Abstract
BackgroundScrub typhus, a bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. Limited access to health care and the disease’s non-specific symptoms mean that many patients are undiagnosed and untreated, but the mortality from untreated scrub typhus is unknown. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes.Methodology/Principal FindingsA literature search was performed to identify patient series containing untreated patients. Patients were included if they were symptomatic and had a clinical or laboratory diagnosis of scrub typhus and excluded if they were treated with antibiotics. The primary outcome was mortality from untreated scrub typhus and secondary outcomes were total days of fever, clinical symptoms, and laboratory results. A total of 76 studies containing 89 patient series and 19,644 patients were included in the final analysis. The median mortality of all patient series was 6.0% with a wide range (min-max) of 0–70%. Many studies used clinical diagnosis alone and had incomplete data on secondary outcomes. Mortality varied by location and increased with age and in patients with myocarditis, delirium, pneumonitis, or signs of hemorrhage, but not according to sex or the presence of an eschar or meningitis. Duration of fever was shown to be long (median 14.4 days Range (9–19)).ConclusionsResults show that the untreated mortality from scrub typhus appears lower than previously reported estimates. More data are required to clarify mortality according to location and host factors, clinical syndromes including myocarditis and central nervous system disease, and in vulnerable mother-child populations. Increased surveillance and improved access to diagnostic tests are required to accurately estimate the untreated mortality of scrub typhus. This information would facilitate reliable quantification of DALYs and guide empirical treatment strategies.
Highlights
Scrub typhus is caused by infection with the intracellular bacteria Orientia tsutsugamushi, which is transmitted by the bite of larval trombiculid mites
The disease is most common in rural areas, where there is limited access to healthcare, diagnostics and treatment, and is difficult to differentiate from other infections, such as leptospirosis and dengue, on a clinical basis alone
Diagnosis was considered Grade I if O. tsutsugamushi were cultured or there was a 4-fold rise in titre on Immunofluorescence Assay (IFA), Grade II if there was a single high titre on IFA, or Weil-Felix (OXK) test was positive for all Seventy-six articles, containing 89 patient series, and a total of 20,307 patients were identified for inclusion (Fig 1)
Summary
Scrub typhus is caused by infection with the intracellular bacteria Orientia tsutsugamushi, which is transmitted by the bite of larval trombiculid mites. In Southeastern Asia, it is thought that up to 1 million cases occur per year [5,6], and a significant proportion of hospital admissions for acute undifferentiated fever have been shown to be attributable to scrub typhus [5,7]. The disease is most common in rural areas, where there is limited access to healthcare, diagnostics and treatment, and is difficult to differentiate from other infections, such as leptospirosis and dengue, on a clinical basis alone. A bacterial infection caused by Orientia tsutsugamushi, is increasingly recognized as an important cause of fever in Asia, with an estimated one million infections occurring each year. This review systematically summarizes the literature on the untreated mortality from scrub typhus and disease outcomes
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