Tropical Medicine & International Health最新文献

Objectives: Non-invasive methods based on exhaled breath samples have emerged as promising alternatives for the diagnosis of pulmonary tuberculosis, especially in settings where sputum collection is challenging and laboratory infrastructure is limited. We aimed to map the evidence on advanced technologies available for detecting pulmonary tuberculosis using alveolar breath, bioaerosols, or exhaled breath condensate.

Methods: A comprehensive scoping review following international guidelines was performed (OSF: 10.17605/OSF.IO/TRJ7W). Searches were conducted in PubMed, Scopus and Web of Science (June 2025). Primary studies evaluating physical or chemical diagnostic methods based on biological exhaled breath samples for detecting pulmonary tuberculosis in symptomatic patients were included. Studies' metadata, including method accuracy metrics, were extracted for diagnosis performance comparison. Evidence was synthesised using descriptive statistical and qualitative methods.

Results: Overall, 19 studies published between 2010 and 2025 were included, mostly conducted in high tuberculosis-burden countries such as South Africa (16%), China (11%) and Paraguay (11%). The most evaluated techniques were electronic nose (e-nose) (42%), gas chromatography coupled with mass spectrometry (GC-MS/MS-based) (21%) and machine learning applied to mass spectrometry (ML-MS) approaches (11%). Important heterogeneity in studies' design and analytical approaches was observed. All included studies used non-invasive samples and were classified as intended for screening purposes; none aimed for confirmatory diagnosis. Among the included studies, 10 (53%) were classified as near point-of-care approaches. Of these, 8 (80%) met the minimum sensitivity requirement for screening tests, although only one also achieved the corresponding specificity threshold. The highest diagnostic performance reported showed a sensitivity of 98.5% (95% CI: 92.1-100) and a specificity of 100% (95% CI: 93.5-100).

Conclusions: Although research on exhaled breath-based technologies for pulmonary tuberculosis diagnosis is advancing, with some alternatives presenting moderate-to-high performance, their implementation still requires standardised validation, methodological improvements and field testing in real-world settings.

Background: Irritable bowel syndrome (IBS) is associated with impaired quality of life (QoL), anxiety and depression. Intestinal parasitic infections may exacerbate this burden, but their impact on psychological and functional outcomes remains underexplored.

Methods: In this Phase II case-control study, 100 IBS patients and 100 age- and sex-matched healthy controls were assessed using a 36-item disease-specific QoL questionnaire and the Hospital Anxiety and Depression Scale (HADS). IBS patients were categorised as parasite-negative or parasite-positive (Giardia lamblia or Entamoeba histolytica). Subgroup analyses examined the effect of parasitic infection on QoL and psychological outcomes. Correlations between HADS scores and QoL were evaluated using Pearson's coefficient.

Results: IBS patients exhibited significantly higher anxiety (13.8 ± 4.5 vs. 8.5 ± 4.3; p < 0.01) and depression (13.7 ± 4.4 vs. 6.9 ± 3.8; p < 0.01) scores compared to controls. QoL scores were lowest in E. histolytica-infected patients (41.0 ± 9.1), intermediate in Giardia-infected patients (54.5 ± 8.5) and highest in parasite-free IBS patients (72.0 ± 7.2). HADS anxiety (r = -0.61, p < 0.001) and depression (r = -0.58, p < 0.001) correlated negatively with QoL.

Conclusion: IBS is associated with substantial psychological morbidity and QoL impairment, both of which are exacerbated by intestinal parasitic infection. These findings highlight the importance of addressing both infection and psychological health in comprehensive IBS management.

Objectives: The primary objectives of this study are to (1) summarise the current landscape of ETEC vaccine development by describing, characterising and comparing ETEC vaccine candidates in clinical development, (2) assess key characteristics of the phases 1, 2 and 3 clinical trials that have been designed to evaluate ETEC vaccines in development and (3) compare ETEC vaccine candidates being evaluated in clinical trials to the WHO Preferred Product Characteristics (PPC) for an ETEC vaccine.

Methods: To identify vaccine candidates, we searched 24 trial registries and PubMed. Searches were completed on 6 February 2024 and updated on 27 September 2024. We extracted information about the characteristics of each vaccine candidate and information about the most recently registered clinical trial for candidates in active development. We qualitatively synthesised the information available and compared each vaccine candidate to the WHO PPC.

Results: Our search returned 262 trial records and 821 publications, from which we identified 13 unique vaccine candidates with clinical development spanning three decades, with six vaccine candidates that had at least one clinical trial registered in 2014 or later. These six candidates (dmLT, dscCfAE, ETVAX, CssBA, CVD1208S-122 and ShigETEC) are in Phase 1 or Phase 2 trials with sample sizes from 50 to 4936 participants, with no Phase 3 trials registered by September 2024. Trials take place in the United States, Bangladesh and the Gambia. The candidates vary in their route of administration (oral, intradermal, intramuscular). Two candidates are being evaluated as two doses with or without a booster, and four require three doses. Three candidates are adjuvanted. Most trials are evaluating endpoints about safety and reactogenicity.

Conclusions: We identified diverse ETEC vaccine candidates. Comparison with the PPC emphasised differences in approach and the limited information available from early-stage trials, and the importance of generating evidence for populations with a high burden of ETEC diarrhoea.

Background: Chagas disease, caused by Trypanosoma cruzi, has become increasingly relevant in non-endemic countries due to migration. Spain hosts large Latin American communities, making physicians' awareness key for timely diagnosis and treatment. We aimed to assess knowledge of Chagas disease among physicians nationwide and to identify barriers to its clinical management.

Methods: We conducted a nationwide cross-sectional online survey of practising physicians in Spain (1 June-30 September 2025). The self-administered online questionnaire was developed through expert consensus and an extensive review of relevant literature and included demographic and professional data, 31 knowledge items across five domains (transmission, clinical presentation, screening, diagnosis, and treatment), as well as questions addressing perceived barriers. Knowledge was classified into five categories from very low to very high, with difficulty indices calculated per item. Associations used χ², Kruskal-Wallis, or Spearman tests; independent predictors were examined with multivariable ordinal logistic regression.

Findings: Of 745 respondents (65.5% female; mean age 39.0 years [SD 11.7]; mean practise duration 12.8 years [SD 11.0]), knowledge was moderate in 55.8%, high in 32.6%, very high in 2.1%, low in 8.6%, and very low in 0.8%. Highest scores occurred in Infectious Diseases, Microbiology, and Internal Medicine; lowest score in Geriatrics. Higher knowledge was associated with perceiving clinical relevance (adjusted odds ratio [aOR] 2.51, 95% CI 1.79-3.53), specific training in the past 5 years (aOR 1.96, 1.32-2.90), and speciality (Internal Medicine, aOR 3.02, 1.96-4.65); less frequent nationality inquiry was associated with lower knowledge (frequently aOR 0.41, 0.23-0.72; occasionally 0.56, 0.35-0.89). Clinically relevant gaps were identified in diagnostic and therapeutic domains: fewer than half of physicians correctly identified PCR as the preferred diagnostic method in the acute phase or in immunocompromised patients, and only 63.1% recognised benznidazole or nifurtimox as first-line therapy. In contrast, awareness of congenital screening was high (94.0%). Main perceived barriers were low population risk perception and insufficient training.

Conclusions: Physicians showed moderate knowledge of Chagas disease, with important gaps in diagnosis and treatment. Targeted, large-scale educational initiatives supported by institutions are urgently needed to strengthen awareness and clinical preparedness in non-endemic settings with significant Latin American migrant populations.

Objective: The purpose of this study was to assess the levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α) in the tears and serum of patients with age-related macular degeneration, as well as to identify the factors associated with IL-6 and TNF-α levels in tears.

Methods: This was a comparative, cross-sectional study involving age-related macular degeneration patients and a control group. Tear samples were collected using Schirmer paper strips, while 3 mL of blood was obtained from each patient. IL-6 and TNF-α levels in tears and serum were measured using a commercial human enzyme-linked immunosorbent assay (ELISA) kit. The study analysed the effects of duration of age-related macular degeneration, disease stage, and smoking status on IL-6 and TNF-α levels in tears, aiming to determine their associations.

Results: A total of 142 patients were recruited for this study, including 56 patients with early age-related macular degeneration, 56 patients with late neovascular age-related macular degeneration, and 30 patients in the control group. Age-related macular degeneration patients exhibited significantly higher mean levels of IL-6 in both tears and serum, as well as TNF-α in serum, compared to the control group, both before and after adjusting for covariates (21.97 ± 10.95 vs. 16.06 ± 10.00 pg/mL, p = 0.008 and p = 0.014; 12.00 ± 6.04 vs. 8.53 ± 4.13 pg/mL, p = 0.004 and p = 0.004; 18.58 ± 7.90 vs. 13.61 ± 4.86 pg/mL, p = 0.001 and p = 0.004, respectively). Within the age-related macular degeneration group, the mean IL-6 level in serum was significantly higher in patients with late neovascular age-related macular degeneration compared to those with early age-related macular degeneration (13.89 ± 6.08 vs. 10.11 ± 5.41 pg/mL, p = 0.001). The levels of IL-6 and TNF-α in tears were not associated with the duration of age-related macular degeneration, the stages of age-related macular degeneration, or smoking status.

Conclusion: There are significantly higher levels of IL-6 in both tears and serum, whereas tears and serum TNF-α serve as non-specific biomarkers for age-related macular degeneration. This study could serve as a basis for future research.

Introduction: Neurocysticercosis is a leading cause of acquired epilepsy in endemic regions. Scarce longitudinal data sets exist to allow assessment of secular trends in prevalence. This study analysed temporal trends of cysticercosis seropositivity among suspected patients across Peru over two decades.

Materials and methods: An ecological study was conducted using anonymized serological data from patients who underwent enzyme-linked immunoelectrotransfer blot (EITB) testing for the first time at a neurological referral centre in Lima, Peru. Seropositivity was defined as antibody reactivity to ≥ 1 glycoprotein band, and higher thresholds (≥ 3, ≥ 4 bands) were also assessed considering their association with active disease. Temporal trends were analysed using generalised linear models with Poisson regression.

Results: Among 39,481 individuals, seropositivity was 31.3% (12,350/39,481). The prevalence of seropositivity increased from 27.3% in the initial 5-year period (2000-2004) to 37.4% in the last (2014-2019), while the numbers of requested tests decreased from 15,074 to 5130 and the overall numbers of new seropositive individuals decreased from 4109 cases to 1918. High-reactivity cases also increased in proportion but decreased in number (≥ 3 bands: 18.1% to 27.1% and 2734 to 1392; ≥ 4 bands: 7.9% to 17.5% and 1194 to 897), suggesting a greater proportion of active or clinically relevant infections.

Conclusions: Over 20 years, the demand for cysticercosis serology and the numbers of seropositive cases by 5-year periods decreased while the proportion of seropositive cases rose significantly within a single specialised referral centre. While data from suspected clinical cases do not necessarily represent disease burden at the population level, the reduction in case numbers may represent reduced disease prevalence. At the same time, the persistence of significant numbers of cases in this single centre study through the last examined period and the increased proportion of strong seropositive cases demonstrate that cysticercosis is still endemic in Peru.

Objectives: Few randomised trials have been done to assess the impact of hygiene interventions on trachoma even though hygiene improvements feature prominently in the strategy for global elimination of trachoma. This study's aim was to determine if implementing an integrated water, sanitation, and hygiene (WASH) intervention in a hyperendemic region of Ethiopia would reduce clinical signs of trachoma.

Methods: In a parallel-group cluster-randomised trial, 40 Ethiopian communities were randomised in a 1:1 ratio to a WASH intervention or to delayed intervention (i.e., control) (ClinicalTrials.gov NCT02754583). No antibiotic mass drug administration was undertaken. Annual monitoring visits included photography of the superior tarsal conjunctiva. Clinical trachoma-a pre-specified secondary outcome-was assessed from photographs presented in a random order to masked photo-graders.

Results: At baseline, conjunctival photographs were taken on 1131 children aged 0-9 years in the WASH arm and 1229 children in the control arm. The mean number of follicles at baseline was 3.8 (95% CI: 3.1, 4.6) in the WASH arm and 3.7 (95% CI: 2.9, 4.4) in the control arm, which increased to a mean of 5.9 (95% CI: 5.1-6.6) in the WASH arm and 5.4 (95% CI: 4.6-6.1) in the control arm after 3 years (0.5 higher in the WASH arm, 95% CI: -0.6 to 1.5, p = 0.66). The mean papillary score increased from 3.3 (95% CI: 3.1-3.5) to 3.7 (95% CI: 3.5-3.9) in the WASH arm and from 3.2 (95% CI: 3.0-3.4) to 3.5 (95% CI: 3.3-3.7) in the control arm (month 36 values 0.2 greater in the WASH arm, 95% CI: -0.1 to 0.4; p = 0.49). No adverse events were reported in either treatment arm.

Conclusions: An integrated WASH intervention delivered in the absence of mass antibiotic distributions did not reduce clinical trachoma outcomes in an area with hyperendemic trachoma.

Objectives: The resurgence of Visceral Leishmaniasis (VL) is a natural cyclical phenomenon with an inter-epidemic period of 10-15 years. It might be due to the persistence of a silent parasite pool amongst post kala-azar dermal leishmaniasis (PKDL) and asymptomatic leishmanial infection (ALI). The present study targeted to find out the obstacles for unearthing and proper management of the hidden parasite pool for prevention of the resurgence of VL in erstwhile endemic districts of West Bengal, India.

Methods: Two strategies were employed to identify the latent parasite reservoirs: follow-up of individuals having a previous history of VL and/or PKDL and limited mass sero-surveillance within a 500-m radius of recently treated VL and PKDL. Diagnosed PKDL and VL cases were treated and ALI were followed up.

Results: A total of 95 new PKDL and 70 relapse PKDL were diagnosed during the entire study period; those remained undiagnosed in spite of ongoing case searching methods recommended by the national VL elimination programme. 'Relapse PKDL'-a new challenge for VL elimination has been identified. The incidence of PKDL declined steadily during successive study years. Limited mass survey revealed 17 VL, 2 PKDL and 124 ALI. Most of the ALI sero-reverted during the follow up period and 2 of them converted to disease VL.

Conclusions: The present work revealed three major obstacles. First, identification of the occult parasite pool may be resolved by applying the searching methods used in this study. Second, case confirmation of 'relapse PKDL' may be achieved by examining slit skin samples at the local level by existing staff with proper training. Alternative short duration treatment strategy for the treatment of new and relapse PKDL is needed. Third, considering the long inter-epidemic period and observed declining trend of incident PKDL, such surveillance should be continued for 10-15 years for the prolonged post-elimination phase and finally to achieve eradication.

Objective: Malaria remains a significant public health challenge in India, with genetic factors potentially influencing both susceptibility and disease severity. This study aimed to investigate the relationship between blood group polymorphisms, α-globin gene deletions, Complement Receptor 1 (CR1) variants, and Gerbich phenotypes with malaria susceptibility in the Chiplun region of Maharashtra, India.

Methods: In this case-control study, we enrolled 228 microscopically confirmed malaria cases and 2149 healthy individuals as controls from the Chiplun taluka from Ratnagiri district. ABO and Rh blood group typing was performed using standard tube agglutination techniques. α-globin gene deletions were analysed using multiplex PCR. CR1 polymorphisms (intron 27 and exon 22) and Gerbich blood group variations were determined using PCR-RFLP and multiplex PCR approaches respectively. Statistical analyses included chi-square tests, Fisher's exact tests, regression analysis and odds ratios with 95% confidence intervals.

Results: Blood group B⁺ was associated with increased malaria risk (OR = 1.36, 95% CI: 1.02-1.80, p < 0.05), whilst A⁺ appeared protective (OR = 0.72, 95% CI: 0.52-0.99, p < 0.05). Most notably, individuals with homozygous-α³·⁷ deletion genotype showed significantly higher malaria susceptibility (OR = 3.33, 95% CI: 2.00-5.53, p < 0.001). No significant associations were observed between Rh phenotypes, CR1 polymorphisms, or Gerbich variants and malaria susceptibility.

Conclusions: Our findings demonstrate significant associations between certain blood group phenotypes and α-globin genotypes with malaria susceptibility in the population from Chiplun. The strong association of homozygous-α³·⁷ deletion with increased malaria risk contradicts the protective effect reported in some populations, highlighting the complex and potentially region-specific nature of genetic factors influencing malaria susceptibility. These results contribute to understanding the genetic epidemiology of malaria in India and may inform targeted public health interventions in similar endemic regions.

Objectives: A three-arm, open, parallel-group randomised trial compared three face-washing methods for cleaning Chlamydia trachomatis from the faces of children with severe active trachoma. The impact of face-washing on Chlamydia trachomatis on the hands of children and their caregivers and Chlamydia trachomatis duration on faces and hands were investigated as secondary objectives.

Methods: Children aged 1-7 years in Oromia, Ethiopia, were screened for active trachoma. We aimed to recruit 470 children with severe conjunctival inflammation; 141 were expected to have concurrent conjunctival infection and facial Chlamydia trachomatis, detected by qPCR. Those with severe inflammation were randomly assigned to water alone, water with soap or damp, microfibre towel protocols. Swabs (children's faces/hands, caregivers' hands) were collected pre-wash, post-wash, and at 1, 2, 4, 6 and 8 h. Conjunctival swabs were tested for ocular Chlamydia trachomatis infection; only infected children with facial Chlamydia trachomatis were included in primary analysis, comparing the proportion of faces without Chlamydia trachomatis after each washing method.

Results: Of 470 children screened with severe inflammation, 25 (5%) had conjunctival infection and facial Chlamydia trachomatis. All three protocols (n = 12 water only, n = 8 water and soap, n = 5 damp towel) reduced discharge, but none removed Chlamydia trachomatis from faces immediately post-wash. No major facial Chlamydia trachomatis load reduction was observed. Face-washing removed Chlamydia trachomatis from some children's and caregivers' hands, but loads were not significantly reduced where Chlamydia trachomatis persisted. Though Chlamydia trachomatis was transiently absent from one face at 1 h and four at 2 h post-wash, all baseline Chlamydia trachomatis-positive children retained it at 8 h.

Conclusions: No evidence of differential or overall effectiveness of the three washing methods at removing facial Chlamydia trachomatis from children with trachoma was found. This finding is limited by a smaller-than-anticipated sample size, potentially hindering detection of subtle differences or overall effects.

Trial registration: ISRCTN registry: ISRCTN12814010 (April 2023).