Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107929
Amel Youssef Shehab , Engy Mosbah Hassan , Esraa A. Moneer , Heba Essam Sedky , Fatma A. Abdelkader , Mona Mohamed Tolba , Amal Farahat Allam , Heba Elhadad
Cryptosporidiosis remains a major health concern, particularly in immunocompromised individuals, due to limited effective treatment options. Nitazoxanide (NTZ) is currently the only FDA-approved drug for cryptosporidiosis, yet its efficacy is significantly reduced in immunosuppressed hosts. This study evaluated the therapeutic potential of disulfiram, an FDA-approved drug for alcoholism, alone and in combination with NTZ, against Cryptosporidium infection in immunocompromised mice. Forty immunosuppressed Swiss albino mice were divided into five equal groups: uninfected controls, infected untreated, NTZ-treated, disulfiram-treated, and combination-treated (NTZ + disulfiram). All infected mice were orally inoculated with ∼10⁴ Cryptosporidium oocysts and were treated with NTZ (250 mg/kg/day) and/or disulfiram (25 mg/kg/day) for 10 consecutive days. Efficacy was assessed through parasitological, histopathological, and ultrastructural analyses. The combination therapy achieved the highest fecal oocyst reduction: 34.3 % after one week and 88.3 % after two weeks. In comparison, NTZ and disulfiram monotherapies achieved 24 % and 76 % reductions, respectively, at two-weeks mark. In intestinal contents, the combination therapy resulted in 62.6 % oocyst reduction versus 11.4 % for NTZ and 36.2 % for disulfiram at week two post treatment. Histopathological analysis revealed near-complete mucosal restoration in the combination group, whereas monotherapies showed limited or moderate recovery. Transmission electron microscopy confirmed full epithelial regeneration only in the dual therapy group, with intact microvilli, normal mitochondria, and restored cellular junctions. In conclusion, disulfiram, particularly when combined with NTZ, demonstrated enhanced anti-cryptosporidial efficacy and may serve as a promising adjunct therapy, mostly for immunocompromised patients.
{"title":"Repurposing disulfiram in a promising combination therapy for cryptosporidiosis in immunocompromised mice","authors":"Amel Youssef Shehab , Engy Mosbah Hassan , Esraa A. Moneer , Heba Essam Sedky , Fatma A. Abdelkader , Mona Mohamed Tolba , Amal Farahat Allam , Heba Elhadad","doi":"10.1016/j.actatropica.2025.107929","DOIUrl":"10.1016/j.actatropica.2025.107929","url":null,"abstract":"<div><div>Cryptosporidiosis remains a major health concern, particularly in immunocompromised individuals, due to limited effective treatment options. Nitazoxanide (NTZ) is currently the only FDA-approved drug for cryptosporidiosis, yet its efficacy is significantly reduced in immunosuppressed hosts. This study evaluated the therapeutic potential of disulfiram, an FDA-approved drug for alcoholism, alone and in combination with NTZ, against <em>Cryptosporidium</em> infection in immunocompromised mice. Forty immunosuppressed Swiss albino mice were divided into five equal groups: uninfected controls, infected untreated, NTZ-treated, disulfiram-treated, and combination-treated (NTZ + disulfiram). All infected mice were orally inoculated with ∼10⁴ <em>Cryptosporidium</em> oocysts and were treated with NTZ (250 mg/kg/day) and/or disulfiram (25 mg/kg/day) for 10 consecutive days. Efficacy was assessed through parasitological, histopathological, and ultrastructural analyses. The combination therapy achieved the highest fecal oocyst reduction: 34.3 % after one week and 88.3 % after two weeks. In comparison, NTZ and disulfiram monotherapies achieved 24 % and 76 % reductions, respectively, at two-weeks mark. In intestinal contents, the combination therapy resulted in 62.6 % oocyst reduction versus 11.4 % for NTZ and 36.2 % for disulfiram at week two post treatment. Histopathological analysis revealed near-complete mucosal restoration in the combination group, whereas monotherapies showed limited or moderate recovery. Transmission electron microscopy confirmed full epithelial regeneration only in the dual therapy group, with intact microvilli, normal mitochondria, and restored cellular junctions. In conclusion, disulfiram, particularly when combined with NTZ, demonstrated enhanced anti-cryptosporidial efficacy and may serve as a promising adjunct therapy, mostly for immunocompromised patients.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107929"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107927
Nancy E. Rodríguez-Garza , Miguel Marín , Javier Sánchez-Montejo , Ana L. Delgado-Miranda , Aldo F. Bazaldúa-Rodríguez , Ramiro Quintanilla-Licea , Azael Flores-Treviño , César I. Romo-Sáenz , Antonio Muro , Rafael Peláez , Julio López-Abán
Ruta chalepensis L. is a medicinal species widely used in ethnomedicine for gastrointestinal disorders and parasitic diseases. Among its bioactive compounds, the furanocoumarins chalepensin and graveoline have shown antiparasitic activity. This study aimed to evaluate the nematocidal potential of graveoline and chalepensin, isolated from R. chalepensis, against Trichinella spiralis in both in vitro cultures and an experimental in vivo model. The compounds were obtained from leaves and stems and first tested against first-stage larvae (L1) in culture. Selectivity indices (SI) were calculated based on cytotoxicity in Vero cells. Based on in vitro efficacy, chalepensin was selected for evaluation in a murine model of trichinellosis at 50 mg/kg/day administered over three consecutive days against three different infection stages: intestinal (days 0–2), migrating (days 13–15), and encysted (days 34–36). Larvae per gram of muscle were quantified on day 43. Histological sections were analyzed for capsule morphology and inflammation. Additionally, molecular docking was performed to explore potential parasite targets. Both compounds exhibited superior activity compared to the R. chalepensis extract (LC₅₀ = 28.2 µg/mL; SI = 22.4). Chalepensin exhibited strong in vitro activity (LC₅₀ = 0.1 µg/mL; SI = 8561), superior to graveoline (LC₅₀ = 1.1 µg/mL; SI = 162). In vivo, chalepensin reduced larval burden by 90.7% (intestinal), 37.5% (migrating), and 37.0% (encysted). Histology revealed reduced capsule thickness and pericystic inflammation. Docking predicted high affinity for thymidylate synthase (ΔG = –7.175 kcal/mol), suggesting interference with DNA synthesis. Chalepensin demonstrates potent nematocidal activity against T. spiralis, supporting its potential utility as a phytochemical-based therapeutic candidate for the management of trichinellosis.
芦丁是一种广泛应用于胃肠疾病和寄生虫病的民族医学药用植物。其生物活性成分中呋喃香豆素、chalepensin和graveoline具有抗寄生虫活性。本研究旨在评价从chalepensis中分离的graveoline和chalepensin对旋毛虫（Trichinella spiralis）的体外培养和体内实验模型的杀线虫能力。这些化合物从叶片和茎中获得，并在培养中对第一阶段幼虫（L1）进行了初步试验。根据Vero细胞毒性计算选择性指数（SI）。根据体外疗效，选择chalepensin在旋毛虫病小鼠模型中进行评估，剂量为50 mg/kg/天，连续3天给药，针对3个不同的感染阶段：肠道（0-2天）、迁移（13-15天）和成囊（34-36天）。第43天定量测定每克肌肉的幼虫数。组织切片分析胶囊形态及炎症情况。此外，还进行了分子对接，以探索潜在的寄生虫靶点。这两种化合物都比沙勒坡菌提取物具有更强的活性（LC₅₀ = 28.2µg/mL; SI = 22.4）。Chalepensin具有很强的体外活性（LC₅₀ = 0.1µg/mL; SI = 8561），优于砾石碱（LC₅₀ = 1.1µg/mL; SI = 162）。在体内，chalepensin减少了90.7%（肠道）、37.5%（迁移）和37.0%（成囊）的幼虫负担。组织学显示囊膜厚度减小，囊周炎症。对接预测胸苷酸合成酶具有高亲和力（ΔG = -7.175 kcal/mol），提示干扰DNA合成。Chalepensin显示出对螺旋体的有效杀线虫活性，支持其作为一种基于植物化学的治疗旋毛虫病的候选药物的潜在效用。
{"title":"Antiparasitic Efficacy of Chalepensin from Ruta chalepensis L. Against Trichinella spiralis: In Vitro, In Vivo, and Molecular Docking Study","authors":"Nancy E. Rodríguez-Garza , Miguel Marín , Javier Sánchez-Montejo , Ana L. Delgado-Miranda , Aldo F. Bazaldúa-Rodríguez , Ramiro Quintanilla-Licea , Azael Flores-Treviño , César I. Romo-Sáenz , Antonio Muro , Rafael Peláez , Julio López-Abán","doi":"10.1016/j.actatropica.2025.107927","DOIUrl":"10.1016/j.actatropica.2025.107927","url":null,"abstract":"<div><div><em>Ruta chalepensis</em> L. is a medicinal species widely used in ethnomedicine for gastrointestinal disorders and parasitic diseases. Among its bioactive compounds, the furanocoumarins chalepensin and graveoline have shown antiparasitic activity. This study aimed to evaluate the nematocidal potential of graveoline and chalepensin, isolated from <em>R. chalepensis</em>, against <em>Trichinella spiralis</em> in both in vitro cultures and an experimental in vivo model. The compounds were obtained from leaves and stems and first tested against first-stage larvae (L1) in culture. Selectivity indices (SI) were calculated based on cytotoxicity in Vero cells. Based on in vitro efficacy, chalepensin was selected for evaluation in a murine model of trichinellosis at 50 mg/kg/day administered over three consecutive days against three different infection stages: intestinal (days 0–2), migrating (days 13–15), and encysted (days 34–36). Larvae per gram of muscle were quantified on day 43. Histological sections were analyzed for capsule morphology and inflammation. Additionally, molecular docking was performed to explore potential parasite targets. Both compounds exhibited superior activity compared to the <em>R. chalepensis</em> extract (LC₅₀ = 28.2 µg/mL; SI = 22.4). Chalepensin exhibited strong in vitro activity (LC₅₀ = 0.1 µg/mL; SI = 8561), superior to graveoline (LC₅₀ = 1.1 µg/mL; SI = 162). In vivo, chalepensin reduced larval burden by 90.7% (intestinal), 37.5% (migrating), and 37.0% (encysted). Histology revealed reduced capsule thickness and pericystic inflammation. Docking predicted high affinity for thymidylate synthase (ΔG = –7.175 kcal/mol), suggesting interference with DNA synthesis. Chalepensin demonstrates potent nematocidal activity against <em>T. spiralis</em>, supporting its potential utility as a phytochemical-based therapeutic candidate for the management of trichinellosis.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107927"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145666414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107922
Bárbara da Rocha Fonseca , Guilherme Senna dos Santos , Fernanda Kanaan de Azambuja , Gustavo dos Santos Hartleben , Luiza Domingues Moron , Fernanda Severo Sabedra Souza , Fabiana Kommling Seixas , Tiago Veiras Collares , Edmundo Carlos Grisard , Sibele Borsuk
Chagas disease is a globally widespread parasitic infection caused by the flagellated protozoan Trypanosoma cruzi. It is classified as a neglected tropical disease, primarily affecting impoverished and rural regions where access to diagnosis and treatment is limited. Although treatment for this disease is effective, it is restricted to the acute phase, during which diagnosis is more challenging, reducing cure rates. Consequently, prevention remains the most effective control method, and recombinant proteins offer a promising strategy for vaccine development. Specifically, the proteins ASP-2 and TC24 have demonstrated immunoprotective activity in various experimental models. This study aimed to characterize the immune response elicited by the combined use of recombinant ASP-2 (from the intracellular stage) and TC24 (from the bloodstream stage), seeking to promote a synergistic protective effect compared to the response generated by the proteins used individually. To evaluate this, recombinant proteins rASP-2 and rTC24 were used as vaccine formulations to immunize female BALB/c mice as follows: Group 1: Saline solution; Group 2: 25 µg of rTC24 + aluminum hydroxide; Group 3: 25 µg of rASP-2 + aluminum hydroxide; Group 4: 12.5 µg of rTC24 + 12.5 µg of rASP-2 + aluminum hydroxide. The humoral immune response assessed IgG antibody levels by indirect ELISA of animal sera collected on days 0, 21, and 42 of the experiment, while the cellular response was evaluated by collecting and culturing splenocytes, assessing cytokines IFN-γ, TNF-α, interleukins 1β, 4, 6, 12, 17, and Toll-like receptor 4, quantified by real-time PCR. The results indicated a significant antibody production in the group where the proteins were combined (G4) compared to the control group (G1) on days 21 and 42. A significant increase in antibody production was also observed in group G4 on day 42 when compared to both groups using the isolated proteins (G2 and G3). Conversely, the cellular response showed an increase in IFN-γ and interleukins 1β and 17 in Group D, while the isolated ASP-2 protein induced the expression of TNF-α, interleukins 4 and 12, and Toll-like receptor 4. Western blotting using T. cruzi lysate and pooled serum confirmed the ability of the antibodies to recognize native parasite proteins. In conclusion, the combined use of proteins from different parasite life stages proved advantageous, indicating the induction of a mixed cellular immune response, predominantly of the Th1 and Th17 profiles.
{"title":"Association of recombinant proteins rASP-2 and rTC24 from Trypanosoma cruzi as a vaccine strategy against Chagas disease induces a mixed Th1/ Th17 immune response","authors":"Bárbara da Rocha Fonseca , Guilherme Senna dos Santos , Fernanda Kanaan de Azambuja , Gustavo dos Santos Hartleben , Luiza Domingues Moron , Fernanda Severo Sabedra Souza , Fabiana Kommling Seixas , Tiago Veiras Collares , Edmundo Carlos Grisard , Sibele Borsuk","doi":"10.1016/j.actatropica.2025.107922","DOIUrl":"10.1016/j.actatropica.2025.107922","url":null,"abstract":"<div><div>Chagas disease is a globally widespread parasitic infection caused by the flagellated protozoan <em>Trypanosoma cruzi</em>. It is classified as a neglected tropical disease, primarily affecting impoverished and rural regions where access to diagnosis and treatment is limited. Although treatment for this disease is effective, it is restricted to the acute phase, during which diagnosis is more challenging, reducing cure rates. Consequently, prevention remains the most effective control method, and recombinant proteins offer a promising strategy for vaccine development. Specifically, the proteins ASP-2 and TC24 have demonstrated immunoprotective activity in various experimental models. This study aimed to characterize the immune response elicited by the combined use of recombinant ASP-2 (from the intracellular stage) and TC24 (from the bloodstream stage), seeking to promote a synergistic protective effect compared to the response generated by the proteins used individually. To evaluate this, recombinant proteins rASP-2 and rTC24 were used as vaccine formulations to immunize female BALB/c mice as follows: Group 1: Saline solution; Group 2: 25 µg of rTC24 + aluminum hydroxide; Group 3: 25 µg of rASP-2 + aluminum hydroxide; Group 4: 12.5 µg of rTC24 + 12.5 µg of rASP-2 + aluminum hydroxide. The humoral immune response assessed IgG antibody levels by indirect ELISA of animal sera collected on days 0, 21, and 42 of the experiment, while the cellular response was evaluated by collecting and culturing splenocytes, assessing cytokines IFN-γ, TNF-α, interleukins 1β, 4, 6, 12, 17, and Toll-like receptor 4, quantified by real-time PCR. The results indicated a significant antibody production in the group where the proteins were combined (G4) compared to the control group (G1) on days 21 and 42. A significant increase in antibody production was also observed in group G4 on day 42 when compared to both groups using the isolated proteins (G2 and G3). Conversely, the cellular response showed an increase in IFN-γ and interleukins 1β and 17 in Group D, while the isolated ASP-2 protein induced the expression of TNF-α, interleukins 4 and 12, and Toll-like receptor 4. Western blotting using <em>T. cruzi</em> lysate and pooled serum confirmed the ability of the antibodies to recognize native parasite proteins. In conclusion, the combined use of proteins from different parasite life stages proved advantageous, indicating the induction of a mixed cellular immune response, predominantly of the Th1 and Th17 profiles.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107922"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Protection against malaria induced by the sickle cell trait has been a major example of genetic selection for over half a century. It has been demonstrated that human populations in Africa have acquired a high frequency of haemoglobin S (HbS) allele because the heterozygous genotype (sickle cell trait) provides protection against the severe symptoms of Plasmodium falciparum infection leading to lower parasite numbers and increased clearance of infected cells by the body. However, there is scarcity of data from Chad. This study was conducted to determine the HbS allele frequency, and also to assess the possible protection, in subjects with uncomplicated malaria from N'Djamena, Chad. Dry blood spot samples were collected from patients with uncomplicated Plasmodium falciparum malaria, whose infection was identified by microscopy. To assess HbS allele frequency, human DNA was analyzed by PCR-RFLP. We collected samples from 320 (2/3 females) uncomplicated falciparum malaria cases, among which the allele frequency of the HbS variant allele was 6.72 %. Not significant association with the parasite density was found among the different HbS genotypes. This result confirms a non-negligible frequency of the HbS allele in the study population, providing for the first time data from Chad. The present report provides some information on the sickle prevalence in the study population but can not be interpreted as being representative of the wider population, since the subjects were recruited in a malaria survey.
{"title":"Allele frequency of Hemoglobin S among patients with uncomplicated Plasmodium falciparum malaria in N'Djamena, Chad","authors":"Suitombaye Noubaramadji Yamti , Amine Akouya , Koutaya Dezoumbe , Leabaneng Tawe , Setho Ruth Taboka Kgakatsi , Abel Dafogo Djibagaou , Monique Routoubé , Giulia Cappelli , Sabrina Atturo , Ghyslaine Bruna Djeunang Dongho , Gianluca Russo , Guy Rodrigue Takoudjou Dzomo , Vittorio Colizzi , Giacomo Maria Paganotti","doi":"10.1016/j.actatropica.2025.107923","DOIUrl":"10.1016/j.actatropica.2025.107923","url":null,"abstract":"<div><div>Protection against malaria induced by the sickle cell trait has been a major example of genetic selection for over half a century. It has been demonstrated that human populations in Africa have acquired a high frequency of haemoglobin S (HbS) allele because the heterozygous genotype (sickle cell trait) provides protection against the severe symptoms of <em>Plasmodium falciparum</em> infection leading to lower parasite numbers and increased clearance of infected cells by the body. However, there is scarcity of data from Chad. This study was conducted to determine the HbS allele frequency, and also to assess the possible protection, in subjects with uncomplicated malaria from N'Djamena, Chad. Dry blood spot samples were collected from patients with uncomplicated <em>Plasmodium falciparum</em> malaria, whose infection was identified by microscopy. To assess HbS allele frequency, human DNA was analyzed by PCR-RFLP. We collected samples from 320 (2/3 females) uncomplicated falciparum malaria cases, among which the allele frequency of the HbS variant allele was 6.72 %. Not significant association with the parasite density was found among the different HbS genotypes. This result confirms a non-negligible frequency of the HbS allele in the study population, providing for the first time data from Chad. The present report provides some information on the sickle prevalence in the study population but can not be interpreted as being representative of the wider population, since the subjects were recruited in a malaria survey.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107923"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145601672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107910
Shimaa E Mohammed , Hend M Hussein , Noha A Elleboudy , Mariam I Ibrahim , Asmaa M Ammar
Cerebral schistosomiasis is a severe complication of chronic Schistosoma mansoni infection, yet the temporal relationship between parasitic burden and central nervous system pathology remains incompletely understood. This study investigated the temporal dynamics of worm burden and corresponding histopathological changes in experimental murine CNS schistosomiasis from 7 to 23 weeks post-infection. Adult worm counts (male, female, copula, and total) were determined at nine time points (weeks 7–23 post-infection) using hepatic portal perfusion. Histopathological evaluation of brain sections was performed using hematoxylin and eosin staining with a semi-quantitative scoring system (0–3). Total worm burden fluctuated significantly over time (H = 19.78, p = 0.011), peaking at week 11 (8.0 [7–9] worms). Histopathological scores exhibited a biphasic pattern: an acute inflammatory phase (weeks 7–13) with increasing gliosis and mononuclear infiltration, peaking at week 13 (score = 2.5), followed by a chronic phase (weeks 17–23) marked by vascular damage, neuronal degeneration, and fibrosis (score = 3.0 at week 17). Total worm burden correlated strongly with histopathological severity (rs = 0.724, p < 0.001), with the strongest associations observed during weeks 9–15. Murine cerebral schistosomiasis follows a predictable biphasic progression, with peak worm burden preceding maximal neuropathological damage. The mid-infection period (weeks 9–15) may represent a critical therapeutic window for intervention. These findings provide quantitative evidence for timing treatment strategies to mitigate CNS damage.
{"title":"Temporal evolution of neuropathological changes in the brain of Schistosoma mansoni-infected mice: A histopathological study","authors":"Shimaa E Mohammed , Hend M Hussein , Noha A Elleboudy , Mariam I Ibrahim , Asmaa M Ammar","doi":"10.1016/j.actatropica.2025.107910","DOIUrl":"10.1016/j.actatropica.2025.107910","url":null,"abstract":"<div><div>Cerebral schistosomiasis is a severe complication of chronic <em>Schistosoma mansoni</em> infection, yet the temporal relationship between parasitic burden and central nervous system pathology remains incompletely understood. This study investigated the temporal dynamics of worm burden and corresponding histopathological changes in experimental murine CNS schistosomiasis from 7 to 23 weeks post-infection. Adult worm counts (male, female, copula, and total) were determined at nine time points (weeks 7–23 post-infection) using hepatic portal perfusion. Histopathological evaluation of brain sections was performed using hematoxylin and eosin staining with a semi-quantitative scoring system (0–3). Total worm burden fluctuated significantly over time (H = 19.78, <em>p</em> = 0.011), peaking at week 11 (8.0 [7–9] worms). Histopathological scores exhibited a biphasic pattern: an acute inflammatory phase (weeks 7–13) with increasing gliosis and mononuclear infiltration, peaking at week 13 (score = 2.5), followed by a chronic phase (weeks 17–23) marked by vascular damage, neuronal degeneration, and fibrosis (score = 3.0 at week 17). Total worm burden correlated strongly with histopathological severity (r<sub>s</sub> = 0.724, <em>p</em> < 0.001), with the strongest associations observed during weeks 9–15. Murine cerebral schistosomiasis follows a predictable biphasic progression, with peak worm burden preceding maximal neuropathological damage. The mid-infection period (weeks 9–15) may represent a critical therapeutic window for intervention. These findings provide quantitative evidence for timing treatment strategies to mitigate CNS damage.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107910"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145530362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107921
Jorge Jesús Rodríguez-Rojas , Edith Araceli Fernández-Figueroa , Pilar de Jesús Salas-Rodríguez , Josué Severo Ortiz-Barrera , Herón Huerta , Mario Octavio González-Reyes , Rosa María Sánchez-Casas , Ildefonso Fernández-Salas , Gabriel Gutiérrez-Granados , Ángel Rodríguez-Moreno
The primary transmission of Trypanosoma cruzi, causative agent of Chagas disease, to humans and animals is through the feces and urine of Triatominae. Therefore, knowledge of their ecology and distribution is crucial for establishing effective surveillance programs with citizen participation. This is coupled with geographic distribution models to predict the risk of transmission in the areas most affected by Chagas disease. Therefore, this study aims to: a) document and validate citizen participation on the iNaturalist in the collection and observation of triatomines, as well as exploring risk factors; b) detect natural T. cruzi infection in triatomines using molecular and parasitological methods; c) to review the historical and recent literature of Triatoma gerstaeckeri (Stål 1859) in Mexico, and d) develop current and potential distribution models of T. gerstaeckeri to infer risk zones for parasite transmission in Mexico. Data of T. gerstaeckeri were collected from three sources: iNaturalist (n = 87), fieldwork data (n = 68), and scientific articles and theses (n = 882). iNaturalist observations were validated from photographs, specimen capture, and distribution overlap. The prevalence of natural infection by T. cruzi was 21.73 % (5/23) in T. gerstaeckeri from Nuevo Leon, with DTU strains TcI and TcIII, the first reports of DTU in the state. Citizen participation data like iNaturalist can potentially document the presence of triatomines at broad spatial scales. Still, they also represent an opportunity to engage and educate the public in the surveillance and control of these insect vectors associated with Chagas disease.
{"title":"Citizen science to complement the surveillance of Triatominae (Hemiptera: Reduviidae) with data of Trypanosoma cruzi (Kinetoplastea: Trypanosomatidae) infection and spatial distribution models in northeast Mexico","authors":"Jorge Jesús Rodríguez-Rojas , Edith Araceli Fernández-Figueroa , Pilar de Jesús Salas-Rodríguez , Josué Severo Ortiz-Barrera , Herón Huerta , Mario Octavio González-Reyes , Rosa María Sánchez-Casas , Ildefonso Fernández-Salas , Gabriel Gutiérrez-Granados , Ángel Rodríguez-Moreno","doi":"10.1016/j.actatropica.2025.107921","DOIUrl":"10.1016/j.actatropica.2025.107921","url":null,"abstract":"<div><div>The primary transmission of <em>Trypanosoma cruzi</em>, causative agent of Chagas disease, to humans and animals is through the feces and urine of Triatominae. Therefore, knowledge of their ecology and distribution is crucial for establishing effective surveillance programs with citizen participation. This is coupled with geographic distribution models to predict the risk of transmission in the areas most affected by Chagas disease. Therefore, this study aims to: a) document and validate citizen participation on the iNaturalist in the collection and observation of triatomines, as well as exploring risk factors; b) detect natural <em>T. cruzi</em> infection in triatomines using molecular and parasitological methods; c) to review the historical and recent literature of <em>Triatoma gerstaeckeri</em> (Stål 1859) in Mexico, and d) develop current and potential distribution models of <em>T. gerstaeckeri</em> to infer risk zones for parasite transmission in Mexico. Data of <em>T. gerstaeckeri</em> were collected from three sources: iNaturalist (<em>n</em> = 87), fieldwork data (<em>n</em> = 68), and scientific articles and theses (<em>n</em> = 882). iNaturalist observations were validated from photographs, specimen capture, and distribution overlap. The prevalence of natural infection by <em>T. cruzi</em> was 21.73 % (5/23) in <em>T. gerstaeckeri</em> from Nuevo Leon, with DTU strains TcI and TcIII, the first reports of DTU in the state. Citizen participation data like iNaturalist can potentially document the presence of triatomines at broad spatial scales. Still, they also represent an opportunity to engage and educate the public in the surveillance and control of these insect vectors associated with Chagas disease.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107921"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107919
Willy Ramos , Alfredo Enrique Oyola-García , Aída Aguirre Gonzáles , Jhony A. De La Cruz-Vargas , Miguel Luna , Tania Alarcón , Mónica Meléndez , Juan Huaccho-Rojas , Yudy Cley Cóndor-Rojas
Background
This study analyzed the time of dengue-related deaths in two regions of Peru during the atmospheric phenomena of El Niño Costero and Cyclone Yaku, which caused the largest dengue epidemic ever registered in Peru at that time.
Methods
We included 40 dengue-related deaths between January 1 and June 3, 2023. A death was considered to be dengue-related if it occurred as a consequence of the clinical signs or the clinical evolution of dengue during the medical care process, or in which dengue significantly contributed to the clinical worsening of another disease. We reviewed the research database of the deaths as well as the clinical epidemiology records, death certificates, and laboratory test results. A time analysis was performed from the date of onset of symptoms, the date of the first visit to a health establishment, the date the dengue diagnosis was first registered, and the date of death.
Results
The median age of death was 51 years, 51.2% had at least one comorbidity, and 14% had self-medicated. The median times from symptom onset to first consultation, diagnosis and from diagnosis to death were 3, 0, and 1 day, respectively. Adults presented a time from symptom onset to first consultation that was significantly greater than that of the other age groups (p = 0.048). The diagnosis time was significantly less than that seen at regional government (GORE) public establishments compared to private establishments (p = 0.014) and greater in pediatrics (p = 0.018). The time from diagnosis until death was significantly less in those who self-medicated (p = 0.041).
Conclusion
Several factors significantly influenced time from symptom onset to first consultation, diagnosis time, and diagnosis-to-death time in dengue-related deaths during the FENC epidemic and Cyclone Yaku in 2023. These factors should be analyzed to reduce mortality in Peru during future climate-related epidemics.
{"title":"Time analysis of dengue-related deaths that occurred in two regions of Peru during the climatic-atmospheric phenomena El Niño Costero and Cyclone Yaku","authors":"Willy Ramos , Alfredo Enrique Oyola-García , Aída Aguirre Gonzáles , Jhony A. De La Cruz-Vargas , Miguel Luna , Tania Alarcón , Mónica Meléndez , Juan Huaccho-Rojas , Yudy Cley Cóndor-Rojas","doi":"10.1016/j.actatropica.2025.107919","DOIUrl":"10.1016/j.actatropica.2025.107919","url":null,"abstract":"<div><h3>Background</h3><div>This study analyzed the time of dengue-related deaths in two regions of Peru during the atmospheric phenomena of El Niño Costero and Cyclone Yaku, which caused the largest dengue epidemic ever registered in Peru at that time.</div></div><div><h3>Methods</h3><div>We included 40 dengue-related deaths between January 1 and June 3, 2023. A death was considered to be dengue-related if it occurred as a consequence of the clinical signs or the clinical evolution of dengue during the medical care process, or in which dengue significantly contributed to the clinical worsening of another disease. We reviewed the research database of the deaths as well as the clinical epidemiology records, death certificates, and laboratory test results. A time analysis was performed from the date of onset of symptoms, the date of the first visit to a health establishment, the date the dengue diagnosis was first registered, and the date of death.</div></div><div><h3>Results</h3><div>The median age of death was 51 years, 51.2% had at least one comorbidity, and 14% had self-medicated. The median times from symptom onset to first consultation, diagnosis and from diagnosis to death were 3, 0, and 1 day, respectively. Adults presented a time from symptom onset to first consultation that was significantly greater than that of the other age groups (<em>p</em> = 0.048). The diagnosis time was significantly less than that seen at regional government (GORE) public establishments compared to private establishments (<em>p</em> = 0.014) and greater in pediatrics (<em>p</em> = 0.018). The time from diagnosis until death was significantly less in those who self-medicated (<em>p</em> = 0.041).</div></div><div><h3>Conclusion</h3><div>Several factors significantly influenced time from symptom onset to first consultation, diagnosis time, and diagnosis-to-death time in dengue-related deaths during the FENC epidemic and Cyclone Yaku in 2023. These factors should be analyzed to reduce mortality in Peru during future climate-related epidemics.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107919"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145556042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107920
Amanda Andrade do Rosário , Laura Posada-Lopez , Marília Fonseca Rocha , Guilherme Loureiro Werneck , Fredy Galvis-Ovallos
Visceral leishmaniasis is a zoonosis of high epidemiological relevance, caused by protozoan parasites of the Leishmaniinae subfamily, mainly of the Leishmania genus and transmitted by hematophagous phlebotomine sand flies. Vector-borne disease control faces significant challenges, and innovative strategies towards the vector – such as the use of the endosymbiont bacteria Wolbachia – have gained prominence for their ability to manipulate the reproduction of their hosts and modulate their immunity, reducing pathogen transmission. However, little is known about natural Wolbachia infection in the sand fly population. This study aimed to assess the circulation of Wolbachia in sand flies from Montes Claros, a visceral leishmaniasis-endemic area in Minas Gerais, Brazil. A total of 1.191 females Lutzomyia longipalpis were analyzed, and Wolbachia DNA was detected in 30 samples (2.5%), with a homogeneous presence among the points sampled. DNA sequences revealed a single strain, wPup, that has not been previously described in sand flies. The positive Wolbachia samples were also tested for Leishmania spp, however, no DNA was detected.
{"title":"Natural occurrence of Wolbachia in Phlebotominae (Diptera: Psychodidae) in Montes Claros, Minas Gerais - Brazil","authors":"Amanda Andrade do Rosário , Laura Posada-Lopez , Marília Fonseca Rocha , Guilherme Loureiro Werneck , Fredy Galvis-Ovallos","doi":"10.1016/j.actatropica.2025.107920","DOIUrl":"10.1016/j.actatropica.2025.107920","url":null,"abstract":"<div><div>Visceral leishmaniasis is a zoonosis of high epidemiological relevance, caused by protozoan parasites of the Leishmaniinae subfamily, mainly of the <em>Leishmania</em> genus and transmitted by hematophagous phlebotomine sand flies. Vector-borne disease control faces significant challenges, and innovative strategies towards the vector – such as the use of the endosymbiont bacteria <em>Wolbachia</em> – have gained prominence for their ability to manipulate the reproduction of their hosts and modulate their immunity, reducing pathogen transmission. However, little is known about natural <em>Wolbachia</em> infection in the sand fly population. This study aimed to assess the circulation of <em>Wolbachia</em> in sand flies from Montes Claros, a visceral leishmaniasis-endemic area in Minas Gerais, Brazil. A total of 1.191 females <em>Lutzomyia longipalpis</em> were analyzed, and <em>Wolbachia</em> DNA was detected in 30 samples (2.5%), with a homogeneous presence among the points sampled. DNA sequences revealed a single strain, <em>w</em>Pup, that has not been previously described in sand flies. The positive <em>Wolbachia</em> samples were also tested for <em>Leishmania</em> spp, however, no DNA was detected.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107920"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107936
Shyam Sundar Sah
{"title":"Comment on “When microbiology is missing: A prospective observational study on empirical first-line antibiotic treatment (FLAT) in Ethiopia”","authors":"Shyam Sundar Sah","doi":"10.1016/j.actatropica.2025.107936","DOIUrl":"10.1016/j.actatropica.2025.107936","url":null,"abstract":"","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107936"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145706884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-12-01DOI: 10.1016/j.actatropica.2025.107930
Arineia Soares Silva , Rejane Lima Leda , Wilsandrei Cella , Victor Irungu Mwangi , Rosa Amélia Gonçalves Santana , Alexandre Vilhena Silva-Neto , Maria de Nazaré Paula da Silva , Rogério Santos Pereira , Stefanie Costa Pinto Lopes , Gisely Cardoso Melo , Paulo Filemon Paolucci Pimenta , Fernando Fonseca Almeida-Val , Adalberto Luis Val , Djane Clarys Baía-da-Silva , Wuelton Marcelo Monteiro
Anopheles aquasalis mosquito, a key Plasmodium vivax vector in coastal Latin America, can be sensitive to environmental shifts. This study assessed the impact of IPCC AR5-projected climate scenarios on mosquito survival, infectivity, and immunity. Four scenarios were simulated in digitally controlled climate rooms: a forest-based environmental control and three IPCC projections - (i) Scenario RCP 4.5 (light, +1.0°C and +250 ppm CO2 on current scenario); RCP Scenario 6.0 (intermediate, +2.5°C and +400 ppm CO2 over current scenario) and RCP Scenario 8.5 (extreme, +4.5°C and +850 ppm CO2 over current scenario). Female An. aquasalis mosquitoes were infected with P. vivax via artificial membrane feeding, and survival, infection, and expression of immune genes (Attacin, Cecropin, and Defensin) evaluated. All conditions supported parasite development, with no significant differences in infection rates (54 - 68 %) or oocyst intensity. However, mosquito survival declined significantly under RCPs 6.0 and 8.5, with probabilities of 18.6 % and 6.5 % by day 7 post-infection respectively, versus 40 % in the non-blood-fed controls (p<0.001). Attacin expression differed significantly between the experimental control and RCP 4.5 (P = 0.0379), and RCP 8.5 (P = 0.0016); RCPs 6.0 and 8.5 (P = 0.0210). Defensin also varied between RCP 4.5 and 6.0 (P = 0.0359); RCP 6.0 and experimental control (P = 0.0464), and RCP 8.5 and experimental control (P = 0.0274), suggesting decreased immune activation under higher heat and CO₂ stress. Cecropin showed no significant variations. While An. aquasalis retained infectivity under all simulated conditions, the increased mortality and altered immune gene expression observed in RCPs 6.0 and 8.5 suggest that future climatic stress may compromise vector fitness.
{"title":"Predicted future climate scenarios impact survival and immune response but not Plasmodium vivax infection in Anopheles aquasalis (Diptera, Culicidae), the primary vector of coastal Central and South America and the Caribbean Islands","authors":"Arineia Soares Silva , Rejane Lima Leda , Wilsandrei Cella , Victor Irungu Mwangi , Rosa Amélia Gonçalves Santana , Alexandre Vilhena Silva-Neto , Maria de Nazaré Paula da Silva , Rogério Santos Pereira , Stefanie Costa Pinto Lopes , Gisely Cardoso Melo , Paulo Filemon Paolucci Pimenta , Fernando Fonseca Almeida-Val , Adalberto Luis Val , Djane Clarys Baía-da-Silva , Wuelton Marcelo Monteiro","doi":"10.1016/j.actatropica.2025.107930","DOIUrl":"10.1016/j.actatropica.2025.107930","url":null,"abstract":"<div><div><em>Anopheles aquasalis</em> mosquito, a key <em>Plasmodium vivax</em> vector in coastal Latin America, can be sensitive to environmental shifts. This study assessed the impact of IPCC AR5-projected climate scenarios on mosquito survival, infectivity, and immunity. Four scenarios were simulated in digitally controlled climate rooms: a forest-based environmental control and three IPCC projections - (i) Scenario RCP 4.5 (light, +1.0°C and +250 ppm CO2 on current scenario); RCP Scenario 6.0 (intermediate, +2.5°C and +400 ppm CO2 over current scenario) and RCP Scenario 8.5 (extreme, +4.5°C and +850 ppm CO2 over current scenario). Female <em>An. aquasalis</em> mosquitoes were infected with <em>P. vivax</em> via artificial membrane feeding, and survival, infection, and expression of immune genes (<em>Attacin, Cecropin, and Defensin</em>) evaluated. All conditions supported parasite development, with no significant differences in infection rates (54 - 68 %) or oocyst intensity. However, mosquito survival declined significantly under RCPs 6.0 and 8.5, with probabilities of 18.6 % and 6.5 % by day 7 post-infection respectively, versus 40 % in the non-blood-fed controls (p<0.001). <em>Attacin</em> expression differed significantly between the experimental control and RCP 4.5 (P = 0.0379), and RCP 8.5 (P = 0.0016); RCPs 6.0 and 8.5 (P = 0.0210). <em>Defensin</em> also varied between RCP 4.5 and 6.0 (P = 0.0359); RCP 6.0 and experimental control (P = 0.0464), and RCP 8.5 and experimental control (P = 0.0274), suggesting decreased immune activation under higher heat and CO₂ stress. <em>Cecropin</em> showed no significant variations. While <em>An. aquasalis</em> retained infectivity under all simulated conditions, the increased mortality and altered immune gene expression observed in RCPs 6.0 and 8.5 suggest that future climatic stress may compromise vector fitness.</div></div>","PeriodicalId":7240,"journal":{"name":"Acta tropica","volume":"272 ","pages":"Article 107930"},"PeriodicalIF":2.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号