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A systematic review of the untreated mortality of murine typhus.

ABSTRACT: Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aimed to describe the outcomes and estimate the mortality of untreated murine typhus through a comprehensive systematic literature review. We systematically searched the literature for articles describing untreated murine typhus patients, excluding cases with no laboratory assay confirmed diagnosis, those who received efficacious treatment, had incomplete information on primary outcome and articles describing less than 10 patients and performed a narrative synthesis of the study findings. The study protocol followed the PRISMA guidelines and was part of a more extensive protocol registered at PROSPERO (CRD42018101991). Twelve studies including a total of 239 untreated patients matched the eligibility criteria. Only a single study reported one death in 28 patients, giving a patient series mortality of 3.6% and an overall mortality of 0.4% in 239 untreated patients. Complications were reported in 10 of the 12 studies and included involvement of the central nervous system, kidney and lung, with a hospitalisation rate of 70% and ICU admission rate of 27% in one study. The mean duration of fever in untreated patients was 15 days in two and 12.7 days in one study. Although the untreated mortality in this study was low, the sample size was small. Murine typhus caused significant morbidity when untreated, leading to high hospitalisation rates and highlighting the importance of early diagnosis and treatment of this neglected disease to reduce disease burden and health-care related costs.

SUBMITTER: Doppler JF

PROVIDER: S-EPMC7515178 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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A systematic review of the untreated mortality of murine typhus.

Doppler Johannes F JF Newton Paul N PN

PLoS neglected tropical diseases 20200914 9

Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aim ...[more]

PMID: 32925913

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Project description: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.

Project description:BackgroundScrub typhus is a vector-borne zoonotic disease that can be life-threatening. There are no licensed vaccines, or vector control efforts in place. Despite increasing awareness in endemic regions, the public health burden and global distribution of scrub typhus remains poorly known.MethodsWe systematically reviewed all literature from public health records, fever studies and reports available on the Ovid MEDLINE, Embase Classic + Embase and EconLit databases, to estimate the burden of scrub typhus since the year 2000.FindingsIn prospective fever studies from Asia, scrub typhus is a leading cause of treatable non-malarial febrile illness. Sero-epidemiological data also suggest that Orientia tsutsugamushi infection is common across Asia, with seroprevalence ranging from 9.3%-27.9% (median 22.2% IQR 18.6-25.7). A substantial apparent rise in minimum disease incidence (median 4.6/100,000/10 years, highest in China with 11.2/100,000/10 years) was reported through passive national surveillance systems in South Korea, Japan, China, and Thailand. Case fatality risks from areas of reduced drug-susceptibility are reported at 12.2% and 13.6% for South India and northern Thailand, respectively. Mortality reports vary widely around a median mortality of 6.0% for untreated and 1.4% for treated scrub typhus. Limited evidence suggests high mortality in complicated scrub typhus with CNS involvement (13.6% mortality), multi-organ dysfunction (24.1%) and high pregnancy miscarriage rates with poor neonatal outcomes.InterpretationScrub typhus appears to be a truly neglected tropical disease mainly affecting rural populations, but increasingly also metropolitan areas. Rising minimum incidence rates have been reported over the past 8-10 years from countries with an established surveillance system. A wider distribution of scrub typhus beyond Asia is likely, based on reports from South America and Africa. Unfortunately, the quality and quantity of the available data on scrub typhus epidemiology is currently too limited for any economical, mathematical modeling or mapping approaches.

Project description:BackgroundScrub typhus, a vector-borne zoonotic infection caused by the bacteria Orientia tsutsugamushi, is one of the most common and clinically important rickettsial infections worldwide. An estimated one million cases occur annually with a high case fatality rate. Although scrub typhus is a major public health threat in India, the burden and distribution remains unclear. We aimed to estimate the burden of scrub typhus in India.MethodologyWe performed a systematic review of published literature on scrub typhus from India to extract information on epidemiology, morbidity, and mortality. Important databases were searched using keywords and appropriate combinations. We identified observational, interventional, and population-based studies and extracted the data to evaluate the number of cases diagnosed using serology or PCR and the number of deaths due to scrub typhus. We conducted a systematic narrative synthesis to summarize included studies.Principal findingsIn the last decade, there were 18,781 confirmed scrub typhus cases reported in 138 hospital-based studies and two community-based studies. IgM ELISA was used in 122 studies to confirm the cases in majority (89%). The proportion of scrub typhus among acute undifferentiated febrile illness (AUFI) studies was 25.3%, and community seroprevalence was 34.2%. Ninety studies had data published on multiple organ involvement out of which 17.4% of cases had multiple organ dysfunction syndromes, 20.4% patients required ICU admission, and 19.1% needed ventilation. The overall case-fatality rate was 6.3%, and the mortality among those with multi-organ dysfunction syndrome was as high as 38.9%.Conclusion/significanceScrub typhus, a common acute febrile illness in India causing severe morbidity, accounts for a large number of deaths. The burden of the disease has been underappreciated. Early diagnosis and prompt treatment can significantly reduce complications and mortality. Establishing good surveillance and instituting appropriate control measures are urgently needed.

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A systematic review of the untreated mortality of murine typhus.

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A systematic review of the untreated mortality of murine typhus.

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