Reduced dengue incidence following city-wide wMel Wolbachia mosquito releases throughout three Colombian cities: Interrupted time series analysis and a prospective case-control study.

BACKGROUND: The introduction of Wolbachia (wMel strain) into Aedes aegypti mosquitoes reduces their capacity to transmit dengue and other arboviruses. Randomised and non-randomised studies in multiple countries have shown significant reductions in dengue incidence following field releases of wMel-infected Ae. aegypti. We report the public health outcomes from phased, large-scale releases of wMel-Ae. aegypti mosquitoes throughout three contiguous cities in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Following pilot releases in 2015-2016, staged city-wide wMel-Ae. aegypti deployments were undertaken in the cities of Bello, Medellín and Itagüí (3.3 million people) between October 2016 and April 2022. The impact of the Wolbachia intervention on dengue incidence was evaluated in two parallel studies. A quasi-experimental study using interrupted time series analysis showed notified dengue case incidence was reduced by 95% in Bello and Medellín and 97% in Itagüí, following establishment of wMel at ≥60% prevalence, compared to the pre-intervention period and after adjusting for seasonal trends. A concurrent clinic-based case-control study with a test-negative design was unable to attain the target sample size of 63 enrolled virologically-confirmed dengue (VCD) cases between May 2019 and December 2021, consistent with low dengue incidence throughout the Aburrá Valley following wMel deployments. Nevertheless, VCD incidence was 45% lower (OR 0.55 [95% CI 0.25, 1.17]) and combined VCD/presumptive dengue incidence was 47% lower (OR 0.53 [95% CI 0.30, 0.93]) among participants resident in wMel-treated versus untreated neighbourhoods. CONCLUSIONS/SIGNIFICANCE: Stable introduction of wMel into local Ae. aegypti populations was associated with a significant and sustained reduction in dengue incidence across three Colombian cities. These results from the largest contiguous Wolbachia releases to-date demonstrate the real-world effectiveness of the method across large urban populations and, alongside previously published results, support the reproducibility of this effectiveness across different ecological settings. TRIAL REGISTRATION: NCT03631719.

Large-scale releases and establishment of wMel Wolbachia in Aedes aegypti mosquitoes throughout the Cities of Bello, Medellín and Itagüí, Colombia.

BACKGROUND: The wMel strain of Wolbachia has been successfully introduced into Aedes aegypti mosquitoes and has been shown to reduce the transmission of dengue and other Aedes-borne viruses. Here we report the entomological results from phased, large-scale releases of Wolbachia infected Ae. aegypti mosquitoes throughout three contiguous cities located in the Aburrá Valley, Colombia. METHODOLOGY/PRINCIPAL FINDINGS: Local wMel Wolbachia-infected Ae. aegypti mosquitoes were generated and then released in an initial release pilot area in 2015-2016, which resulted in the establishment of Wolbachia in the local mosquito populations. Subsequent large-scale releases, mainly involving vehicle-based releases of adult mosquitoes along publicly accessible roads and streets, were undertaken across 29 comunas throughout Bello, Medellín and Itagüí Colombia between 2017-2022. In 9 comunas these were supplemented by egg releases that were undertaken by staff or community members. By the most recent monitoring, Wolbachia was found to be stable and established at consistent levels in local mosquito populations (>60% prevalence) in the majority (67%) of areas. CONCLUSION: These results, from the largest contiguous releases of wMel Wolbachia mosquitoes to date, highlight the operational feasibility of implementing the method in large urban settings. Based on results from previous studies, we expect that Wolbachia establishment will be sustained long term. Ongoing monitoring will confirm Wolbachia persistence in local mosquito populations and track its establishment in the remaining areas.

Incidence and Risk Factors Associated with Latent Tuberculosis Infection and Pulmonary Tuberculosis among People Deprived of Liberty in Colombian Prisons.

People deprived of liberty (PDL) are at high risk of acquiring Mycobacterium tuberculosis infection (latent tuberculosis infection [LTBI]) and progressing to active tuberculosis (TB). We sought to determine the incidence rates and factors associated with LTBI and active TB in Colombian prisons. Using information of four cohort studies, we included 240 PDL with two-step tuberculin skin test (TST) negative and followed them to evaluate TST conversion, as well as, 2,134 PDL that were investigated to rule out active TB (1,305 among people with lower respiratory symptoms of any duration, and 829 among people without respiratory symptoms and screened for LTBI). Latent tuberculosis infection incidence rate was 2,402.88 cases per 100,000 person-months (95% CI 1,364.62-4,231.10) in PDL with short incarceration at baseline, and 419.66 cases per 100,000 person-months (95% CI 225.80-779.95) in individuals with long incarceration at baseline (who were enrolled for the follow after at least 1 year of incarceration). The TB incidence rate among PDL with lower respiratory symptoms was 146.53 cases/100,000 person-months, and among PDL without respiratory symptoms screened for LTBI the incidence rate was 19.49 cases/100,000 person-months. History of Bacillus Calmette-Guerin vaccination decreased the risk of acquiring LTBI among PDL who were recently incarcerated. Female sex, smoked drugs, and current cigarette smoking were associated with an increased risk of developing active TB. This study shows that PDL have high risk for LTBI and active TB. It is important to perform LTBI testing at admission to prison, as well as regular follow-up to control TB in prisons.

Delayed HIV treatment, barriers in access to care and mortality in tuberculosis/HIV co-infected patients in Cali, Colombia / Retraso en el tratamiento para VIH, barreras en el acceso a la atención en salud y mortalidad en personas coinfectadas con tuberculosis y VIH en Cali, Colombia

Abstract Objective: To determine factors associated with mortality in tuberculosis/HIV co-infected patients in Cali, Colombia Methods: This retrospective cohort design included tuberculosis/HIV co-infected persons. Kaplan-Meier and Cox regression were used to estimate survival and risk factors associated with mortality. Results: Of the 279 tuberculosis/HIV co-infected participants, 27.2% died during the study. Participants mainly were adults and males. CD4 count information was available for 41.6% (the median count was 83 cells/mm3), and half were subject to tuberculosis susceptibility testing. The median time between HIV diagnosis and antiretroviral therapy initiation was 372 days. HIV was identified prior to tuberculosis in 53% and concurrent HIV-tuberculosis were diagnosed in 37% of patients. 44.8% had tuberculosis treatment success. Body mass index above 18 kg/m2, initiation of tuberculosis treatment within two weeks, having any health insurance coverage and CD4 count information conferred a survival advantage. Conclusions: Delays in treatment initiation and factors associated with limited health care access or utilization were associated with mortality. As HIV and tuberculosis are both reportable conditions in Colombia, strategies should be focused on optimizing treatment outcomes within both tuberculosis and HIV programs, particularly improving early HIV diagnosis, early antiretroviral therapy treatment initiation, and adherence to tuberculosis treatment.

Resumen Objetivo: Determinar factores asociados con mortalidad en personas con co-infeccion Tuberculosis/VIH en Cali, Colombia. Métodos: Este diseño de cohorte retrospectiva incluyó personas co-infectadas con tuberculosis /VIH. Se utilizó Kaplan Meier y regresion de Cox para estimar supervivencia y factores de riesgo asociados con mortalidad. Resultados: De los 279 participantes coinfectados con tuberculosis/VIH, el 27.2% falleció durante el estudio. Los participantes fueron principalmente adultos y hombres. Se dispuso de información de recuento de CD4 en el 41.6% (la mediana del recuento fue 83 células/mm3), y en la mitad se realizaron pruebas de susceptibilidad para tuberculosis. La mediana de tiempo entre el diagnóstico de VIH e inicio de terapia antirretroviral fue 372 días. Se identificó VIH previo a tuberculosis en un 53%, e infección concurrente tuberculosis-VIH en el 37% de los pacientes. El 44.8% presentó éxito en el tratamiento para tuberculosis. Un índice de masa corporal superior a 18 kg/m2, inicio del tratamiento para TB dentro de las primeras dos semanas, contar con aseguramiento en salud y con recuento de CD4 se asociaron con mayor supervivencia. Conclusiones: Retraso en el inicio de tratamiento y factores relacionados con brechas en el acceso a atención en salud se asociaron con mortalidad. Dado que VIH y tuberculosis son enfermedades de notificación obligatoria en Colombia, las estrategias deben centrarse en optimizar los desenlaces del tratamiento dentro de ambos programas, en particular mejorar el diagnóstico temprano de VIH, el inicio temprano de la terapia antirretroviral y fomentar la adherencia al tratamiento para tuberculosis.

Critical reflections on the Municipal Epidemiological Resilience Index used for public policy decision-making regarding the control of the COVID-19 pandemic in Colombia

On June 2, 2021, the Colombian Ministry of Health and Social Protection, through Resolution No. 777, laid down the requirements to resume all restricted economic and social activities. Similarly, said Resolution established the Municipal Epidemiological Resilience Index (IREM by its acronym in Spanish) as a tool to support decision-making regarding this economic reactivation amid the third epidemic peak of COVID-19 in the country. The purpose of this article is to perform a critical analysis of the technical aspects of the IREM and to explore the feasibility of its implementation as a support for the resumption of economic and social activities as proposed in the Resolution. The present critical analysis emphasizes on the lack of a clear definition of epidemiological resilience that is consistent with the scientific literature. Furthermore, the face and content validity of the index, as well as the construct validity of the index and of its dimensions, are called into question and, therefore, the feasibility of using it to determine said resumption.

El 2 de junio de 2021, el Ministerio de Salud y Protección Social de Colombia expidió la Resolución 777, mediante la cual se determinan las condiciones para el reinicio de todas las actividades económicas y sociales restringidas. Asimismo, en esta resolución se define el Índice de resiliencia epidemiológica municipal (IREM) como la herramienta para apoyar la toma de decisiones relacionadas con esta reactivación económica en medio del tercer pico epidémico de la COVID-19 en el país. El objetivo de este artículo es hacer un análisis crítico de los aspectos técnicos del IREM y explorar la conveniencia de su implementación como soporte del reinicio de las actividades económicas y sociales propuesto en la resolución. Dentro de este análisis crítico se destaca la falta de una clara definición de resiliencia epidemiológica que se ajuste a la literatura científica. Además, se cuestiona tanto la validez de apariencia, contenido y constructo del índice global, como la validez del constructo de sus dimensiones y, por tanto, la pertinencia de usarlo como herramienta para definir dicho reinicio.

Delayed HIV treatment, barriers in access to care and mortality in tuberculosis/HIV co-infected patients in Cali, Colombia.

Objective: To determine factors associated with mortality in tuberculosis/HIV co-infected patients in Cali, Colombia. Methods: This retrospective cohort design included tuberculosis/HIV co-infected persons. Kaplan-Meier and Cox regression were used to estimate survival and risk factors associated with mortality. Results: Of the 279 tuberculosis/HIV co-infected participants, 27.2% died during the study. Participants mainly were adults and males. CD4 count information was available for 41.6% (the median count was 83 cells/mm3), and half were subject to tuberculosis susceptibility testing. The median time between HIV diagnosis and antiretroviral therapy initiation was 372 days. HIV was identified prior to tuberculosis in 53% and concurrent HIV-tuberculosis were diagnosed in 37% of patients. 44.8% had tuberculosis treatment success. Body mass index above 18 kg/m2, initiation of tuberculosis treatment within two weeks, having any health insurance coverage and CD4 count information conferred a survival advantage. Conclusions: Delays in treatment initiation and factors associated with limited health care access or utilization were associated with mortality. As HIV and tuberculosis are both reportable conditions in Colombia, strategies should be focused on optimizing treatment outcomes within both tuberculosis and HIV programs, particularly improving early HIV diagnosis, early antiretroviral therapy treatment initiation, and adherence to tuberculosis treatment.

Objetivo: Determinar factores asociados con mortalidad en personas con co-infeccion Tuberculosis/VIH en Cali, Colombia. Métodos: Este diseño de cohorte retrospectiva incluyó personas co-infectadas con tuberculosis /VIH. Se utilizó Kaplan Meier y regresion de Cox para estimar supervivencia y factores de riesgo asociados con mortalidad. Resultados: De los 279 participantes coinfectados con tuberculosis/VIH, el 27.2% falleció durante el estudio. Los participantes fueron principalmente adultos y hombres. Se dispuso de información de recuento de CD4 en el 41.6% (la mediana del recuento fue 83 células/mm3), y en la mitad se realizaron pruebas de susceptibilidad para tuberculosis. La mediana de tiempo entre el diagnóstico de VIH e inicio de terapia antirretroviral fue 372 días. Se identificó VIH previo a tuberculosis en un 53%, e infección concurrente tuberculosis-VIH en el 37% de los pacientes. El 44.8% presentó éxito en el tratamiento para tuberculosis. Un índice de masa corporal superior a 18 kg/m2, inicio del tratamiento para TB dentro de las primeras dos semanas, contar con aseguramiento en salud y con recuento de CD4 se asociaron con mayor supervivencia. Conclusiones: Retraso en el inicio de tratamiento y factores relacionados con brechas en el acceso a atención en salud se asociaron con mortalidad. Dado que VIH y tuberculosis son enfermedades de notificación obligatoria en Colombia, las estrategias deben centrarse en optimizar los desenlaces del tratamiento dentro de ambos programas, en particular mejorar el diagnóstico temprano de VIH, el inicio temprano de la terapia antirretroviral y fomentar la adherencia al tratamiento para tuberculosis.

The impact of city-wide deployment of Wolbachia-carrying mosquitoes on arboviral disease incidence in Medellín and Bello, Colombia: study protocol for an interrupted time-series analysis and a test-negative design study.

Background: Dengue, chikungunya and Zika are viral infections transmitted by Aedes aegypti mosquitoes, and present major public health challenges in tropical regions. Traditional vector control methods have been ineffective at halting disease transmission. The World Mosquito Program has developed a novel approach to arbovirus control using Ae. aegypti stably transfected with the Wolbachia bacterium, which have significantly reduced ability to transmit dengue, Zika and chikungunya in laboratory experiments. Field releases in eight countries have demonstrated Wolbachia establishment in local Ae. aegypti populations. Methods: We describe a pragmatic approach to measuring the epidemiological impact of city-wide Wolbachia deployments in Bello and Medellín, Colombia. First, an interrupted time-series analysis will compare the incidence of dengue, chikungunya and Zika case notifications before and after Wolbachia releases, across the two municipalities. Second, a prospective case-control study using a test-negative design will be conducted in one quadrant of Medellín. Three of the six contiguous release zones in the case-control area were allocated to receive the first Wolbachia deployments in the city and three to be treated last, approximating a parallel two-arm trial for the >12-month period during which Wolbachia exposure remains discordant. Allocation, although non-random, aimed to maximise balance between arms in historical dengue incidence and demographics. Arboviral disease cases and arbovirus-negative controls will be enrolled concurrently from febrile patients presenting to primary care, with case/control status classified retrospectively following laboratory diagnostic testing. Intervention effect is estimated from an aggregate odds ratio comparing Wolbachia-exposure odds among test-positive cases versus test-negative controls. Discussion: The study findings will add to an accumulating body of evidence from global field sites on the efficacy of the Wolbachia method in reducing arboviral disease incidence, and can inform decisions on wider public health implementation of this intervention in the Americas and beyond. Trial registration: ClinicalTrials.gov: NCT03631719. Registered on 15 August 2018.

Eligibility criteria and outcome measures adopted in clinical trials of treatments of cutaneous leishmaniasis: systematic literature review covering the period 1991-2015.

OBJECTIVE: To document the sources of heterogeneity in outcomes and shortcomings in trial designs reported by previous systematic reviews. METHODS: Systematic review of clinical trials of CL treatments published since 1991, to assess and compare eligibility criteria and outcome measures in trials (any type of treatment) of CL (any form) reported before and after the publication of the CONSORT statement. RESULTS: We identified 106 eligible trials published between 1991 and 2015, 74% after the 2001 CONSORT statement; 58% (n = 63) were on Old-World CL and 37% (n = 40) in New-World CL; overall, 11 531 patients enrolled in 243 treatment groups on 30 different treatments. Both requirements and definitions for eligibility and outcome criteria varied. Compliance with CONSORT requirements increased for studies published after the 2010 update. As for entry criteria, 94% of studies had a requirement for sex (74% of those enrolling also women excluded those who were pregnant or lactating), 69% for age (variable age ranges), 99% parasitological confirmation, 43% prior duration of illness (14% excluded cases with previous episodes), 46% defined the number, 28% the size and 13% the type of lesions (27% with restrictions as to their anatomical location). Follow-up ranged 1-24 months, with 14% and 91% of studies, respectively, having defined initial and final cure. CONCLUSIONS: This review documents changes in reporting before and after the publication of the CONSORT statement. Lack of standardisation, compounded with the small number of trials relative to the magnitude of the disease in its multiple forms, and with the range of treatments tested explains why evidence to inform treatment guidelines is generally weak for CL. Adopting standardised methodologies will improve the quality and consistency of clinical trials, and ultimately yield better treatments for CL.

Hepatitis E Virus Genotype 3 in Colombia: Survey in Patients with Clinical Diagnosis of Viral Hepatitis.

BACKGROUND: Hepatitis E virus is a major cause of outbreaks as well as sporadic hepatitis cases worldwide. The epidemiology of this enterically transmitted infection differs between developing and developed countries. The aims of this study were to describe HEV infection in Colombian patients and to characterize the genotype. METHODS: A prospective study was carried out on 40 patients aged over 15 with a clinical diagnosis of viral hepatitis, recruited from five primary health units in the city of Medellin, Colombia. Fecal samples obtained from the 40 consecutives cases were analyzed for HEV RNA using nested reverse transcription PCR for both ORF1 and ORF2-3. The amplicons were sequenced for phylogenetic analyses. RESULTS: Nine (22.5%) cases of HEV infection were identified in the study population. Three HEV strains obtained from patients were classified as genotype 3. No significant association was found between cases of Hepatitis E and the variables water drinking source, garbage collection system and contact with pigs. CONCLUSIONS: This is the first prospective study of hepatitis E in Colombian patients. The circulation of the genotype 3 in this population is predictable considering the reports of the region and the identification of this genotype from pigs in the state of Antioquia, of which Medellin is the capital. Further studies are necessary to establish whether zoonotic transmission of HEV is important in Colombia.

Hepatitis D virus and hepatitis B virus infection in Amerindian communities of the Amazonas state, Colombia.

BACKGROUND: In Colombia, cases of Hepatitis D virus (HDV) infection have been officially described since 1985 mainly in Amerindian population from Sierra Nevada de Santa Marta (North Caribbean Coast), Uraba (North West), and Amazon (South East). The last official report of a clinical case of HDV infection in Colombia was registered in 2005. OBJECTIVES: The aims of this study were to identify cases of HDV and/or Hepatitis B virus (HBV) infection in asymptomatic Amerindians from Amazonas state, South East Colombia, and to describe the circulating viral genotypes in this population. STUDY DESIGN: The study population was recruited in 19 Amerindian communities in the Amazonas state. Individuals over 18 years old were screened by rapid test for Hepatitis B surface Antigen (HBsAg). Blood samples obtained from individuals positives for HBsAg in the rapid-test assay were analyzed for HBsAg, anti-HBc, anti-HDV IgM/IgG by ELISA. The detection of HBV DNA and HDV RNA was performed by PCR amplification. The viral genotype was determined by sequencing and phylogenetic analysis. RESULTS: A total of 23/861 individuals were positive for HBsAg detection by rapid test. Serological and/or molecular markers of HDV infection were demonstrated in 43.5 % (10/23) of samples from Amerindians. The phylogenetic analysis demonstrated the exclusive circulation of HBV subgenotype F1b of and HDV 3 in this population. CONCLUSIONS: A high frequency of HBV/HDV infection was found in Amerindian population from Amazonas State, Colombia (43.5 %, 10/23). Nine cases were identified in a population of 861 asymptomatic Amerindian individuals; one symptomatic case (with diagnosis of end-stage hepatic disease) was also identified in the study. The circulation of HDV 3 and HBV subgenotype F1b suggests a constant flow of these viral genotypes as a result of the interaction of the Amerindian populations from Amazon basin. Further studies are necessary to confirm whether HBV subgenotype F1b is the prevalent in the population from South East region in Colombia.

Sputum induction is a safe procedure to use in prisoners and MGIT is the best culture method to diagnose tuberculosis in prisons: a cohort study.

OBJECTIVES: To evaluate the concordance and safety of induced sputum (IS) and spontaneous sputum (SS), and estimate concordance and time to detection of M. tuberculosis between Lowenstein-Jensen (LJ), thin-layer agar (TLA), and the Mycobacteria Growth Indicator Tube system (MGIT). METHODS: This was a cohort study. Prisoners with pulmonary tuberculosis (PTB) were followed for 2 years. At baseline and every follow-up visit, three sputum samples were taken on consecutive days (one IS and two SS) and adverse events occurring before, during, and 30 min after IS were registered. All sputum samples were stained with auramine and cultured in LJ, TLA (to test resistance), and MGIT. RESULTS: Five hundred eighty-six IS and 532 SS were performed on 64 PTB patients. Breathlessness (1.6%), cough (1.2%), hemoptysis (0.3%), and cyanosis (0.2%) were the only complications. Concordance between IS and SS was 0.78 (95% confidence interval 0.69-0.87); 11 positive cultures from IS samples were negative in SS, and 11 positive cultures from SS samples were negative in IS. One hundred seventy-eight cultures were positive by any technique: MGIT 95%, LJ 73%, and TLA 57%. Time to detection of M. tuberculosis in LJ, TLA, and MGIT was 31, 18, and 11 days, respectively. CONCLUSIONS: The IS procedure is safe in prisons. The MGIT system is better and faster than LJ and TLA in the diagnosis of M. tuberculosis.

[Hepatitis E virus infection in patients with clinical diagnosis of viral hepatitis in Colombia]. / Infección por el virus de la hepatitis E en pacientes con diagnóstico clínico de hepatitis viral en Colombia.

INTRODUCTION: Hepatitis E virus (HEV) is an emergent virus of global importance; it is the etiological agent of sporadic cases and outbreaks of hepatitis. The epidemiology of this infection in Colombia is unknown. OBJECTIVE: To determine the seropositivity for hepatitis E virus in Colombia in cases with clinical diagnosis of viral hepatitis. MATERIALS AND METHODS: Serum samples from patients that were sent to the Instituto Nacional de Salud during the period 2005-2010 (group 1) and samples sent to the Laboratorio Departamental de Salud Pública de Antioquia during the 2008-2009 period were included in this study (group 2). Serum samples were analyzed by immunoassay with commercial kits. RESULTS: From the 344 analyzed samples, 8.7% were positive for anti-HEV; the frequency of anti-HEV IgM was 1.74% (6/344) and the frequency of anti-HEV IgG was 7.5% (26/344). A difference in frequency of anti-HEV between group 1 (6.3%) and group 2 (1.3%) was observed. The cases were identified in nine departments of Colombia. CONCLUSIONS: This is the first study of hepatitis E virus infection in patients with diagnosis of hepatitis in Colombia. The frequency of anti-HEV described in this population of patients in Colombia is similar to that described in other Latin American countries like Brazil, Perú and Uruguay. Considering the results of this study, it could be necessary to include hepatitis E virus infection serological markers in the differential diagnosis of viral hepatitis in Colombia.

Infección por el virus de la hepatitis E en pacientes con diagnóstico clínico de hepatitis viral en Colombia / Hepatitis E virus infection in patients with clinical diagnosis of viral hepatitis in Colombia

Introducción. El virus de la hepatitis E (HEV), agente etiológico de casos esporádicos y epidemias de hepatitis, es un virus emergente de importancia global. En Colombia se desconoce la epidemiología de la infección causada por este virus. Objetivo. Determinar la seropositividad para el virus de la hepatitis E en muestras de suero de pacientes con diagnóstico clínico de hepatitis viral en Colombia. Materiales y métodos. Se estudiaron muestras de pacientes remitidas al Instituto Nacional de Salud en el periodo 2005-2010 provenientes de 15 departamentos de Colombia (grupo 1) y muestras remitidas al Laboratorio Departamental de Salud Pública de Antioquia en el periodo 2008-2009 (grupo 2). Las muestras de suero se analizaron por inmunoensayo con estuches comerciales. Resultados. La frecuencia de seropositividad para el virus de la hepatitis E en las 344 muestras analizadas fue de 8,7 % (30/344); de estas, 1,74 % (6/344) presentó IgM anti-HEV y 7,5 % (26/344), IgG anti-HEV. Se observó una diferencia en el resultado positivo entre el grupo 1 (6,3 %) y el grupo 2 (15,3 %). Los casos provenían de nueve departamentos del país. Conclusiones. Este es el primer estudio de infección por el virus de la hepatitis E en muestras de pacientes con diagnóstico de hepatitis en Colombia. La seropositividad descrita en esta población de pacientes es similar a la descrita en otros países de América Latina, como Brasil, Perú y Uruguay. Teniendo en cuenta estos resultados, se debe considerar la inclusión de los marcadores de la infección por el virus de la hepatitis E en el diagnóstico diferencial de la hepatitis viral en Colombia.

Introduction: Hepatitis E virus (HEV) is an emergent virus of global importance; it is the etiological agent of sporadic cases and outbreaks of hepatitis. The epidemiology of this infection in Colombia is unknown. Objective: To determine the seropositivity for hepatitis E virus in Colombia in cases with clinical diagnosis of viral hepatitis. Materials and methods: Serum samples from patients that were sent to the Instituto Nacional de Salud during the period 2005-2010 (group 1) and samples sent to the Laboratorio Departamental de Salud Pública de Antioquia during the 2008-2009 period were included in this study (group 2). Serum samples were analyzed by immunoassay with commercial kits. Results: From the 344 analyzed samples, 8.7% were positive for anti-HEV; the frequency of anti-HEV IgM was 1.74% (6/344) and the frequency of anti-HEV IgG was 7.5% (26/344). A difference in frequency of anti-HEV between group 1 (6.3%) and group 2 (1.3%) was observed. The cases were identified in nine departments of Colombia. Conclusions: This is the first study of hepatitis E virus infection in patients with diagnosis of hepatitis in Colombia. The frequency of anti-HEV described in this population of patients in Colombia is similar to that described in other Latin American countries like Brazil, Perú and Uruguay. Considering the results of this study, it could be necessary to include hepatitis E virus infection serological markers in the differential diagnosis of viral hepatitis in Colombia.

Population structure among mycobacterium tuberculosis isolates from pulmonary tuberculosis patients in Colombia.

BACKGROUND: Phylogeographic composition of M. tuberculosis populations reveals associations between lineages and human populations that might have implications for the development of strategies to control the disease. In Latin America, lineage 4 or the Euro-American, is predominant with considerable variations among and within countries. In Colombia, although few studies from specific localities have revealed differences in M. tuberculosis populations, there are still areas of the country where this information is lacking, as is a comparison of Colombian isolates with those from the rest of the world. PRINCIPAL FINDINGS: A total of 414 M. tuberculosis isolates from adult pulmonary tuberculosis cases from three Colombian states were studied. Isolates were genotyped using IS6110-restriction fragment length polymorphism (RFLP), spoligotyping, and 24-locus Mycobacterial interspersed repetitive units variable number tandem repeats (MIRU-VNTRs). SIT42 (LAM9) and SIT62 (H1) represented 53.3% of isolates, followed by 8.21% SIT50 (H3), 5.07% SIT53 (T1), and 3.14% SIT727 (H1). Composite spoligotyping and 24-locus MIRU- VNTR minimum spanning tree analysis suggest a recent expansion of SIT42 and SIT62 evolved originally from SIT53 (T1). The proportion of Haarlem sublineage (44.3%) was significantly higher than that in neighboring countries. Associations were found between M. tuberculosis MDR and SIT45 (H1), as well as HIV-positive serology with SIT727 (H1) and SIT53 (T1). CONCLUSIONS: This study showed the population structure of M. tuberculosis in several regions from Colombia with a dominance of the LAM and Haarlem sublineages, particularly in two major urban settings (Medellín and Cali). Dominant spoligotypes were LAM9 (SIT 42) and Haarlem (SIT62). The proportion of the Haarlem sublineage was higher in Colombia compared to that in neighboring countries, suggesting particular conditions of co-evolution with the corresponding human population that favor the success of this sublineage.

Prevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia) / Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)

Objetivos: Determinar las frecuencias alélicas y genotípicas del gen de la apolipoproteína E (APOE) en adultos de Medellín durante el año 2010. Métodos: Se tomó una muestra representativa de la población adulta de Medellín, mediante un muestreo polietápico estratificado por conglomerados. Se realizó genotipificación para APOE a cada uno de los sujetos participantes. En el análisis de frecuencias y asociación, se tuvo en cuenta el diseño muestral. Resultados: Las frecuencias de los alelos E2, E3 y E4 de APOE fueron del 3,9, el 92,0 y el 4,1% respectivamente. Las frecuencias genotípicas fueron: 2/2, el 0,2%; 2/3, el 6,8%; 2/4, el 0,6%; 3/3, el 85,0%; 3/4, el 7,2%, y 4/4, el 0,3%. Conclusiones: Las frecuencias alélicas y genotípicas de APOE en adultos de Medellín tienen una distribución similar a las reportadas en poblaciones suramericanas, y son datos que tienen valor para conocer el impacto poblacional de estas variantes genéticas en distintos trastornos psiquiátricos.

Objective: To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. Methods: A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. Results: The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. Conclusions: The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.

[Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia)]. / Prevalencia de variantes en el gen de la apolipoproteína E (APOE) en adultos de la población general del área urbana de Medellín (Antioquia).

OBJECTIVE: To determine the allelic and genotype frequencies of apolipoproteine E (APOE) gene in a representative sample of the adult population of Medellin in 2010. METHODS: A representative sample of the adult population of Medellin, was obtained by means of a multi-stage, stratified, conglomerate based sampling method. APOE genotyping was carried out on each of the participants. The sampling design was taken into consideration for the frequencies and association analysis. RESULTS: The frequencies of the APOE alleles E2, E3 and E4 were 3.9, 92.0 and 4.1%, respectively. The frequencies of the different APOE genotypes were as follows: 2/2, 0.2%; 2/3, 6.8%; 2/4, 0.6%; 3/3, 85.0%; 3/4, 7.2%, and 4/4, 0.3%. CONCLUSIONS: The allelic and genotype frequencies of APOE in an adult population of Medellin did not differ substantially from other series reported in South America. These data are important to determine the real impact of APOE on the population risk of several psychiatric diseases.

High incidence of tuberculosis, low sensitivity of current diagnostic scheme and prolonged culture positivity in four colombian prisons. A cohort study.

OBJECTIVE: To determine the incidence of pulmonary tuberculosis (TB) in inmates, factors associated with TB, and the time to sputum smear and culture conversion during TB treatment. METHODS: Prospective cohort study. All prisoners with respiratory symptoms (RS) of any duration were evaluated. After participants signed consent forms, we collected three spontaneous sputum samples on consecutive days. We performed auramine-rhodamine staining, culturing with the thin-layer agar method, Löwestein-Jensen medium and MGIT, susceptibility testing for first-line drugs; and HIV testing. TB cases were followed, and the times to smear and culture conversion to negative were evaluated. RESULTS: Of 9,507 prisoners held in four prisons between April/30/2010 and April/30/2012, among them 4,463 were screened, 1,305 were evaluated for TB because of the lower RS of any duration, and 72 were diagnosed with TB. The annual incidence was 505 cases/100,000 prisoners. Among TB cases, the median age was 30 years, 25% had <15 days of cough, 12.5% had a history of prior TB, and 40.3% had prior contact with a TB case. TB-HIV coinfection was diagnosed in three cases. History of prior TB, contact with a TB case, and being underweight were risk factors associated with TB. Overweight was a protective factor. Almost a quarter of TB cases were detected only by culture; three cases were isoniazid resistant, and two resistant to streptomycin. The median times to culture conversion was 59 days, and smear conversion was 33. CONCLUSIONS: The TB incidence in prisons is 20 times higher than in the general Colombian population. TB should be considered in inmates with lower RS of any duration. Our data demonstrate that patients receiving adequate anti-TB treatment remain infectious for prolonged periods. These findings suggest that current recommendations regarding isolation of prisoners with TB should be reconsidered, and suggest the need for mycobacterial cultures during follow-up.

[Cost-effectiveness of an alternative tuberculosis treatment: home-based guardian monitoring of patients]. / Costo-efectividad de un tratamiento antituberculoso alternativo: seguimiento a convivientes residenciales de los pacientes.

OBJECTIVE: Estimate the cost-effectiveness ratio of the directly observed treatment short course (DOTS) for treatment of tuberculosis (TB), comparing it to a variation of this treatment that includes increased home-based guardian monitoring of patients (DOTS-R). METHODS: Taking a social perspective that includes the costs for the health institutions, the patients, and their family members, and for other entities that contribute to making operation of the program effective, the costs incurred with each of the two strategies were evaluated and the cost-effectiveness ratios were estimated adopting the measures of effect used by the control programs. The estimate of the cost of each of the two strategies includes the cost to the health institutions that administer treatment, the patients and their family members, and the cost to the Ministry of Health that manages public health programs on the municipal level. Based on these costs and the number of cases cured and treatments completed as outcome measures of each of the strategies evaluated, the cost-effectiveness ratio and incremental cost were calculated. RESULTS: The DOTS-R was found to be more cost-effective for achievement of successful treatments than the DOTS. The DOTS-R recorded costs of US$ 1 122.40 to US$ 1 152.70 for each case cured compared to values of US$ 1 137.00 to US$ 1 494.30 for the DOTS. The percentage of cases treated successfully was higher with DOTS-R than with DOTS. CONCLUSIONS: The DOTS-R is a promising cost-effective alternative for improved control of TB in endemic areas. It is recommended that the health authorities include home-based guardian monitoring of patients in their institutional management of the TB program, with the participation of health workers and the physical and financial resources that currently support this program.

Molecular characterization of hepatitis c virus in multi-transfused Colombian patients.

BACKGROUND: Hepatitis C virus (HCV) infects 170 million persons worldwide and is a public health problem. Considering that HCV is principally transmitted by exposure to infected blood, multi-transfused patients constitute one of the most important risk groups in developing countries. To explore the dynamics of this infection in Colombia, we performed a study to determine the genotypes of HCV in a cohort of multi-transfused patients. RESULTS: The serum samples from patients positive for anti-HCV were evaluated for HCV RNA by nested-PCR of the 5'untranslated region (5'UTR). Viral genotype was determined by RFLP and/or automated sequencing. HCV subtype 1b was found in eight cases (66.7%) and subtype 1a in two cases (16.7%); seven isolates of subtype 1b were obtained from patients who had received the first transfusion before 1986. Either genotypes 2b (8.3%) or 3a (8.3%) were found in the remaining positive specimens. CONCLUSIONS: This is the first HCV genotyping study developed in multi-transfused patients in Colombia where HCV subtype 1b was the most prevalent. The mutation G235A in the 5'UTR of three isolates generated an additional restriction site and an RFLP pattern different from those previously described for genotype 1.

Costo-efectividad de un tratamiento antituberculoso alternativo: seguimiento a convivientes residenciales de los pacientes / Cost-effectiveness of an alternative tuberculosis treatment: home-based guardian monitoring of patients

Objetivo. Estimar la relación de costo-efectividad del tratamiento de corta duración bajoobservación directa (DOTS), comparándolo con una variación de dicho tratamiento, que incluyeun mayor seguimiento a los convivientes residenciales de los pacientes (DOTS-R) parael tratamiento de tuberculosis (TB).Métodos. Tomando una perspectiva social que incluye los costos para las institucionesde salud, para los pacientes y sus familiares, y para otras entidades que contribuyen a hacerefectiva la operación del programa, se evaluaron los costos incurridos con cada una de las dosestrategias y se estimaron razones costo-efectividad adoptando las medidas de efecto usadas porlos programas de control. La estimación de los costos de cada una de las dos estrategias incluyelos correspondientes a las instituciones de salud que administran el tratamiento, los pacientesy sus familiares, y los de la secretaría de salud que gestiona los programas de salud pública anivel municipal. Con base en estos costos y el número de casos curados y tratamientos terminadoscomo medidas de resultado de cada una de las estrategias evaluadas, se calcularon lasrazones costo-efectividad y costo incremental.Resultados. El DOTS-R se halló más costo-efectivo para lograr tratamientos exitosos queel DOTS. El DOTS-R registró costos de entre US$ 1 122,4 y US$ 1 152,7 por caso curado,comparados con valores de entre US$ 1 137,0 y US$ 1 494,3 correspondientes al DOTS. Laproporción de casos tratados con éxito fue mayor con DOTS-R que con DOTS.Conclusiones. El DOTS-R es una alternativa costo-efectiva promisoria para mejorar elcontrol de la TB en sitios endémicos. Se recomienda a las autoridades del sector salud incorporaren su gestión institucional del programa contra la TB, acciones de seguimiento de losconvivientes de pacientes, con la participación del personal de salud y los recursos físicos yfinancieros que apoyan actualmente dicho programa.

Objective. Estimate the cost-effectiveness ratio of the directly observed treatmentshort course (DOTS) for treatment of tuberculosis (TB), comparing it to a variation ofthis treatment that includes increased home-based guardian monitoring of patients(DOTS-R).Methods. Taking a social perspective that includes the costs for the healthinstitutions, the patients, and their family members, and for other entities thatcontribute to making operation of the program effective, the costs incurred with eachof the two strategies were evaluated and the cost-effectiveness ratios were estimatedadopting the measures of effect used by the control programs. The estimate of the costof each of the two strategies includes the cost to the health institutions that administertreatment, the patients and their family members, and the cost to the Ministry ofHealth that manages public health programs on the municipal level. Based on thesecosts and the number of cases cured and treatments completed as outcome measuresof each of the strategies evaluated, the cost-effectiveness ratio and incremental costwere calculated.Results. The DOTS-R was found to be more cost-effective for achievement ofsuccessful treatments than the DOTS. The DOTS-R recorded costs of US$ 1 122.40 toUS$ 1 152.70 for each case cured compared to values of US$ 1 137.00 to US$ 1 494.30for the DOTS. The percentage of cases treated successfully was higher with DOTS-Rthan with DOTS.Conclusions. The DOTS-R is a promising cost-effective alternative for improvedcontrol of TB in endemic areas. It is recommended that the health authorities includehome-based guardian monitoring of patients in their institutional management of theTB program, with the participation of health workers and the physical and financialresources that currently support this program.