Tropical Medicine & International Health最新文献

Objectives: Nipah and Hendra are deadly zoonotic diseases with pandemic potential. To date, no human vaccine or monoclonal antibody (mAb) has been licensed to prevent disease caused by these pathogens. The aim of this scoping review was to identify and describe all Phase I, II, and III clinical trials of vaccine candidates or mAbs candidates designed to prevent Nipah and Hendra in humans and to compare the characteristics of the vaccine candidates to characteristics outlined in the Target Product Profile drafted by the World Health Organisation as part of the WHO Research & Development Blueprint for Action to Prevent Epidemics.

Methods: We searched 23 clinical trial registries, the Cochrane Central Register of Clinical Trials, and grey literature up to June 2023 to identify vaccine and mAb candidates being evaluated in registered clinical trials. Vaccine candidate and trial characteristics were double-extracted for evaluation and the vaccine candidate characteristics were compared with the preferred and critical criteria of the World Health Organisation's Target Product Profile for Nipah virus vaccine.

Results: Three vaccine candidates (Hendra Virus Soluble Glycoprotein Vaccine [HeV-sG-V], PHV02, and mRNA-1215) and one mAb (m102.4) had a registered human clinical trial by June 2023. All trials were phase 1, dose-ranging trials taking place in the United States of America or Australia and enrolling healthy adults. Although all vaccine candidates meet the dose regimen and route of administration criteria of the Target Product Profile, other criteria such as measures of efficacy and reactogenicity will need to be evaluated in the future as evidence becomes available.

Conclusion: Multiple vaccine candidates and one mAb candidate have reached the stage of human clinical trials and are reviewed here. Monitoring progress during evaluation of these candidates and candidates entering clinical trials in the future can help highlight many of the challenges that remain.

Background: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community.

Methods: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated.

Results: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50).

Discussion: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.

Objectives: Treatment interruption is associated with poor tuberculosis (TB) treatment outcomes and increased drug resistance. To address the issue, we aimed to investigate the characteristics, predictors and consequences of treatment interruption.

Methods: We conducted a retrospective cohort study by retrieving 4 years (2018-2021) of TB patients' records at 10 public health clinics in Sarawak, Malaysia. Adult patients (≥18 years) with drug-susceptible TB were selected. Treatment interruption was defined as ≥2 weeks of cumulative interruption during treatment. The Chi-square test, Mann-Whitney U test, Kaplan-Meier and Cox proportional hazards regression were used to analyse the data, with p < 0.05 being considered statistically significant.

Results: Out of 2953 eligible patients, 475 (16.1%) experienced TB treatment interruption. Interruptions were most frequent during the intensive phase (46.9%, n = 223), with the greatest risk within the first 4 weeks of treatment. The median time to interruption was 2 weeks in the intensive phase and the cumulative interruption probability at the end of the intensive phase was 12.9%. Notably, treatment interruption occurred during both intensive and continuation phases for 144 patients (30.3%), while the remaining 108 (22.7%) experienced interruptions only during the continuation phase with a median time to interruption of 16 weeks. Three predictors were identified to increase the risk of treatment interruption: adverse drug reaction (aHR = 8.53, 95% Cl: 6.73-10.82), smoking (aHR = 2.67, 95% Cl: 2.03-3.53) and illicit drug use (aHR = 1.88, 95% Cl: 1.03-3.45). Conversely, underlying diabetes was associated with a reduced likelihood of treatment interruption (aHR = 0.72, 95% Cl: 0.58-0.90). Treatment interruption led to significant differences in treatment restarts (62.3% vs. 0.7%), changes in medications (47.8% vs. 4.9%), prolonged treatment duration (247 days [IQR = 105] vs. 194 days [IQR = 44.3]) and lower successful outcomes (86.5% vs. 99.9%).

Conclusion: Understanding the temporal characteristics, predictors and negative consequences of treatment interruption can guide the development of time-relevant approaches to mitigate the problem.

Aim: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks.

Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries.

Results: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics.

Conclusion: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable.

Background: Cholangiocarcinoma (CCA) caused by Opisthorchis viverrini is a well-known and significant public health issue in northeastern Thailand; however, a link between pesticide exposure (PE) and CCA risk has not yet been established. Therefore, our research objective was to investigate the relationship between PE and CCA risk.

Methods: A hospital-based matched case-control study was carried out. All cases (in-patients) and controls (out-patients) were volunteers at a tertiary hospital in northeast Thailand. Between 2015 and 2019, 178 incident cases of pathologically-confirmed CCA and 356 controls were selected from the check-up clinic from the Srinagarind Hospital outpatient database (two controls per case). The recruited controls were individually-matched to the CCA cases based on sex, age (±5 years) and admission date (±3 months). During face-to-face interviews, a standardised pre-tested questionnaire was used to collect data. Multivariable conditional logistic regression was used to analyse the data.

Results: The respective frequency of PE between the 178 CCA cases and 356 controls was 77.0% versus 87.6% for never used, 14.6% versus 5.3% for have used but stopped and 8.4% versus 7.0% for currently using. After adjusting for the highest educational attainment, smoking behaviour, alcohol use and family history of cancer, PE was not significantly associated with CCA (p-value = 0.086). Using volunteers who have never used PE as the reference group, the respective odds of developing CCA for those who have ever used but have since stopped and are currently using was 2.04 (adjusted OR = 2.04; 95% CI: 1.03-4.04) versus 0.83 (adjusted OR = 0.83; 95% CI: 0.39-1.76) times more likely to develop CCA than those who had never used PE.

Conclusion: There is no association between PE and the risk of CCA. Notwithstanding the finding, future research should focus on enhancing PE assessment methods that consider complex chemical mixtures, chemicals of interest, historical exposure and exposure pathways. Moreover, there is need for more extensive and longer population-based cohort studies that include younger, non-occupationally exposed individuals during periods of developmental susceptibility.