Estimating Leptospirosis Incidence Using Hospital-Based Surveillance and a Population-Based Health Care Utilization Survey in Tanzania

Background

The incidence of leptospirosis, a neglected zoonotic disease, is uncertain in Tanzania and much of sub-Saharan Africa, resulting in scarce data on which to prioritize resources for public health interventions and disease control. In this study, we estimate the incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania.

Methodology/Principal Findings

We conducted a population-based household health care utilization survey in two districts in the Kilimanjaro Region of Tanzania and identified leptospirosis cases at two hospital-based fever sentinel surveillance sites in the Kilimanjaro Region. We used multipliers derived from the health care utilization survey and case numbers from hospital-based surveillance to calculate the incidence of leptospirosis. A total of 810 households were enrolled in the health care utilization survey and multipliers were derived based on responses to questions about health care seeking in the event of febrile illness. Of patients enrolled in fever surveillance over a 1 year period and residing in the 2 districts, 42 (7.14%) of 588 met the case definition for confirmed or probable leptospirosis. After applying multipliers to account for hospital selection, test sensitivity, and study enrollment, we estimated the overall incidence of leptospirosis ranges from 75–102 cases per 100,000 persons annually.

Conclusions/Significance

We calculated a high incidence of leptospirosis in two districts in the Kilimanjaro Region of Tanzania, where leptospirosis incidence was previously unknown. Multiplier methods, such as used in this study, may be a feasible method of improving availability of incidence estimates for neglected diseases, such as leptospirosis, in resource constrained settings.     

Diagnostic method-based underestimation of leptospirosis in clinical and research settings; an experience from a large prospective study in a high endemic setting

BackgroundLeptospirosis has globally significant human mortality and morbidity, yet estimating the clinical and public health burden of leptospirosis is challenging because timely diagnosis remains limited. The goal of the present study was to evaluate leptospirosis undercounting by current standard methods in both clinical and epidemiological study settings.Methodology/Principal findingsA prospective hospital-based study was conducted in multiple hospitals in Sri Lanka from 2016 to 2019. Culture, whole blood, and urine samples were collected from clinically suspected leptospirosis cases and patients with undifferentiated fever. Analysis of biological samples from 1,734 subjects confirmed 591 (34.1%) cases as leptospirosis and 297 (17.1%) were classified as “probable” leptospirosis cases. Whole blood quantitative PCR (qPCR) did identify the most cases (322/540(60%)) but missed 40%. Cases missed by each method include; urine qPCR, 70% (153/220); acute sample microscopic agglutination test (MAT), 80% (409/510); paired serum sample MAT, 58% (98/170); and surveillance clinical case definition, 53% (265/496). qPCR of negative culture samples after six months of observation was of diagnostic value retrospectively with but missed 58% of positives (109/353).ConclusionLeptospirosis disease burden estimates should consider the limitations of standard diagnostic tests. qPCR of multiple sample types should be used as a leading standard test for diagnosing acute leptospirosis.     

Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand

AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.     

Major Neutrophilia Observed in Acute Phase of Human Leptospirosis Is Not Associated with Increased Expression of Granulocyte Cell Activation Markers

It has long been known that pathogenic Leptospira can mobilize the immune system but the specific contribution of neutrophils to control the infectious challenge remains to be clarified. We herein analyzed the phenotype of circulating neutrophils of patients with leptospirosis and healthy controls for the expression of toll-like receptor (TLR) type 2 (TLR2, to sense the leptospiral LPS) and several activation markers: interleukin 8 chemokine receptor CD182 (CXCR2), CD11b of the integrin/opsonin complement receptor type 3 (CR3) and CD15 (ligand of the selectin). The plasmatic level of the main CD182 ligand, interleukin 8 (CXCL8), was measured by ELISA. Hospitalized leptospirosis cases showed marked neutrophilia, particularly in the most severe cases. Interestingly, TLR2 was significantly increased in leptospirosis but identical levels of CD182 and CD11b were detected when compared to controls. CD15 was significantly decreased on neutrophils in leptospirosis but returned to normal within 1 month. Basal levels of IL-8 were measured in control subjects and were not increased in leptospirosis cases at the initial stage of the disease. In conclusion, we observed that neutrophils failed to regulate the expression of several of the receptors involved in cell activation and recruitment. This study further emphasizes the paradigm that neutrophils may be impaired in their overall capacity to thwart bacterial infection in leptospirosis patients.     

Leptospirosis in pregnancy: A systematic review

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.     

Leptospirosis: Public health perspectives

Leptospirosis, caused by a spirochete of genus Leptospira, is considered the most widespread zoonosis in the world. It has a global distribution with a higher incidence in the tropics and subtropics, ranging from 10 to 100 human cases per 100,000 individuals. Leptospirosis is considered an “emerging” zoonosis due to increased contact between animals and humans and the resulting human encroachment into wildlife habitat. Climate change and its associated environmental shifts can affect the degree of transmission of leptospirosis. Surveillance for leptospirosis is important for early detection of cases because early treatment is crucial to decrease morbidity and mortality. In June 2012, the Council of State and Territorial Epidemiologists approved reinstatement of leptospirosis as a Nationally Notifiable Condition. Reinstatement of national surveillance will facilitate the assessment of the incidence, geographic distribution, trends, and risk factors associated with human cases and the identification of outbreaks and potential new animal reservoirs.     

Towards the Burden of Human Leptospirosis: Duration of Acute Illness and Occurrence of Post-Leptospirosis Symptoms of Patients in The Netherlands

Background

Leptospirosis is a global zoonotic disease. Although important for the assessment of the burden of leptospirosis, data on the duration of the illness and the occurrence of post-leptospirosis complaints are not well documented. Hence the main objective of this study was to estimate the occurrence of persistent complaints and duration of hospital stay in laboratory confirmed leptospirosis patients in the Netherlands during 1985 to 2010. Additionally, several risk factors potentially impacting on the occurrence of post-leptospirosis complaints were investigated.

Methods/Principal Findings

The duration of the acute phase of leptospirosis was 16 days (IQR 12–23); 10 days (IQR 7–16) were spent hospitalized. Eighteen fatal cases were excluded from this analysis. Complaints of leptospirosis patients by passive case investigations (CPC) derived from files on ambulant consultations occurring one month after hospital discharge, revealed persistent complaints in 108 of 236 (45.8%) laboratory confirmed cases. Data on persistent complaints after acute leptospirosis (PCAC), assessed in 225 laboratory confirmed leptospirosis cases collected through questionnaires during 1985-1993, indicated 68 (30.2%) PCAC cases. Frequently reported complaints included (extreme) fatigue, myalgia, malaise, headache, and a weak physical condition. These complaints prolonged in 21.1% of the cases beyond 24 months after onset of disease. There was no association between post-leptospirosis complaints and hospitalization. However, individuals admitted at the intensive care unit (ICU) were twice as likely to have continuing complaints after discharge adjusting for age and dialysis (OR 2.0 95% CI 0.8-4.8). No significant association could be found between prolongation of complaints and infecting serogroup, although subgroup analysis suggest that infection with serogroups Sejroe (OR 4.8, 95%CI 0.9-27.0) and icterohaemorrhagiae (OR 2.0, 95%CI 0.9-4.3 CI) are more likely to result in CPC than infections with serogroup Grippotyphosa.

Conclusion/Significance

In addition to the acute disease, persistent complaints have an impact on the burden of leptospirosis.     

The impact of climate on Leptospirosis in São Paulo,Brazil

In this work, we correlate the daily number of human leptospirosis cases with several climatic factors. We used a negative binomial model that considers hospital daily admissions due to leptospirosis as the dependent variable, and the climatic variables of daily precipitation pattern, and maximum and minimum temperature as independent variables. We calculated the monthly leptospirosis admission probabilities from the precipitation and maximum temperature variables. The month of February showed the highest probability, although values were also high during the spring months. The month of February also showed the highest number of hospital admissions. Another interesting result is that, for every 20 mm precipitation, there was an average increase of 31.5% in hospital admissions. Additionally, the relative risk of leptospirosis varied from 1.1 to 2.0 when the precipitation varied from 20 to 140 mm.     

The mechanisms maintaining epidemic foci of leptospirosis]

24,419 samples of blood serum, collected in the Azerbaijan SSR among different professional groups of the population, have been tested for leptospirosis. The comparison of the results with those obtained in the natural foci of leptospirosis and in the foci of this infection appearing as a consequence of human activities has made it possible to come to the conclusion that the epidemic foci of leptospirosis are maintained due to the existence of foci among cattle. The cases of contamination among persons professionally linked with large cattle breeding complexes have been found to exceed those among persons working at farms of a nonindustrial type.     

Rainfall and other meteorological factors as drivers of urban transmission of leptospirosis

BackgroundLeptospirosis is an important public health problem affecting vulnerable urban slum populations in developing country settings. However, the complex interaction of meteorological factors driving the temporal trends of leptospirosis remain incompletely understood.Methods and findingsFrom March 1996—March 2010, we investigated the association between the weekly incidence of leptospirosis and meteorological anomalies in the city of Salvador, Brazil by using a dynamic generalized linear model that accounted for time lags, overall trend, and seasonal variation. Our model showed an increase of leptospirosis cases associated with higher than expected rainfall, lower than expected temperature and higher than expected humidity. There was a lag of one-to-two weeks between weekly values for significant meteorological variables and leptospirosis incidence. Independent of the season, a weekly cumulative rainfall anomaly of 20 mm increased the risk of leptospirosis by 12% compared to a week following the expected seasonal pattern. Finally, over the 14-year study period, the annual incidence of leptospirosis decreased significantly by a factor of 2.7 (8.3 versus 3.0 per 100,000 people), independently of variations in climate.ConclusionsStrategies to control leptospirosis should focus on avoiding contact with contaminated sources of Leptospira as well as on increasing awareness in the population and health professionals within the short time window after low-level or extreme high-level rainfall events. Increased leptospirosis incidence was restricted to one-to-two weeks after those events suggesting that infectious Leptospira survival may be limited to short time intervals.     

Leptospirotic etiology in pulmonary and upper respiratory tract pathology

A number of 3,200 febrile patients who presented upon admission to hospital primary pulmonary or upper respiratory tract impairment either as single forms of manifestation or associated to other syndromes were tested. The cases were screened by the rapid slide agglutination reaction with heat inactivated Patoc antigen and leptospirotic etiology was confirmed by the ultramicroscopic agglutination reaction with 18 live circulating pathogenic antigens. 64 leptospirosis cases with pulmonary impairment were confirmed and in 52 cases the upper respiratory tract was involved. Particular aspects of leptospirosis with pulmonary impairment: 71.8% of cases had a clinical diagnosis of interstitial pneumonia; 89% of cases presented important chest x-ray modifications; in an approximately equal number of cases the pulmonary involvement was the single manifestation or was associated with other syndromes; icterohaemorrhagiae, wolffi and pomona were the frequently encountered infecting serotypes. Particular aspects for leptospirosis involving the upper respiratory tract: 84.6% of cases had a clinical diagnosis of acute rhino-pharyngotracheitis; in 86.5% of cases the upper respiratory tract impairment was the single feature; the infecting serotypes were in decreasing order of frequency as follows: icterohaemorrhagiae, pomona, wolffi, canicola, grippotyphosa.     

Epidemiology of Leptospirosis in California: A Cause of Aseptic Meningitis

Twenty-one cases of leptospirosis, including three that were fatal, were reported in California during 1961-1965. An additional 18 cases were detected for the same period by screening sera from patients with central nervous system (CNS) disease of suspected viral origin. This finding supports a hypothesis that leptospirosis frequently is not considered in the differential diagnosis of CNS disease in which viral infection is suspected.The 39 patients, six of them females, ranged in age from six to 66 years. Most infections occurred in the summer. A history of exposure to animals or of swimming in potentially contaminated waters was obtained from 32 of the 39.     

Immunologic monitoring of leptospirosis in the Maritime Territory

The epidemiological and epizootic situation in Leptospira infections at the Maritime [correction of Primorski] Territory is evaluated on the basis of complex studies carried out in 1984-1989. As revealed in these studies, cases of leptospirosis among humans have a sporadic character and are mainly registered among professional high risk groups of the population. In the immunological structure of persons covered by the survey L. hebdomadis, L. pomona and L. javanica prevail. The anthropourgic foci of leptospirosis caused by L. pomona are of the leading epidemiological importance. Swine serves as the main source of infection in these foci. The study revealed the epidemic danger of the natural foci of leptospirosis caused by L. grippotyphosa and L. javanica in rice fields where the decisive factors of leptospirosis proved to be reed voles and striped field mice serving as reservoirs of this infection, as well as the synanthropic foci of leptospirosis caused by L. hebdomadis with house mice serving as the main carriers.     

Leptospirosis distribution related to freshwater habitats in the Vojvodina region (Republic of Serbia)

The retrospective study (2002—2007) for human leptospirosis in Vojvodina was undertaken in order to describe the distribution of the disease in relation with some environmental factors. Regarding the presented results, the major detected number of leptospirosis cases concurs with stagnant waters, wetlands, fish pond areas and protected regions, which comprised the basis for mapping of the region in three risk zones: very high risk (incidence rate higher than 5.0), high risk (2.5—5.0) and medium risk of leptospirosis infection (1.0—2.5). During the investigated period, 97 cases were registered with an average of 13.85 cases per year: 2002, 32 cases; 2003, 7; 2004, 22; 2005, 16; 2006, 4 and 2007, 16. Out of these 97 cases only 5 were women. Serovars from 11 presumptive serogroups caused infection, with a predominance of Icterohaemorrhagiae and Bratislava, accounting for 72.72% of cases together. Icterohaemorrhagiae was the commonest infecting serogroup mostly connected with fish ponds. Case fatality ratio was 9.4%.     

Aseptic meningitis caused by Leptospira spp diagnosed by polymerase chain reaction

Leptospirosis is a zoonotic disease caused by the pathogenic Leptospira spp. The clinical presentations are diverse, ranging from undifferentiated fever to fulminant disease including meningeal forms. The neurological leptospirosis forms are usually neglected. The aim of this study was to investigate leptospirosis as the cause of aseptic meningitis using different diagnostic techniques including the polymerase chain reaction (PCR). Thirty-nine cerebrospinal fluid (CSF) samples from patients presenting with meningeal abnormalities, predominance of lymphocytes and negative results by traditional microbiological tests were processed by leptospiral culture, anti-leptospiral antibody response and PCR. Leptospira spp DNA was detected in 23 (58.97%) of the CSF samples. Anti-leptospiral antibodies were found in 13 (33.33%) CSF samples. Twelve CSF samples were positive by PCR assay and negative by microscopic agglutination test (MAT) assay. Two CSF samples were positive by MAT and negative by PCR. The positive and negative agreement between both tests was 11 and 14, respectively. CSF samples from six cases of unknown diagnosis were positive by PCR assay. Eight cases showed positive results using PCR and MAT. Leptospirosis could be detected by PCR assay from the 3rd-26th day after illness onset. The sensitivity of the PCR was assessed with confirmed cases of leptospirosis (by MAT) and found to be 89.5%. All CSFs were negative by culture. PCR was found to be a powerful tool for diagnosing meningitis cases of leptospirosis. We recommend that it may be used as a supplementary diagnostic tool, especially in the early stages of the disease, when other diagnostic techniques such as serology are not sensitive.     

Risk factors for an outbreak of leptospirosis in California sea lions (Zalophus californianus) in California, 2004

Leptospirosis has been reported in California sea lions (Zalophus californianus) since 1970; however, the source of infection and mode of transmission remain unknown. To elucidate these features, demographic and environmental risk factors for leptospirosis were evaluated. California sea lion stranding records from northern California for 2004 were used to identify cases of leptospirosis (n = 316) and controls (n = 143). Demographic characteristics (age class, sex) and environmental factors, representing surrogates for exposure to dogs, cattle, rainfall, and freshwater sources, were compared between cases and controls with the use of a geographic information system (GIS) and logistic regression. Multivariate analyses revealed that summer and autumn seasons, juvenile age class, male sex, high dog-park density, and close proximity to dog parks were significantly associated with leptospirosis in sea lions, whereas county farmland cattle density, rainfall levels 30 days prior to stranding, human density, and proximity to freshwater sources were not associated. Thus, dogs and dog parks, or factors associated with them, might be further investigated to assess their relationship to leptospirosis in sea lions.     

Human and animal leptospirosis in irrigated lands

To study the influence of amelioration on the spread of leptospirosis, the survey of humans, agricultural animals and rodent was made on the territory where the irrigation system was under construction and during 2 years after the beginning of irrigation. This survey failed to establish the occurrence of significant changes in the number of rodents and their species composition, as well as in the number of agricultural animals showing the positive reaction to leptospirosis. No cases of leptospirosis were registered, and during the first years after the beginning of irrigation antibodies in low titers were detected only in 4 out of 536 subjects. The results obtained in this survey suggest that during the first years of artificial irrigation the conditions for a wider spread of leptospirosis do not appear, but the final solution of this problem can be made on the basis of observations lasting for many years.     

Detection and ecology of leptospirosis in Iowa wildlife

To gain additional information on the extent of leptospirosis in wildlife following a human outbreak in Iowa, wild mammals and lower forms of life were collected. Isolation, darkfield microscopic, serologic and pathologic procedures were used to identify past or present evidence of leptospiral infection. Leptospires were isolated from 7 of 75 (9%) mammals. Serotype grippotyphosa was isolated from three raccoons (procyon lotor) and one Western Harvest Mouse (Reithrodontomys megalotis). Serotype ballum was isolated from three opossums (Didelphis marsupialis). Leptospires, unidentified to date, were isolated from frog (Rana pipiens) kidneys. Other positive serologic and pathologic tests gave evidence of infection or previous infection. Utilization of Darkfield microscopic and silver staining techniques did not detect all cases of leptospiral infection. Macroscopic and microscopic serologic methods failed to identify evidence of leptospirosis in all mammals from which leptospires were isolated. Pathologic lesions could only be considered presumptive evidence for leptospirosis. These findings indicate that detection of leptospirosis in wildlife cannot be limited to a single diagnostic test. A combination of diagnostic procedures and clinical evaluation is necessary. Although serotype pomona was implicated as the predominant infecting leptospire in the human cases and domestic animals and was isolated from water at a swimming site, only serotypes grippotyphosa, ballum and ICF (frog isolate) were isolated from wild mammals and lower forms of life in the same vicinity.     

Epidemiology of leptospirosis in the Kirov region

The dynamics of leptospirosis morbidity in the Kirov region for many years is presented. The wide spread of leptospirosis foci, both natural and formed as the result of human activities, in the region is shown. The main role in infecting humans with leptospires belonged to the latter foci in a number of districts in the region was established. The etiological structure of leptospirosis cases among humans was represented, primarily, by leptospires of serogroup Grippotyphosa, following by serogroup Canicola and then serogroups Pomona, Tarassovi, Sejroe, Australis, Javanica. The dominating serogroups of leptospires were Grippotyphosa in wild rodents and Sejroe in agricultural animals. Persons belonging to the age group constituting the mainstay of work force (20-49 years) prevailed among the patients: town dwellers, factory and office workers. The main role in the transmission of infection to the population was played by the water factor.     

Leptospirosis: Morbidity,mortality, and spatial distribution of hospitalized cases in Ecuador. A nationwide study 2000-2020

BackgroundIn Ecuador, leptospirosis surveillance involves a mandatory notification of all cases and a hospitalization for severe illness. Morbidity and mortality are, nevertheless, underestimated and contribute directly to the status of leptospirosis as a neglected disease. Leptospira spp. is zoonotic in Ecuador with established endemic transmission in the Tropics. Here, we review retrospective national data within the country to aid in control strategies.Methodology/Principal findingsIn a population-based nationwide study, we analysed morbidity, mortality, and spatial distribution on confirmed hospital-discharged leptospirosis cases from 2000–2020 from a publicly accesible National Database, including males and females of all ages. We computed data for the 24 provinces across the four-geoclimatic regions of Ecuador based on seasonal and monthly variations and calculated rates according to age and sex. The spatial distribution was estimated at the level of ecoregions, provinces, and cantons. A total of 2,584 hospitalizations were recorded over all three continental regions in 22 provinces, except Carchi province and the Galapagos Islands. The annual incidence varied from 0.27 to 2.45 cases per 100,000 inhabitants with ages ranging from 1 to 98 years-old and an overall male/female ratio of 1.92:1. Most hospitalizations and deaths occurred in males ages 25–34 years. We registered 79 fatalities (3.06%); the highest mortality rate was 0.05 per 100,000 inhabitants. More cases clustered in the tropical cantons of central and north of the Coast and in the southern Amazon when compared to the Andes.Conclusions and significanceOur findings evidence leptospirosis endemicity and pinpoint the highest incidence within resource-poor tropical settings. The highest incidence occurred in males of adult age, with those also exhibiting the highest mortality. The national incidence rate was stable, but peaks occurred intermittently during the rainy seasons. Thus, strategies aimed at leptospirosis monitoring and control involving the application of preventive measures should consider this season and the aforementioned high-risk groups.