A Systematic Review of the Mortality from Untreated Leptospirosis.
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ABSTRACT: 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.
SUBMITTER: Taylor AJ
PROVIDER: S-EPMC4482028 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
A Systematic Review of the Mortality from Untreated Leptospirosis.
Taylor Andrew J AJ Paris Daniel H DH Newton Paul N PN
PLoS neglected tropical diseases 20150625 6
<h4>Background</h4>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.<h4>Methodology/principal findings</h4>A comprehensive literatur ...[more]
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Project description:BackgroundLeptospirosis, a spirochaetal zoonosis, occurs in diverse epidemiological settings and affects vulnerable populations, such as rural subsistence farmers and urban slum dwellers. Although leptospirosis is a life-threatening disease and recognized as an important cause of pulmonary haemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected disease status.Methodology/principal findingsWe conducted a systematic review of published morbidity and mortality studies and databases to extract information on disease incidence and case fatality ratios. Linear regression and Monte Carlo modelling were used to obtain age and gender-adjusted estimates of disease morbidity for countries and Global Burden of Disease (GBD) and WHO regions. We estimated mortality using models that incorporated age and gender-adjusted disease morbidity and case fatality ratios. The review identified 80 studies on disease incidence from 34 countries that met quality criteria. In certain regions, such as Africa, few quality assured studies were identified. The regression model, which incorporated country-specific variables of population structure, life expectancy at birth, distance from the equator, tropical island, and urbanization, accounted for a significant proportion (R(2) = 0.60) of the variation in observed disease incidence. We estimate that there were annually 1.03 million cases (95% CI 434,000-1,750,000) and 58,900 deaths (95% CI 23,800-95,900) due to leptospirosis worldwide. A large proportion of cases (48%, 95% CI 40-61%) and deaths (42%, 95% CI 34-53%) were estimated to occur in adult males with age of 20-49 years. Highest estimates of disease morbidity and mortality were observed in GBD regions of South and Southeast Asia, Oceania, Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa.Conclusions/significanceLeptospirosis is among the leading zoonotic causes of morbidity worldwide and accounts for numbers of deaths, which approach or exceed those for other causes of haemorrhagic fever. Highest morbidity and mortality were estimated to occur in resource-poor countries, which include regions where the burden of leptospirosis has been underappreciated.
| S-EPMC4574773 | biostudies-literature
Project description: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.
| S-EPMC7515178 | biostudies-literature
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.
| S-EPMC4537241 | biostudies-literature
Project description:IntroductionLeptospirosis is a leading zoonotic disease worldwide with more than 1 million cases in the general population per year. With leptospirosis being an emerging infectious disease and as the world's environment changes with more floods and environmental disasters, the burden of leptospirosis is expected to increase. The objectives of the systematic review were to explore how leptospirosis affects pregnancy, its burden in this population, its effects on maternal and fetal outcomes and the evidence base surrounding treatment options.MethodsWe performed a systematic review of published and unpublished literature using automated and manual methods to screen nine electronic databases since inception, with no language restriction. Two reviewers independently screened articles, completed the data extraction and assessment of risk of bias. Due to significant heterogeneity and paucity of data, we were unable to carry out a meta-analysis, but we conducted a pooled analysis of individual patient data from the case reports and case series to examine the patient and disease characteristics, diagnostic methods, differential diagnoses, antibiotic treatments, and outcomes of leptospirosis in pregnancy. The protocol for this review was registered on the International Prospective Register of Systematic Reviews, PROSPERO: CRD42020151501.ResultsWe identified 419 records, of which we included eight observational studies, 21 case reports, three case series and identified four relevant ongoing studies. Overall the studies were with moderate bias and of 'fair' quality. We estimated the incidence of leptospirosis in pregnancy to be 1.3 per 10,000 in women presenting with fever or with jaundice, but this is likely to be higher in endemic areas. Adverse fetal outcomes were found to be more common in pregnant patients who presented in the second trimester compared with patients who presented in the third trimester. There is overlap between how leptospirosis presents in pregnancy and in the general population. There is also overlap between the signs, symptoms and biochemical disturbances associated with leptospirosis in pregnancy and the presentation of pregnancy associated conditions, such as Pre-Eclampsia (PET), Acute Fatty Liver of Pregnancy (AFLP) and HELLP Syndrome (Haemolysis Elevated Liver enzymes Low Platelets). In 94% of identified cases with available data, there was an indicator in the patient history regarding exposure that could have helped include leptospirosis in the clinician's differential diagnosis. We also identified a range of suitable antibiotic therapies for treating leptospirosis in pregnancy, most commonly used were penicillins.ConclusionThis is the first systematic review of leptospirosis in pregnancy and it clearly shows the need to improve early diagnosis and treatment by asking early, treating early, and reporting well. Ask early-broaden differential diagnoses and ask early for potential leptospirosis exposures and risk factors. Treat early-increase index of suspicion in pregnant patients with fever in endemic areas and combine with rapid field diagnosis and early treatment. Report well-need for more good quality epidemiological studies on leptospirosis in pregnancy and better quality reporting of cases in literature.
| S-EPMC8462732 | biostudies-literature
Project description:INTRODUCTION:Leptospirosis is the most common zoonotic disease that causes morbidity and mortality worldwide. The disease can cause sporadic epidemics and recent epidemics have become more apparent in urban localities. There is lack of documented evidence on the specific risk factors of leptospirosis infection among the urbanites, thereby impeding initiatives for prevention in urban settings. We aim to systematically search published articles and synthesise evidence on the risk factors associated with leptospirosis infection among the susceptible populations in urban localities, particularly to identify the risk factors of non-recreational leptospirosis infection. METHODS AND ANALYSIS:We will conduct a systematic review of observational studies that investigated environmental risk factors of leptospirosis in urban localities. The search will be performed for any eligible articles from selected electronic databases from 1970 until May 2018. The study will include any studies that investigated risk factors of confirmed leptospirosis cases who acquired the infection in urban locality, particularly exposures from the non-recreational and non-water-related activities. Study selection and reporting will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guideline. All data will be extracted using a standardised data extraction form and quality of the studies will be assessed using the Newcastle-Ottawa Scale guideline. Descriptive and meta-analysis will be performed by calculating the standardised median ORs and risk ratios for types of the non-recreational risk factors stratified by social, living conditions and environmental exposures, types of reservoirs and transmissions and types of activities and employments associated with leptospirosis infection in urban locality. ETHICS AND DISSEMINATION:No primary data will be collected thus no formal ethical approval is required. The results will be disseminated though a peer-reviewed publication and conference presentation. PROSPERO REGISTRATION NUMBER:CRD42018090820.
| S-EPMC6347878 | biostudies-other
Project description:BackgroundLeptospirosis is one of the most widespread zoonotic diseases, which is of global medical and veterinary importance, and also a re-emerging infectious disease. The main tracks of transmission are known; however, the relative importance of each of the components and the respective environmental risk factors are unclear. We aimed to assess and specify quantitative evidence of environmental risks of leptospirosis transmission.Methods/findingsA database of pre-selected studies, with publication dates from 1970 until 2008, was provided by an expert group. The database has been updated until 2015 using a text mining algorithm. Study selection was based on stringent quality criteria. A descriptive data analysis was performed to calculate the medians of the log transformed odds ratios. From a selection of 2723 unique publications containing information on leptospirosis, 428 papers dealing with risk factors were identified. Of these, 53 fulfilled the quality criteria, allowing us to identify trends in different geo-climatic regions. Water associated exposures were, with few exceptions, associated with an increased leptospirosis risk. In resource poor countries, floods and rainfall were of particular importance, whereas recreational water activities were more relevant in developed countries. Rodents were associated with increased leptospirosis risk, but the variation among studies was high, which might be partly explained by differences in exposure definition. Livestock contact was commonly associated with increased risk; however, several studies found no association. The median odds ratios associated with dog and cat contacts were close to unity. Sanitation and behavioural risk factors were almost always strongly associated with leptospirosis, although their impact was rarely investigated in Europe or North America.ConclusionThis review confirms the complex environmental transmission pathways of leptospirosis, as previously established. Although, floods appeared to be among the most important drivers on islands and in Asia, the consistent pattern observed for exposure to rodents and behavioural and sanitation related risk factors indicate potential areas for intervention.
| S-EPMC4574979 | biostudies-literature
Project description:BACKGROUND:Although the assessment of disease burden should be a priority for allocating resources, leptospirosis is grossly underestimated despite its true burden in Sri Lanka. This study aimed to assess the morbidity and mortality of leptospirosis based on routine surveillance data, hospital reported data and scientific publications from Sri Lanka. METHOD:A systematic review was carried out, and Pub Med, MEDLINE®, BIOSIS Previews, Zoological Record, Web of Science Core Collection, Current Contents Connect, KCI-Korean Journal Database, BIOSIS Citation Index, Data Citation Index, SciELO Citation Index and Google Scholar databases were searched. Quarterly epidemiological bulletin (QEB), indoor morbidity & mortality returns (IMMR) and hand searches of local literature were performed in local libraries. Forty-two relevant full texts, 32 QEBs, and 8 IMMR were included in the full text review. Adjustments were made for under diagnosis, underreporting and chance variability. RESULTS:The estimated annual caseload of leptospirosis in Sri Lanka from 2008 to 2015, was 10,423, and the cumulative annual incidence of leptospirosis that required hospitalization was 52.1 (95% CI 51.7-52.6) per 100,000 people. The estimated number of annual deaths due to leptospirosis was approximately 730 (95% CI 542-980), with an estimated pooled case fatality ratio of 7.0% (95% CI 5.2-9.4). The most common organs involved were the kidney, liver and heart, with median rates of 48.7, 30, and 14.2%, respectively. CONCLUSION:Our systematic review shows gross underestimation of the true leptospirosis burden in the national statistics of Sri Lanka, and the hospitalization rates estimated in our study were compatible with the total burden estimate of 300·6 (95% CI 96·54-604·23) per 100,000 people published previously.
| S-EPMC6364467 | biostudies-literature
Project description:BACKGROUND:Leptospirosis is a neglected zoonotic disease which is a major challenge for clinicians and public health professionals in tropical countries. The cytokine storm during the second (immune) phase is thought to be a major contributory factor for the leptospirosis disease severity. We aim to summarize evidence for cytokine response in leptospirosis at different clinical outcomes. METHODS:A systematic review was carried out to examine the cytokine response in leptospirosis patients using relevant scientific databases. Reference lists of the selected articles were also screened. Quality of the selected studies was assessed by using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. RESULTS:Of the 239 articles retrieved in the initial search, 18 studies fulfilled the selection criteria. India and Thailand have produced the highest number of studies (17% each, n?=?3). The majority were comparative cross-sectional studies (72%, n?=?13). Overall the quality of the selected studies was fair regardless of few drawbacks such as reporting of sample size and the lack of adjustment for confounders. Microscopic agglutination test (67% - 12/18) and enzyme-linked immunosorbent assay (50% - 9/18) were commonly used for the confirmation of leptospirosis and the measurement of cytokines respectively. IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10 and TNF-? levels were found to be significantly higher in severe than in mild leptospirosis. There were equivocal findings on the association between IL-1?, TNF-? and IL-10/TNF-? ratio and disease severity. CONCLUSIONS:Leptospirosis had a wide-range of elevated cytokines. However, prospective studies in-relation to the onset of the symptom are required to better understand the pathophysiology of cytokine response in leptospirosis.
| S-EPMC7137275 | biostudies-literature
Project description:BACKGROUND:Phenylketonuria (PKU) is often considered as the classical example of a genetic disorder in which severe symptoms can nowadays successfully be prevented by early diagnosis and treatment. In contrast, untreated or late-treated PKU is known to result in severe intellectual disability, seizures, and behavioral disturbances. Rarely, however, untreated or late-diagnosed PKU patients with high plasma phenylalanine concentrations have been reported to escape from intellectual disability. The present study aimed to review published cases of such PKU patients. METHODS:To this purpose, we conducted a literature search in PubMed and EMBASE up to 8th of September 2017 to identify cases with 1) PKU diagnosis and start of treatment after 7 years of age; 2) untreated plasma phenylalanine concentrations ?1200 ?mol/l; and 3) IQ ?80. Literature search, checking reference lists, selection of articles, and extraction of data were performed by two independent researchers. RESULTS:In total, we identified 59 published cases of patients with late-diagnosed PKU and unexpected favorable outcome who met the inclusion criteria. Although all investigated patients had intellectual functioning within the normal range, at least 19 showed other neurological, psychological, and/or behavioral symptoms. CONCLUSIONS:Based on the present findings, the classical symptomatology of untreated or late-treated PKU may need to be rewritten, not only in the sense that intellectual dysfunction is not obligatory, but also in the sense that intellectual functioning does not (re)present the full picture of brain damage due to high plasma phenylalanine concentrations. Further identification of such patients and additional analyses are necessary to better understand these differences between PKU patients.
| S-EPMC6116368 | biostudies-literature
Project description:IntroductionLeptospirosis is a zoonotic disease with high prevalence in low-income and middle-income countries and tropical and subtropical regions. The clinical symptoms of the disease are similar to symptoms presented by other endemic infectious diseases that could be present simultaneously. Thus, leptospirosis could be masked by similar infections like dengue, malaria, hantavirus, melioidosis and borreliosis, among others. Therefore, leptospirosis could present itself as an under-reported infection or as a coinfection with another pathogen, as has been reported in the literature. However, there is a lack of documented evidence about the specific risk factors of leptospirosis infection, the symptoms, the coinfection's mortality and the frequency of coinfection. Additionally, leptospirosis coinfections have not been considered a neglected public health concern. Therefore, this systematic review aims to evaluate published articles that show the risk factors associated with leptospirosis infection and coinfection with other pathogens.Methods and analysisThe search process to identify eligible studies will be conducted including the LILACS, ProQuest, PubMed and Scopus databases with no restriction in terms of publication date. Also, grey literature will be included in the research. Authors will independently screen the title and abstracts of the articles identified from the search using Rayyan free software. Eligibility criteria include peer-reviewed research articles written in English or Spanish, including observational studies, cohorts, case-control, cross-sectional, ecological studies and report cases. The systematic review will include studies that report descriptions of leptospirosis cases with coinfection or co-occurrence. The search will be accomplished by articles from 1950 to May 2022. The data will be extracted in a standard extraction form using an Excel format.Ethics and disseminationResults will be published in a peer-reviewed journal. Also, findings will be disseminated through scientific meetings. Ethical approval will not be required as this is a systematic review and primary data will be not collected or included.Prospero registration numberCRD42021234754.
| S-EPMC9764663 | biostudies-literature