Flow chart showing selection of studies for the review.

<p>Flow chart showing selection of studies for the review.</p

Mortality (red line) and number of patients (grey bar) by increasing frequency of jaundice (blue line).

<p>Mortality (red line) and number of patients (grey bar) by increasing frequency of jaundice (blue line).</p

A Systematic Review of Mortality from Untreated Scrub Typhus (<i>Orientia tsutsugamushi</i>)

<div><p>Background</p><p>Scrub typhus, a bacterial infection caused by <i>Orientia tsutsugamushi</i>, 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.</p><p>Methodology/Principal Findings</p><p>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)).</p><p>Conclusions</p><p>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.</p></div

Demographics, clinical symptoms and laboratory data across patient series.

<p>* <i>Definition of raised urea ranged from >8</i>.<i>9mmol/L to 21</i>.<i>4mmol/L</i>.</p><p>Demographics, clinical symptoms and laboratory data across patient series.</p

Descending median series mortality by location.

<p>Mortality is displayed in red with error bars displaying maximum and minimum values across studies. Grey bars indicate total number of patients for included studies in each location. Number of studies in each region is displayed in brackets after each location label.</p

Characteristics of included studies, arranged alphabetically by first author.

<p>When studies contained more than one patient series each series was displayed separately. All available data are included, but if data were not extractable it is indicated by a “-“. Percentage and (number/total number of patients) are quoted, but if no patient number was quoted then a “NA” is used. If no information on serovars is present a “*” is used.</p><p>Characteristics of included studies, arranged alphabetically by first author.</p

Flow diagram for selection of studies included in the review.

<p>Flow diagram for selection of studies included in the review.</p

Patient mortality by age.

<p>Patient mortality by age.</p

Mortality according to serovar.

<p>Mortality according to serovar.</p

Mortality (%) across patient series.

<p>Median series mortality is displayed as red squares and number of patients in each series as grey bars.</p