A Systematic Review of Mortality from Untreated Scrub Typhus ( Orientia tsutsugamushi)

Abstract

Background

Scrub 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 Findings

A 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)).

Conclusions

Results 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.

Author Summary

Scrub typhus is a common cause of fever in rural Asia where there is limited access to healthcare, diagnostics, and treatment. It is thought that up to 1 million cases occur per year, but the disease is difficult to differentiate clinically from other infections, such as leptospirosis and dengue, meaning that many infections go undiagnosed and untreated. This review systematically summarizes the literature on the untreated mortality of scrub typhus and describes the outcome from untreated disease. Many articles had incomplete data and relied on a clinical diagnosis of disease, but results showed that scrub typhus is associated with a lower mortality than previously described, at approximately 6%, ranging from 0–70%. Further information is required to clarify the mortality according to location, host factors, and clinical syndromes. More widespread access to medical care, coupled with the increased use of affordable and accurate rapid tests, would improve the diagnosis and treatment of scrub typhus. Increased surveillance and investigation into differences in strain virulence by region are required to reliably quantify DALYs and the disease burden from scrub typhus, and to guide empirical treatment strategies.