Frontiers in tropical diseases最新文献

{"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}

{"title":"Operationalizing One Health: strategic guidance for prevention and control of emerging and re-emerging vector-borne and zoonotic diseases in the Eastern Mediterranean Region","authors":"Chiori Kodama, Amira S. El Rifay, Rebecca Badra, Rana Abu Salbi, Abdinasir Abubakar, Ghazi Kayali","doi":"10.3389/fitd.2023.1237688","DOIUrl":"https://doi.org/10.3389/fitd.2023.1237688","url":null,"abstract":"Operationalizing global One Health strategies at the field level to prevent and control vector-borne and zoonotic diseases (VBZDs) is of significant public health importance. Such strategies should be coordinated at the human–animal–ecosystems interface and applied at the national, regional, and global levels through the enforcement of effective policies. We aimed to develop a regional framework that can aid countries of the World Health Organization Eastern Mediterranean region to better prevent, detect, and respond to VBZDs events. This strategic guidance is a twelve-element framework drafted using various guidance documents and peer-reviewed scientific literatures, incorporating recommendations made through expert consultations. The framework elements were then integrated within a logical framework designed for practical implementation of One Health at regional and country level.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"200 3","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135475658","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 hierarchical model-based framework for evaluating probabilities of area-wide freedom from lymphatic filariasis infection based on sentinel site surveillance data","authors":"Morgan E. Smith, Ken Newcomb, Yilian Alonso Otano, Edwin Michael","doi":"10.3389/fitd.2023.1233763","DOIUrl":"https://doi.org/10.3389/fitd.2023.1233763","url":null,"abstract":"The design of population surveys to substantiate the elimination of disease transmission across large implementation units (IUs) has become important as many parasite control efforts approach their final stages. This is especially true for the global program to eliminate lymphatic filariasis (LF), which has successfully reduced infection prevalence in many endemic countries, such that the focus has shifted to how best to determine that the area-wide elimination of this macroparasitic disease has been achieved. The WHO has recommended a two-stage lot quality assurance sampling (LQAS) framework based on sampling children from selected clusters within an IU, called the Transmission Assessment Survey (TAS), for supporting such decision-making, but questions have emerged regarding the reliability of this strategy for assessing if LF transmission is broken effectively everywhere within an area. In this study, we develop and describe an alternative probabilistic framework that combines infection status information from longitudinal parasitological surveys of whole communities carried out in sentinel sites, imperfect diagnostic tests, and locally-applicable extinction thresholds predicted by transmission models, to overcome the problems associated with TAS. We applied the framework to LF infection and intervention data from the country of Malawi, and demonstrated how our hierarchical coupled model-sentinel site survey tool can be used to estimate the probability that LF transmission has occurred at the individual survey, village, and countrywide scales. We also further demonstrated how the framework can be used in conjunction with zonal or areal design prevalences to estimate the number of sentinel sites and durations of interventions required to acquire sufficiently high confidence that an area is free from infection. Our results indicate that the application of the spatially driven model-data freedom-from-infection tool developed here to follow up data from high-risk sentinel sites in a region may offer a highly cost-effective framework for guiding the making of high-fiducial and defensible area-wide LF intervention stopping decisions.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"19 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135973844","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":"Using a model-based geostatistical approach to design and analyse the prevalence of schistosomiasis in Kenya","authors":"Collins Okoyo, Mark Minnery, Idah Orowe, Chrispin Owaga, Christin Wambugu, Nereah Olick, Jane Hagemann, Wyckliff P. Omondi, Paul M. Gichuki, Kate McCracken, Antonio Montresor, Claudio Fronterre, Peter Diggle, Charles Mwandawiro","doi":"10.3389/fitd.2023.1240617","DOIUrl":"https://doi.org/10.3389/fitd.2023.1240617","url":null,"abstract":"Background Infections caused by both Schistosoma mansoni and Schistosoma haematobium are endemic in Kenya, with over six million children at risk. A national school-based deworming programme was launched in 2012 with the goal of eliminating parasitic worms as a public health problem. This study used a model-based geostatistical (MBG) approach to design and analyse the impact of the programme and inform treatment strategy changes for schistosomiasis (SCH). Methods A cross-sectional survey of 200 schools across 27 counties of Kenya was utilised. The study design, selection of the schools, and analysis followed the MBG approach, which incorporated historical data on treatment, morbidity, and environmental covariates. Results The overall SCH prevalence was 5.0% (95% CI 4.9%–5.2%) and was estimated, with a high predictive probability of 0.999, to be between 1% and&amp;lt; 10%. The predictive probabilities at county level revealed county heterogeneity, with that of four counties estimated to be between 0% and&amp;lt; 1%, that of 20 counties estimated to be between 1% and&amp;lt; 10%, that of two counties estimated to be between 10% and&amp;lt; 20%, and that of one county estimated to be between 20% and&amp;lt; 50%. Conclusion SCH treatment requirements can now be confidently refined based on the World Health Organization’s guidelines. The four counties with prevalences of between 0% and&amp;lt; 1% may consider suspending treatment only in areas (i.e., sub-counties and wards) where the prevalence is&amp;lt; 1%.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"20 5","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135973983","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":"Antibodies to Aedes spp. salivary proteins: a systematic review and pooled analysis","authors":"Veronique Etienne, Adriana Gallagher, Rebecca C. Christofferson, Michael K. McCracken, Derek A.T. Cummings, Maureen T. Long","doi":"10.3389/fitd.2023.1145340","DOIUrl":"https://doi.org/10.3389/fitd.2023.1145340","url":null,"abstract":"Aedes spp. mosquitos are responsible for transmitting several viruses that pose significant public health risks, including dengue, Zika, yellow fever, chikungunya, and West Nile viruses. However, quantifying the number of individuals at risk and their exposure to Aedes spp. mosquitos over time is challenging due to various factors. Even accurate estimation of mosquito numbers at the population level may not fully capture the fluctuations in human exposure based on factors that affect biting rates of mosquitoes. Measuring the antibody response of humans to mosquito salivary proteins (MSP) has been proposed as a method to assess human exposure to mosquito bites and predict disease risk. The presence of antibodies to MSP can be quantified using the enzyme-linked immunosorbent assay (ELISA). While there is known variability in laboratory methods, the consistency of MSP measurements across different research groups has not been quantitatively examined. Variation in laboratory protocols, antigens used, and the human populations sampled all may contribute to differences observed in measured anti-MSP responses. In this study, we conducted a systematic review of the published literature focusing on antibody responses to MSP in humans and other vertebrate hosts. Whenever possible, we extracted individual-level anti-MSP IgG data from these studies and performed a pooled analysis of quantitative outcomes obtained from ELISAs, specifically optical densities (OD). We analyzed the pooled data to quantify variation between studies and identify sample and study characteristics associated with OD scores. Our candidate list of characteristics included the type of antigen used, age of human subjects, mosquito species, population-level mosquito exposure, collection season, Köppen-Geiger climate classification, and OD reporting method. Our findings revealed that the type of antigen, population-level mosquito exposure, and Köppen-Geiger climate classification were significantly associated with ELISA values. Furthermore, we developed a classification algorithm based on OD scores, which successfully distinguished samples from individuals living in areas where a specific mosquito species was present from those where it was not, with a high degree of accuracy. The pooled analysis we conducted provides a harmonized assessment of ELISA testing, which can be utilized to refine the use of antibody responses as markers for mosquito exposure. In conclusion, our study contributes to the understanding of antibody responses to MSP and their utility as indicators of mosquito exposure. By identifying the factors associated with variations in ELISA values, we have provided valuable insights for future research and the refinement of antibody-based assessments of mosquito exposure.","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"73 2","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135271071","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":"Editorial: Response predictors in diagnosis and prognosis of meningitis and pneumonia","authors":"Priyanka Kumari, Sangeetha Gopalakrishnan, Rabbani Syed, James John","doi":"10.3389/fitd.2023.1304998","DOIUrl":"https://doi.org/10.3389/fitd.2023.1304998","url":null,"abstract":"","PeriodicalId":73112,"journal":{"name":"Frontiers in tropical diseases","volume":"129 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139309595","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}