Kidney Injury Biomarkers in Leptospirosis

ABSTRACT Leptospirosis is a zoonotic infection with a global distribution, though it has a greater impact on marginalized rural agricultural and urban communities in developing countries. Kidney injury, which can lead to severe and lethal infections, is the most frequent complication associated with leptospirosis. Novel biomarkers are being studied as tools for assessing kidney injury in different pathological processes to improve early detection. This review aimed to gather information on the use of novel kidney biomarkers for human leptospirosis. A search of the literature was carried out in September 2021 using the parameters "((kidney) OR (renal) OR (chronic kidney disease) OR (acute kidney injury)) AND ((biomarker) OR (marker)) AND ((Leptospira) OR (leptospirosis))". The review identified 11 original studies that evaluated the performance of 15 kidney biomarkers related to leptospirosis. Assessment of the evidence for biomarker utility was limited because of the small number of studies and sample sizes. Although some biomarkers were associated with kidney disease, no specific biomarker appeared to be ready for clinical practice, and more research in this field is necessary.

A systematic literature review of leptospirosis outbreaks worldwide, 1970-2012 / Revisión sistemática de los brotes de leptospirosis en el mundo, 1970-2012

ABSTRACT Objective. This review describes the geographic and temporal distribution of, detection methods for, and other epidemiological features of published leptospirosis outbreaks, with the aim of informing efforts to standardize outbreak-reporting practices. Methods. We conducted a systematic review of leptospirosis outbreaks reported in the scientific literature and ProMED during 1970-2012. Predefined criteria were used to identify and classify outbreaks and a standard form was used to extract information. Results. During 1970-2012, we identified 318 outbreaks (average: 7 outbreaks/year; range: 1-19). Most outbreaks were reported in the Latin America and the Caribbean region (36%), followed by Southern Asia (13%), and North America (11%). Most outbreaks were located in tropical and subtropical ecoregions (55%). Quality classification showed that there was clear description of laboratory-confirmed cases in 40% of outbreaks. Among those, the average outbreak size was 82 cases overall (range: 2-2 259) but reached 253 cases in tropical/subtropical ecoregions. Common risk factors included outdoor work activities (25%), exposure to floodwaters (23%), and recreational exposure to water (22%). Epidemiologic investigation was conducted in 80% of outbreaks, mainly as case interviews. Case fatality was 5% overall (range: 0%-60%). Conclusions. Outbreak reporting increased over the study period with outbreaks covering tropical and non-tropical regions. Outbreaks varied by size, setting, and risk factors; however, data reviewed often had limited information regarding diagnosis and epidemiology. Guidelines are recommended to develop standardized procedures for diagnostic and epidemiological investigations during an outbreak and for reporting.(AU)

RESUMEN Objetivo. Describir la distribución geográfica y temporal, los métodos de detección y otras características epidemiológicas de los brotes de leptospirosis publicados con el fin de fundamentar los esfuerzos tendientes a estandarizar las prácticas empleadas en la notificación de brotes. Métodos. Se llevó a cabo una revisión sistemática de los brotes de leptospirosis notificados en la bibliografía científica y en ProMED entre 1970 y 2012. Se utilizaron criterios predefinidos para identificar y clasificar los brotes y se empleó un formulario estándar para extraer la información. Resultados. Entre 1970 y 2012 se identificaron 318 brotes (promedio: 7 brotes/año; rango: 1-19), la mayoría de ellos en América Latina y el Caribe (36%), región seguida por Asia meridional (13%) y América del Norte (11%). La mayoría de los brotes se localizaron en ecorregiones tropicales y subtropicales (55%). La clasificación cualitativa reveló que en el 40% de los brotes había una clara descripción de los casos confirmados por laboratorio. Entre ellos, el tamaño promedio del brote fue de 82 casos (rango: 2-2259 casos) pero alcanzó los 253 casos en ecorregiones tropicales o subtropicales. Entre los factores de riesgo frecuentes figuraban las actividades laborales al aire libre (25%), la exposición a agua proveniente de inundaciones (23%) y la exposición a agua con fines recreativos (22%). En el 80% de los brotes se realizaron investigaciones epidemiológicas, principalmente entrevistas de casos. La mortalidad específica de los casos fue del 5% (rango: 0%-60%). Conclusiones. La notificación de brotes aumentó durante el período de estudio, y los brotes abarcaron regiones tropicales y no tropicales. Los brotes fueron diferentes en cuanto a su tamaño, el entorno y los factores de riesgo; sin embargo, los datos examinados con frecuencia incluían una información limitada respecto del diagnóstico y la epidemiología. Se recomiendan directrices para elaborar procedimientos estandarizados para las investigaciones diagnósticas y epidemiológicas durante un brote y para su notificación.(AU)

The Use of Chemoprophylaxis after Floods to Reduce the Occurrence and Impact of Leptospirosis Outbreaks.

Record-breaking and devastating rainfall events have occurred in the past decade. Rain and floods are considered the main risk factors for leptospirosis and several outbreaks have been reported following extreme weather events. In such situations, one possible intervention to prevent leptospirosis cases in high-risk groups is the use of chemoprophylaxis. However, not enough evidence of its effect is available. The objectives of this study were to review the literature on the current practices of chemoprophylaxis for leptospirosis and to explore, using a mathematical model, how various chemoprophylaxis scenarios may affect the progression of a leptospirosis outbreak. Twenty-six peer-reviewed publications were selected (10 quantitative studies, two systematic reviews and 14 articles of other types). Oral doxycycline was the most used antibiotic for chemoprophylaxis of leptospirosis. Post-exposure prophylaxis was assessed in four studies following a natural disaster. Although evidence of the effectiveness of post-exposure prophylaxis is inconsistent, the direction of association supported a protective effect for morbidity and mortality. The theoretical model showed how the assumed benefit of chemoprophylaxis was influenced by the time and rate of administration. Future models should consider the heterogeneity of affected communities, improved estimates of the effect of chemoprophylaxis on leptospirosis infection and disease, as well as potential detrimental impacts. Additional research is critical to provide clear evidence-based recommendations for leptospirosis control during an outbreak. The results of this study suggest that chemoprophylaxis may provide some protection in reducing the number of leptospirosis cases after a high-risk exposure; however, the effective benefit may depend on a variety of factors such as the timing and coverage of prophylaxis. The information summarized can be used to support decision-making during a high-risk event.

Leptospirosis in Rio Grande do Sul, Brazil: An Ecosystem Approach in the Animal-Human Interface.

BACKGROUND: Leptospirosis is an epidemic-prone neglected disease that affects humans and animals, mostly in vulnerable populations. The One Health approach is a recommended strategy to identify drivers of the disease and plan for its prevention and control. In that context, the aim of this study was to analyze the distribution of human cases of leptospirosis in the State of Rio Grande do Sul, Brazil, and to explore possible drivers. Additionally, it sought to provide further evidence to support interventions and to identify hypotheses for new research at the human-animal-ecosystem interface. METHODOLOGY AND FINDINGS: The risk for human infection was described in relation to environmental, socioeconomic, and livestock variables. This ecological study used aggregated data by municipality (all 496). Data were extracted from secondary, publicly available sources. Thematic maps were constructed and univariate analysis performed for all variables. Negative binomial regression was used for multivariable statistical analysis of leptospirosis cases. An annual average of 428 human cases of leptospirosis was reported in the state from 2008 to 2012. The cumulative incidence in rural populations was eight times higher than in urban populations. Variables significantly associated with leptospirosis cases in the final model were: Parana/Paraiba ecoregion (RR: 2.25; CI95%: 2.03-2.49); Neossolo Litolítico soil (RR: 1.93; CI95%: 1.26-2.96); and, to a lesser extent, the production of tobacco (RR: 1.10; CI95%: 1.09-1.11) and rice (RR: 1.003; CI95%: 1.002-1.04). CONCLUSION: Urban cases were concentrated in the capital and rural cases in a specific ecoregion. The major drivers identified in this study were related to environmental and production processes that are permanent features of the state. This study contributes to the basic knowledge on leptospirosis distribution and drivers in the state and encourages a comprehensive approach to address the disease in the animal-human-ecosystem interface.

Toxoplasmosis, zoonosis parasitaria prevalente en Chile: recuento y desafíos / Toxoplasmosis, a parasitic zoonoses prevalent in Chile: count and challenges

Background: Toxoplasmosis, cosmopolitan parasitic zoonosis often found in humans, is transmitted mainly by food and water, and is considered a significant risk of morbidity and mortality in pregnant women, newborns and immunocompromised patients. Objective: To identify the information about this zoonosis and its first reports in Chile. Materials and Methods: Review of publications in Pubmed, Mesh search of systematic reviews, case studies, cross-sectional studies, systematic reviews, meta-analysis and specialty publications. In addition, other publications in parasitology journals were analyzed. Conclusions: There are reports of the presence of this disease in Chile for 60 years. During this time several differences in prevalence depending on geographic location, age and education level of the population have been detected. There is low epidemiological vigilance and lack of specific official preventive measures for this disease, despite the possible introduction of new parasite genotypes of an increased virulence and pathogenicity in the country through the importation of meat. New enigmas have arisen in relation to this disease associating it with Alzheimer, Parkinson’s disease, autism, learning disabilities, among others.

Antecedentes: La toxoplasmosis, zoonosis parasitaria cosmopolita frecuente en humanos, es transmitida principalmente por alimentos y agua, constituye un riesgo importante de morbilidad y mortalidad, en mujeres embarazadas, recién nacidos e inmunodeprimidos. Objetivo: Caracterizar la información existente de esta zoonosis y sus primeros reportes en Chile. Materiales y Métodos: Revisión de publicaciones en PubMed, búsqueda MeSH de revisiones sistemáticas, estudios de casos, estudios transversales, revisiones sistemáticas, meta-análisis y publicaciones de la especialidad. Conclusiones: Existen reportes de esta enfermedad en Chile desde hace 60 años. Durante ese período se han observado diferencias en su prevalencia dependiendo de la ubicación geográfica, edad y nivel de educación de la población en riesgo. Se observa baja vigilancia epidemiológica y escasas medidas preventivas oficiales específicas, posible introducción de nuevos genotipos del parásito de mayor virulencia y patogenicidad, a traves de la importación de carnes. Surgen, en torno a esta enfermedad, nuevos enigmas que la asocian a patología como Alzheimer, Enfermedad de Parkinson y problemas de aprendizaje, entre otros.

A sero-survey of toxoplasmosis in farm and non-farm children from Wisconsin, United States, 1997-1999.

BACKGROUND: Toxoplasmosis is among the most widespread and prevalent zoonosis in the world. People can become infected through ingestion of oocysts shed by felids or of tissue cysts contained in meat from infected animals. Acute infection can result in a wide spectrum of consequences, including flu-like illness and retinitis, as well as congenital infection in pregnant women. Severe disease can occur, especially if people are immunocompromised. Frequency of human infection varies substantially by region due to ecological, social, and cultural factors. The most recent nationwide prevalence estimates in children from United States were 3.6% in 6-11 year olds and 5.8% in 12-19 year olds. Because of the limited knowledge of the occurrence of common zoonotic pathogens in children in the United States, the objective of this study was to estimate the sero-prevalence of T. gondii-specific antibodies in children from the Marshfield area in Wisconsin and to examine the association between sero-positivity and farm living. METHODS: Banked sera from 342 Wisconsin children collected in 1997-1999, aged 2 to 18 years, were tested for Toxoplasma gondii-specific IgG antibodies using ELISA. Recorded information included age, sex, and whether the child resided on a farm. Impact of assay accuracy, sensitivity and specificity, on sero-prevalence was examined using Bayesian methods. RESULTS: Observed prevalence of T. gondii-specific antibodies was 10.8% (37/347). Adjusting for sensitivity and specificity of the assays yielded a prevalence estimate of 8.0% (95% probability interval: 4%-12.4%). Children living on a farm had a 5 times higher odds of T. gondii-specific antibodies than children not living on a farm (OR=5.08, 95% CI: 2.2-11.6). CONCLUSION: Results suggest that even in apparently low-risk populations, the true extent of the infection in children is significant. In this study population, children living on farms were differentially exposed, with earlier and higher infection risk than children not living on farms. Findings highlight the need to increase awareness about toxoplasmosis acquired early in life and to improve our understanding of the ecology of T. gondii in rural environments from developed and developing countries.

Identification of a sporozoite-specific antigen from Toxoplasma gondii.

Reduction of risk for human and food animal infection with Toxoplasma gondii is hampered by the lack of epidemiological data documenting the predominant routes of infection (oocyst vs. tissue cyst consumption) in horizontally transmitted toxoplasmosis. Existing serological assays can determine previous exposure to the parasite, but not the route of infection. We have used difference gel electrophoresis, in combination with tandem mass spectroscopy and Western blot, to identify a sporozoite-specific protein (T. gondii embryogenesis-related protein [TgERP]), which elicited antibody and differentiated oocyst- versus tissue cyst-induced infection in pigs and mice. The recombinant protein was selected from a cDNA library constructed from T. gondii sporozoites; this protein was used in Western blots and probed with sera from T. gondii -infected humans. Serum antibody to TgERP was detected in humans within 6-8 mo of initial oocyst-acquired infection. Of 163 individuals in the acute stage of infection (anti- T. gondii IgM detected in sera, or < 30 in the IgG avidity test), 103 (63.2%) had detectable antibodies that reacted with TgERP. Of 176 individuals with unknown infection route and in the chronic stage of infection (no anti- T. gondii IgM detected in sera, or > 30 in the IgG avidity test), antibody to TgERP was detected in 31 (17.6%). None of the 132 uninfected individuals tested had detectable antibody to TgERP. These data suggest that TgERP may be useful in detecting exposure to sporozoites in early T. gondii infection and implicates oocysts as the agent of infection.

Toxoplasma gondii in feral American minks at the Maullín river, Chile.

American mink (Neovison vison) is a widely distributed invasive species in southern Chile. Thirty four feral minks were trapped at two distinct sites (rural and peri-urban), diet analyzed and Toxoplasma gondii exposure compared using PCR and specific antibodies. Serum samples were evaluated using a commercial latex agglutination test where a titer ≥ 1:32 was considered positive. Of 30 mink analyzed, 21 (70%) were positive to T. gondii antibodies, with titers ranging from 1:32 to 1:2048. As expected, adult mink showed higher seroprevalence of exposure to T. gondii (18/21) than young mink (3/9) (P=0.008). There was not statistically significant difference between sex groups (P=0.687). Differences in seroprevalence were observed between the two sample sites with a higher proportion of positive individuals in the peri-urban area, and therefore, closer to human settlements (35.7% vs. 100%, P=0.0001). Individuals positive to T. gondii using PCR and/or serology showed similar differences by site with higher infected individuals in peri-urban areas (58.8% vs. 100%, P=0.007). Diet of American mink based in fecal composition analyses was mainly based on crustaceans (frequency of occurrence: crustaceans=100%, birds and rodents<7%), suggesting that the high observed prevalence of T. gondii infection might be more associated with its aquatic behavior (e.g. ingestion of oocysts in contaminated fresh water) than with their trophic behavior (e.g. preying over species that can have T. gondii cysts in their tissues). As an invasive species potentially subject to routine culling to maintain population sizes under control, minks could be used as a sentinel species to monitor pathogens of public and wildlife health importance, such as T. gondii, in aquatic environments.

Factors affecting sensitivity and specificity of pooled-sample testing for diagnosis of low prevalence infections.

Testing of pooled samples has been proposed as a low-cost alternative for diagnostic screening and surveillance for infectious agents in situations where the prevalence of infection is low and most samples can be expected to test negative. The present study extends our previous work in pooled-sample testing (PST) to evaluate effects of the following factors on the overall PST sensitivity (SE(k)) and specificity (SP(k)): dilution (pool size), cross-contamination, and cross-reaction. A probabilistic model, in conjunction with Monte Carlo simulations, was used to calculate SE(k) and SP(k), as applied to detection of bovine viral diarrhea virus (BVDV) persistently infected (PI) animals using RT-PCR. For an average prevalence of BVDV PI of 0.01 and viremia in each animal between 10(2) and 10(7)virusparticles/mL, the pool size associated with the lowest number of tests, and lowest cost, corresponded to eight samples/pool. However, the least-cost pool size (lowest number of tests) was associated with a SE(k) of 0.90 (0.75-1), which corresponded to a decrease of 0.04, relative to the assay sensitivity for a single sample. The SP(k) for the same pool size, considering the effect of detection of BVDV acutely infected animals and cross-contamination as source of false positive results, was 0.90 (0.85-0.95). The effect of a hypothetical cross-reacting agent was to markedly decrease SP(k), especially as the prevalence of the cross-reacting agent increased. For a pool size of eight samples and a prevalence of the cross-reacting agent of 0.3, SP(k) ranged from 0.67 to 0.86, depending on the probability that the assay would detect the cross-reacting agent. The methods presented offer a means of evaluating and understanding the various factors that can influence overall accuracy of PST procedures.