Acute human leptospirosis in a Caribbean region of Colombia: From classic to emerging risk factors.

BACKGROUND: Leptospirosis is a zoonosis of worldwide incidence, with a broad spectrum of health risk factors. AIM: The objective was to determine risk factors associated with acute human leptospirosis and to explore predictive variables of risk to human leptospirosis. METHODS: The study was carried out in the Department of Córdoba, in the north of Colombia. We conducted a longitudinal prospective descriptive study with non-probabilistic sampling, which included 339 patients suspected of leptospirosis. Positive cases were confirmed by MAT and PCR. The determination of social and environmental risk factors was done with a survey on epidemiological and environmental variables to establish an association between cases of leptospirosis and risk factors as well as predictive variables. RESULTS: We found 19.8% (67/339) cases of acute leptospirosis, and the seroprevalence was 27.1% (92/339). The most frequent serogroups were Sejroe, Australis, Pomona, Batavie, Pyrogenes and Grippotyphosa. We identified the following risk factors: age between 10 and 19 years (OR = 2.571; 95% CI); pig ownership (OR = 2.019; 95% CI); bathing or recreational activities in lake/lagoon (OR = 3.85; 95% CI) and in dams (OR = 3.0; 95% CI); floodings 30 days before the onset of symptoms (OR = 2.019; 95% CI), and a mean temperature of 28°C (p 0.044; 95%CI). As significant predictor variables, we identified age (10-19 years), bathing or recreational activities in the lake/lagoon, and flooding 30 days before symptoms were again evidenced. This region presents classic risk factors (pig ownership) and emerging environmental risk factors (recreational practice or bathing in a lake/lagoon and flooding 30 days before the onset of symptoms), and demographic factors such as young age (10-19 years). CONCLUSIONS: These factors are also predictors of human cases of acute leptospirosis and provide contextual information on environmental and public health that should be considered for epidemiological surveillance in this endemic area.

Etiological characterization of acute undifferentiated febrile illness in Apartadó and Villeta municipalities, Colombia, during COVID-19 pandemic.

Background: Acute undifferentiated febrile illness (AUFI) is one of the leading causes of illness in tropical regions. Although malaria is the most important cause, other pathogens such as Dengue (DENV), Leptospira and recently, Coronavirus Disease 2019 (COVID-19) have gained importance. In Colombia, few studies aimed to identify the etiology of AUFI. Most of them performed in Apartadó and Villeta municipalities, identifying the active circulation of several pathogens. Thus, we conducted a cross-sectional study in these municipalities to characterize the etiologies of AUFI during COVID-19 pandemic. Methods: An active surveillance was conducted between September and December 2021 in local hospitals of Apartadó and Villeta municipalities. Febrile patients were enrolled after voluntarily agreeing to participate in the study. Ten different etiologies were evaluated through direct, serological, molecular and rapid diagnostic methods. Results: In Apartadó a confirmed etiology was found in 60% of subjects, DENV (25%) being the most frequent, followed by leptospirosis (16.7%), malaria (10%), COVID-19 (8.3%), spotted fever group (SFG) rickettsiosis (6.7%) and Chikungunya (1.7%). In Villeta, a specific etiology was confirmed in 55.4% of patients, of which SFG rickettsiosis (39.3%) was the most frequent, followed by leptospirosis (21.4%), DENV (3.6%) and malaria (1.8%). No cases due to Mayaro, Yellow Fever, Oropouche and Venezuelan Equine Encephalitis viruses were detected. Conclusion: We confirm the relevance of dengue fever, leptospirosis, SFG rickettsiosis, COVID-19 and malaria as causes of AUFI in the municipality of Apartadó, and highlight the great importance of SFG rickettsiosis as the main cause of AUFI in the municipality of Villeta.

Molecular Diagnosis as an Alternative for Public Health Surveillance of Leptospirosis in Colombia.

Leptospirosis represents a public health problem in Colombia. However, the underreporting of the disease is an unfortunate reality, with a clear trend towards a decrease in cases since 2019, when the guidelines for its confirmatory diagnosis changed with the requirement of two paired samples. The purpose of this review is to highlight the importance of leptospirosis. While the access to rapid diagnosis is available at practically all levels of care for dengue and malaria, leptospirosis-a doubly neglected disease-deserves recognition as a serious public health problem in Colombia. In this manner, it is proposed that molecular tests are a viable diagnostic alternative that can improve the targeted treatment of the patient and the timeliness of data and case reporting to SIVIGILA, and reduce the underreporting of the disease. Taking advantage of the strengthened technological infrastructure derived from the SARS-CoV-2 pandemic for molecular diagnosis in Colombia, with a network of 227 laboratories distributed throughout the national territory, with an installed capacity for PCR testing, it is proposed that molecular diagnosis can be used as an alternative for early diagnosis. This would allow case confirmation through the public health network in Colombia, and, together with the microagglutination (MAT) technique, the epidemiological surveillance of this disease in this country would be strengthened.

Kidney Injury Biomarkers in Leptospirosis.

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.

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.

Highly Multiplexed Serology for Nonhuman Mammals.

Emerging infectious diseases represent a serious and ongoing threat to humans. Most emerging viruses are maintained in stable relationships with other species of animals, and their emergence within the human population results from cross-species transmission. Therefore, if we want to be prepared for the next emerging virus, we need to broadly characterize the diversity and ecology of viruses currently infecting other animals (i.e., the animal virosphere). High-throughput metagenomic sequencing has accelerated the pace of virus discovery. However, molecular assays can detect only active infections and only if virus is present within the sampled fluid or tissue at the time of collection. In contrast, serological assays measure long-lived antibody responses to infections, which can be detected within the blood, regardless of the infected tissues. Therefore, serological assays can provide a complementary approach for understanding the circulation of viruses, and while serological assays have historically been limited in scope, recent advancements allow thousands to hundreds of thousands of antigens to be assessed simultaneously using <1 µL of blood (i.e., highly multiplexed serology). The application of highly multiplexed serology for the characterization of the animal virosphere is dependent on the availability of reagents that can be used to capture or label antibodies of interest. Here, we evaluate the utility of commercial immunoglobulin-binding proteins (protein A and protein G) to enable highly multiplexed serology in 25 species of nonhuman mammals, and we describe a competitive fluorescence-linked immunosorbent assay (FLISA) that can be used as an initial screen for choosing the most appropriate capture protein for a given host species. IMPORTANCE Antibodies are generated in response to infections with viruses and other pathogens, and they help protect against future exposures. Mature antibodies are long lived, are highly specific, and can bind to their protein targets with high affinity. Thus, antibodies can also provide information about an individual's history of viral exposures, which has important applications for understanding the epidemiology and etiology of disease. In recent years, there have been large advances in the available methods for broadly characterizing antibody-binding profiles, but thus far, these have been utilized primarily with human samples only. Here, we demonstrate that commercial antibody-binding reagents can facilitate modern antibody assays for a wide variety of mammalian species, and we describe an inexpensive and fast approach for choosing the best reagent for each animal species. By studying antibody-binding profiles in captive and wild animals, we can better understand the distribution and prevalence of viruses that could spill over into humans.

Canine Leptospirosis in a Northwestern Region of Colombia: Serological, Molecular and Epidemiological Factors.

Canine leptospirosis is a zoonosis of epidemiological importance. Dogs are recognized as primary reservoirs of Leptospira interrogans serogroup Canicola and a source of infection to the environment through urine. This study aimed to determine the presence of antibodies against Leptospira in canines from 49 municipalities in the Department of Antioquia, Colombia. We performed a cross-sectional study of dogs included in a neutering control program. We collected 1335 sera samples, assayed by a microagglutination test (MAT), and performed PCR detection in 21 urine samples. We also surveyed 903 dog owners. We found a seroreactivity of 11.2% (150/1335) in Antioquia with titers ≥1:50. Municipalities with the highest number of cases were Belmira (46.1%), Turbo (34.5%), and Concepción (31.0%). L. santarosai was identified by phylogenetic analysis in one urine sample from the municipality of Granada. The most important factor associated with a positive result was the lack of vaccination against leptospirosis (PR 3.3, p ≤ 0.014). Environmental factors such as water presence and bare soil around the household were also associated with Leptospira seroreactivity in the Department of Antioquia. We reviewed a national epidemiological surveillance database for human cases in those municipalities. We found a correlation between the high number of cases in canines and humans, especially in the Uraba. Serological and molecular results showed the circulation of Leptospira. Future public health efforts in the municipalities with the highest numbers of seroreactivity should be directed towards vaccination to prevent animal disease and decrease the probability of transmission of Leptospira. Dogs actively participate in the Leptospira cycle in Antioquia and encourage the implementation of vaccination protocols and coverage.

High Diversity of Leptospira Species Infecting Bats Captured in the Urabá Region (Antioquia-Colombia).

Leptospirosis is a globally distributed zoonotic disease caused by pathogenic bacteria of the genus Leptospira. This zoonotic disease affects humans, domestic animals and wild animals. Colombia is considered an endemic country for leptospirosis; Antioquia is the second department in Colombia, with the highest number of reported leptospirosis cases. Currently, many studies report bats as reservoirs of Leptospira spp. but the prevalence in these mammals is unknown. The goal of this study was to better understand the role of bats as reservoir hosts of Leptospira species and to evaluate the genetic diversity of circulating Leptospira species in Antioquia-Colombia. We captured 206 bats in the municipalities of Chigorodó (43 bats), Carepa (43 bats), Apartadó (39 bats), Turbo (40 bats), and Necoclí (41 bats) in the Urabá region (Antioquia-Colombia). Twenty bats tested positive for Leptospira spp. infection (20/206-9.70%) and the species of infected bats were Carollia perspicillata, Dermanura rava, Glossophaga soricina, Molossus molossus, Artibeus planirostris, and Uroderma convexum. These species have different feeding strategies such as frugivorous, insectivores, and nectarivores. The infecting Leptospira species identified were Leptospira borgpetersenii (3/20-15%), Leptospira alexanderi (2/20-10%), Leptospira noguchii (6/20-30%), Leptospira interrogans (3/20-15%), and Leptospira kirschneri (6/20-30%). Our results showed the importance of bats in the epidemiology, ecology, and evolution of Leptospira in this host-pathogen association. This is the first step in deciphering the role played by bats in the epidemiology of human leptospirosis in the endemic region of Urabá (Antioquia-Colombia).

Leptospirosis and rickettsiosis, a diagnostic challenge for febrile syndrome in endemic areas / [Leptospirosis y rickettsiosis, reto diagnóstico para el síndrome febril en zonas endémicas].

This is the case of a 50-year-old male from the region of Urabá, Colombia, with a mixed infection by Rickettsia rickettsii and Leptospira interrogans serovar Copenhageni ST78 and negative test for malaria and dengue fever. The patient presented with febrile syndrome and was unresponsive to systemic antibiotic treatment, who finally died in the intensive care unit. We established the postmortem diagnosis through molecular typification of the two etiological agents. In the inspection at the patient's home, we found a Rattus rattus specimen infected with L. interrogans of the same serovar found in him. We found no ticks parasitizing the domestic animals cohabitating with the patient. This case of a mixed infection with progressive and fatal symptoms in a patient with occupational risk in a tropical disease endemic zone highlights the importance of considering the potential presentation of simultaneous etiologies in patients with multiple medical visits for unresolved febrile syndromes associated with risky exposure during agricultural activities.

Se presenta el caso de un hombre de 50 años de edad proveniente de la región de Urabá, Colombia, con una infección mixta por Rickettsia rickettsii y Leptospira interrogans serovar Copenhageni ST78, y pruebas negativas para malaria y dengue. El paciente presentó un síndrome febril que no mejoró con el tratamiento antibiótico sistémico y, finalmente, falleció en la unidad de cuidados intensivos. El diagnóstico post mortem se hizo mediante tipificación molecular de los dos agentes etiológicos. En la inspección del domicilio del paciente, se encontró un ejemplar de Rattus rattus infectado con L. interrogans del mismo serovar detectado en él. No se encontraron garrapatas en los animales domésticos que habitaban con el paciente. Se reporta una infección mixta con síntomas clínicos progresivos y fatales en un paciente con antecedentes laborales de riesgo en una zona endémica para enfermedades tropicales, lo que obliga a tener presente la posibilidad de infecciones simultáneas en personas procedentes de áreas endémicas que consulten reiteradamente por síndrome febril sin resolución y tengan riesgo laboral relacionado con actividades agrícolas.

Leptospirosis y rickettsiosis, reto diagnóstico para el síndrome febril en zonas endémicas / Leptospirosis and rickettsiosis, a diagnostic challenge for febrile syndrome in endemic areas

Resumen. Se presenta el caso de un hombre de 50 años de edad proveniente de la región de Urabá, Colombia, con una infección mixta por Rickettsia rickettsii y Leptospira interrogans serovar Copenhageni ST78, y pruebas negativas para malaria y dengue. El paciente presentó un síndrome febril que no mejoró con el tratamiento antibiótico sistémico y, finalmente, falleció en la unidad de cuidados intensivos. El diagnóstico post mortem se hizo mediante tipificación molecular de los dos agentes etiológicos. En la inspección del domicilio del paciente, se encontró un ejemplar de Rattus rattus infectado con L. interrogans del mismo serovar detectado en él. No se encontraron garrapatas en los animales domésticos que habitaban con el paciente. Se reporta una infección mixta con síntomas clínicos progresivos y fatales en un paciente con antecedentes laborales de riesgo en una zona endémica para enfermedades tropicales, lo que obliga a tener presente la posibilidad de infecciones simultáneas en personas procedentes de áreas endémicas que consulten reiteradamente por síndrome febril sin resolución y tengan riesgo laboral relacionado con actividades agrícolas.

Abstract. This is the case of a 50-year-old male from the region of Urabá, Colombia, with a mixed infection by Rickettsia rickettsii and Leptospira interrogans serovar Copenhageni ST78 and negative test for malaria and dengue fever. The patient presented with febrile syndrome and was unresponsive to systemic antibiotic treatment, who finally died in the intensive care unit. We established the postmortem diagnosis through molecular typification of the two etiological agents. In the inspection at the patient's home, we found a Rattus rattus specimen infected with L. interrogans of the same serovar found in him. We found no ticks parasitizing the domestic animals cohabitating with the patient. This case of a mixed infection with progressive and fatal symptoms in a patient with occupational risk in a tropical disease endemic zone highlights the importance of considering the potential presentation of simultaneous etiologies in patients with multiple medical visits for unresolved febrile syndromes associated with risky exposure during agricultural activities.

New molecular target for the phylogenetic identification of Leptospira species directly from clinical samples: an alternative gene to 16S rRNA.

INTRODUCTION: Phylogenetic analysis of the 16S ribosomal gene initial region is used to identify Leptospira isolates at the species level from clinical samples. Unfortunately, this method cannot differentiate between some intermediates and saprophytic species. METHODS: We used comparative genomic analysis between 35 Leptospira species to find new molecular targets for Leptospira species identification. RESULTS: We proposed the use of the rpoC gene, encoding the DNA-directed RNA polymerase ß-subunit, for identifying 35 Leptospira species. CONCLUSIONS: The rpoC gene can be a molecular target to identify the main species of the Leptospira genus directly from clinical samples.

New molecular target for the phylogenetic identification of Leptospira species directly from clinical samples: an alternative gene to 16S rRNA

Abstract INTRODUCTION: Phylogenetic analysis of the 16S ribosomal gene initial region is used to identify Leptospira isolates at the species level from clinical samples. Unfortunately, this method cannot differentiate between some intermediates and saprophytic species. METHODS: We used comparative genomic analysis between 35 Leptospira species to find new molecular targets for Leptospira species identification. RESULTS: We proposed the use of the rpoC gene, encoding the DNA-directed RNA polymerase β-subunit, for identifying 35 Leptospira species. CONCLUSIONS: The rpoC gene can be a molecular target to identify the main species of the Leptospira genus directly from clinical samples.

Inmunología de la leptospirosis / Immunology of leptospirosis

Resumen Leptospirosis es una enfermedad re-emergente de distribución mundial ocasionada por espiroquetas patogénicas del género Leptospira que afectan humanos, animales domésticos o silvestres. Las manifestaciones clínicas de la enfermedad son diversas y son el resultado de la interacción de la respuesta inmune del hospedador y las condiciones de virulencia propias de las especies patógenas. Aunque se desconocen muchos aspectos de la inmunidad en la infección por Leptospira spp, es reconocido que los hospe deros susceptibles presentan diferencias en su respuesta inmune, como la activación/evasión del sistema del complemento, la activación de sub poblaciones celulares, la producción de citoquina y el desarrollo de anti cuerpos. El estudio del perfil inmunológico en pacientes con leptospirosis ha sido documentado y contribuye en la identificación de biomarcadores asociados con severidad. Esta revisión presenta algunos de los eventos relacionados con la respuesta inmune desde el ingreso de la bacteria en la fase inicial de la infección hasta su multiplicación y generación de enfer medad en el humano.

Abstract Leptospirosis is a re-emergent disease of worldwide distribution caused by pathogenic spirochetes of the Leptospira genus that affect humans, do mestic and wild animals. The clinical manifestations of the disease are diverse and are the result of the interaction of the immune response of the host and the virulence conditions of the pathogenic species. Although many aspects of immunity in infection with Leptospira spp are unknown, it is recognized that susceptible hosts show differences in their immune res ponse, such as activation / evasion of the complement system, activation of cellular subpopulations, production of cytokines, development of anti bodies. Study of the immunological profile in patients with leptospirosis has been documented and contributes in the identification of bio-markers associated with severity. This review presents updated events related to the immune response from the entry of the bacteria in the initial phase of the infection to its multiplication and generation of human disease.

Incidence and underreporting of leptospirosis comparing three diagnostic methods in the endemic region of Urabá, Colombia / Incidencia y subregistro de casos de leptospirosis diagnosticados con tres métodos diferentes en Urabá, Colombia

Introduction: Leptospirosis represents a public health problem and is a significant cause of morbidity and mortality in the region of Urabá. However, its notification reveals diagnostic limitations. Objective: To establish the incidence of leptospirosis in the municipalities of the so-called eje bananero in the Urabá region, to describe the magnitude of underreporting, and to propose guidelines for laboratory diagnosis by the public health network. Materials and methods: Two leptospirosis information sources were used: The national official surveillance system and a cross-sectional study of 479 acute-phase patients from April, 2010, to May, 2012. The diagnosis was made using three different tests: Indirect immunofluorescence, microagglutination test, and blood cultures. The exhaustiveness percentage of each information source was calculatedusing the capture and recapture test. Results: From the total number of cases, 58% (278/479) were positive for leptospirosis at least by a test and 10.43% (29/278) of cases were positive by all three methods. The inclusion of a native strain in the microagglutination test panel increased the percentage of positivity by 15%. The cumulative incidence rate was 66.5/100,000 inhabitants and the case fatality ratio was 2.15%. The underreporting rates of leptospirosis in the Urabá region were 27.8% in morbidity and 66.6% in mortality. Conclusion: Under-registration of leptospirosis in the region highlights the necessity to use more than one diagnostic test to identify Leptospira in patients from endemic areas. Underregistration could be a common situation throughout the country.

Introducción. La leptospirosis representa un problema de salud pública y es una causa importante de morbimortalidad en la región de Urabá, cuya notificación se ve afectada por las deficiencias en el diagnóstico. Objetivo. Establecer la incidencia de la leptospirosis en los municipios del llamado 'eje bananero' de la región de Urabá, documentar la magnitud del subregistro y proponer orientaciones para el diagnóstico por laboratorio por parte de la red de salud pública. Materiales y métodos. Se compararon dos fuentes de información sobre la leptospirosis: el sistema oficial nacional de vigilancia y un estudio transversal de 479 pacientes febriles, llevado a cabo entre abril de 2010 y mayo de 2012. El diagnóstico se hizo con base en tres pruebas: inmunofluorescencia indirecta, microaglutinación y hemocultivo. La exhaustividad de cada fuente de información se estimó mediante el método de captura y recaptura. Resultados. El 58 % (278/479) de los pacientes fueron positivos para leptospirosis, por lo menos, en una de las pruebas y, el 10,43 % (29/278), en las tres. La inclusión de una cepa nativa en el panel de la prueba de microaglutinación aumentó el porcentaje de positividad en 15 %. La tasa acumulada de incidencia fue de 66,5 por 100.000 habitantes y la proporción de letalidad fue de 2,15 %. El subregistro de la morbilidad por leptospirosis en la región de Urabá, fue de 27,8 % y, el de la mortalidad, de 66,6 %. Conclusión. El subregistro de leptospirosis en la región reitera la necesidad de usar más de una prueba diagnóstica para identificar Leptospira spp. en pacientes de zonas endémicas. Este subregistro podría ser una situación común en todo el país.

Incidencia y subregistro de casos de leptospirosis diagnosticados con tres métodos diferentes en Urabá, Colombia / Incidence and underreporting of leptospirosis comparing three diagnostic methods in the endemic region of Urabá, Colombia

Resumen Introducción. La leptospirosis representa un problema de salud pública y es una causa importante de morbimortalidad en la región de Urabá, cuya notificación se ve afectada por las deficiencias en el diagnóstico. Objetivo. Establecer la incidencia de la leptospirosis en los municipios del llamado 'eje bananero' de la región de Urabá, documentar la magnitud del subregistro y proponer orientaciones para el diagnóstico por laboratorio por parte de la red de salud pública. Materiales y métodos. Se compararon dos fuentes de información sobre la leptospirosis: el sistema oficial nacional de vigilancia y un estudio transversal de 479 pacientes febriles, llevado a cabo entre abril de 2010 y mayo de 2012. El diagnóstico se hizo con base en tres pruebas: inmunofluorescencia indirecta, microaglutinación y hemocultivo. La exhaustividad de cada fuente de información se estimó mediante el método de captura y recaptura. Resultados. El 58 % (278/479) de los pacientes fueron positivos para leptospirosis, por lo menos, en una de las pruebas y, el 10,43 % (29/278), en las tres. La inclusión de una cepa nativa en el panel de la prueba de microaglutinación aumentó el porcentaje de positividad en 15 %. La tasa acumulada de incidencia fue de 66,5 por 100.000 habitantes y la proporción de letalidad fue de 2,15 %. El subregistro de la morbilidad por leptospirosis en la región de Urabá, fue de 27,8 % y, el de la mortalidad, de 66,6 %. Conclusión. El subregistro de leptospirosis en la región reitera la necesidad de usar más de una prueba diagnóstica para identificar Leptospira spp. en pacientes de zonas endémicas. Este subregistro podría ser una situación común en todo el país.

Abstract Introduction: Leptospirosis represents a public health problem and is a significant cause of morbidity and mortality in the region of Urabá. However, its notification reveals diagnostic limitations. Objective: To establish the incidence of leptospirosis in the municipalities of the so-called eje bananero in the Urabá region, to describe the magnitude of underreporting, and to propose guidelines for laboratory diagnosis by the public health network. Materials and methods: Two leptospirosis information sources were used: The national official surveillance system and a cross-sectional study of 479 acute-phase patients from April, 2010, to May, 2012. The diagnosis was made using three different tests: Indirect immunofluorescence, microagglutination test, and blood cultures. The exhaustiveness percentage of each information source was calculatedusing thecapture and recapture test. Results: From the total number of cases, 58% (278/479) were positive for leptospirosis at least by a test and 10.43% (29/278) of cases were positive by all three methods. The inclusion of a native strain in the microagglutination test panel increased the percentage of positivity by 15%. The cumulative incidence rate was 66.5/100,000 inhabitants and the case fatality ratio was 2.15%. The underreporting rates of leptospirosis in the Urabá region were 27.8% in morbidity and 66.6% in mortality. Conclusion: Under-registration of leptospirosis in the region highlights the necessity to use more than one diagnostic test to identify Leptospira in patients from endemic areas. Under-registration could be a common situation throughout the country.

Evaluation of variants in IL6R, TLR3, and DC-SIGN genes associated with dengue in sampled Colombian population. / Evaluación de variantes en los genes IL6R, TLR3 y DC-SIGN asociadas con dengue en una población colombiana muestreada

INTRODUCTION: Host genetics is recognized as an influential factor for the development of dengue disease. OBJECTIVE: This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN. MATERIALS AND METHODS: Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry. RESULTS: For Afro-Colombians, the allele rs8192284 C offered protection against dengue [OR=0.425,(0.204-0.887), p=0.020]. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians [OR=2.389, (1.170-4.879), p=0.015] and Mestizos [OR=2.329, (1.283-4.226), p=0.005]. The reproducibility for rs8192284 C/C [OR=2.45, (1.05-5.76), p=0.013] remained after adjustment by Amerindian ancestry [OR=2.52, (1.04-6.09), p=0.013]. The reproducibility for rs3775290 A/A [OR=2.48, (1.09-5.65), p=0.033] remained after adjustment by European [OR=2.34, (1.02-5.35), p=0.048], Amerindian [OR=2.49, (1.09-5.66), p=0.035], and African ancestry [OR=2.37, (1.04-5.41), p=0.046]. Finally, the association of dengue fever with the allelic combination CAG [OR=2.07, (1.06-4.05), p=0.033] remained after adjustment by Amerindian ancestry [OR=2.16, (1.09-4.28), p=0.028]. CONCLUSIONS: Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population.

Introducción. La genética del huésped se reconoce como un factor que influye en el desarrollo del dengue. Objetivo. Este estudio evaluó la asociación del dengue con los polimorfismos rs8192284 del gen IL6R, rs3775290 del TLR3 y rs7248637 del DC-SIGN. Materiales y métodos. De los 292 sujetos encuestados, en 191 se confirmó la presencia de fiebre por dengue y los restantes 101 se incluyeron como controles. Los genotipos se resolvieron mediante reacción en cadena de la polimerasa y polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). En un intento por determinar el riesgo de sufrir dengue, los datos se analizaron mediante la prueba de ji al cuadrado para los alelos y la regresión logística para los genotipos y las combinaciones alélicas. Los intervalos de confianza se calcularon a 95 % para todas las pruebas independientemente ajustadas por autoidentificación o componente genético ancestral. Resultados. En los afrocolombianos, el alelo C rs8192284 ofreció protección contra el dengue (OR=0,425; 0,204-0,887, p=0,020). Los alelos A rs7248637 y A rs3775290 plantearon un mayor riesgo de dengue para los afrocolombianos (OR=2,389; 1,170-4,879; p=0,015) y los mestizos (OR=2,329; 1,283-4,226: p=0,005), respectivamente. La reproducibilidad para rs8192284 C/C (OR=2,45; 1,05-5,76; p=0,013) permaneció después del ajuste por el componente genético ancestral amerindio (OR=2,52; 1,04-6,09; p=0,013). La reproducibilidad del rs3775290 A/A (OR=2,48; 1,09-5,65; p=0,033) permaneció después del ajuste por el componente europeo (OR=2,34; 1,02-5,35; p=0,048), el amerindio (OR=2,49; 1,09- 5,66; p=0,035), y el africano (OR=2,37; 1,04-5,41; p=0,046). Por último, la asociación del dengue con la combinación alélica CAG (OR=2,07; 1,06-4,05; p=0,033) permaneció después del ajuste por el componente genético amerindio (OR=2,16; 1,09-4,28; p=0,028). Conclusión. Los polimorfismos rs8192284 en IL6R, rs3775290 en TLR3 y rs7248637 en DC-SIGN, se asociaron con la propensión a sufrir dengue en una muestra de población colombiana.

Brotes emergentes de leptospirosis del Amazonas colombiano / Emerging leptospirosis outbreaks in the Colombian Department of Amazonas

Se describe por primera vez una serie de nueve casos con clínica indicativa de leptospirosis en el municipio Puerto Nariño en el departamento Amazonas, Colombia. Se muestran evidencias serológicas de exposición con Rickettsia del grupo de las fiebres manchadas. Los casos fueron clínicamente considerados como síndrome febril de origen desconocido. Se descartó infección por dengue y malaria. El diagnóstico de Leptospira se realizó mediante el método de reacción en cadena de la polimerasa en tiempo real. Igualmente, se detectó la presencia de anticuerpos contra rickettsias del grupo de las fiebres manchadas por inmunofluorescencia Indirecta. Finalmente, se realiza revisión del tema(AU)

A description is provided for the first time of a series of nine cases with a clinical examination suggestive of leptospirosis in the municipality of Puerto Nariño, Department of Amazonas, Colombia. Serological evidence is presented of exposure to Rickettsia, spotted fever group. The cases were clinically considered as febrile syndrome of unknown origin. Infection with dengue or malaria was ruled out. Diagnosis of leptospirosis was achieved by real-time polymerase chain reaction. Additionally, indirect immunofluorescence detected the presence of antibodies against rickettsia, spotted fever group. Finally, a review was conducted about the topic(AU)

Evaluation of variants in IL6R, TLR3, and DC-SIGN genes associated with dengue in a sampled Colombian population / Evaluación de las variantes en los genes IL6R, TLR3 y DC-SIGN asociadas con dengue en una muestra de población colombiana

Abstract Introduction: Host genetics is recognized as an influential factor for the development of dengue disease. Objective: This study evaluated the association of dengue with the polymorphisms rs8192284 for gene IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN. Materials and methods: Of the 292 surveyed subjects, 191 were confirmed for dengue fever and the remaining 101 were included as controls. The genotypes were resolved using polymerase chain reaction and restriction fragment length polymorphism (PCR- RFLP). In an attempt to determine the risk (Odds Ratio) of suffering dengue fever, data were analyzed using chi-square for alleles and logistic regression for both genotypes and allelic combinations. Confidence intervals were set to 95% for all tests regardless of the adjustment by either self-identification or ancestry. Results: For Afro-Colombians, the allele rs8192284 C offered protection against dengue [OR=0.425,(0.204-0.887), p=0.020]. The alleles rs7248637 A and rs3775290 A posed, respectively, an increased risk of dengue for Afro-Colombians [OR=2.389, (1.170-4.879), p=0.015] and Mestizos [OR=2.329, (1.283-4.226), p=0.005]. The reproducibility for rs8192284 C/C [OR=2.45, (1.05-5.76), p=0.013] remained after adjustment by Amerindian ancestry [OR=2.52, (1.04-6.09), p=0.013]. The reproducibility for rs3775290 A/A [OR=2.48, (1.09-5.65), p=0.033] remained after adjustment by European [OR=2.34, (1.02-5.35), p=0.048], Amerindian [OR=2.49, (1.09-5.66), p=0.035], and African ancestry [OR=2.37, (1.04-5.41), p=0.046]. Finally, the association of dengue fever with the allelic combination CAG [OR=2.07, (1.06-4.05), p=0.033] remained after adjustment by Amerindian ancestry [OR=2.16, (1.09-4.28), p=0.028]. Conclusions: Polymorphisms rs8192284 for IL6R, rs3775290 for TLR3, and rs7248637 for DC-SIGN were associated with the susceptibility to suffer dengue fever in the sampled Colombian population.

Resumen Introducción. La genética del huésped se reconoce como un factor que influye en el desarrollo del dengue. Objetivo. Este estudio evaluó la asociación del dengue con los polimorfismos rs8192284 del gen IL6R, rs3775290 del TLR3 y rs7248637 del DC-SIGN. Materiales y métodos. De los 292 sujetos encuestados, en 191 se confirmó la presencia de fiebre por dengue y los restantes 101 se incluyeron como controles. Los genotipos se resolvieron mediante reacción en cadena de la polimerasa y polimorfismos en la longitud de los fragmentos de restricción (PCR-RFLP). En un intento por determinar el riesgo de sufrir dengue, los datos se analizaron mediante la prueba de ji al cuadrado para los alelos y la regresión logística para los genotipos y las combinaciones alélicas. Los intervalos de confianza se calcularon a 95 % para todas las pruebas independientemente ajustadas por autoidentificación o componente genético ancestral. Resultados. En los afrocolombianos, el alelo C rs8192284 ofreció protección contra el dengue (OR=0,425; 0,204-0,887, p=0,020). Los alelos A rs7248637 y Ars3775290 plantearon un mayor riesgo de dengue para los afrocolombianos (OR=2,389; 1,170- 4,879; p=0,015) y los mestizos (OR=2,329; 1,283-4,226: p=0,005), respectivamente. La reproducibilidad para rs8192284 C/C (OR=2,45; 1,05-5,76; p=0,013) permaneció después del ajuste por el componente genético ancestral amerindio (OR=2,52; 1,04- 6,09; p=0,013). La reproducibilidad del rs3775290 A/A (OR=2,48; 1,09-5,65; p=0,033) permaneció después del ajuste por el componente europeo (OR=2,34; 1,02-5,35; p=0,048), el amerindio (OR=2,49; 1,09- 5,66; p=0,035), y el africano (OR=2,37; 1,04- 5,41; p=0,046). Por último, la asociación del dengue con la combinación alélica CAG (OR=2,07; 1,06-4,05; p=0,033) permaneció después del ajuste por el componente genético amerindio (OR=2,16; 1,09-4,28;p=0,028). Conclusión. Los polimorfismos rs8192284 en IL6R, rs3775290 en TLR3 y rs7248637 en DC-SIGN, se asociaron con la propensión a sufrir dengue en una muestra de población colombiana.

Variantes en los genes TNFA , IL6 e IFNG asociadas con la gravedad del dengue en una muestra de población colombiana / Variants in the TNFA , IL6 and IFNG genes associated with dengue severity in a sample of Colombian population

Resumen Introducción. La composición genética del huésped determina, entre otros aspectos, el perfil clínico del dengue, lo cual se debería al efecto de variantes en los genes que codifican citocinas proinflamatorias. Objetivo. Evaluar la asociación entre las variantes de tres polimorfismos en los genes candidatos TNFA, IL6 e IFNG con la gravedad del dengue en una población colombiana. Materiales y métodos. Se evaluaron los polimorfismos rs1800750, rs2069843 y rs2069705 de los genes TNFA, IL6 e IFNG, respectivamente, en 226 pacientes con dengue. Los genotipos se tipificaron usando la reacción en cadena de la polimerasa (PCR) y los polimorfismos de la longitud de los fragmentos de restricción (Restriction Fragment Length Polymorphism, RFLP). Para determinar el riesgo de diferentes fenotipos del dengue, se compararon las frecuencias alélicas con la prueba de ji al cuadrado, y los genotipos y los haplotipos, con regresión logística. Por último, los análisis se ajustaron utilizando datos de autoidentificación o del componente genético ancestral. Resultados. El alelo A del rs2069843, ajustado por autoidentificación, se asoció con casos de dengue hemorrágico en afrocolombianos. En la muestra completa, dicho polimorfismo, ajustado por componente genético ancestral, fue reproducible. Además, hubo asociaciones significativas entre las combinaciones alélicas GGT y GAC de los rs1800750, rs2069843 y rs2069705 en pacientes con dengue hemorrágico, con ajuste por componente genético ancestral y sin él. Además, la combinación alélica AGC produjo 58,03 pg/ml más de interleucina 6 que la GGC, independientemente de los componentes genéticos europeo, amerindio y africano. Conclusión. Las variantes de los polimorfismos GGT y GAC de los rs1800750, rs2069843 y rs2069705 en los genes TNFA, IL6 e IFNG, respectivamente, se correlacionaron con la gravedad del dengue en esta muestra de población colombiana.

Abstract Introduction: The genetic makeup of the host contributes to the clinical profile of dengue. This could be due to the effect of variants in the genes encoding pro-inflammatory cytokines. Objective: To evaluate the association between the variants of three polymorphisms in TNFA, IL6 and IFNG candidate genes with dengue severity in a sample of Colombian population. Materials and methods: We evaluated the rs1800750, rs2069843, and rs2069705 polymorphisms in TNFA, IL6 and IFNG candidate genes, respectively, in 226 patients with dengue infection. The genotypes were typed using both polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). To determine the risk of different dengue phenotypes, we compared allele frequencies with chisquare and genotypes and haplotypes using logistic regression. Finally, these analyzes were adjusted with data from self-identification or the ancestral genetic component. Results: The A allele in the rs2069843 polymorphism, adjusted by self-identification, was associated with dengue hemorrhagic fever cases in Afro-Colombians. In the entire sample, this polymorphism, adjusted by the ancestral genetic component, was reproducible. In addition, there were significant associations between GGT and GAC allelic combinations of rs1800750, rs2069843, and rs2069705 in dengue hemorrhagic fever patients, with and without adjustment by ancestral genetic component. Additionally, the AGC allelic combination produced 58.03 pg/ml of interleukin-6 more than the GGC combination, regardless of European, Amerindian and African genetic components. Conclusions: The variants of GGT and GAC polymorphisms of rs1800750, rs2069843, and rs2069705 in the TNFA, IL6 and IFNG genes, respectively, were correlated with the susceptibility to dengue severity in a sample of Colombian population.