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14 pages, 747 KiB  
Article
Prevalence, Infection Intensity, and Risk Factors for Soil-transmitted Helminth Infections among School Children in Northwestern Tanzania
by Nyanda C. Justine, Jeffer Bhuko, Sarah L. Rubagumya, Namanya S. Basinda, Deodatus M. Ruganuza, Maria M. Zinga, Matthieu Briet, Vyacheslav R. Misko, Filip Legein, Hussein Mohamed, Vivian Mushi, Donath S. Tarimo, Humphrey D. Mazigo and Wim De Malsche
Pathogens 2024, 13(8), 627; https://doi.org/10.3390/pathogens13080627 - 27 Jul 2024
Viewed by 329
Abstract
Soil-transmitted helminthiases (STH) are among the neglected tropical diseases and infect more than 24% of the world population. The World Health Organization recommends regular monitoring of STH’s prevalence and intensity following mass drug administrations to evaluate their effectiveness and inform future control strategies. [...] Read more.
Soil-transmitted helminthiases (STH) are among the neglected tropical diseases and infect more than 24% of the world population. The World Health Organization recommends regular monitoring of STH’s prevalence and intensity following mass drug administrations to evaluate their effectiveness and inform future control strategies. This study evaluated the prevalence, intensity, and risk factors of STH infections among school children aged 6 to 14 years old in northwestern Tanzania. A cross-sectional study was conducted among 728 school children in the Kagera region in 2021. Participants were selected using a two-stage cluster sampling method. A questionnaire was used to collect data on the risk factors. Stool samples were examined using the Kato–Katz technique. The data were analysed using STATA. The overall prevalence of STH was 56.2% (95% CI: 52.5–59.8, 409/728). About 5.7% and 1.1% of the infected children had moderate-intensity infections with Ascaris lumbricoides and Trichuris trichiura, respectively. Risk factors included the mother’s occupation as a farmer (aOR: 1.2, p = 0.002) and not washing hands with water and soap (aOR: 1.4, p = 0.035). Washing one’s hands after using the toilet (aOR: 0.6; p = 0.024) is a preventive measure against STH infections. STH was prevalent in the study area. The mother’s occupation (farmer) and the lack of handwashing with water and soap influenced STH transmission. Conversely, washing hands after visiting the toilet and after playing with soil reduced the risk of STH infection. Full article
(This article belongs to the Special Issue Parasites: Epidemiology, Treatment and Control: 2nd Edition)
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8 pages, 3193 KiB  
Data Descriptor
Data Descriptor of Snakebites in Brazil from 2007 to 2020
by Alexandre Vilhena Silva-Neto, Gabriel Santos Mouta, Antônio Alcirley Silva Balieiro, Jady Shayenne Mota Cordeiro, Patricia Carvalho Silva Balieiro, Tatyana Costa Amorin Ramos, Djane Clarys Baia-da-Silva, Élisson Silva Rocha, Patricia Takako Endo, Theo Lynn, Wuelton Marcelo Monteiro and Vanderson Souza Sampaio
Data 2024, 9(8), 91; https://doi.org/10.3390/data9080091 - 24 Jul 2024
Viewed by 448
Abstract
Snakebite envenomations (SBE) are a significant global public health threat due to their morbidity and mortality. This is a neglected public health issue in many tropical and subtropical countries. Brazil is in the top ten countries affected by SBE, with 32,160 cases reported [...] Read more.
Snakebite envenomations (SBE) are a significant global public health threat due to their morbidity and mortality. This is a neglected public health issue in many tropical and subtropical countries. Brazil is in the top ten countries affected by SBE, with 32,160 cases reported only in 2020, posing a high burden for this population. In this paper, we describe the data structure of snakebite records from 2007 to 2020 in the Notifiable Disease Information System (SINAN), made available by the Brazilian Ministry of Health (MoH). In addition, we also provide R scripts that allow a quick and automatic updating of data from the SINAN according to its availability. The data presented in this work are related to clinical and demographic information on SBE cases. Also, data on outcomes, laboratory results, and treatment are available. The dataset is available and freely accessible; however, preprocessing, adjustments, and standardization are necessary due to incompleteness and inconsistencies. Regardless of these limitations, it provides a solid basis for assessing different aspects and the national burden of envenoming. Full article
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14 pages, 777 KiB  
Article
Chagas Disease in the Non-Endemic Area of Rome, Italy: Ten Years of Experience and a Brief Overview
by Maria Letizia Giancola, Andrea Angheben, Laura Scorzolini, Stefania Carrara, Ada Petrone, Antonella Vulcano, Raffaella Lionetti, Angela Corpolongo, Rosalia Marrone, Francesca Faraglia, Tommaso Ascoli Bartoli, Patrizia De Marco, Maria Virginia Tomassi, Carla Fontana and Emanuele Nicastri
Infect. Dis. Rep. 2024, 16(4), 650-663; https://doi.org/10.3390/idr16040050 - 24 Jul 2024
Viewed by 400
Abstract
Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to [...] Read more.
Chagas disease (CD) is a parasitic infection endemic in Latin America and also affects patients in Western countries due to migration flows. This has a significant impact on health services worldwide due to its high morbidity and mortality burden. This paper aims to share our experience at the National Institute for Infectious Diseases “Lazzaro Spallanzani”, IRCCS, in Rome, Italy, where to date, a total of 47 patients—mainly Bolivian women—diagnosed with CD have received treatment with benznidazole, with all but one presenting with chronic disease. Most of the patients were recruited through the first extensive screening program held in 2014 at our Institute. About a quarter of our patients showed adverse effects to benznidazole, including a case of severe drug-induced liver injury, but 83% completed a full course of treatment. In addition to the description of our cohort, the paper reports a brief overview of the disease compiled through a review of the existing literature on CD in non-endemic countries. The growing prevalence of CD in Western countries highlights the importance of screening at-risk populations and urges public concern and medical awareness about this neglected tropical disease. There are still many unanswered questions that need to be addressed to develop a personalized approach in treating patients. Full article
(This article belongs to the Section Neglected Tropical Diseases)
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18 pages, 2923 KiB  
Article
In Vitro and In Vivo Wide-Spectrum Dual Antimycetomal Activity of Eight Essential Oils Coupled with Chemical Composition and Metabolomic Profiling
by Shereen O. Abd Algaffar, Prabodh Satyal, Naglaa S. Ashmawy, Annelies Verbon, Wendy W. J. van de Sande and Sami A. Khalid
Microbiol. Res. 2024, 15(3), 1280-1297; https://doi.org/10.3390/microbiolres15030086 - 22 Jul 2024
Viewed by 412
Abstract
Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to [...] Read more.
Mycetoma, a neglected infection of subcutaneous tissues, poses a significant health burden, especially in tropical regions. It is caused by fungal (eumycetoma) and bacterial (actinomycetoma) pathogens, with current treatments often providing unsatisfactory outcomes. This study aims to discover novel broad-spectrum antimicrobial agents to circumvent the lengthy and costly diagnostic procedures. Eight essential oils (EOs) from the roots and aerial parts of Geigeria alata, Lavandula angustifolia, Melaleuca alternifolia, Myristica fragrans, Pimpinella anisum, Syzigum aromaticum, and Thymus vulgaris were prepared using steam distillation. The in vitro antimycetomal activity against Madurella mycetomatis and Actinomadura madurae strains was assessed using resazurin assays. The chemical compositions of the EOs were analyzed using gas chromatography and mass spectrometry (GC–MS). Promising EOs underwent further in vivo toxicity and efficacy testing in Galleria mellonella larvae models. EOs of G. alata roots, M. fragrans, P. anisum, S. aromaticum, and T. vulgaris showed wide-spectrum dual in vitro antimycetomal activity against all tested strains, with minimum inhibitory concentrations (MICs) ranging from 0.004 to 0.125% v/v. G. alata aerial parts and L. angustifolia EOs demonstrated activity predominantly against A. madurae, while M. alternifolia EO did not inhibit any tested strains. M. fragrans and P. anisum EOs significantly enhanced the survival of M. mycetomatis-infected larvae without inducing toxicity in uninfected larvae. Notably, P. anisum EO tended to enhance the survival of A. madurae-infected larvae, ranking it as the most promising EO among those tested. The investigated EOs, particularly P. anisum, exhibited promising broad-spectrum antimycetomal activity against fungal and bacterial pathogens responsible for mycetoma. These findings highlight the potential of essential oils as a basis for developing novel antimycetomal agents, offering hope for improved treatment strategies for this neglected disease. Full article
(This article belongs to the Special Issue Antifungal Activities of Plant Extracts)
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18 pages, 3364 KiB  
Article
Superior Anticancer and Antifungal Activities of New Sulfanyl-Substituted Niclosamide Derivatives
by Jingyi Ma, Dileepkumar Veeragoni, Hindole Ghosh, Nicole Mutter, Gisele Barbosa, Lauren Webster, Rainer Schobert, Wendy van de Sande, Prasad Dandawate and Bernhard Biersack
Biomedicines 2024, 12(7), 1621; https://doi.org/10.3390/biomedicines12071621 - 21 Jul 2024
Viewed by 515
Abstract
The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested [...] Read more.
The approved anthelmintic salicylanilide drug niclosamide has shown promising anticancer and antimicrobial activities. In this study, new niclosamide derivatives with trifluoromethyl, trifluoromethylsulfanyl, and pentafluorosulfanyl substituents replacing the nitro group of niclosamide were prepared (including the ethanolamine salts of two promising salicylanilides) and tested for their anticancer activities against esophageal adenocarcinoma (EAC) cells. In addition, antifungal activity against a panel of Madurella mycetomatis strains, the most abundant causative agent of the neglected tropical disease eumycetoma, was evaluated. The new compounds revealed higher activities against EAC and fungal cells than the parent compound niclosamide. The ethanolamine salt 3a was the most active compound against EAC cells (IC50 = 0.8–1.0 µM), and its anticancer effects were mediated by the downregulation of anti-apoptotic proteins (BCL2 and MCL1) and by decreasing levels of β-catenin and the phosphorylation of STAT3. The plausibility of binding to the latter factors was confirmed by molecular docking. The compounds 2a and 2b showed high in vitro antifungal activity against M. mycetomatis (IC50 = 0.2–0.3 µM) and were not toxic to Galleria mellonella larvae. Slight improvements in the survival rate of G. mellonella larvae infected with M. mycetomatis were observed. Thus, salicylanilides such as 2a and 3a can become new anticancer and antifungal drugs. Full article
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13 pages, 2348 KiB  
Article
Effectiveness of Three Sampling Approaches for Optimizing Mapping and Preventive Chemotherapy against Schistosoma mansoni in the Western Part of Côte d’Ivoire
by Jean-Baptiste K. Sékré, Mamadou Ouattara, Nana R. Diakité, Fidèle K. Bassa, Rufin K. Assaré, Jules N. Kouadio, Gaoussou Coulibaly, Agodio Loukouri, Mathieu N. Orsot, Jürg Utzinger and Eliézer K. N’Goran
Trop. Med. Infect. Dis. 2024, 9(7), 159; https://doi.org/10.3390/tropicalmed9070159 - 14 Jul 2024
Viewed by 630
Abstract
The elimination of schistosomiasis as a public health problem by 2030 is one of the main goals put forth in the World Health Organization’s roadmap for neglected tropical diseases. This study aimed to compare different sampling approaches to guide mapping and preventive chemotherapy. [...] Read more.
The elimination of schistosomiasis as a public health problem by 2030 is one of the main goals put forth in the World Health Organization’s roadmap for neglected tropical diseases. This study aimed to compare different sampling approaches to guide mapping and preventive chemotherapy. A cross-sectional parasitological survey was conducted from August to September 2022 in the health districts of Biankouma, Ouaninou, and Touba in the western part of Côte d’Ivoire. The prevalence and intensity of Schistosoma mansoni infection were assessed in children aged 5–14 years using three sampling approaches. The first approach involved a random selection of 50% of the villages in the health districts. The second approach involved a random selection of half of the villages selected in approach 1, thus constituting 25% of the villages in the health district. The third approach consisted of randomly selecting 15 villages from villages selected by approach 2 in each health district. The overall prevalence of S. mansoni was 23.5% (95% confidence interval (CI): 19.9–27.6%), 21.6% (95% CI: 17.1–26.8%), and 18.3% (95% CI: 11.9–27.1%) with the first, second, and third approach, respectively. The respective geometric mean S. mansoni infection intensity was 117.9 eggs per gram of stool (EPG) (95% CI: 109.3–127.3 EPG), 104.6 EPG (95% CI: 93.8–116.6 EPG), and 94.6 EPG (95% CI 79.5–112.7 EPG). We conclude that, although randomly sampling up to 50% of villages in a health district provides more precise population-based prevalence and intensity measures of S. mansoni, randomly selecting only 15 villages in a district characterized by low heterogeneity provides reasonable estimates and is less costly. Full article
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7 pages, 214 KiB  
Viewpoint
High Rates of Miscarriage and Stillbirth among Pregnant Women with Clade I Mpox (Monkeypox) Are Confirmed during 2023–2024 DR Congo Outbreak in South Kivu Province
by David A. Schwartz
Viruses 2024, 16(7), 1123; https://doi.org/10.3390/v16071123 - 13 Jul 2024
Viewed by 835
Abstract
Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade [...] Read more.
Mpox (monkeypox) is a neglected tropical disease that has received increased attention since the multi-nation outbreak that began in 2022. The virus is endemic in West and Central Africa, where the Democratic Republic of the Congo (DRC) is the most affected country. Clade I monkeypox virus (MPXV) infection is endemic in the DRC and has an overall case fatality rate of 10.6% among children and adults. A study conducted in Sankuru Province, DRC, from 2007 to 2011 demonstrated that 75% of pregnant women with mpox had miscarriages or stillbirth. Further analysis of a stillborn fetus showed that MPXV could infect both the placenta and fetus, causing congenital infection. No additional cases of Clade I MPXV in pregnant women were reported until a new outbreak occurred in South Kivu Province during 2023 and 2024. Eight pregnant women having Clade I MPXV infection were identified, of whom four had either miscarriages or stillbirth, representing a 50% fetal mortality rate. These reports confirm previous data from the DRC that indicate the capability of Clade I MPXV to affect the fetus, causing congenital infection and fetal loss in a high percentage of cases. In this article, we review both past and new data from the DRC on the effects of Clade I MPXV during pregnancy and discuss the association of mpox with fetal loss. Full article
14 pages, 2808 KiB  
Article
Serological Screening and Risk Factors Associated with Leishmania infantum Positivity in Newly Diagnosed HIV Patients in Greece
by Chrysa Voyiatzaki, Apollon Dareios Zare Chormizi, Maria E. Tsoumani, Antonia Efstathiou, Konstantinos Konstantinidis, Georgios Chrysos, Aikaterini Argyraki, Vasileios Papastamopoulos, Effie G. Papageorgiou and Marika Kotsianopoulou
Microorganisms 2024, 12(7), 1397; https://doi.org/10.3390/microorganisms12071397 - 10 Jul 2024
Viewed by 546
Abstract
A serological screening was conducted to detect IgG antibodies against Leishmania infantum (L. infantum) in newly diagnosed human immunodeficiency virus (HIV) patients in Greece. The study also examined potential risk factors and the agreement of commercially available serological methods. IgG antibodies [...] Read more.
A serological screening was conducted to detect IgG antibodies against Leishmania infantum (L. infantum) in newly diagnosed human immunodeficiency virus (HIV) patients in Greece. The study also examined potential risk factors and the agreement of commercially available serological methods. IgG antibodies against L. infantum were detected using enzyme-linked immunosorbent assay (ELISA), indirect immunofluorescence antibody test (IFAT), and Western blot (WB). Out of 155 samples, 14 (9.0%) tested positive for IgG antibodies against L. infantum using at least two methods. Statistical analysis showed substantial agreement between WB and IFAT methods (Cohen’s kappa = 0.75) but moderate overall agreement among the three methods (Fleiss’ kappa = 0.42). Additionally, HIV+ intravenous drug users faced 3.55 times (p = 0.025) higher risk of testing positive for L. infantum IgG, positing that anthroponotic transmission between these patients is a plausible hypothesis based on existing literature. Non-invasive and cost-effective techniques are preferred to detect asymptomatic infections, and leishmaniasis screening should be conducted immediately after HIV diagnosis in endemic regions to enable prophylactic treatment for leishmaniasis in addition to antiretroviral therapy. To maximize sensitivity, performing at least two different serological methods for each patient is recommended. Full article
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9 pages, 233 KiB  
Review
Antibiotic Chemoprophylaxis for Leptospirosis: Previous Shortcomings and Future Needs
by Kyle Petersen and Ashley Maranich
Trop. Med. Infect. Dis. 2024, 9(7), 148; https://doi.org/10.3390/tropicalmed9070148 - 2 Jul 2024
Viewed by 775
Abstract
Leptospirosis is a neglected tropical disease that remains potentially life threatening and hard to diagnose. Climate change combined with overlapping reservoir and human habitats will likely lead to increasing incidence, outbreaks, and mortality in the future. Preventative vaccines are either of limited scope [...] Read more.
Leptospirosis is a neglected tropical disease that remains potentially life threatening and hard to diagnose. Climate change combined with overlapping reservoir and human habitats will likely lead to increasing incidence, outbreaks, and mortality in the future. Preventative vaccines are either of limited scope and availability, or under development. Antibiotic chemoprophylaxis for prevention has been the subject of numerous clinical trials. However, despite 40 years of effort, clinical trials to better define protective efficacy, dosing, and the preferred medication are of poor quality and offer limited evidence. We reviewed the literature and offer critiques of the existing trials as well as potential areas for future exploration that may better define the epidemiology and yield a better evidence base for both travel medicine and public health efforts. Full article
21 pages, 4910 KiB  
Article
Qualitative Profiling of Venom Toxins in the Venoms of Several Bothrops Species Using High-Throughput Venomics and Coagulation Bioassaying
by Dimoetsha J. C. Weekers, Luis L. Alonso, Anniek X. Verstegen, Julien Slagboom and Jeroen Kool
Toxins 2024, 16(7), 300; https://doi.org/10.3390/toxins16070300 - 1 Jul 2024
Viewed by 819
Abstract
Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The Bothrops genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into Bothrops venom composition [...] Read more.
Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The Bothrops genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into Bothrops venom composition is important to aid in the development of safer and more effective snakebite treatments. In addition, the discovery of Bothrops toxins that could potentially be used for medical or diagnostic purposes is of interest to the pharmaceutical industry. This study aimed to employ high-throughput (HT) venomics to qualitatively analyze venom composition while utilizing coagulation bioassays for identifying coagulopathic toxins and characterizing coagulopathic activity in various Bothrops venoms. Using the recently demonstrated HT venomics workflow in combination with post-column coagulopathic bioassaying, focus was placed at anticoagulant toxins. Well-known procoagulant toxins were also investigated, taking into account that using the HT venomics workflow, procoagulant toxins are especially prone to denaturation during the reversed-phase chromatographic separations performed in the workflow. The findings revealed that the venoms of B. atrox and B. jararaca harbored procoagulant toxins, whereas those of B. alternatus and B. neuwiedi contained both procoagulant and anticoagulant toxins. In general, anticoagulation was associated with phospholipases A2s, while procoagulation was associated with snake venom metalloproteinases and snake venom serine proteases. These results showed the identification of coagulopathic venom toxins in the Bothrops venoms analyzed using multiple analytical methods that complement each other. Additionally, each venom underwent qualitative characterization of its composition. Full article
(This article belongs to the Special Issue Toxins: 15th Anniversary)
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19 pages, 725 KiB  
Article
Timeliness of Childhood Vaccinations Following Strengthening of the Second Year of Life (2YL) Immunization Platform and Introduction of Catch-Up Vaccination Policy in Ghana
by Pierre Muhoza, Monica P. Shah, Kwame Amponsa-Achiano, Hongjiang Gao, Pamela Quaye, William Opare, Charlotte Okae, Philip-Neri Aboyinga, Joseph Kwadwo Larbi Opare, Daniel C. Ehlman, Melissa T. Wardle and Aaron S. Wallace
Vaccines 2024, 12(7), 716; https://doi.org/10.3390/vaccines12070716 - 27 Jun 2024
Viewed by 1378
Abstract
Strengthening routine immunization systems to successfully deliver childhood vaccines during the second year of life (2YL) is critical for vaccine-preventable disease control. In Ghana, the 18-month visit provides opportunities to deliver the second dose of the measles–rubella vaccine (MR2) and for healthcare workers [...] Read more.
Strengthening routine immunization systems to successfully deliver childhood vaccines during the second year of life (2YL) is critical for vaccine-preventable disease control. In Ghana, the 18-month visit provides opportunities to deliver the second dose of the measles–rubella vaccine (MR2) and for healthcare workers to assess for and provide children with any missed vaccine doses. In 2016, the Ghana Health Service (GHS) revised its national immunization policies to include guidelines for catch-up vaccinations. This study assessed the change in the timely receipt of vaccinations per Ghana’s Expanded Program on Immunizations (EPI) schedule, an important indicator of service quality, following the introduction of the catch-up policy and implementation of a multifaceted intervention package. Vaccination coverage was assessed from household surveys conducted in the Greater Accra, Northern, and Volta regions for 392 and 931 children aged 24–35 months with documented immunization history in 2016 and 2020, respectively. Age at receipt of childhood vaccines was compared to the recommended age, as per the EPI schedule. Cumulative days under-vaccinated during the first 24 months of life for each recommended dose were assessed. Multivariable Cox regression was used to assess the associations between child and caregiver characteristics and time to MR2 vaccination. From 2016 to 2020, the proportion of children receiving all recommended doses on schedule generally improved, the duration of under-vaccination was shortened for most doses, and higher coverage rates were achieved at earlier ages for the MR series. More timely infant doses and caregiver awareness of the 2YL visit were positively associated with MR2 vaccination. Fostering a well-supported cadre of vaccinators, building community demand for 2YL vaccination, sustaining service utilization through strengthened defaulter tracking and caregiver-reminder systems, and creating a favorable policy environment that promotes vaccination over the life course are critical to improving the timeliness of childhood vaccinations. Full article
(This article belongs to the Special Issue Inequality in Immunization 2024)
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14 pages, 1509 KiB  
Article
Simultaneous LC-MS/MS Method for the Quantitation of Probenecid, Albendazole, and Its Metabolites in Human Plasma and Dried Blood Spots
by Mamunur Rashid, Yashpal S. Chhonker, Sandeep K. Singh and Daryl J. Murry
Separations 2024, 11(7), 197; https://doi.org/10.3390/separations11070197 - 25 Jun 2024
Viewed by 896
Abstract
Millions of individuals throughout the world suffer from lymphatic filariasis (LF), which is a morbid disease caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. These infections belong to tissue-invading nematodes and are one of the major neglected tropical diseases [...] Read more.
Millions of individuals throughout the world suffer from lymphatic filariasis (LF), which is a morbid disease caused by Wuchereria bancrofti, Brugia malayi, and Brugia timori. These infections belong to tissue-invading nematodes and are one of the major neglected tropical diseases that often result in permanent and enduring disability among individuals in endemic regions. Due to combination therapy, LF eradication has drastically decreased infections globally. The development of blood micro-sampling techniques allowing precise quantitation of drugs in blood would facilitate pharmacokinetic (PK) studies in remote populations. Therefore, an LC-MS/MS bioanalytical method was utilized to analyze albendazole (ABZ), albendazole sulfone (ABZ-ON), albendazole sulfoxide (ABZ-OX), and probenecid (PR) in plasma and dried blood spots. Solid-phase extraction was utilized to extract the analyte from both plasma and blood-spiked DBS. Analytes of interest were eluted with a gradient mobile system using 0.05% formic acid in water (A) and 0.05% formic acid in methanol (B) and separated using a reversed-phase Acquity ®BEH C18 UPLC column (100 × 2.1 mm, 1.7 µm). Precision and accuracy at each QC level were within the acceptable limit, i.e., ±15% for all analytes in both the matrices. Tests for stability under laboratory and storage conditions indicated that no notable changes were observed for plasma and DBS. The LC-MS/MS method demonstrated its capability to consistently identify all target analytes (ABZ, ABZ-ON, ABZ-OX, and PR) at low concentrations, even at the small specimen volumes obtained from DBS cards. This confirms the efficacy and durability of DBS cards as a micro-sampling technique. Moreover, it enhances collection efforts for therapeutic drug monitoring in remote locations for patients infected with lymphatic filariasis. Full article
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23 pages, 4099 KiB  
Article
Investigating Snake-Venom-Induced Dermonecrosis and Inflammation Using an Ex Vivo Human Skin Model
by Jaffer Alsolaiss, Gail Leeming, Rachael Da Silva, Nessrin Alomran, Nicholas R. Casewell, Abdulrazaq G. Habib, Robert A. Harrison and Cassandra M. Modahl
Toxins 2024, 16(6), 276; https://doi.org/10.3390/toxins16060276 - 17 Jun 2024
Viewed by 918
Abstract
Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the [...] Read more.
Snakebite envenoming is a neglected tropical disease that causes >100,000 deaths and >400,000 cases of morbidity annually. Despite the use of mouse models, severe local envenoming, defined by morbidity-causing local tissue necrosis, remains poorly understood, and human-tissue responses are ill-defined. Here, for the first time, an ex vivo, non-perfused human skin model was used to investigate temporal histopathological and immunological changes following subcutaneous injections of venoms from medically important African vipers (Echis ocellatus and Bitis arietans) and cobras (Naja nigricollis and N. haje). Histological analysis of venom-injected ex vivo human skin biopsies revealed morphological changes in the epidermis (ballooning degeneration, erosion, and ulceration) comparable to clinical signs of local envenoming. Immunostaining of these biopsies confirmed cell apoptosis consistent with the onset of necrosis. RNA sequencing, multiplex bead arrays, and ELISAs demonstrated that venom-injected human skin biopsies exhibited higher rates of transcription and expression of chemokines (CXCL5, MIP1-ALPHA, RANTES, MCP-1, and MIG), cytokines (IL-1β, IL-1RA, G-CSF/CSF-3, and GM-CSF), and growth factors (VEGF-A, FGF, and HGF) in comparison to non-injected biopsies. To investigate the efficacy of antivenom, SAIMR Echis monovalent or SAIMR polyvalent antivenom was injected one hour following E. ocellatus or N. nigricollis venom treatment, respectively, and although antivenom did not prevent venom-induced dermal tissue damage, it did reduce all pro-inflammatory chemokines, cytokines, and growth factors to normal levels after 48 h. This ex vivo skin model could be useful for studies evaluating the progression of local envenoming and the efficacy of snakebite treatments. Full article
(This article belongs to the Section Animal Venoms)
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14 pages, 2156 KiB  
Article
Novel Compound MMV1804559 from the Global Health Priority Box Exhibits In Vitro and In Vivo Activity against Madurella mycetomatis
by Jingyi Ma, Kimberly Eadie, Marij Schippers, Ahmed Fahal, Benoît Laleu, Annelies Verbon and Wendy W. J. van de Sande
Int. J. Mol. Sci. 2024, 25(11), 6227; https://doi.org/10.3390/ijms25116227 - 5 Jun 2024
Viewed by 615
Abstract
Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel [...] Read more.
Objectives: Eumycetoma is a neglected tropical disease (NTD) characterized by subcutaneous lesions and the formation of grains. Attempts to treat eumycetoma involve a combination of antifungal treatment and surgery, although the outcome is frequently disappointing. Therefore, there is a need to identify novel antifungal drugs to treat eumycetoma. In this respect, Medicines for Malaria Venture (MMV) has assembled libraries of compounds for researchers to use in drug discovery research against NTD. Therefore, we screened two MMVOpen compound libraries to identify novel leads for eumycetoma. Methods: A total of 400 compounds from the COVID Box and the Global Health Priority Box were screened in vitro at 100 µM and 25 µM against the most common causative agents of eumycetoma, namely Madurella mycetomatis and Falciformispora senegalensis, and the resulting IC50 and MIC50 values were obtained. Compounds with an IC50 < 8 µM were identified for possible in vivo efficacy studies using an M. mycetomatis grain model in Galleria mellonella larvae. Results: Out of the 400 compounds, 22 were able to inhibit both M. mycetomatis and F. senegalensis growth at 100 µM and 25 µM, with compounds MMV1593278, MMV020335, and MMV1804559 being selected for in vivo testing. Of these three, only the pyrazolopyrimidine derivative MMV1804559 was able to prolong the survival of M. mycetomatis-infected G. mellonella larvae. Furthermore, the grains in MMV1804559-treated larvae were significantly smaller compared to the PBS-treated group. Conclusion: MMV1804559 shows promising in vitro and in vivo activity against M. mycetomatis. Full article
(This article belongs to the Special Issue Antifungal Drug Discovery: Progresses, Challenges, Opportunities)
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Article
Oropouche Virus Exposure in Febrile Patients during Chikungunya Virus Introduction in the State of Amapá, Amazon Region, Brazil
by Raquel Curtinhas de Lima, Helver Gonçalves Dias, Thiara Manuele Alves de Souza, Débora Familiar-Macedo, Edcelha D’Athaide Ribeiro, Valmir Corrêa e Corrêa, Alex Pauvolid-Corrêa, Elzinandes Leal de Azeredo and Flávia Barreto dos Santos
Pathogens 2024, 13(6), 469; https://doi.org/10.3390/pathogens13060469 - 3 Jun 2024
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Abstract
Oropouche orthobunyavirus (OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical [...] Read more.
Oropouche orthobunyavirus (OROV) is an arbovirus transmitted by midges that has been involved in outbreaks throughout Central and South America. In Brazil, human cases have been historically concentrated in the northern region of the country. Oropouche fever in humans range from mild clinical signs to rare neurological events, and is considered a neglected tropical disease in Brazil. Due to the clinical similarities to other arboviruses, such as chikungunya and dengue viruses, OROV infections are likely to be underreported. Chikungunya virus (CHIKV) cases in Brazil were first recognized in 2014 in the states of Amapá and Bahia in the north and northeast regions, respectively. Both OROV and CHIKV cause nonspecific symptoms, making clinical diagnosis difficult in a scenario of arbovirus cocirculation. Aiming to investigate OROV transmission during the CHIKV introduction in the state of Amapá located in the Brazilian Amazon, we conducted a retrospective molecular (RT-qPCR) and serological investigation in febrile cases (N = 166) collected between August 2014 and May 2015. All acute serum samples were negative for OROV RNA using RT-qPCR. However, neutralizing antibodies for OROV were detected using a plaque reduction neutralization test (PRNT90) in 10.24% (17/166) of the patients, with neutralizing antibody titers ranging from 20 to ≥640, suggesting the previous exposure of patients to OROV. Regarding CHIKV, recent exposure was confirmed by the detection of CHIKV RNA in 20.25% (33/163) of the patients and by the detection of anti-CHIKV IgM in 28.57% (44/154) of the patients. The additional detection of anti-CHIKV IgG in 12.58% (19/151) of the febrile patients suggests that some individuals had been previously exposed to CHIKV. Whether the OROV exposure reported here occurred prior or during the CHIKV circulation in Amapá, is unknown, but because those arboviral infections share similar clinical signs and symptoms, a silent circulation of enzootic arboviruses during the introduction of exotic arboviruses may occur, and highlights the importance of syndromic cases’ surveillance to arboviruses in Brazil. Full article
(This article belongs to the Special Issue Emerging Arboviruses: Epidemiology, Vector Dynamics, and Pathogenesis)
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