal bleeding due to its favorable safety profile. This study aimed to assess the effectiveness of a 2-day octreotide infusion against a 5-day octreotide infusion following endoscopic intervention in avoiding early rebleeding of esophageal varices in individuals with cirrhosis. This study was a prospective, parallel, randomised controlled experiment conducted on a cohort of 184 subjects who were recruited from the endoscopy unit of the Tropical Medicine and Infectious Diseases Department at Tanta University Hospital in Egypt. The five days rate of rebleeding was 16.85% in the 2-days group against 15.91% in the 5- days group without significant difference (P= 0.865). In cirrhotic individuals with bleeding esophageal varices, a 2-day regimen of octreotide is equally efficacious as a 5-day regimen in avoiding rebleeding over a 5-day period, following successful control of bleeding with endoscopic intervention.