Tropical Medicine and Health最新文献

Background: While telomeres traditionally protect against cancer through genomic stability, recent evidence suggests a paradoxical association with increased malignancy risk. This study employed comprehensive Mendelian randomization (MR) to investigate the causal relationship between telomere length (TL) and colorectal cancer (CRC) risk and elucidate the underlying biological mechanisms through systematic mediation analysis.

Methods: We performed two-sample MR using genetic instruments from large-scale genome-wide association studies (GWASs). CRC data were obtained from FinnGen R12 (discovery cohort: 11,790 cases and 378,749 controls) and the GWAS Catalog (replication cohort: 19,948 cases and 12,124 controls). The inverse-variance weighted method served as the primary analysis, complemented by MR‒Egger, weighted median, and MR-PRESSO sensitivity analyses. The multivariable MR was adjusted for body mass index (BMI), processed meat intake, inflammatory bowel disease (IBD), and colorectal polyps. Two-step mediation analysis investigated 35 blood and urine biomarkers as potential mediators, with colocalization analysis performed to distinguish linkage from pleiotropy.

Results: Genetically predicted longer telomeres were consistently positively associated with increased CRC risk across both cohorts (discovery: odds ratio [OR] = 1.282, 95% confidence interval [CI] 1.126-1.459, P < 0.001; replication: OR = 1.253, 95% CI 1.067-1.472, P = 0.006). This association remained robust across multiple analytical methods and was independent of BMI, processed meat intake, IBD, and colorectal polyps. Mediation analysis revealed three significant mediators representing dual parallel mechanisms: insulin-like growth factor-1 (IGF-1) mediated 4.2% of the total effect through enhanced growth signaling (P = 0.0265), whereas total protein (TP) and nonalbumin protein (NAP) collectively mediated 19.67% through compromised protein homeostasis (10.33% and 9.34%, respectively; both P < 0.005). Colocalization analysis revealed the shared genetic architecture underlying these associations.

Conclusions: Longer telomeres causally increase CRC risk through dual parallel pathways: enhanced cellular proliferation via IGF-1 signaling and compromised immune surveillance through protein metabolic dysfunction. These findings challenge conventional protective roles attributed to telomeres and suggest that individuals with genetically longer telomeres may benefit from enhanced screening protocols and targeted interventions addressing both growth factor signaling and protein metabolic homeostasis.

Background: Oral cancer including lip, oral cavity cancer contributes to cancer burden importantly in the world. It is crucial for effective policy planning to comprehensively evaluate oral cancer burden regionally.

Methods: The incidence, mortality, and disability-adjusted life years (DALYs) due to oral cancer from 1990 to 2021 were estimated according to Global Burden of Disease (GBD) 2021 methods. The GBD comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for oral cancer attributable to smoking, tobacco, and alcohol consumption in 2021.

Results: The male-to-female ratio of age-standardized incidence rate (ASIR) for oral cancer was 2.99 in China, 2.7 in Europe, 2.24 in the United States, 1.73 in Southeast Asia, and 1.51 in Africa. The corresponding ratios of age-standardized mortality rate (ASMR) for oral cancer were 3.82, 3.16, 2.45, 1.89, and 1.60 respectively. Key risk factors for oral cancer-related deaths and DALYs varied by region and showed distinct age- and sex-stratified patterns. In China, tobacco was the primary contributor, accounting for 51.4% of oral cancer deaths in men, with a higher impact among older males aged ≥ 55 years. In Europe and the United States (US), alcohol consumption dominated, contributing a larger proportion of deaths in younger men (20-54 years) and showing higher attributable fractions than smoking in these age groups. In Southeast Asia, chewing tobacco was the major driver, responsible for 48.79% of oral cancer deaths in women, with this proportion exceeding 50% in females aged ≥ 55 years. Among men in Southeast Asia, smoking was the predominant risk factor for oral cancer mortality.

Conclusions: The burden of oral cancer exhibits distinct temporal and regional variations, with significant differences in incidence, mortality, and DALYs across global regions. Such differences are strongly associated with region-specific risk factor patterns, and these patterns also vary by age and sex. These insights highlight the need for targeted prevention strategies tailored to regional, age, and sex characteristics, including anti-smoking interventions in older Chinese men, alcohol control measures in younger European and American men, and efforts to reduce chewing tobacco use among older Southeast Asian women, to effectively mitigate the global burden of oral cancer.

Background: Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis, remains a major public health challenge. The emergence of drug-resistant strains has further limited effective treatment options. Therefore, discovering novel antimycobacterial agents from underexplored habitats is essential. In this study, the marine actinobacterial extract Streptomyces qinglanensis VITABS23, isolated from mangrove sediments was evaluated for its antimycobacterial activity. The active protein was extracted and identified as a potential therapeutic candidate, and its toxicity profile was evaluated in animal models.

Methods: The cell-free extract of Streptomyces qinglanensis VITABS23 was screened for antimycobacterial activity against M. tuberculosis strains using agar well diffusion and microplate Alamar blue assays. Aqueous extracts were precipitated with 70% ammonium sulphate, dialyzed and purified by DEAE Sepharose ion exchange chromatography. The purified protein was characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS PAGE) and MALDI TOF analysis. For toxicity evaluation, in vivo studies were carried out in albino Wistar rats to determine the safety profile through acute (single doses of 100 and 350 mg/kg body weight) and sub-acute (repeated oral dosing) studies following OECD guideline 423. Body weights, hematological and biochemical parameters, and organ histopathology were assessed at the end of the experimental period.

Results: The extract showed maximum inhibition zones against M. smegmatis (26 mm) and M. tuberculosis H37Ra (22 mm) at 50 mg/ml. Minimum Inhibitory Concentration assays showed strong activity at a 500 µg/mL concentration, with 85% inhibition for M. tuberculosis H37Ra and 78% for M. smegmatis. Ion exchange chromatography yielded a 156-fold purification with a protein yield of 0.085% and a specific activity of 4166 IU/mg. The active protein had an intact molecular weight of 20 kDa. Acute toxicity studies showed no adverse effects at doses of 100 and 350 mg/kg body weight. Sub-acute studies with repeated dosing for 28 days revealed no mortality, toxic symptoms or significant differences compared with controls. Histopathological analysis of the vital organs in both studies revealed normal tissue architecture suggesting no morphological changes.

Conclusion: The S. qinglanensis VITABS23 extract from mangrove sediments demonstrates potent antimycobacterial activity and a favorable safety profile, highlighting its potential as a candidate for tuberculosis treatment.

Background: Insulin resistance (IR) is increasingly recognized as a significant factor for cancer development and progression. While the triglyceride-glucose (TyG) index and its derivatives (TyG-BMI (body mass index), TyG-WC (waist circumference), and TyG-WHtR (waist-to-height ratio)) have been developed as reliable and straightforward surrogate tools for reflecting IR status, their comparative associations with pan-cancer incidence and mortality remain unclear. This study aimed to systematically evaluate the associations of these four IR-related indices with pan-cancer incidence and cancer-specific mortality in a large prospective cohort.

Methods: This prospective cohort study analyzed data from 333,297 participants in the UK Biobank. The four IR-related indices mentioned above were calculated from baseline measurements. The primary outcomes were pan-cancer incidence and pan-cancer-specific mortality. Cox regression models, adjusted for demographic, socioeconomic, lifestyle, and clinical factors, were used to estimate hazard ratios (HRs) across participants' quartiles for each index. Besides, we assessed Dose-response relationships via restricted cubic splines (RCSs), and robustness via sensitivity and subgroup analyses.

Results: Over a median follow-up of 15.2 years, 49,695 cases of different types of cancer and 12,852 cancer-specific deaths were recorded. All four IR-related indices showed significant non-linear associations with both outcomes (p < 0.001). After full adjustment, TyG-WC demonstrated the strongest and most graded association with pan-cancer incidence, with HRs progressively increasing from Q2 to Q4 (all p < 0.05 vs. Q1), and HR of Q4 was 1.11 (95% CI (confidence interval): 1.08, 1.15, p = 0.001). For pan-cancer-specific mortality, TyG-WC (HR = 1.37, 95% CI 1.28, 1.46; p < 0.001), TyG-WHtR (HR = 1.25, 95% CI 1.18, 1.33; p < 0.001), and TyG-BMI (HR = 1.22, 95% CI 1.15,1.29; p < 0.001) were significantly elevated in Q4, with TyG-WC again showing a significant dose-response trend across all quartiles. In contrast, the original TyG index showed the weakest predictive performance. Subgroup analyses indicated effect modifications by sex, smoking status, and comorbidities. Sensitivity analyses confirmed the robustness of the associations, particularly for TyG-WC.

Conclusion: IR-related indices, especially TyG-WC, are significantly associated with both pan-cancer incidence and cancer-specific mortality. Compared with TyG, TyG-BMI, and TyG-WHtR, TyG-WC demonstrated stronger associations, suggesting its potential utility for stratifying cancer risk and prognosis in clinical and public health settings.

Background: Tetanus remains a rare but potentially fatal disease, typically associated with traumatic wounds. However, necrotic malignancies such as fungating breast tumors may also serve as an entry point for Clostridium tetani infection.

Case presentation: We report the case of a 58-year-old female with a 3-year history of a fungating left breast mass who presented with trismus. A diagnosis of tetanus was made clinically. The patient received treatment with anti-tetanus globulin, metronidazole, and she was placed in a dark room with sound insulation and shielding. The surgical team was consulted for wound management. However, in accordance with the patient's refusal, surgical debridement was not performed. Instead, local wound cleansing and supportive management were initiated.

Conclusions: Tetanus should be considered in patients with necrotic tumors presenting with trismus, especially in low-resource settings where immunization histories are uncertain. Early intervention is crucial to reduce morbidity and prevent complications.

Background: Migration significantly influences tuberculosis (TB) epidemiology in the Western Pacific Region (WPR), posing challenges to its control and elimination. This study examines the burden of TB among foreign-born individuals at regional and national levels in the WPR.

Methods: Using data from the WHO Global TB Database and the United Nations' International Migrant Stock dataset, we analysed the number and proportion of foreign-born TB case notifications across the region from 2008 to 2023. We also compared estimated TB incidence among international migrants with regional and national averages in WPR destinations.

Results: Foreign-born TB notifications increased from 5,639 in 2008 to 10,056 in 2023, with trends varying across the WPR. Malaysia (40.4%), Japan (16.0%), and Australia (12.7%) accounted for the largest caseloads in 2023. Between 2021 and 2023, foreign-born TB cases represented 0.8% of total case notifications in the region, with Australia (89.9%), and New Zealand (86.5%) reporting the highest proportions. As of 2020, international migrants in the WPR (24.8 million, 77.9% of whom originated from high-burden countries) had an estimated TB incidence rate of 130 per 100,000, exceeding national averages in many countries and areas.

Conclusions: Significant disparities remain in the foreign-born TB burden across the WPR. Strengthening surveillance, improving data comparability, and enhancing cross-border collaboration through migrant-sensitive approaches may help address existing gaps and support progress towards the End TB targets.

This Matters Arising article provides a methodological commentary on the recent study by Rivadeneira et al. concerning the impact of hepatic cystic echinococcosis (HCE) recurrence on postoperative outcomes. While acknowledging the importance of their findings from an endemic region of Chile, we aim to critically examine key methodological aspects to clarify the independent prognostic role of recurrence. We discuss considerations including potential residual confounding from unadjusted cyst characteristics and surgical variables, the ascertainment of recurrence based on imaging, and the generalizability of the results from a high-endemicity population. The core purpose is to build upon this valuable work by proposing methodological refinements for future research. We recommend multi-center studies, standardized outcome sets, and combined follow-up protocols to precisely quantify the burden of HCE recurrence and enhance the global applicability of the findings for improved clinical guidelines.

Background: Acinetobacter baumannii has emerged as a significant global pathogen, and community-acquired infections are concerning due to their severe clinical outcomes and high mortality. Despite this, the molecular epidemiology and phenotypic characteristics of community-acquired/community-onset A. baumannii (CAAB/COAB) strains remain poorly understood. This study analyzed the genotypes, virulence traits, and clinical manifestations of 32 COAB isolates collected in Taiwan between 2015 and 2017.

Methods: Capsular types (KLs), sequence types (STs) from the Oxford and Pasteur schemes, and international clones (ICs) were identified among the 32 COAB isolates. In vitro virulence was assessed by evaluating biofilm formation, motility, resistance to desiccation and serum, and in vivo virulence was confirmed in a Galleria mellonella larvae model. Associations between KL/ST types and virulence phenotypes, as well as between KL/ST types and the clinical manifestations of patients, were also analyzed.

Results: The results showed that among the tested COAB isolates, KL49 was the predominant capsular type, representing 18.8% (n = 6) of samples, and ST10^Pas/IC8 (ST10^Pas: ST10 under the Pasteur scheme, IC8: international clone 8) was the major clone (15.6%, n = 5). Interestingly, we found that KL49/ST10^Pas, which is predominant in America and Australia but has never been reported for CAAB/COAB in Taiwan, had a hypervirulent phenotype with high serum resistance and high mortality in the G. mellonella larvae model. Furthermore, clinical records showed higher incidences of chronic obstructive pulmonary disease, pneumonia, elevated Pitt bacteremia scores, and 30-day mortality for patients with KL49/ST10^Pas infections than for patients with non-KL49/ST10^Pas infections.

Conclusions: This is the first report identifying KL49/ST10^Pas as a major clone of COAB in Taiwan. Its high virulence was demonstrated, highlighting a potential public health threat. This study lays a foundation for understanding the molecular epidemiology of COAB in Taiwan and supports future research on virulence and disease control strategies.

Background: Tuberculosis (TB) remains a significant public health challenge in the Western Pacific Region, which accounts for approximately 20% of the global TB burden. Despite effective diagnostic tools and treatment, many individuals with TB remain undiagnosed or unreported, particularly in high-burden countries. Systematic screening is a key strategy for identifying cases early and reducing transmission. This study presents a situational analysis of TB screening policies, practices, and challenges across seven high-burden countries in the region: Cambodia, China, Lao PDR, Mongolia, Papua New Guinea, the Philippines, and Viet Nam.

Main body: Data were collected through questionnaires, follow-up discussions, and a regional workshop involving National TB Programme representatives and WHO staff. Most countries have national guidelines for systematic screening, prioritising high-risk groups, like people living with HIV and household contacts. Common screening tools include symptom screening, chest X-rays, and WHO-recommended rapid molecular diagnostics. Although asymptomatic TB is increasingly recognised, symptom screening remains the primary initial tool. Chest X-rays with computer-aided detection technologies are available in most countries, but are often limited to donor-funded projects. Screening is conducted through routine healthcare visits, scheduled checks for specific populations (e.g., prisoners, older adults), and ad hoc campaigns. Implementation varies due to resource and infrastructure limitations. While integration with other health services and community-based approaches shows promise, these remain underutilised. Key challenges include limited funding, workforce shortages, low provider awareness, and stigma. The COVID-19 pandemic disrupted TB services, underscoring the need for resilient health systems.

Conclusion: Improving systematic TB screening requires scaling up sensitive diagnostic tools, decentralising implementation, and strengthening community engagement. Sustainable financing, robust health systems, and multi-sectoral collaboration are critical to reaching the "missing millions" and achieving the End TB goals. This analysis underscores the need for targeted, evidence-based strategies to enhance screening coverage and effectiveness across diverse epidemiological and resource settings.

Background: Hepatitis E virus (HEV) is recognized as a cause of acute viral hepatitis, particularly in low-resource and humanitarian settings, although its burden varies across different populations and geographic areas. Internally displaced persons (IDPs) are at high risk due to inadequate sanitation and contaminated water. This study aimed to characterize the molecular epidemiology and genotypes of HEV among IDPs in Al-Azaza Camp, Blue Nile State, Sudan.

Methods: A cross-sectional study was conducted from August to December 2021 during the rainy season. Serum samples from 1,078 participants were screened for anti-HEV IgM and IgG antibodies. A subset of 20 IgM-positive samples was selected for molecular analysis using real-time RT-PCR. Eighteen high-quality RNA-positive samples were sequenced, and genotyping was performed based on the ORF2 region. Phylogenetic analysis was conducted using the HEV Genotyping Tool and Geneious Prime software.

Results: Overall, 75.6% of participants tested positive for IgG antibodies. All sequenced isolates (n = 18) were classified as genotype 1, subtype 1e (HEV-1e), closely related to Paslahepevirus balayani. The isolates clustered with reference strains from Chad and Nigeria, indicating regional circulation and genetic conservation of HEV-1e in sub-Saharan Africa.

Conclusion: Despite the single-site scope and low RNA yield limitations, the study findings align with regional HEV-1e circulation patterns and emphasize the need for sustained surveillance and consideration of cross-border transmission.