Prevalence of malaria and scrub typhus co-infection in febrile patients: a systematic review and meta-analysis

Background: Little information is available about malaria and scrub typhus co-infection. This study aimed to investigate the pooled prevalence of malaria and scrub typhus co-infection in febrile patients. Further, it aimed to estimate the prevalence of scrub typhus infection among patients with malaria and the odds of co-infection. This will aid the diagnosis and management of co-infected patients in endemic areas. Methods: We searched for relevant studies in three databases: PubMed, Scopus, and Web of Science. We assessed the quality of the included studies using the Joanna Briggs Institute checklist for analytical cross-sectional studies. We estimated (1) the pooled prevalence of malaria and scrub typhus co-infection, (2) the pooled prevalence of scrub typhus infection in malaria-positive patients, and (3) the pooled odds of co-infection using the DerSimonian-Laird method for random-effects models. The study results and summary estimates were visualized on a forest plot as point estimates (effect size, prevalence) and 95% confidence intervals (CI). We assessed the heterogeneity of the studies by Cochrane Q or I-2 statistics. We performed subgroup analyses of countries and scrub typhus diagnostic tests to explore the sources of heterogeneity of the included studies. We assessed publication bias if more than 10 studies were used to estimate the outcome. All data analyses were conducted using Stata version 14 (StataCorp, College Station, TX, USA). Results: Of the 542 studies retrieved from three databases, we included 14 meeting the inclusion criteria in the systematic review and meta-analysis. The pooled prevalence of malaria and scrub typhus co-infection (56 cases) among febrile patients (7920 cases) was 1% (95% CI: 0-1%, I-2: 78.28%), while the pooled prevalence of scrub typhus infection (321 cases) in patients with malaria (1418 cases) was 21% (95% CI: 12-30%, I-2: 98.15%). Subgroup analysis showed that the pooled prevalence of scrub typhus infection among patients with malaria in India was 8% (95% CI: 4-13%, I-2: 85.87%, nine studies with 59/794 cases), while the pooled prevalence of scrub typhus infection among patients with malaria in Thailand was 35% (95% CI: 7-64%, I-2: 98.9%, four studies with 262/624 cases). The co-infections did not occur by chance (P = 0.013, odds: 0.43, 95% CI: 0.22-0.84%, I-2: 60.9%). In the sensitivity analysis, the pooled prevalence of malaria and scrub typhus co-infection among febrile patients was 0% (95% CI: 0-1%, I-2: 59.91%). Conclusions: The present study showed the pooled prevalence and a significant association between malaria and scrub typhus. The results show the status of co-infection. Further research into co-infection in endemic areas is needed, in particular, to determine whether co-infection can accelerate disease progression or protect against severe disease.