C-reactive protein: An easy marker for early differentiation between leptospirosis and dengue fever in endemic area.

In tropical regions, leptospirosis and dengue fever (DF) are infectious diseases of epidemiological importance and have overlapping symptomatic features. The objective of this study was to identify the factors associated to diagnosing leptospirosis that differentiate it to DF at the initial hospital evaluation. A multicenter retrospective study was conducted comparing confirmed leptospirosis to DF cases. Clinical/laboratory findings were compiled at hospital admission on Reunion Island between 2018 and 2019. Multivariable logistic regression was used to identify the predictors of leptospirosis. In total, 98 leptospirosis and 673 DF patients were included with a mean age of 47.8 (±17.1) and 48.9 (±23.3) years, respectively. In the multivariate analyses, the main parameters associated with leptospirosis were: i) increased neutrophil counts, ii) C-reactive protein values, iii) the absence of prolonged partial thromboplastin time, and iv) a decrease of platelets. The most discriminating parameter was C-reactive protein (CRP). With a threshold of 50mg/L, CRP taken alone had a sensitivity of 94% and a specificity of 93.5%. The positive and negative likelihood ratios were 14.5 and 0.06, respectively. In the setting of an early presumptive diagnosis, we found that an increased CRP value (>50 mg/L) could help diagnose leptospirosis and aid the decision process for hospital surveillance and/or a potential antibiotic treatment regimen.

A rare case of complicated pancreatitis due to leptospirosis.

The COVID-19 pandemic and the actions taken to combat it have greatly impacted the health infrastructure of all nations. Here we present a rare case of leptospirosis with severe acute pancreatitis, bilateral peripheral gangrene, disseminated intravascular coagulopathy and multiorgan failure. This is a rare presentation of leptospirosis wherein the patient had no history suggestive of acquisition of leptospires. The patient was started on doxycycline but still could not be saved due to the multisystem involvement.

One Health activities to reinforce intersectoral coordination at local levels in India.

India's dense human and animal populations, agricultural economy, changing environment, and social dynamics support conditions for emergence/re-emergence of zoonotic diseases that necessitate a One Health (OH) approach for control. In addition to OH national level frameworks, effective OH driven strategies that promote local intersectoral coordination and collaboration are needed to truly address zoonotic diseases in India. We conducted a literature review to assess the landscape of OH activities at local levels in India that featured intersectoral coordination and collaboration and supplemented it with our own experience conducting OH related activities with local partners. We identified key themes and examples in local OH activities. Our landscape assessment demonstrated that intersectoral collaboration primarily occurs through specific research activities and during outbreaks, however, there is limited formal coordination among veterinary, medical, and environmental professionals on the day-to-day prevention and detection of zoonotic diseases at district/sub-district levels in India. Examples of local OH driven intersectoral coordination include the essential role of veterinarians in COVID-19 diagnostics, testing of human samples in veterinary labs for Brucella and leptospirosis in Punjab and Tamil Nadu, respectively, and implementation of OH education targeted to school children and farmers in rural communities. There is an opportunity to strengthen local intersectoral coordination between animal, human and environmental health sectors by building on these activities and formalizing the existing collaborative networks. As India moves forward with broad OH initiatives, OH networks and experience at the local level from previous or ongoing activities can support implementation from the ground up.

Leptospirosis during the COVID-19 pandemic: a case report.

Since SARS-CoV-2 disease (COVID-19) has been labeled as a pandemic, it took the spotlight in the differential diagnosis for patients presenting with acute respiratory and systemic symptoms. Leptospirosis is one of the most common zoonoses in the world, yet it is mainly a disease of differential diagnosis for places that do not have it as an endemic. Due to the high burden of COVID-19 on the healthcare field, patients suffering from other infections may have been inadvertently neglected. COVID-19 infection can mimic other infectious diseases and can confuse physicians in their search for a confirmatory diagnosis. Nonetheless, it is very crucial to broaden the differential diagnosis and keep diseases like leptospirosis within the differential diagnosis despite its rarity, especially in patients presenting with unexplained systemic infectious symptoms. This is a unique case of a patient who presented with dyspnea, jaundice and change in urine color who was suspected to be COVID-19 positive. After a detailed investigation, the patient was diagnosed with leptospirosis instead of COVID-19 and was treated with plasmapheresis and antibiotics accordingly.

Ocular leptospirosis: lack of awareness among ophthalmologists and challenges in diagnosis.

PURPOSE OF REVIEW: Systemic leptospirosis exists worldwide. But leptospiral uveitis, an important late complication is not identified by ophthalmologists in several countries. RECENT FINDINGS: In the last 18 months numerous publications, especially on epidemiology, surveillances, and novel rapid diagnostic kits to test at the point of care site on leptospirosis have been published from all over the world. However, publications from ophthalmologists are very scarce. Remarkably ophthalmologists should know the global burden of leptospirosis, prevalence of the disease in their country, demographic factors associated, risk factors, and systemic signs to elicit relevant history and travel history. They should be aware of recent advances in investigations to confirm their clinical diagnosis. SUMMARY: It is quite evident from this work that leptospirosis is prevalent worldwide. Ophthalmologists' awareness has to improve to identify the etiological diagnosis. They should have access to simple, less expensive, and less cumbersome laboratory tests.

Molecular Evidence of Leptospira spp. in Isolated Fijian Bats.

Bats host several zoonotic pathogens. Island biogeography and epidemiologic theory predict small remote islands have lower infection diversity. Molecular studies of urine and feces from three species at 10 sites from three islands suggest multiple pathogenic Leptospira, but not coronavirus, paramyxovirus, or Histoplasma, circulate in isolated Pacific Fijian bat populations.

Emerging canine leptospirosis in Sydney and the role of population demographics.

An outbreak of canine leptospirosis commenced in Sydney, Australia in 2017. The aim of this retrospective study was to determine if clusters of leptospirosis occurred during this outbreak, and if these were associated with host factors, to assist investigation of the drivers of emerging leptospirosis at this location. Within the City of Sydney local government area, 13 cases were reported during the outbreak. Administrative data on the canine population were collected and mapped. Clusters of leptospirosis cases were detected using a retrospective space-time analysis and a discrete Poisson probability statistical model. Sydney dog population registration [55.6%, 95% confidence interval (CI) 51.8-58.1%] was lower than the Australian national average (80%). The distribution of dog types, based on the United Kennel Club standards, was significantly (p < .0001) different to that of the national profile: there was a distinct preference in Sydney for companion dogs. The age distribution of dogs in Sydney did not reflect a typical right-skewed curve; instead, a relatively uniform distribution was observed between the age group of 1 to 8 years. A primary disease cluster (radius 1.1 km) in the eastern area of the Sydney City Council was identified (4 cases observed between 24 May and 9 August 2019 vs. 0.10 cases expected), p = .0450. When adjusted for the age, breed type and sex distribution of the population, similar clusters were identified; in the case of age-adjustment, the spatiotemporal cluster identified was larger and of longer duration (seven cases observed between 28 June and 11 November 2019 versus 0.34 cases expected), p = .0025. The presence of clusters of canine leptospirosis in the City of Sydney during this outbreak, which persisted after adjustment for demographics (age, sex, breed type), suggest that environmental factors - rather than host or pathogen factors - might be responsible for the emergence of leptospirosis. Environmental factors that potentially might be linked to this outbreak of canine leptospirosis and the clusters observed require investigation.

A global one health perspective on leptospirosis in humans and animals.

Leptospirosis is a quintessential one health disease of humans and animals caused by pathogenic spirochetes of the genus Leptospira. Intra- and interspecies transmission is dependent on 1) reservoir host animals in which organisms replicate and are shed in urine over long periods of time, 2) the persistence of spirochetes in the environment, and 3) subsequent human-animal-environmental interactions. The combination of increased flooding events due to climate change, changes in human-animal-environmental interactions as a result of the pandemic that favor a rise in the incidence of leptospirosis, and under-recognition of leptospirosis because of nonspecific clinical signs and severe signs that resemble COVID-19 represents a "perfect storm" for resurgence of leptospirosis in people and domestic animals. Although often considered a disease that occurs in warm, humid climates with high annual rainfall, pathogenic Leptospira spp have recently been associated with disease in animals and humans that reside in semiarid regions like the southwestern US and have impacted humans that have a wide spectrum of socioeconomic backgrounds. Therefore, it is critical that physicians, veterinarians, and public health experts maintain a high index of suspicion for the disease regardless of geographic and socioeconomic circumstances and work together to understand outbreaks and implement appropriate control measures. Over the last decade, major strides have been made in our understanding of the disease because of improvements in diagnostic tests, molecular epidemiologic tools, educational efforts on preventive measures, and vaccines. These novel approaches are highlighted in the companion Currents in One Health by Sykes et al, AJVR, September 2022.

Linking longitudinal and cross-sectional biomarker data to understand host-pathogen dynamics: Leptospira in California sea lions (Zalophus californianus) as a case study.

Confronted with the challenge of understanding population-level processes, disease ecologists and epidemiologists often simplify quantitative data into distinct physiological states (e.g. susceptible, exposed, infected, recovered). However, data defining these states often fall along a spectrum rather than into clear categories. Hence, the host-pathogen relationship is more accurately defined using quantitative data, often integrating multiple diagnostic measures, just as clinicians do to assess their patients. We use quantitative data on a major neglected tropical disease (Leptospira interrogans) in California sea lions (Zalophus californianus) to improve individual-level and population-level understanding of this Leptospira reservoir system. We create a "host-pathogen space" by mapping multiple biomarkers of infection (e.g. serum antibodies, pathogen DNA) and disease state (e.g. serum chemistry values) from 13 longitudinally sampled, severely ill individuals to characterize changes in these values through time. Data from these individuals describe a clear, unidirectional trajectory of disease and recovery within this host-pathogen space. Remarkably, this trajectory also captures the broad patterns in larger cross-sectional datasets of 1456 wild sea lions in all states of health but sampled only once. Our framework enables us to determine an individual's location in their time-course since initial infection, and to visualize the full range of clinical states and antibody responses induced by pathogen exposure. We identify predictive relationships between biomarkers and outcomes such as survival and pathogen shedding, and use these to impute values for missing data, thus increasing the size of the useable dataset. Mapping the host-pathogen space using quantitative biomarker data enables more nuanced understanding of an individual's time course of infection, duration of immunity, and probability of being infectious. Such maps also make efficient use of limited data for rare or poorly understood diseases, by providing a means to rapidly assess the range and extent of potential clinical and immunological profiles. These approaches yield benefits for clinicians needing to triage patients, prevent transmission, and assess immunity, and for disease ecologists or epidemiologists working to develop appropriate risk management strategies to reduce transmission risk on a population scale (e.g. model parameterization using more accurate estimates of duration of immunity and infectiousness) and to assess health impacts on a population scale.

Impact of Plantation Induced Forest Degradation on the Outbreak of Emerging Infectious Diseases-Wayanad District, Kerala, India.

The world has been facing a pandemic owing to COVID-19. We have also seen the geographic expansion and outbreaks of other emerging infectious diseases (EID) in recent years. This paper investigates the direct and indirect effects of land use land cover change (LULCC) on EID outbreaks in the context of Wayanad District of Kerala, India. Wayanad is in the vulnerable tropical forested region, and it is named as one of the four environmental change hotspots. The focus of this project is mainly three EIDs prevalent in this region: Kyasanur forest disease (KFD), Dengue and Leptospirosis. Our results, based on topographical map, remote sensing and extensive field work, show that the natural forest in Wayanad was replaced with agriculture and forest plantation during 1950-2018. This paper further suggests that encroachment of forest by forest plantation causes the human-animal conflict resulting in the outbreak of KFD cases. Our analysis reveals that a high number of Dengue cases is found in the forested regions of the district and over the adjacent human-made agriculture plantation areas. High and medium number of Leptospirosis cases contain a high portion of land area devoted to paddy cultivation and agricultural plantation. In summary, the results clearly show the linkage between the outbreak of above mentioned EIDs and LULCC in the context of Wayanad district, Kerala. We also discuss in detail the causal pathway involving human-environmental dynamics through which plantation leads to the outbreak of KFD. Replacing forests with plantations poses an alarming threat of disease outbreak in the community.

Coinfection of leptospirosis and coronavirus disease 2019: A retrospective case series from a coastal region in South India.

During the monsoon season of 2020, the coastal areas of South India were endemic to both leptospirosis and coronavirus disease 2019 (COVID-19). This study aimed to investigate the clinical features and outcomes of patients infected with both infections. A retrospective review of charts of all patients with COVID-19 who were also diagnosed with leptospirosis by immunoglobulin M enzyme-linked immunosorbent assay was undertaken. The clinical features, laboratory report, treatment details, and outcomes of all the included patients were recorded. The collected data were summarized as the frequency with percentage for categorical data and the mean or median for continuous data. Twenty-four cases of coinfections were admitted between July and November 2020. Most of these patients were categorized as severe COVID-19 (n = 15, 62.5%). Acute kidney injury was seen in 79.2% (n = 19) patients, while raised bilirubin was present in 79.2% (n = 19) of the patients. All patients had raised C-reactive protein, while all but one had raised procalcitonin. Thrombocytopenia, leucocytosis, and leukocytopenia were seen in 91.7% (n = 22), 45.8% (n = 11), and 12.5% (n = 3) of the patients. The median duration of hospital stay was 11 (8.25-15) days. A total of 79.2% (n = 19) of the patients improved and were discharged, while 20.8% (n = 5) died during the hospital stay. In conclusion, patients with fever and atypical manifestations such as hepatic dysfunction, renal dysfunction, and thrombocytopenia should be evaluated for leptospirosis even if they are COVID positive.

Assessment of the Current Surveillance System for Human Leptospirosis in Ecuador by Decision Analytic Modeling.

Leptospirosis is a globally disseminated zoonotic disease with no national surveillance systems. On the other hand, surveillance is crucial for improving population health, and surveillance systems produce data that motivates action. Unfortunately, like many other countries, Ecuador put in place a monitoring system that has never been tested. The goal of this study was to use scenario tree modeling to assess the sensitivity of Ecuador's current national surveillance system to human leptospirosis as the basis for an economic assessment of the system. We created a decision-tree model to analyze the current system's sensitivity. The inputs were described as probabilities distributions, and the model assessed the program's sensitivity as an output. The model also considers the geographical and weather variations across Ecuador's three continental regions: Andean, Amazonia, and the Coast. Several data sources were used to create the model, including leptospirosis records from Ecuador's Ministry of Public Health, national and international literature, and expert elicitation, all of which were incorporated in a Bayesian framework. We were able to determine the most critical parameters influencing each scenario's output (CSU) sensitivity through sensitivity analysis. The Coast region had the best sensitivity scenario, with a median of 0.85% (IC 95% 0.41-0.99), followed by the Amazonia with a median of 0.54% (CI 95% 0.18-0.99) and the Andes with a median of 0.29% (CI 95% 0.02-0.89). As per the sensitivity study, the most influential criteria on the system's sensitivity were "Attendance or probability of going to a health center" and "probability of having symptoms," notably for the Coast and Amazonia Regions.

Compatibility between a rabies vaccine and two canine combined vaccines against canine distemper, adenovirosis, parvovirosis, parainfluenza virus disease and leptospirosis, with or without canine coronavirus.

In many countries, vaccination programs still require dogs to be vaccinated against rabies in addition to Canine distemper virus (CDV), adenovirus (CAV), parvovirus (CPV), parainfluenza virus (CPiV), Leptospira (L) or Canine coronavirus (CCV= Cv). Few vaccines containing all these antigens are commercially available and, unless compatibility between the vaccines was demonstrated, concurrent administration of a DAPPi-L(Cv) vaccine and a vaccine against rabies should not be recommended. This may be of concern for practitioners who wish to vaccinate dogs with all components on the same day. This study aimed at evaluating immunological compatibility between a monovalent rabies vaccine (Rabisin™) and two large combination vaccines against CDV, CAV, CPV, CPiV with 2 leptospira components +Cv (Recombitek® C6/Cv) or with 4 Leptospira components (Recombitek® C8), when injected concomitantly at two separate injection sites. Fourteen days after administration of the rabies vaccine, with or without concomitant administration of combo vaccines, all dogs had seroconverted against rabies and maintained protective titers over the duration of the study. In addition, 100% of the puppies vaccinated with one or the other combo vaccines seroconverted against CDV, CAV, CPV, CPiV (CCV) and Leptospira, whatever the vaccination group. Lack of immunological interference between Rabisin™ and all components of the Recombitek® C6/Cv or Recombitek® C8 Combo vaccines was demonstrated by non-inferiority analysis, except for CDV in the Recombitek®C8+ Rabisin™ group. Based on these results, a concomitant administration of Rabisin™ with Recombitek® C6/Cv or Recombitek® C8 can be recommended in daily practice, which can be essential for facilitating vaccination compliance.

Neglecting the neglected during the COVID-19 pandemic: the case of leptospirosis in Sri Lanka.

The coronavirus disease 2019 (COVID-19) pandemic has disrupted global health systems and affected the transmission dynamics as well as the surveillance of other infectious diseases. This study described the probable effect of the COVID-19 pandemic on the surveillance and control of leptospirosis in Sri Lanka. With 8,579 reported cases and more than 800 estimated deaths, the Sri Lankan public health surveillance system documented the largest outbreak of leptospirosis in Sri Lankan history in 2020. This was the worst infectious disease outbreak Sri Lanka experienced in 2020, but it was neglected, primarily due to the COVID-19 pandemic.

Leptospirosis in pregnancy: A systematic review.

INTRODUCTION: Leptospirosis 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. METHODS: We 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. RESULTS: We 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. CONCLUSION: This 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.

Dengue and leptospirosis infection during the coronavirus 2019 outbreak in Sri Lanka.

A significant decrease in dengue fever cases and a contrasting increase in leptospirosis cases were reported for the second quarter of 2020 compared with 2019 in Sri Lanka. In the absence of significant environmental and weather-related differences to account for these changes in incidence, we investigated the possibility that the effects of the COVID-19 pandemic on public health, social behaviour and the restrictions imposed during the lockdown influenced the fluctuations in dengue and leptospirosis infections.

Blood Levels of Galectin-9, an Immuno-Regulating Molecule, Reflect the Severity for the Acute and Chronic Infectious Diseases.

Galectin-9 (Gal-9) is a ß-galactoside-binding lectin capable of promoting or suppressing the progression of infectious diseases. This protein is susceptible to cleavage of its linker-peptides by several proteases, and the resulting cleaved forms, N-terminal carbohydrate recognition domain (CRD) and C-terminal CRD, bind to various glycans. It has been suggested that full-length (FL)-Gal-9 and the truncated (Tr)-Gal-9s could exert different functions from one another via their different glycan-binding activities. We propose that FL-Gal-9 regulates the pathogenesis of infectious diseases, including human immunodeficiency virus (HIV) infection, HIV co-infected with opportunistic infection (HIV/OI), dengue, malaria, leptospirosis, and tuberculosis (TB). We also suggest that the blood levels of FL-Gal-9 reflect the severity of dengue, malaria, and HIV/OI, and those of Tr-Gal-9 markedly reflect the severity of HIV/OI. Recently, matrix metallopeptidase-9 (MMP-9) was suggested to be an indicator of respiratory failure from coronavirus disease 2019 (COVID-19) as well as useful for differentiating pulmonary from extrapulmonary TB. The protease cleavage of FL-Gal-9 may lead to uncontrolled hyper-immune activation, including a cytokine storm. In summary, Gal-9 has potential to reflect the disease severity for the acute and chronic infectious diseases.

A case of neglected hepatorenal dysfunction during the COVID pandemic.

As the world fights with the Coronavirus, most of the hospitals are gearing up for the care of these patients. As most of the attention these days is being given on Coronavirus, the patients suffering from other clinical infections are being neglected. SARS-CoV-2 is being kept as the top differential in patients presenting with fever and respiratory distress. We hereby present a case of patient returning from Indonesia during the pandemic presenting with a history of hepatic, renal dysfunction with fever and cough. Due to the pandemic, the patient's fever and cough outweighed the hepatic and renal dysfunction, and the patient had to undergo dialysis before the final diagnosis of leptospirosis could be made.