Tropical Medicine & International Health最新文献

{"title":"Korat-Scrub Typhus Score: A Clinical Tool for Predicting Scrub Typhus in Patients With Acute Undifferentiated Febrile Illness.","authors":"Wilawan Thipmontree, Ekkarat Wongsawat, Saowaluk Silpasakorn, Yupin Suputtamongkol","doi":"10.1111/tmi.70154","DOIUrl":"10.1111/tmi.70154","url":null,"abstract":"<p><strong>Objective: </strong>Scrub typhus is a major cause of acute undifferentiated febrile illness (AUFI) in the Asia-Pacific region. Nonspecific presentation, limited diagnostic accuracy and delayed treatment increase morbidity and mortality. This study aimed to develop a simple clinical score for early diagnosis in adults with AUFI.</p><p><strong>Methods: </strong>A cross-sectional study of adults (≥ 18 years) with AUFI was conducted at a tertiary hospital in northeastern Thailand from June 2021 to May 2022. The Korat-Scrub Typhus Score was developed by analysing all clinically relevant variables using multivariable logistic regression with backward stepwise selection. Model performance was assessed using the Hosmer-Lemeshow goodness-of-fit test and the area under the receiver operating characteristic curve (AUC), with internal validation via 1000 bootstrap replications.</p><p><strong>Results: </strong>Among 366 AUFI patients, 75 had scrub typhus. Most were male (66.7%), with mean age of 53.6 ± 17.6 years and median illness duration of 4 days (IQR 2-7). Five predictors were identified: outdoor activities, rash (excluding eschar), headache, abnormal chest radiograph findings and aspartate aminotransferase ≥ 100 U/L. The Korat-Scrub Typhus Score (0-13) stratified risk into low (< 5), moderate (5-6) and high (> 6) groups, with likelihood ratios of 0.55 (95% CI, 0.43-0.71), 2.20 (95% CI, 1.37-3.53) and 9.22 (95% CI, 4.19-20.25), respectively. The model showed good calibration, acceptable discrimination (AUC = 0.783, 95% CI 0.725-0.842) and minimal overfitting after internal validation.</p><p><strong>Conclusion: </strong>Scrub typhus is a common cause of AUFI. The Korat-Scrub Typhus Score uses simple clinical and laboratory data to support early diagnosis and timely treatment.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1066-1072"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Serum Ferritin Levels in Dengue Fever Severity in Elderly People.","authors":"Hinpetch Daungsupawong, Viroj Wiwanitkit","doi":"10.1111/tmi.70141","DOIUrl":"10.1111/tmi.70141","url":null,"abstract":"","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1135-1136"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147700002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive Ability of Sonographic Characteristics Alone to Diagnose Tuberculous Pleural Effusions in a Resource-Limited Setting: A Cross-Sectional Pilot Study in Zambia.","authors":"Lukonde Zimba, Salomé-Joëlle Gass, Mpundu C Makasa, Matthew S Haldeman","doi":"10.1111/tmi.70143","DOIUrl":"10.1111/tmi.70143","url":null,"abstract":"<p><strong>Background: </strong>Tuberculous pleural effusion (TPE), the second most common form of extra-pulmonary tuberculosis (TB), remains difficult to diagnose due to low-yield, invasive and often unavailable diagnostics in resource-limited settings. This study aimed to evaluate the diagnostic accuracy of sonographic characteristics alone to predict TB aetiology of pleural effusions using point-of-care ultrasound (POCUS).</p><p><strong>Methods: </strong>This cross-sectional study included 45 participants in Zambia who underwent ultrasound scanning and diagnostic thoracentesis. Key sonographic characteristics of pleural effusions-presence of septations, presence of plankton sign and unilateral location-were evaluated for their association with TB, using pleural fluid adenosine deaminase (ADA) ≥ 40 IU/L, combined with Xpert MTB/RIF and lipoarabinomannan, as the gold standard. Sensitivity, specificity, positive predictive values and negative predictive values were calculated for each characteristic alone and in combination and multivariate logistic regression was used to determine statistical significance. Interrater reliability between clinician and expert image interpretation was calculated using a kappa statistic.</p><p><strong>Results: </strong>Significant associations were found between TB positivity and unilateral location (either side) (p = 0.037), right-sided location (p = 0.043) and any two POCUS signs (p = 0.044). Diagnostic performance varied across the three POCUS signs, with the presence of any two POCUS signs demonstrating the highest sensitivity (90.9%) but moderate specificity (41.7%) and the presence of all 3 POCUS signs showing strong specificity (83.3%) but poor sensitivity (45.5%). Agreement also varied, with the lowest kappa score observed for the plankton sign and the highest for unilateral location.</p><p><strong>Conclusions: </strong>Multiple sonographic characteristics, including unilateral location (either side), unilateral right-sided location and any two positive signs were significantly associated with TB aetiology. Limitations included small sample size, potential selection bias, imperfect gold standard options, and inability to fully assess potential confounders. With additional study, these findings may be used to inform development of a non-invasive tool to predict TB aetiology of pleural effusions-and expedite initiation of anti-TB therapy-in high TB settings globally.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1128-1134"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432728/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Life Course Malaria Exposure and SARS-CoV-2 Seroepidemiology in Ugandan Adolescents: A Longitudinal Study Nested in a Birth Cohort.","authors":"Ludoviko Zirimenya, Doreen Nayebare, Claire Baine, Jacent Nassuuna, Milly Namutebi, Christopher Zziwa, Denis Nsubuga, Fred Kiwudhu, Florence Akello, Josephine Tumusiime, Gloria Oduru, Grace Kabami, Hellen Akurut, Rachel Nakyesige, Agnes Natukunda, Anne Wajja, Lawrence Lubyayi, Simon Kimuda, Gyaviira Nkurunungi, Jennifer Serwanga, Katie J Doores, Emily L Webb, Alison M Elliott","doi":"10.1111/tmi.70148","DOIUrl":"10.1111/tmi.70148","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 has had major global health impacts, yet reported morbidity and mortality have been lower in Africa despite serological evidence of widespread infection. Malaria has been proposed as a potential modifier of susceptibility to and outcomes of SARS-CoV-2 infection. We investigated whether prospectively measured life-course malaria exposure was associated with serologically defined SARS-CoV-2 infection among adolescents in a malaria-endemic setting and explored symptomatic COVID-19 during follow-up.</p><p><strong>Methods: </strong>We conducted a longitudinal study nested within the Entebbe Mother and Baby Study birth cohort in Uganda. Adolescents were enrolled and followed up 6 and 12 months later. Blood samples were collected at each visit for SARS-CoV-2 serology. Malaria exposure was defined using prospectively collected data on clinical malaria (from birth to 10 years), asymptomatic parasitaemia at annual visits and antibody responses to Plasmodium falciparum merozoite surface protein 2 (PfMSP-2) and apical membrane antigen 1 (PfAMA-1). The primary outcome was SARS-CoV-2 seropositivity, based on spike and nucleocapsid IgG responses, with seropositivity cut-offs derived from pre-pandemic samples. Secondary outcomes, including antibody concentrations and symptomatic PCR-confirmed disease, were explored. Vaccinated participants were excluded from subsequent serological analyses. Logistic and linear regression models assessed associations with seropositivity and log₁₀-transformed antibody concentrations, adjusting for key demographic, socioeconomic and exposure-related confounders.</p><p><strong>Results: </strong>Between August and November 2021, 476 adolescents (mean age 16.4 years (SD = 0.75); 205 (43.1%) female) were enrolled. Overall, 12.0% had ever had asymptomatic parasitaemia, and 61.3% had experienced clinical malaria. SARS-CoV-2 seropositivity among unvaccinated participants increased from 63% at baseline to 89.3% at 6 months and 94.9% at 12 months; no PCR-positive cases were reported. Multivariable analyses showed no consistent association between malaria exposure and SARS-CoV-2 seropositivity or antibody concentration levels.</p><p><strong>Conclusions: </strong>We found no consistent evidence that life-course malaria exposure was associated with SARS-CoV-2 infection as measured by serology or antibody levels.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1012-1027"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432706/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783140","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Short-Course Low-Dose Primaquine for Radical Cure in G6PD-Normal Patients in the Pre-Elimination Context of Nepal.","authors":"Prakash Ghimire, Gokarna Dahal, Nabaraj Adhikari, Komal Raj Rijal, Sanjib Adhikari, Megha Raj Banjara, Hellen Mnjala, Grant Lee, Sophie Weston, Angela Rumaseb, Anjana Rai, Benedikt Ley, Mohammad Sharif Hossain, Julie A Simpson, Megha Rajasekhar, Bipin Adhikari, Ric N Price, Bibek K Lal, Kamala Thriemer","doi":"10.1111/tmi.70145","DOIUrl":"10.1111/tmi.70145","url":null,"abstract":"<p><strong>Background: </strong>Plasmodium vivax remains a challenge for malaria elimination in Nepal due to its ability to relapse. Radical cure with primaquine is effective but limited by poor adherence to the standard 14-day low-dose regimen. In 2022, the WHO recommended administering the same total dose (3.5 mg/kg) over 7 days to improve adherence. This study aimed to evaluate the 7-day low-dose primaquine regimen in G6PD-normal patients with uncomplicated P. vivax and/or P. falciparum malaria in the pre-elimination context of Nepal.</p><p><strong>Methods: </strong>A randomised study was conducted in south-west Nepal. Adult patients with microscopically confirmed P. vivax and/or P. falciparum malaria and glucose-6-phosphate dehydrogenase (G6PD) activity ≥ 30% were randomised 1:1 to receive either a 7-day low-dose primaquine regimen (0.5 mg/kg/day; total 3.5 mg/kg) or standard of care (14-day primaquine [0.25 mg/kg/day; total 3.5 mg/kg] for patients with P. vivax malaria and single-dose primaquine for P. falciparum malaria patients) in addition to their schizonticidal treatment. All treatment was directly observed, and patients were followed for 6 months. The primary outcome was the risk of P. vivax recurrence at 6 months. Safety outcomes included adverse events, gastrointestinal symptoms and haematological parameters.</p><p><strong>Results: </strong>Of 5842 individuals screened, 27 eligible participants were enrolled. Among these, 21 had P. vivax, four had P. falciparum and two had mixed infections. Eleven participants had intermediate G6PD activity (≥ 30%-70% activity). At 6 months there were no recurrences in the 7-day primaquine arm (n = 14) and the risk of P. vivax recurrence in the standard primaquine arm (n = 13) was 9.1% (95% CI: 1.3-49.2). No participants vomited study drugs, and gastrointestinal symptoms were infrequent. Three participants experienced a ≥ 25% haemoglobin drop between baseline and Day 2, all of whom had baseline values > 15 g/dL. No presentations of haemoglobinuria, severe anaemia, serious adverse events, or deaths occurred during the study period.</p><p><strong>Conclusions: </strong>In this small study, the 7-day low-dose primaquine regimen was well tolerated, including among individuals with intermediate G6PD activity. Although the small sample size limits conclusions about efficacy, the findings support the feasibility and safety of this regimen in Nepal, offering potential programmatic advantages for radical cure delivery in a setting close to elimination.</p><p><strong>Trial registration: </strong>Clinicaltrials.gov: NCT04079621.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1028-1034"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147783071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploration of Various Diagnostic Modalities for Detection of Amoebic Liver Abscess and Co-Occurrence of Other Infective Aetiology, Eastern India.","authors":"P Harishni, Srujana Mohanty, Manas Kumar Panigrahi, Anupam Dey, Baijayantimala Mishra, Nonika Rajkumari, Vinaykumar Hallur","doi":"10.1111/tmi.70149","DOIUrl":"10.1111/tmi.70149","url":null,"abstract":"<p><strong>Background: </strong>Liver abscess (LA) remains a major clinical entity across the globe. Pyogenic liver abscess (PLA) caused by bacteria and amoebic liver abscess (ALA) caused by Entamoeba histolytica (Eh) constitute the two predominant varieties, whilst other infective aetiologies such as tubercular and fungal LA are reported uncommonly. The true frequency of ALA often remains underestimated, owing to constraints related to the poor sensitivity of conventional methods. Hence, we performed this study to explore the usefulness of various diagnostic modalities for detection of ALA to select optimal strategies for incorporation in our routine diagnostic repertoire. The co-occurrence of other infective aetiologies of LA was also investigated.</p><p><strong>Methods: </strong>This observational, cross-sectional study conducted from August 2021 to July 2023 included provisionally diagnosed cases of LA whose pus samples obtained under relevant radio-imaging guidance were subjected to various conventional and molecular tests primarily for detection of amoebic aetiology, including microscopy, antigen detection, serology and nested multiplex polymerase chain reaction (PCR). Cultures and cartridge-based nucleic acid amplification test were performed for detection of pyogenic/fungal and tubercular aetiology, respectively.</p><p><strong>Results: </strong>Of 82 samples, a positive microbial yield was obtained in 69 patients (84.1%) with, ALA in 31 (44.9%), PLA in 26 (37.7%), ALA with superimposed bacterial co-infection in 10 (14.5%), tubercular in one (1.4%) and fungal in one (1.4%). Maximum number of ALA cases were detected by nested-multiplex PCR (41/82, 50.0%) followed by amoebic serology (28, 34.1%). Further, 45 bacterial isolates were obtained from 36 culture-positive specimens, with Escherichia coli as the predominant isolate followed by Klebsiella pneumoniae and Burkholderia pseudomallei.</p><p><strong>Conclusions: </strong>Molecular investigations are useful tests for the diagnosis of ALA and need to be incorporated in routine clinical practise for maximum detection of cases. Amoebic serology can serve as an alternative option.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1082-1092"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432745/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Impact of Active Versus Passive Surveillance on Hepatitis C Virus Testing Uptake, Diagnosis and Linkage to Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis.","authors":"Katekani Precious Motau, Maureen Moyo Chilufya, Nyeleti P Chauke, Smangaliso Morerwa, Kuhlula Maluleke","doi":"10.1111/tmi.70137","DOIUrl":"10.1111/tmi.70137","url":null,"abstract":"<p><strong>Background: </strong>Hepatitis C virus (HCV) infection remains a major global health challenge, particularly in low- and middle-income countries (LMICs), where limited diagnostic access and weak surveillance hinder progress toward the World Health Organization's 2030 elimination targets. This review compared the effectiveness of active versus passive surveillance on HCV testing uptake, diagnosis, and linkage to care in LMICs.</p><p><strong>Methods: </strong>A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines. Studies published between 2000 and July 2025 were retrieved from eight databases, including PubMed, Scopus, and EMBASE. Eligible studies reported HCV testing, diagnosis, or linkage outcomes among adults (≥ 18 years) in LMICs. We conducted the meta-analysis using the random-effects model to estimate pooled prevalence, and qualitative findings were thematically synthesised.</p><p><strong>Results: </strong>Forty-four studies met the inclusion criteria, of which 17 conducted across 21 countries in Sub-Saharan Africa and South and Southeast Asia contributed to the meta-analysis, reflecting regional rather than global estimates of HCV-RNA prevalence. The pooled HCV-RNA prevalence was 53.4% (95% CI: 32.8-74.1; I² = 99.9%). Active surveillance interventions commonly included mobile outreach (n = 7), community screening (n = 12), integration of testing into HIV or TB services (n = 13), or provider-initiated testing (n = 10), with active approaches achieving higher diagnostic yields and uptake than passive facility-based models. Key barriers included stigma, limited infrastructure, and weak referral systems, while facilitators involved decentralisation, integration with HIV/TB services, and point-of-care diagnostics.</p><p><strong>Conclusion: </strong>Active surveillance substantially improves HCV detection and care linkage compared to passive approaches. However, sustainable hybrid systems that combine both models, strengthen laboratories, and engage the community are essential to achieve equitable progress toward HCV elimination in LMICs.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"997-1011"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432773/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-Enhanced Point-of-Care Diagnostics for Infectious Diseases in Resource-Limited Settings: A Scoping Review.","authors":"Hayden Farquhar","doi":"10.1111/tmi.70170","DOIUrl":"10.1111/tmi.70170","url":null,"abstract":"<p><strong>Objectives: </strong>To systematically map the extent and nature of research on AI-enhanced point-of-care (POC) and rapid diagnostic technologies for infectious diseases in resource-limited settings, and to identify gaps in disease coverage, geographic representation and validation rigour.</p><p><strong>Methods: </strong>This scoping review followed JBI methodology and PRISMA-ScR guidelines. The protocol was registered on OSF (https://doi.org/10.17605/OSF.IO/KV8MP). Five databases (PubMed, Embase, Scopus, Web of Science and IEEE Xplore) were searched for studies published from January 2015 to March 2026. Title/abstract and full-text screening used rule-based keyword screening with manual validation (Cohen's kappa = 0.856). Data were extracted using a 19-variable charting form and enriched with PubMed Central full texts.</p><p><strong>Results: </strong>From 1072 records, 551 remained after deduplication and 237 studies were included. Publication volume grew exponentially, with 44% published in 2025-2026. COVID-19 (32%), malaria (27%) and tuberculosis (14%) dominated; neglected tropical diseases accounted for fewer than 8%. Microscopy (21%), molecular diagnostics (17%), biosensors (14%) and rapid diagnostic tests (14%) were the most common modalities. Convolutional neural networks predominated (26%), followed by random forests (10%) and support vector machines (8%). Only 7% of studies reported prospective field validation, while 62% did not report validation level. Geographic analysis revealed concentration in East Africa and South Asia, with underrepresentation of West Africa and Latin America.</p><p><strong>Conclusions: </strong>AI-enhanced POC diagnostics for infectious diseases in resource-limited settings is a rapidly growing field facing critical gaps in validation rigour, disease equity and geographic representation. Only 16 of 237 studies (6.8%) report prospective field validation. Future research should prioritise field validation, expand beyond the COVID-19/malaria/TB triad and involve end-user communities from the design stage.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"966-996"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148228495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental Distribution of Pathogenic Leptospira spp. in Subtropical Rivers of Japan and Implications for Human Infection.","authors":"Atsuhiro Kanayama, Hiroko Ejiri, Yuki Chiko, Ikumi Namihira, Tomoki Yonaha, Kanetaka Kuba, Miyu Yoshimi, Nobuo Koizumi, Shigeto Takeshima, Koki Kaku","doi":"10.1111/tmi.70157","DOIUrl":"10.1111/tmi.70157","url":null,"abstract":"<p><strong>Objectives: </strong>Leptospirosis is a zoonotic disease caused by Leptospira spp. often linked to freshwater exposure in subtropical and tropical regions. Okinawa Prefecture reports the highest number of leptospirosis cases in Japan based on national surveillance data. Although recreational river activities in Okinawa are a major opportunity for exposure, direct evidence connecting environmental contamination with human infection remains limited. We investigated the spatiotemporal distribution of pathogenic Leptospira spp. in rivers on Iriomote Island, Okinawa, a subtropical region with a high leptospirosis incidence.</p><p><strong>Methods: </strong>Ten laboratory-confirmed patients treated at the regional hospital and affiliated clinics in 2024 were assessed for demographics, onset dates and exposure histories. Water samples were collected monthly from seven major rivers (June-September and December 2024). Pathogenic Leptospira spp. were detected by nested polymerase chain reaction targeting flaB, followed by sequencing and phylogenetic analysis.</p><p><strong>Results: </strong>A cluster of six cases occurred with onset on August 26-27; all reported river activities during incubation periods. In the environmental survey, highly and intermediately pathogenic genotypes were identified in all rivers (n = 84 water samples). Leptospira interrogans was frequently identified, particularly during summer. Novel sequences within the highly pathogenic group suggest potentially unreported species. Pathogenic Leptospira were detected in river water both before and after rainfall. The case cluster occurred following heavy rainfall, suggesting a possible temporal association between rainfall and increased exposure risk.</p><p><strong>Conclusion: </strong>Pathogenic Leptospira spp., including clinically relevant L. interrogans, were widely detected in rivers on Iriomote Island. Human case occurrence followed heavy rainfall where pathogenic Leptospira were already present in the environment. While this temporal pattern suggests that rainfall may have exacerbated exposure risk, exposures unrelated to rainfall cannot be excluded. This integrated approach may improve case detection and risk assessment in endemic settings and is adaptable to other tropical and subtropical regions with similar exposure risks.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1073-1081"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repositioning Antibiotics Against Plasmodium falciparum RAD5 and WD11 as Novel Antimalarial Targets.","authors":"Abdullah S Albaqami, Oluwafemi Adebayo Oyewole, Khalid Mohamed Adam","doi":"10.1111/tmi.70147","DOIUrl":"10.1111/tmi.70147","url":null,"abstract":"<p><strong>Background: </strong>The emergence of artemisinin resistance in Plasmodium falciparum threatens the sustainability of malaria control programs and underscores the need for new therapeutic strategies. Recently, two proteins, RAD5 (PfRAD5) and WD40-repeat protein 11 (PfWD11), have been implicated in parasite survival and drug resistance. Their druggability, however, remains underexplored.</p><p><strong>Methods: </strong>We integrated computational and experimental approaches to assess PfRAD5 and PfWD11 as antimalarial targets. Structural models were retrieved from AlphaFold and aligned with orthologues across Plasmodium species. A library of 216 antibiotics was screened by molecular docking, and molecular dynamics simulations. Top-ranked compounds were tested against P. falciparum 3D7 cultures in vitro, alone and in combination, and gene expression changes in PfRAD5 and PfWD11 were quantified by qPCR. Docking identified strong binders to PfRAD5 (talampicillin, dicloxacillin, raltegravir) and PfWD11 (cervinomycin A2 monoacetate, eAmSPC 2593, puromycin).</p><p><strong>Results: </strong>Molecular dynamics confirmed the stability of protein-ligand complexes. In vitro, puromycin exhibited the highest inhibition (85% at 100 μg/mL), while combinations enhanced activity. The triple combination (puromycin + raltegravir + dicloxacillin) achieved complete inhibition, and puromycin + chloroquine exhibited synergistic effects at in a concentration-dependent manner. qPCR showed consistent downregulation of PfRAD5 and PfWD11 following puromycin-based treatments, whereas chloroquine alone upregulated PfRAD5 expression. PfRAD5 and PfWD11 represent novel antimalarial targets.</p><p><strong>Conclusion: </strong>Repurposed antibiotics, particularly puromycin in synergistic regimens, offer a cost-effective strategy to counteract emerging resistance and accelerate therapeutic development.</p>","PeriodicalId":23962,"journal":{"name":"Tropical Medicine & International Health","volume":" ","pages":"1093-1114"},"PeriodicalIF":2.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}