Frontiers in tropical diseases最新文献

{"title":"An assessment of a GMP schistosomiasis vaccine (SchistoShield^®).","authors":"Jiho Kim, Jenn Davis, Jinhee Lee, Sang-Nae Cho, Kiyoung Yang, Jaekyoon Yang, Sungmin Bae, Joohee Son, Boyoung Kim, Dale Whittington, Afzal A Siddiqui, Darrick Carter, Sean A Gray","doi":"10.3389/fitd.2024.1404943","DOIUrl":"10.3389/fitd.2024.1404943","url":null,"abstract":"<p><strong>Introduction: </strong>Schistosomiasis is a neglected tropical disease that puts over 200 million people at risk, and prevention options are sparse with no approved vaccine. Our vaccine candidate, SchistoShield^®, is based on an approximately 87 kDa large subunit of calcium activated neutral protease - termed Sm-p80 - combined with a potent TLR4 agonist-based adjuvant. SchistoShield^® has been shown to prevent disease throughout the parasitic life cycle - including egg, juvenile, and adult worm stages - in numerous animal models up to and including baboons. SchistoShield^® has been shown safe in both preclinical toxicology studies in rabbits and in a Phase 1 clinical trial in the USA. A Phase 1b trial was initiated in 2023 in endemic regions of Africa, and to date no serious safety signals have been reported.</p><p><strong>Methods: </strong>In preparation for large-scale Phase 2 clinical trials and eventual vaccine deployment, the Sm-p80 antigen production process has been transferred to a manufacturing organization, Quratis Corporation in South Korea, which specializes in preparation of vaccines for large-scale European and African trials. The process of scaling from our current production level of ~2000 vaccine doses, to a process that will generate more than 100 million doses has required multiple improvement steps in the process including fermentation, downstream purification of the protein antigen, lyophilization, and fill and finish.</p><p><strong>Results: </strong>In this study, we detail the large-scale production process of the SchistoShield^® protein product by Quratis. In addition, an effort was made to analyze and compare the Quratis-made lot of Sm-p80, referred to as QTP-105, to the cGMP lot of Sm-p80 which is in use in human trials in the USA and Africa, referred to as Sm-p80 DP (made in USA). We show that QTP-105 demonstrates excellent potency, purity, identity, and endotoxin levels compared to our Phase 1 Sm-p80 DP and is suitable for use in Phase 2 studies and beyond.</p>","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11525685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559639","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malaria parasite burden and heterogeneity of risk factors among Central African Republic refugees: a cross-sectional study in the Gado-Badzere refugee camp in Eastern Cameroon.","authors":"Zidedine Nematchoua Weyou, Felicite Djemna Djieyep, Rene Ning Teh, Michel Lontsi-Demano, Cheikh Cambel Dieng, Roland Bamou, Eugenia Lo, Helen Kuokuo Kimbi, Irene Ule Ngole Sumbele","doi":"10.3389/fitd.2024.1508750","DOIUrl":"10.3389/fitd.2024.1508750","url":null,"abstract":"<p><strong>Background: </strong>Refugees are vulnerable populations especially in malaria endemic areas where the disease claims many lives and constitutes an emerging challenge for humanitarian response. This study assessed how the influx and settlement of Central African Republic (CAR) refugees influences malaria burden in the Gado-Badzere refugee camp, Eastern Cameroon.</p><p><strong>Methods: </strong>A cross-sectional malariometric survey was conducted between November 2022 and October 2023 in 324 households comprising 1,304 individuals aged 1 month and above. Malaria parasite burden was determined using rapid diagnostic tests (RDTs) and Giemsa-stained microscopy. Demographic characteristics, malaria risk factors, treatment-seeking behaviors and costs to cure malaria were assessed using semi-structured questionnaires.</p><p><strong>Results: </strong>Of the 1,304 participants, 525 (40.3%) were malaria parasite positive with moderate geometric mean parasite density (GMPD) of 1100 parasites/μl of blood. <i>Plasmodium falciparum</i> was the main species (99.8%), with mixed <i>P. vivax</i> infections (0.2%). Insecticide treated net (ITN) ownership was 53.7%, but its utilization was significantly low (22.4%) (P < 0.001). Reason for no ITN ownership was net damaged (74.7%). Net insufficiency (77.8%) accounted for non-frequent ITN use. Mean expenditure to treat malaria in the hospital was higher (USD 13.64 ± 8.67) than auto-medication (USD 1.13 ± 1.18). Significantly, malaria parasite prevalence and risk were higher for 0-5 years age (43.7%, OR = 1; P = 0.02), residents of sector 8 (49.2%, OR = 2.53; P < 0.001) of the camp, non-frequent ITN users (41.7%, OR = 2.08; P < 0.001), people living around stagnant water (44.4%, OR = 1.55; P < 0.001) and during the rainy season (43.5%, OR = 1.31; P = 0.02). The GMPD/μl was significantly higher in the 0-5 years age group (1456, P < 0.0001), inhabitants of sector 9 (1626, P = 0.04) and participants living around stagnant water (2097, P = 0.01).</p><p><strong>Conclusion: </strong>The malaria burden in CAR refugees may represent the reservoir for malaria transmission, especially with the circulation of <i>P. vivax</i>. The improper use of ITNs could be ameliorated through sensitization. Seasonal chemoprevention mainly during the rainy season and Indoor Residual Spraying (IRS) might be implemented for effective malaria control in refugee settings.</p>","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"5 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11970952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143797248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improved prevention of female genital schistosomiasis: piloting integration of services into the national health system in Côte d’Ivoire","authors":"Ashley Preston, Carlos Torres Vitolas, Alain Claver Kouamin, Johara Nadri, Suzanne Lobohon Lavry, Neerav Dhanani, Norbert Dje, Alain Toh, Fiona M. Fleming, A. Méité","doi":"10.3389/fitd.2023.1308660","DOIUrl":"https://doi.org/10.3389/fitd.2023.1308660","url":null,"abstract":"Female genital schistosomiasis (FGS) is a neglected gynecological condition, putting women at-risk of poor sexual and reproductive health (SRH), including pregnancy complications or infertility. Early treatment of schistosomiasis with praziquantel is important to avoid disease progression to FGS as it is not always possible to reverse these symptoms. However, prevention programs with praziquantel have historically focused on school-aged children. Therefore, there is a gap to provide prevention services for young women in endemic areas, including Côte d’Ivoire.We piloted integration of FGS prevention services into routine SRH care in seven health centers (Soubré district, Côte d’Ivoire, November 2020 to April 2021) and enrolled 56 health workers. We used mixed methods including key informant interviews, focus group discussions, and questionnaires to determine effectiveness, feasibility and acceptability of integration across health system decision makers, health workers and female patients (15 to 29 years old). For qualitative data, we used an inductive coding process to analyze themes. We used descriptive statistics to analyze quantitative data.Interviewed health workers perceived that the integrated services increased access and improved health outcomes for women (15 to 29 years old) due to the more comprehensive approach, although barriers to access included lack of transportation. Female patients surveyed at baseline (n=448) indicated there were no routine FGS prevention services. During the pilot, FGS prevention services were provided to >8500 women at-risk. Health workers interviewed at the end of the pilot indicated they could feasibly provide FGS prevention services as part of routine patient consultations, and they maintained knowledge from training on the key FGS health education points and the consultation processes to follow. The greatest challenge expressed by health workers was the high workload.Provision of integrated healthcare in the health center setting is an effective and acceptable way to increase access to prevention services and provide holistic care for women (15 to 29 years old) in this setting in Côte d’Ivoire. Future scale-up will require further streamlining of the strategy, building on existing platforms, whilst ensuring reduced impact on workload and consideration of how to overcome barriers to accessing health centers.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"89 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138945384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First report of Mansonella sp. and Dipetalonema gracile in the Amazonian city-dwelling threatened primate, Saguinus bicolor","authors":"Cindy Alves Dias, Túllio Romão Ribeiro da Silva, Marcelo Gordo, D. F. Conga, Natália Aparecida de Souza Lima, A. V. S. D. Medeiros, Edson Rodrigues Costa, Sérgio Luiz Bessa Luz, Carlos Henrique Aguiar Costa, Ana Carolina Paulo Vicente, Thaís Pinto Nascimento, Francisca Helena Aguiar-Silva, Viviane Costa da Silva, Diogo César Lagroteria, Laerzio Chiesorin Neto, Alessandra Ferreira Dales Nava","doi":"10.3389/fitd.2023.1080218","DOIUrl":"https://doi.org/10.3389/fitd.2023.1080218","url":null,"abstract":"The pied tamarin, or Saguinus bicolor, is a callitrichid that inhabits Amazon Forest fragments encased within the municipalities of Manaus, Rio Preto da Eva, and Itacoatiara and their outskirts. Therefore, this primate lives in great proximity to humans, and is in critical danger of extinction, resulting from ongoing anthropogenic pressures, with habitat fragmentation being the most prominent threat. Greater conservation efforts and more studies concerning public health need to be carried out in this situation, such as the study of infectious diseases that can affect this primate, including those involving helminths. In this study, we combined necropsy, microscopy with blood smears and quick Panoptic stains, and molecular methods like nested polymerase chain reaction (PCR) targeting the internal transcribed spacer-1 (ITS-1) region, Sanger sequencing and shotgun sequencing to detect and identify filarial parasites in 71 S. bicolor samples. We detected 24 adult filarial worms in 6.45% of the thoracic cavities, microfilaria in 6.38% from blood smears, and filarial DNA in 28.57% positive blood samples via PCR. We identified eight of the adult worms as being from the Onchocercidae family using Sanger sequencing and one specifically as Dipetalonema gracile, using shotgun sequencing. For the positive blood samples, 70.58% of them were for Mansonella sp., 17.64% for Dipetalonema sp., and 11.76% could only be identified as belonging to the Onchocercidae family. There was an event of coinfection that involved Dipetalonema sp. adult worm and Mansonella sp. microfilaria. This is the first report of the detection of Dipetalonema gracile and the genus Mansonella in S. bicolor, as well as an event of coinfection, pointing out this primate as a new host. It is also another step to understand the situation of filarial infections occurring in Amazonian Regions and its municipalities.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":" 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138960660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving access to lymphatic filariasis MMDP services through an enhanced evidence-based, cascaded training model for health worker capacity strengthening in Ghana: an evaluation study","authors":"C. Ahorlu, S. Atinbire, K. M. Sedzro, Bright Alomatu, Dziedzom K. de Souza, Kofi Asamenyi-Mensah, Joseph Opare, Paul Saunderson, Stefanie Weiland","doi":"10.3389/fitd.2023.1282218","DOIUrl":"https://doi.org/10.3389/fitd.2023.1282218","url":null,"abstract":"Ghana has made significant progress in reducing the transmission rate of lymphatic filariasis. However, very little progress has been made in the provision of morbidity management and disability prevention (MMDP) services, which is one of the key requirements for certification of elimination as a disease of public health importance. This study was designed to compare pre-post- intervention to determine the feasibility and effectiveness of a cascade training model for health worker capacity strengthening in Ghana, using the WHO recommended minimum intervention package to improve access to MMDP services.This study used a quasi-experimental design to assess the impact of evidence-based training of patients with lymphatic filariasis (LF) in the Upper West region of Ghana. All lymphedema patients who were available at the time of data collection participated in the study before and after the training.The mean age of respondents was 54.67 years (SD ± 16.89 years) at baseline and 54.70 years (SD ± 15.80 years) at evaluation. The majority (i.e., 76.30% at baseline and 80.50% at evaluation) of the respondents were female. Most of the respondents had not completed primary school (83.82% at baseline and 85.40% at evaluation). We found an improvement in the quality of life among LF patients, that is, the proportion of respondents who reported having a high quality of life increased from 2.9% at baseline to 20.12% at evaluation (p < 0.001). The lymphedema management practice of “hygiene/washing and drying of affected limb” was reported by 73.17% of respondents at evaluation compared with only 32.95% of respondents at baseline (p < 0.001). The acute attack management technique of “cooling the affected limb in cool water/cold compress” was reported by 70.15% of respondents at evaluation compared with 23.70% of respondents at baseline (p < 0.001).The research confirmed that LF-related perceptions remained generally the same at baseline and evaluation among community members. The implementation of the LF-related morbidity management (MMDP) project has led to a significant improvement in the morbidity management practices among patients at evaluation compared with baseline. Our findings also showed that self-care led to an improvement in patients’ quality of life. This justifies the need for investment in morbidity management interventions in endemic communities.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"65 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138596434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Challenges in drug discovery and description targeting Leishmania spp.: enzymes, structural proteins, and transporters","authors":"A. Mendoza-León, María Luisa Serrano G., Alicia Ponte-Sucre","doi":"10.3389/fitd.2023.1241044","DOIUrl":"https://doi.org/10.3389/fitd.2023.1241044","url":null,"abstract":"Leishmaniasis is a complex tropical disease caused by the protozoan parasite Leishmania spp. Classical chemotherapy includes pentavalent antimonial; however, pentamidine, amphotericin B, and miltefosine have been used. Chemo-resistance remains a risk for successful treatment; thus, target identification and development of selective drugs remain a priority in controlling this disease. Evidence indicates that 6-phosphogluconate dehydrogenase (6PGDH), β-tubulin protein, and ATP-dependent transporters (ABCs-T) are potential targets to be addressed. The pentose phosphate pathway key enzyme 6PGDH is essential for protecting kinetoplastid parasites from oxidative stress and differs from the mammalian host enzyme (<35% AA sequence identity). An optimized 3D model has been used to select high -affinity compounds toward the enzyme through virtual screening and subsequent evaluation in vivo. In kinetoplasts, tubulins are highly conserved proteins essential for microtubule formation. However, compared to other eukaryotic cells, there is a differential susceptibility of kinetoplastid proteins to antimicrotubular agents, e.g., colchicine resistance. A comparison of experimental models between bovine and Leishmania β-tubulin protein allowed us to identify structural modification products of various amino acid substitutions, which hinder the access of colchicine to the binding pocket of the Leishmania protein. Similar changes are found in the β-tubulin sequence of other kinetoplastids such as Trypanosoma cruzi, T. brucei, and T. evansi. The evaluation of the β-tubulin protein as a therapeutic target and the compounds that selectively interact with it was carried out using in silico approaches. The activities of ABC-Transporters are related to the main causes of drug resistance, and the collected evidence suggests that for the ABC-Transporter blocker glibenclamide, there is a: (1) differential susceptibility of Leishmania spp. vs. macrophages; (2) greater susceptibility of axenic amastigotes vs. promastigotes; and (3) glibenclamide-glucantime synergistic drug interaction in macrophage-infected cells. Herein, we discuss the potential value of designing ABC-Transporter blockers for combination therapy in the treatment of leishmaniasis. The examples mentioned above highlight the importance of the search for new therapeutic targets and pharmacophores for the design of alternative treatments for the disease.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139201900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Presence of tissue schistosomiasis in KwaZulu-Natal, South Africa: a retrospective histopathologic review","authors":"A. Mwazha, G. Nhlonzi, Eyrun Floerecke Kjetland","doi":"10.3389/fitd.2023.1301485","DOIUrl":"https://doi.org/10.3389/fitd.2023.1301485","url":null,"abstract":"Schistosomiasis affects many parts of the human body including those not usually accessible during routine clinical follow-up. We investigated the presence of schistosomiasis in routine tissue specimens sent to the only public histopathology laboratory in KwaZulu-Natal, South Africa.The catchment area for the Department of Anatomical Pathology constitutes 11 million people in 10 districts. We retrospectively reviewed all the histopathology reports for occurrence of schistosomiasis between 1 January 2015 and 30 June 2020.Schistosomiasis was identified in the appendix, uterine cervix, urinary bladder, lung, liver, fallopian tubes and prostate. During the study period, 725 cases had a diagnosis of schistosomiasis confirmed on histopathology, which equals 0.3% of the total number of specimens sent to the laboratory. Female genital schistosomiasis represented 49.1% (356/725) of the schistosomiasis cases of which 25.1% (182) were from the uterine cervix and 24% (174) from the fallopian tubes. The appendix had 39.7% (289) of all the cases of schistosomiasis. Other organs were urinary bladder (4.4%, 32), lung (3.2%, 23) and liver (2.6%, 19). There were two cases of schistosomiasis in the prostate and four cases in the anorectal region. The main three indications for taking biopsies were acute appendicitis, cervical intraepithelial neoplasia, and sterilization. Majority of the schistosomiasis cases (312) were from eThekwini/Durban metropolitan district, however this represented only 1.2% (312/25 111) of the specimens received from eThekwini/Durban. The districts with the highest percentage positive cases were uMkhanyakude (43/965, 4.5%), followed by Ugu (129/5 251, 2.6%), and King Cetshwayo districts (132/5 360, 2.5%).Clinicians in the KwaZulu-Natal public health sector hospitals did not suspect schistosomiasis when they submitted patient samples for histopathological investigations. The study indicates the prevalence and the diversity of the body organs affected by schistosomiasis.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139219921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high-fat diet protects C57BL/6 mice from Plasmodium berghei ANKA infection in an experimental malaria study","authors":"S. M. Soares, Ana Gualberto, Augusto Cesar da Costa, D. A. Gonçalves, J. Gameiro","doi":"10.3389/fitd.2023.1188902","DOIUrl":"https://doi.org/10.3389/fitd.2023.1188902","url":null,"abstract":"It is well known that dietary changes have a significant impact on the immune system, and modifications in lipid balance may contribute to disease progression in several cases. Malaria is still a major global health concern, and the development of the disease has already been linked to the host’s nutritional status, so it’s critical to understand how environmental factors, such as dietary variations, can influence the outcome of infection. We therefore investigated the effect of a short-term diet in a murine model of experimental cerebral malaria.For this, male C57BL/6 mice were fed a high fat diet containing 60% of the calories from lipids for 5 days. Following this period, the animals were infected with Plasmodium berghei ANKA, and parasitemia, survival, and neurological scores were compared. Considering that one of the first elimination routes of the intracellular parasite is oxidative stress, the antioxidant N-acetylcysteine was administered to assess whether the protection would be reversed.Animals fed a hyperlipidic diet reacted the same way to infection even after NAC administration. Unlike the control group, which died after eight days of infection with roughly 7% parasitized red blood cells, the hyperlipidic diet group was resistant to infection, with no clinical signs and no increase in blood parasitemia. Several proinflammatory cytokines such as TNF-α IFN-γ and IL-6 were increased in the spleen of both infected groups, regardless of their diet. The provision of a high-fat diet to mice for as little as 5 days completely prevents Plasmodium berghei ANKA infection in C57BL/6 mice, while the treatment of an antioxidant failed to reverse the parasite protection.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"132 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139223574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Present drugs and future perspectives in treating soil-transmitted helminthiasis","authors":"Jennifer Keiser","doi":"10.3389/fitd.2023.1282725","DOIUrl":"https://doi.org/10.3389/fitd.2023.1282725","url":null,"abstract":"Soil-transmitted helminthiases caused by Ascaris lumbricoides, Trichuris trichiura, and hookworm (Ancylostoma duodenale and Necator americanus) are responsible for the infection of approximately 1.5 billion people worldwide, mostly in tropical and subtropical regions. Preventive chemotherapy is the mainstay of control, which is the regular administration of anthelminthic drugs, mainly albendazole and mebendazole to at-risk populations. As benzimidazoles face a risk of developing drug resistance and have shortcomings in their therapeutic profile, efforts have been made to develop alternative anthelminthics. The aim of this review is to provide a state-of-the-art update on available treatments and ongoing efforts in Research and Development (R&D) for the three main soil-transmitted helminth infections. Recent findings on the use of drug combinations and advanced drug candidates such as oxantel pamoate and emodepside and how these drugs fulfill the target product profile will be reviewed. Lastly, progress in drug discovery will be summarized.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"285 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139250643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Origin and spread of leprosy in Suriname. A historical and biomedical study","authors":"William R. Faber, Karin Sewpersad, Henk Menke, Charlotte Avanzi, Annemieke Geluk, Els M. Verhard, Maria Tió Coma, Mike Chan, Toine Pieters","doi":"10.3389/fitd.2023.1258006","DOIUrl":"https://doi.org/10.3389/fitd.2023.1258006","url":null,"abstract":"The new world was considered free of leprosy before the arrival of Europeans. In Suriname, historical migration routes suggest that leprosy could have been introduced from West Africa by the slave trade, from Asia by indentured workers, from Europe by the colonizers, and more recently by Brazilian gold miners. Previous molecular studies on environmental and ancient samples suggested a high variability of the strains circulating in the country, possibly resulting from the various migration waves. However, a current overview of such diversity in humans still needs to be explored. The origin and spread of leprosy in Suriname are investigated from a historical point of view and by strain genotyping of Mycobacterium leprae from skin biopsies of 26 patients with multibacillary leprosy using PCR-genotyping and whole-genome sequencing. Moreover, molecular signs of resistance to the commonly used anti-leprosy drugs i.e. dapsone, rifampicin and ofloxacin, were investigated. Molecular detection was positive for M. leprae in 25 out of 26 patient samples, while M. lepromatosis was not found in any of the samples. The predominant M. leprae strain in our sample set is genotype 4P (n=8) followed by genotype 1D-2 (n=3), 4N (n=2), and 4O/P (n=1). Genotypes 4P, 4N, 4O/P are predominant in West Africa and Brazil, and could have been introduced in Suriname by the slave trade from West Africa, and more recently by gold miners from Brazil. The presence of the Asian strains 1D-2 probably reflects an introduction by contract workers from India, China and Indonesia during the late 19th and early 20th century after the abolition of slavery. There is currently no definite evidence for the occurrence of the European strain 3 in the 26 patients. Geoplotting reflects internal migration, and also shows that most patients live in and around Paramaribo. A biopsy of one patient harbored two M. leprae genotypes, 1D-2 and 4P, suggesting co-infection. A mutation in the dapsone resistance determining region of folP1 was detected in two out of 13 strains for which molecular drug susceptibility was obtained, suggesting the circulation of dapsone resistant strains.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"8 6","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135479580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}