Search

BackgroundScrub typhus is an acute febrile illness caused by intracellular bacteria from the genus Orientia. It is estimated that one billion people are at risk, with one million cases annually mainly affecting rural areas in Asia-Oceania. Relative to its burden, scrub typhus is understudied, and treatment recommendations vary with poor evidence base. These knowledge gaps could be addressed by establishing an individual participant-level data (IPD) platform, which would enable pooled, more detailed and statistically powered analyses to be conducted. This study aims to assess the characteristics of scrub typhus treatment studies and explore the feasibility and potential value of developing a scrub typhus IPD platform to address unanswered research questions.Methodology/principal findingsWe conducted a systematic literature review looking for prospective scrub typhus clinical treatment studies published from 1998 to 2020. Six electronic databases (Ovid Embase, Ovid Medline, Ovid Global Health, Cochrane Library, Scopus, Global Index Medicus), ClinicalTrials.gov, and WHO ICTRP were searched. We extracted data on study design, treatment tested, patient characteristics, diagnostic methods, geographical location, outcome measures, and statistical methodology. Among 3,100 articles screened, 127 were included in the analysis. 12,079 participants from 12 countries were enrolled in the identified studies. ELISA, PCR, and eschar presence were the most commonly used diagnostic methods. Doxycycline, azithromycin, and chloramphenicol were the most commonly administered antibiotics. Mortality, complications, adverse events, and clinical response were assessed in most studies. There was substantial heterogeneity in the diagnostic methods used, treatment administered (including dosing and duration), and outcome assessed across studies. There were few interventional studies and limited data collected on specific groups such as children and pregnant women.Conclusions/significanceThere were a limited number of interventional trials, highlighting that scrub typhus remains a neglected disease. The heterogeneous nature of the available data reflects the absence of consensus in treatment and research methodologies and poses a significant barrier to aggregating information across available published data without access to the underlying IPD. There is likely to be a substantial amount of data available to address knowledge gaps. Therefore, there is value for an IPD platform that will facilitate pooling and harmonisation of currently scattered data and enable in-depth investigation of priority research questions that can, ultimately, inform clinical practice and improve health outcomes for scrub typhus patients.

Background: The effectiveness of the first regimen of antiretroviral therapy (ART) is a major key to long-term success and sustainability of HIV treatment program. Aims: The objectives of this study were to determine the incidence rate, reasons, and factors associated with modification of initial ART regimen. Methods: A total of 502 patient files were reviewed. Modification of ART regimen was defined as either substitution or switch of a single drug in the regimen. Results: The total duration of follow-up was 629.8 person-years (PYs) over a median follow-up period of 37 months. About 92 (18.2%) of patients had their initial ART regimen modified, with a resulting incidence rate of modification at 14.6/100 PYs. Drug unavailability 49 (53.3%), drug toxicity 16 (17.4%), treatment failure 10 (10.9%), nonadherence 7 (7.6%), and concomitant condition 7 (7.6%) were common reasons for ART modifications. In the adjusted multivariate Cox proportional hazard model, the type of initial ART regimen (zidovudine/lamivudine (3TC)/efavirenz vs. tenofovir/3TC/nevirapine (NVP), aHR 4.78, 95% confidence interval [CI] [1.42, 16.12], P = 0.012), and duration on regimen (≤1 year vs. >3 years, aHR 4.11, 95% CI [1.02–9.22], P = 0.0001) were significantly associated with modification of initial ART regimen. Conclusion: Our findings indicate that the incidence rate of initial ART regimen modification was high. Hence, implementing better health systems to ensure a steady supply of drugs as well as early HIV diagnosis and ART initiation will reduce the rate of regimen change.