A Systematic Review of the Mortality from Untreated Leptospirosis

Background: Leptospirosis occurs worldwide, but the global incidence of human disease and its mortality are not well understood. Many patients are undiagnosed and untreated due to its non-specific symptoms and a lack of access to diagnostics. This study systematically reviews the literature to clarify the mortality from untreated leptospirosis. Results will help quantify the global burden of disease and guide health policies. Methodology/Principal Findings: A comprehensive literature search was performed to identify untreated patient series. Included patients were symptomatic, but asymptomatic patients and those who had received antibiotics, dialysis or who were treated on Intensive Care Units were excluded. Included patients had a confirmed laboratory diagnosis by culture, PCR, or serological tests. Data was extracted and individual patient series were assessed for bias. Thirty-five studies, comprising 41 patient series and 3,390 patients, were included in the study. A high degree of bias within studies was shown due to limitations in study design, diagnostic tests and missing data. Median series mortality was 2.2% (Range 0.0 – 39.7%), but mortality was high in jaundiced patients (19.1%) (Range 0.0 – 39.7%), those with renal failure 12.1% (Range 0-25.0%) and in patients aged over 60 (60%) (Range 33.3-60%), but low in anicteric patients (0%) (Range 0-1.7%). Conclusions: This systematic review contributes to our understanding of the mortality of untreated leptospirosis and provides data for the estimation of DALYs attributable to this disease. We show that mortality is significantly higher in older patients with icteric disease or renal failure but is lower in younger, anicteric patients. Increased surveillance and accurate point-of-care diagnostics are required to better understand the incidence and improve diagnosis of disease. Empirical treatment strategies should prioritize early treatment to improve outcomes from leptospirosis. Author Summary: Leptospirosis is a common cause of fever in the developing world but often goes undiagnosed and untreated due to its non-specific clinical features and the limited availability of point-of-care diagnostics. This review systematically evaluated available literature to clarify the mortality from untreated leptospirosis. Untreated patients were defined as patients not receiving antibiotics, dialysis, or treatment on an Intensive Care Unit. All patients had a confirmed laboratory diagnosis of leptospirosis through culture, PCR or serological tests. Results showed that mortality from untreated leptospirosis is significant in older patients and those who develop complications such as jaundice and renal failure, but mortality is low in younger patients and those with anicteric disease. There was a high degree of bias within studies due to limitations in diagnostics and missing data. The data presented in this review, when coupled with improved understanding of the true incidence of the disease, will help estimate the burden of disease from leptospirosis. Increased surveillance and accurate point-of-care diagnostics are required to better understand the incidence of disease and outcomes from leptospirosis. Empirical treatment strategies of undifferentiated fever should focus on early treatment of fever to reduce mortality from leptospirosis.