Excess tuberculosis risk during and following incarceration in Paraguay: a retrospective cohort study.

Background: The increased risk of tuberculosis (TB) among people deprived of liberty (PDL) is due to individual and institution-level factors. We followed a cohort of PDL from 5 prisons in Paraguay to describe the risk of TB during incarceration and after they were released. Methods: We linked a 2013 national census of prisons with TB records from the TB Program from 2010 to 2021 to identify TB notifications among incarcerated and formerly incarcerated individuals. We used multivariable Cox regression models to quantify the risk of TB during and following incarceration and to identify risk factors associated with TB. Findings: Among 2996 individuals incarcerated, 451 (15.1%) were diagnosed with TB. Of these, 262 (58.1%) cases occurred during incarceration and 189 (41.9%) occurred in the community after release. In prison, the hazard ratio of developing TB was 1.97 (95% CI: 1.52-2.61) after six months of incarceration and increased to 2.78 (95% CI: 1.82-4.24) after 36 months compared with the first six months. The overall TB notification rate was 2940 per 100,000 person-years. This rate increased with the duration of incarceration from 1335 per 100,000 person-years in the first year to 8455 per 100,000 person-years after 8 years. Among former prisoners, the rate of TB decreased from 1717 in the first year after release to 593 per 100 000 person-years after 8 years of follow up. Interpretation: Our study shows the alarming risk of TB associated with prison environments in Paraguay, and how this risk persists for years following incarceration. Effective TB control measures to protect the health of people during and following incarceration are urgently needed. Funding: Paraguay National Commission of Science and Technology grant CONACYT PIN 15-705 (GS, GES, SA).

Prioritizing persons deprived of liberty in global guidelines for tuberculosis preventive treatment.

In this Policy Forum piece, Aditya Narayan and colleagues discuss the challenges and opportunities for tuberculosis preventive treatment in carceral settings.

Dried Blood Spot Sampling to Assess Rifampicin Exposure and Treatment Outcomes among Native and Non-Native Tuberculosis Patients in Paraguay: An Exploratory Study.

The aim of this study was to evaluate the difference in drug exposure of rifampicin in native versus non-native Paraguayan populations using dried blood spots (DBS) samples collected utilizing a limited sampling strategy. This was a prospective pharmacokinetic study that enrolled hospitalized tuberculosis (TB) patients from both native and non-native populations receiving oral rifampicin 10 mg/kg once-daily dosing. Steady-state DBS samples were collected at 2, 4, and 6 h after intake of rifampicin. The area under the time concentration curve 0-24 h (AUC0-24) was calculated using a Bayesian population PK model. Rifampicin AUC0-24 < 38.7 mg*h/L was considered as low. The probability of target attainment (PTA) was calculated using AUC0-24/MIC > 271 as a target and estimated MIC values of 0.125 and 0.25 mg/L. In total, 50 patients were included. Native patients (n = 30) showed comparable drug exposure to the non-natives (n = 20), median AUC0-24 24.7 (17.1-29.5 IQR) and 21.6 (15.0-35.4 IQR) mg*h/L (p = 0.66), respectively. Among total patients, only 16% (n = 8) had a rifampicin AUC0-24 > 38.7 mg*h/L. Furthermore, PTA analysis showed that only 12 (24%) of the patients met a target AUC0-24 /MIC ≥ 271, assuming an MIC of 0.125 mg/L, which plummeted to 0% at a wild-type MIC of 0.25 mg/L. We successfully used DBS and limited sampling for the AUC0-24 estimation of rifampicin. Currently, our group, the EUSAT-RCS consortium, is preparing a prospective multinational, multicenter phase IIb clinical trial evaluating the safety and efficacy of high-dose rifampicin (35 mg/kg) in adult subjects using the DBS technique for AUC0-24 estimation.

The accuracy of an electronic nose to diagnose tuberculosis in patients referred to an expert centre.

INTRODUCTION: An electronic nose (eNose) device has shown a high specificity and sensitivity to diagnose or rule out tuberculosis (TB) in the past. The aim of this study was to evaluate its performance in patients referred to INERAM. METHODS: Patients aged ≥15 years were included. A history, physical examination, chest radiography (CRX) and microbiological evaluation of a sputum sample were performed in all participants, as well as a 5-minute breath test with the eNose. TB diagnosis was preferably established by the gold standard and compared to the eNose predictions. Univariate and multivariate logistic regression analyses were performed to assess potential risk factors for erroneous classification results by the eNose. RESULTS: 107 participants with signs and symptoms of TB were enrolled of which 91 (85.0%) were diagnosed with TB. The blind eNose predictions resulted in an accuracy of 50%; a sensitivity of 52.3% (CI 95%: 39.6-64.7%) and a specificity of 36.4% (CI 95%: 12.4-68.4%). Risk factors for erroneous classifications by the eNose were older age (multivariate analysis: OR 1.55, 95% CI 1.10-2.18, p = 0.012) and antibiotic use (multivariate analysis: OR 3.19, 95% CI 1.06-9.66, p = 0.040). CONCLUSION: In this study, the accuracy of the eNose to diagnose TB in a tertiary referral hospital was only 50%. The use of antibiotics and older age represent important factors negatively influencing the diagnostic accuracy of the eNose. Therefore, its use should probably be restricted to screening in high-risk communities in less complex healthcare settings.

Phylogeography and transmission of Mycobacterium tuberculosis spanning prisons and surrounding communities in Paraguay.

Recent rises in incident tuberculosis (TB) cases in Paraguay and the increasing concentration of TB within prisons highlight the urgency of targeting strategies to interrupt transmission and prevent new infections. However, whether specific cities or carceral institutions play a disproportionate role in transmission remains unknown. We conducted prospective genomic surveillance, sequencing 471 Mycobacterium tuberculosis complex genomes, from inside and outside prisons in Paraguay's two largest urban areas, Asunción and Ciudad del Este, from 2016 to 2021. We found genomic evidence of frequent recent transmission within prisons and transmission linkages spanning prisons and surrounding populations. We identified a signal of frequent M. tuberculosis spread between urban areas and marked recent population size expansion of the three largest genomic transmission clusters. Together, our findings highlight the urgency of strengthening TB control programs to reduce transmission risk within prisons in Paraguay, where incidence was 70 times that outside prisons in 2021.

Tuberculosis burden in indigenous population of Paraguay from 2018 to 2022

This study aims to report the epidemiological characterization, incidence, mortality and prognostic factors of tuberculosis in indigenous patients of Paraguay from 2018 to 2022. A retrospective cohort study was carried out with data extracted from the National Tuberculosis Program from January 2018 to June 2022. The clinical records of 1659 indigenous patients were included in the study. The indigenous population with tuberculosis in the period 2018-2022 was between 0 and 20 years old (25.4%), mostly female (54.6%), residing in Presidente Hayes (22.4%), and was from the rural area (74.3%), of the Mbya ethnic group (20.4%). The diagnosis was bacteriological in 69.2%, 96.1% had pulmonary location, 94.5% of the study population started treatment and 1.1% presented drug-resistance, while 88.3% corresponded to new cases. The highest number of new cases of tuberculosis in indigenous people was 336 in 2019. The incidence of tuberculosis was associated with age and area of residence, being more incident in the youngest and in the Presidente Hayes area. A total of 11.2% died, and the highest number of deaths occurred in 2019 with 47 cases (14%). We observed that the elderly, who did not start treatment, and who were coinfected with HIV were more likely to die from tuberculosis. The number of new cases and mortality from tuberculosis is high in the Paraguayan indigenous population. Age and coinfection with HIV continue to be risk factors for mortality.

Este estudio tiene como objetivo reportar la caracterización epidemiológica, incidencia, la mortalidad y los factores pronósticos de la tuberculosis en pacientes indígenas en Paraguay de 2018 a 2022. Se realizó un estudio de cohorte retrospectivo con datos extraídos del Programa Nacional de Tuberculosis desde enero 2018 hasta junio de 2022. Se incluyeron en el estudio las historias clínicas de 1.659 pacientes indígenas. La población indígena con tuberculosis en el período 2018-2022 presentaba las siguientes características: entre 0 y 20 años (25,4%), sexo femenino (54,5%), residente en Presidente Hayes (22,4%), del área rural (74,3%), y de la etnia Mbya (20,4%). El diagnóstico fue bacteriológico en el 69,2% y el 96,1% era de localización pulmonar, el 94,5% de la población estudiada inició tratamiento y el 1,1% presentó resistencia, el 88,3% correspondió a casos nuevos. El mayor número de casos nuevos de tuberculosis entre indígenas fue de 336 en 2019. La incidencia de tuberculosis estuvo asociada a la edad y zona de residencia, siendo más frecuente entre los más jóvenes y en la zona de Presidente Hayes. Murió un total del 11,2%, y el mayor número de muertes se produjo en 2019 con 47 casos (14%). Se constató que las personas mayores que no habían iniciado el tratamiento y que estaban coinfectadas con el VIH tenían más probabilidades de morir de tuberculosis. El número de casos nuevos y mortalidad por tuberculosis es alto en la población indígena paraguaya. La edad y la coinfección por el VIH siguen siendo factores de riesgo de mortalidad.

Impacto de la COVID-19 en el control de la Tuberculosis en Paraguay. 2019-2020

La COVID-19 ha provocado una emergencia sanitaria mundial sin precedentes, afectando también negativamente a la prestación de atención a la tuberculosis (TB) en casi todos los países. Por tanto, esta investigación analiza el impacto de la COVID-19 en el control de la TB en Paraguay. Estudio descriptivo, retrospectivo, con enfoque mixto y de corte transversal. Resultados: siete de los 10 indicadores priorizados de la Estrategia "Fin de la TB" registraron resultados por debajo a lo notificado en los últimos tres años, siendo el 2020 el más afectado. Existe una brecha de 1.037 personas que no han sido diagnosticadas y tratadas por TB en Paraguay, de acuerdo a lo estimado por la Organización Mundial de la Salud (OMS) en 2020. Se analizaron 2.598 casos de TB en 2020, frente a 3.083 en el 2019, lo que representa una disminución del 15,7% en la notificación de casos; las notificaciones disminuyeron en un 24% en mujeres, 40,5% en niños y en un 19,6% de éxito de tratamiento. Se presentó una tasa de letalidad de 12%, la mayor en los últimos cuatro años. Las expertas encuestadas, opinan que la situación de la TB empeoró tras la llegada de la COVID-19 en el país, principalmente en la notificación de casos e investigación de contactos. La COVID-19 ha impactado negativamente en el control de la TB en Paraguay, esto representa un riesgo significativo en el control de la enfermedad y el avance a lo largo de los años se ve seriamente comprometido y amenaza con revertir los logros alcanzados.

COVID-19 has caused an unprecedented global health emergency, also negatively affecting the delivery of tuberculosis (TB) care in almost all countries. This research therefore analyses the impact of COVID-19 on TB control in Paraguay. Descriptive, retrospective, mixed-approach, cross-sectional study. Results: seven of the 10 prioritized indicators of the "End TB Strategy" registered results below what was reported in the last three years, with 2020 being the most affected. There is a gap of 1,037 people who have not been diagnosed and treated for TB in Paraguay, as estimated by the World Health Organisation (WHO) in 2020. There were 2,598 TB cases analysed in 2020, compared to 3,083 in 2019, representing a 15.7% decrease in case notification; notifications decreased by 24% in women, 40.5% in children and 19.6% treatment success. There was a case fatality rate of 12%, the highest in the last four years. The experts surveyed were of the opinion that the TB situation worsened after the advent of COVID-19 in the country, mainly in case notification and contact investigation. COVID-19 has had a negative impact on TB control in Paraguay, which represents a significant risk for the control of the disease, and progress over the years is seriously compromised and threatens to reverse the achievements made.

Vigilancia de la resistencia del Mycobacterium tuberculosis a los fármacos en Paraguay, 2014 a 2017 / Surveillance of drug resistance of Mycobacterium tuberculosis in Paraguay, 2014 to 2017

El objetivo del estudio fue identificar la resistencia del Mycobacterium tuberculosis a los fármacos en Paraguay, 2014 a 2017. Se realizó un estudio observacional retrospectivo. Se utilizaron los datos del Programa Nacional de Tuberculosis del Paraguay comprendidos entre los años 2014 a 2017. Se incluyeron todos los pacientes con diagnóstico de Tuberculosis que se realizaron un test de resistencia. Se extrajeron los datos en Excel y fueron analizados con Stata 17.0. Se incluyeron 3429 pacientes con tuberculosis que contaban con resultado de al menos una prueba de sensibilidad. La resistencia se encontró en 2.1% de los pacientes. La resistencia a la Rifampicina estuvo presente en el 0.3% de los casos mientras que a la Izionazida en el 0.6% de los casos. La prevalencia de resistencia fue más alta en hombres 3.4 (IC 95% 2.2 - 4.8) p=0.003, que residían en el chaco 6.0 (IC 95% 3.4 - 9.7) p=0.000, previamente tratados 2.7 (IC 95% 1.1 - 5.1) p=0.010. En el modelo se pudo observar que un paciente previamente tratado tiene mayores posibilidades de tener resistencia OR 2.62 (IC 95% 1.1 - 6.24). La prevalencia de resistencia del Mycobacterium tuberculosis a fármacos estuvo relacionada con haber sido previamente tratado

The objective of the study was to identify the resistance of Mycobacterium tuberculosis to drugs in Paraguay, 2014 to 2017. A retrospective observational study was carried out. The data from the National Tuberculosis Program of Paraguay between the years 2014 to 2017 were used. All patients with a diagnosis of Tuberculosis who underwent a resistance test were included. Data were extracted in Excel and analyzed with Stata 17.0. 3429 tuberculosis patients who had a result of at least one sensitivity test were included. Resistance was found in 2.1% of patients. Resistance to Rifampicin was present in 0.3% of cases while to Izionazide in 0.6% of cases. The prevalence of resistance was higher in men 3.4 (95% CI 2.2 - 4.8) p = 0.003, who resided in the Chaco 6.0 (95% CI 3.4 - 9.7) p = 0.000, previously treated 2.7 (95% CI 1.1 - 5.1) p = 0.010. In the model, it was observed that a previously treated patient has a greater chance of having resistance OR 2.62 (95% CI 1.1 - 6.24). The prevalence of resistance of Mycobacterium tuberculosis to drugs was related to having been previously treated

Factores asociados a la mortalidad por tuberculosis en indígenas en Paraguay, 2014 a 2019

Introducción: La tasa de mortalidad estimada de tuberculosis (TBC) en Paraguay en 2019 fue de 3,9 por 100.000 habs. Las comunidades indígenas presentan un elevado riesgo de padecer TBC. Objetivo: Determinar los factores asociados a la mortalidad en personas de origen indígena con diagnóstico de TBC en Paraguay, 2014-2019. Métodos : Se realizó un estudio observacional retrospectivo. Se utilizaron los datos del Programa Nacional de Control de la TBC del Paraguay comprendidos entre los años 2014 y 2019. Se registraron los datos sociodemográficos y factores de riesgo. Resultados: Se incluyeron 2.210 personas de origen indígena con diagnóstico de TBC, el 53,8% fue de sexo masculino, entre 20 y 39 años (32,3%) y 0 a 19 años de edad (30,2%), la localización de la TBC fue mayoritariamente pulmonar (92,3%). Durante el 2014 a 2019 se observaron 217 muertes (9,8%). Los factores asociados a mortalidad en pacientes con TBC fueron la edad (adOR = 13,95; CI: 7,07-27,55 mayor a 80 años), (adOR = 4,20; CI: 2,59-6,82 mayor a 60 años) y (adOR = 3,30; CI: 2,06-5,28 para 40 a 59 años), la co-infección VIH (adOR =), y la localización de la TBC (adOR = 3,60; CI: 1,88-6,90 para TBC diseminada). Conclusión: La mayor edad, el diagnóstico de co-infección VIH y localización de la TBC diseminada, están asociados a un mayor riesgo de muerte en población indígena con TBC.

Background: The estimated tuberculosis (TB) mortality rate in Paraguay in 2019 was 3.9 per 100,000 people. Indigenous communities are at high risk for TB. Aim: To determine the factors associated with mortality in indigenous people with a diagnosis of TB in Paraguay, 2014-2019. Methods: A retrospective observational study was done. sociodemographic data and risk factors data from the National TB Program of Paraguay between the years 2014 to 2019 were used. Results: A total of 2,210 indigenous people with a diagnosis of TB were included, 53,8% were male, between 20 to 39 (32.3%) and 0 to 19 years old (30.2%), the localization of TBC was majority pulmonary (92.3%). During 2014 to 2019 the were 217 deaths (9.8%). The factors associated to mortality in TB patients were the age (adOR = 13.95; CI: 7.07-27.55 older than 80 years), (adOR = 4.20; CI: 2.59-6.82 older than 60 years), and (adOR = 3.30; CI: 2.06 - 5.2840 to 59 years), HIV co-infection (adOR = 7.07; CI 3.74-13.87), and localization of TB (adOR = 3.60; CI: 1.88-6.90 for disseminated TB). Conclusion: Older age, HIV co-infection and disseminated localization of TBC are associated with a higher risk of death in indigenous people with TB.

Estado actual, retos y soluciones operacionales a las Búsquedas activas de TB 2019-2020, Paraguay

RESUMEN Introducción: La búsqueda activa de casos de Tuberculosis (TB) pretende garantizar la detección temprana para reducir el riesgo de malos resultados de la enfermedad y las consecuencias sociales propias de la misma, así como cortar oportunamente la cadena de transmisión en la comunidad. Objetivo: Determinar el estado actual, retos y soluciones operacionales a las Búsquedas activas en las 18 Regiones Sanitarias del Paraguay. Métodos: Estudio descriptivo retrospectivo de corte transversal, fuente de datos: registros de búsqueda activa disponibles de las regiones sanitarias, sociedad civil y Programa Nacional de Control de Tuberculosis (PNCT) del Paraguay 2019-2020 y Sistema Experto del PNCT (SEPNCT) Para el análisis estadístico se utilizaron medidas de resumen como frecuencias absolutas, relativas y proporciones. Resultados: se analizaron las visitas de campo para búsquedas activas, en tres tipos de intervenciones, 5089 personas investigadas, 26.5% fueron identificadas como SR. La positividad general fue de 5%. Se necesita en promedio de 76 personas para encontrar un caso de TB. Las búsquedas activas que tuvieron mayor impacto fueron las realizadas por el nivel nacional con 49.3% de casos de TB aportados. Conclusiones: Las intervenciones basadas en la comunidad, como el establecimiento de redes de derivación y otras actividades que acercan la información y los servicios sobre la tuberculosis a las personas con síntomas, pueden contribuir a mejorar la notificación de casos de tuberculosis, cortar la cadena de transmisión y reducir la mortalidad por tuberculosis.

SUMMARY Introduction: The active search for cases of Tuberculosis (TB) aims to ensure early detection to reduce the risk of poor outcomes of the disease and the social consequences of the disease, as well as to cut the chain of transmission in the community in a timely manner. Objective . To determine the current status, challenges and operational solutions to the Active Searches in the 18 Health Regions of Paraguay. Methods: Retrospective descriptive cross-sectional study, data source: active search records available from the health regions, civil society and National Tuberculosis Control Program (PNCT) of Paraguay 2019-2020 and Expert System of the PNCT (SEPNCT) For the statistical analysis summary measures such as absolute and relative frequencies and proportions were used. Results: field visits were analyzed for active searches, in three types of interventions, 5089 people investigated, 26.5% were identified as RH. The overall positivity was 5%. It takes an average of 76 persons to find a TB case. The active searches that had the greatest impact were those conducted by the national level with 49.3% of TB cases contributed. Conclusions: Community-based interventions, such as the establishment of referral networks and other activities that bring TB information and services closer to people with symptoms, can help improve TB case notification, cut the chain of transmission, and reduce TB mortality.

Safety of Rifampicin at High Dose for Difficult-to-Treat Tuberculosis: Protocol for RIAlta Phase 2b/c Trial.

Previous clinical trials for drug-susceptible tuberculosis (DS-TB) have shown that first-line treatment with doses of rifampicin up to 40 mg/kg are safe and increase the early treatment response for young adults with pulmonary tuberculosis. This may lead to a shorter treatment duration for those persons with TB and a good baseline prognosis, or increased treatment success for vulnerable subgroups (age > 60, diabetes, malnutrition, HIV, hepatitis B or hepatitis C coinfection, TB meningitis, stable chronic liver diseases). Here, we describe the design of a phase 2b/c clinical study under the hypothesis that rifampicin at 35 mg/kg is as safe for these vulnerable groups as for the participants included in previous clinical trials. RIAlta is an interventional, open-label, multicenter, prospective clinical study with matched historical controls comparing the standard DS-TB treatment (isoniazid, pyrazinamide, and ethambutol) with rifampicin at 35 mg/kg (HR35ZE group) vs. rifampicin at 10 mg/kg (historical HR10ZE group). The primary outcome is the incidence of grade ≥ 3 Adverse Events or Severe Adverse Events. A total of 134 participants will be prospectively included, and compared with historical matched controls with at least a 1:1 proportion. This will provide a power of 80% to detect non-inferiority with a margin of 8%. This study will provide important information for subgroups of patients that are more vulnerable to TB bad outcomes and/or treatment toxicity. Despite limitations such as non-randomized design and the use of historical controls, the results of this trial may inform the design of future more inclusive clinical trials, and improve the management of tuberculosis in subgroups of patients for whom scientific evidence is still scarce. Trial registration: EudraCT 2020-003146-36, NCT04768231.

Estudio comparativo de la reacción de Mantoux con la determinación del Interferon Gamma en pacientes VIH-SIDA para el diagnóstico de la Tuberculosis latente (TBL)

Resumen La OMS estima que un tercio de la población mundial está infectada con Mycobacterium tuberculsosis, permaneciendo la mayoría de los casos en forma de TB latente (TBL). No existe un estándar de oro para el diagnóstico de la TBL, por lo cual la carga global de la misma. Objetivo: Comparar la efectividad en pacientes con VIH/SIDA de dos pruebas diagnósticas de TB latente (TBL): la Prueba de Mantoux y la determinación de Interferón Gamma en sangre periférica. Materiales y métodos: Estudio observacional, descriptivo y prospectivo con componente analítico, en el que se incluyeron consecutivamente por muestreo no probabilístico los pacientes de 18 meses a 60 años pacientes de ambos sexos, que acuden al consultorio del Programa Nacional de Control del VIH/sida con diagnóstico reciente de VIH/sida y en quienes se descartó TB activa. En todos los pacientes incluidos se realizó al mismo tiempo determinación del PPD (por inyección de tuberculina I de 2UI de potencia por inyección intradérmica en antebrazo izquierdo) y se tomó sangre periférica para determinación por el método de ELISA de la producción por los mononucleares de interferón gama en respuesta a antígeno de MTB (ELISA- QIAGEN - Germany). Resultados: Desde octubre 2017 a octubre de 2019, se identificaron 659 pacientes VIH que reunían los criterios de inclusión, de los cuales se incluyeron el 99, 9% (599 pacientes), quienes acudieron a la lectura de la prueba de la PPD. La edad media de los pacientes es de 34,1 años (DE 13,1 años), 415 (69%) son del sexo masculino. El 67,9% (407/599) procede del Dpto. Central y Asunción A todos los pacientes incluidos se les realizó la PPD y el test IGRA. La TBL se detectó en el 7,6% (46/599) pacientes, de los cuales, en 8,7% (52/599) el Gama Interferon fue positivo (IGRA) y en 3,8% (23/599) la PPD fue ≥5 (positivo). El 2% (12/599) pacientes fueron positivos para ambas pruebas. Al comparar los datos mencionados podemos observar que el IGRA resultó ser el método más efectivo para detectar la TBL, ya que con el mismo se identificó a 8,7% de los casos a diferencia de la PPD que solo permitió identificar el 2% de los mismos. El 100% (46/46) de los pacientes con diagnóstico con TBL recibieron quimioprofilaxis con Isoniacida. Conclusión: El presente estudio pretende definir el rendimiento de una nueva metodología para la detección de TB latente en una población de alto riesgo de coinfección como son los infectados con VIH.

Abstract The WHO estimates that one third of the world's population is infected with Mycobacterium tuberculosis, with the majority of cases remaining in the form of latent TB (TBL). There is no gold standard for the diagnosis of TBL, hence the global burden of it. Objective: To compare the effectiveness in patients with HIV / AIDS of two diagnostic tests for latent TB (TBL): the Mantoux Test and the determination of Interferon Gamma in peripheral blood. Materials and methods: An observational, descriptive and prospective study with an analytical component, in which patients between 18 months and 60 years of age, patients of both sexes, were consecutively included by non-probabilistic sampling, who attended the office of the National HIV / AIDS Control Program with a recent diagnosis of HIV / AIDS and in whom active TB was ruled out. In all the patients included, PPD was determined at the same time (by injection of tuberculin I of 2IU of potency by intradermal injection in the left forearm) and peripheral blood was taken for determination by the ELISA method of the production of interferon mononuclear cells. gamma in response to MTB antigen (ELISA- QIAGEN - Germany). Results: From October 2017 to October 2019, 659 HIV patients meeting the inclusion criteria were identified, of which 99.9% (599 patients) were included, who attended the reading of the PPD test. The mean age of the patients is 34.1 years (SD 13.1 years), 415 (69%) are male. 67.9% (407/599) came from the Central and Asunción Departments. All patients included underwent the PPD and the IGRA test. TBL was detected in 7.6% (46/599) patients, of which, in 8.7% (52/599) the Interferon range was positive (IGRA) and in 3.8% (23/599) PPD was ≥5 (positive). 2% (12/599) patients were positive for both tests. When comparing the aforementioned data, we can see that the IGRA turned out to be the most effective method for detecting TBL, since with it 8.7% of the cases were identified, as opposed to the PPD, which only allowed the identification of 2% of the cases. themselves. 100% (46/46) of the patients diagnosed with TBL received chemoprophylaxis with Isoniazid. Conclusion: The present study aims to define the performance of a new methodology for the detection of latent TB in a population at high risk of coinfection such as those infected with HIV.

Increased incarceration rates drive growing tuberculosis burden in prisons and jeopardize overall tuberculosis control in Paraguay.

Incarcerated populations are at high-risk to develop tuberculosis (TB), however their impact on the population-level tuberculosis epidemic has been scarcely studied. We aimed to describe the burden and trends of TB among incarcerated populations over time in Paraguay, its clinical and epidemiological differences and the population attributable fraction. This is an observational, descriptive study including all TB cases notified to the National TB control Program in Paraguay during the period 2009-2018. We also used case registries of prisoners diagnosed with tuberculosis from the Minister of Justice. The population attributable fraction of TB in the community due to incarcerated cases was estimated through Levin's formula. The characteristics of TB cases in and outside of prison were compared as well as the characteristics of TB in prisons were modified over time. During 2009-2018, 2764 (9.7%) of the 28,534 TB reported cases in Paraguay occurred in prisons. The number of prisoners in Paraguay increased from 6258 in 2009 to 14,627 in 2018 (incarceration rate, 101 to 207 per 100,000 persons) while the number of TB cases among prisoners increased by 250% (n = 192 in 2009 versus n = 480 in 2018). The annual TB notification rate among male prisoners was 3218 and 3459 per 100,000 inmates in 2009 and 2018, respectively. The percentage of all TB cases occurring among prisoners increased from 7.1% in 2009 to 14.5% in 2018. The relative risk of TB in prisons compared to community was 70.3 (95% CI, 67.7-73.1); the overall population attributable risk was 9.5%. Among the 16 penitentiary centers in the country, two of them-Tacumbú (39.0%) and Ciudad del Este (23.3%)-represent two thirds of all TB cases in prisons. TB among inmates is predominantly concentrated in those 20-34 years old (77.3% of all), twice the percentage of cases for the same age group outside of prison. Our findings show that the TB epidemic in prisons represents one of the most important challenges for TB control in Paraguay, especially in the country's largest cities. Appropriate TB control measures among incarcerated populations are needed and may have substantial impact on the overall TB burden in the country.

Caracterización clínico-epidemiológica de pacientes con tuberculosis en el Departamento de Caaguazú, Paraguay. 2014 a 2017

Resumen Introducción: La tuberculosis (TBC) es una de las diez principales causas de muerte en todo el mundo. Objetivo: Caracterizar clínica y epidemiológicamente los casos de TBC del Departamento de Caaguazú-Paraguay, entre los años 2014 y 2017. Pacientes y Métodos: Se realizó un estudio observacional, retrospectivo, utilizando datos secundarios del Programa Nacional de Control de la Tuberculosis (PNCT). La población: 659 casos de TBC registrados en el PNCT. Las variables: edad, sexo, grupo poblacional, tipo de TBC, co-infección TBC/VIH, y categoría de egreso. Procesamos la base de datos en Excel 2016 © usando Stata 14.0®. Resultado: El 63,3% de los participantes fue del género masculino. La edad promedio fue de 35,8 años. El 39,6% eran indígenas y 14,5% fueron personas privadas de libertad (PPL) conocidos como reclusos. El 89,6% tuvo TBC pulmonar, 2,4% tuvo co-infección TBC/VIH. La tasa de incidencia fue superior a 21,6/100.000 habts en 2014. La incidencia en indígenas fue de 76,5/100.000 habts en 2017. La incidencia en PPL fue de 2.272,1/100.000 habitantes en 2017. Conclusión: La incidencia de TBC en el Departamento de Caaguazú es baja en la población general afectando principalmente a hombres, mientras que en la población indígena y PPL es alta.

Abstract Background: Tuberculosis (TB) is one of the ten leading causes of death worldwide. Aim: To characterize the clinical and epidemiological point of view of TB cases reported in the Department of Caaguazú-Paraguay, from 2014 to 2017. Methods: Observational, descriptive, retrospective study; Population: 659 cases of TB registered in the National Tuberculosis Control Program (NTCP); variables: age, sex, population group, type of TB, TB/HIV coinfection. We procesed database in Excel 2016 © using Stata 14.0®. Results: 63.3% were of male gender, average age: 35.8 years, 39.6% were indigenous and 85.4% were liberty deprived persons known as inmates (LDP), 89.6% had pulmonary TB and 2,4% had TB/HIV coinfection. Incidence rate exceed 21.6/100,000 inhabitants in 2014. Indigenous incidence was 76.5/100,000 inhabitants in 2017, LDP incidence was 2,272.1/ 100,000 inhabitants in 2017. Conclusion: The incidence of TB in the Department of Caaguazú is low, mainly affecting men, while TB incidence in indigenous people and LDP was high.

[Factors associated with unsuccessful treatment of patients with drug-sensitive tuberculosis in Paraguay]. / Factores asociados al resultado de tratamiento no exitoso de pacientes con tuberculosis sensible en Paraguay.

OBJECTIVE: To determine the factors associated with the unsuccessful treatment of patients diagnosed with drug-sensitive tuberculosis (TB) in Paraguay. METHODS: Retrospective cohort study, with data collected from the national program between January 2016 and March 2017. Unsuccessful treatment was defined as patients who were lost to follow-up, failed treatment, or died. Factors associated with unsuccessful treatment were determined using Poisson regression; the adjusted relative risk (RR) and 95% confidence interval (95% CI) were estimated by health region. RESULTS: A total of 3 034 cases were studied: 2 189 (72.1%) were successfully treated (cured: 1 221 [40.2%], complete treatment: 968 [31.9%]) and 845 (27.9%) were unsuccessfully treated (treatment failure: 40 [1.3%], loss to follow-up: 466 [15.4%] and deaths: 339 [11.2%]). Factors associated with unsuccessful treatment were masculine sex 1.28 (1.14- 1.42), indigenous descent 1.3 (1.09- 1.54), lack of report of area of residence 1.27 (1.02- 1.57), TB/HIV coinfection 1.97 (1, 63- 2.38), illicit drug addiction 1.38 (1.16- 1.63), alcohol consumption 1.25 (1.02- 1.52), previous treatment 1.23 (1.10- 1.38) and lack of treatment monitoring data 4.92 (3.69- 6.56). Being deprived of liberty 0.65 (0.47- 0.89) and TB/diabetes comorbidity 0.80 (0.67- 0.95) were considered protective factors. CONCLUSION: Paraguay has a high percentage of unsuccessful treatment in almost the entire country, without reaching the target proposed by the World Health Organization. Associated risk factors such as HIV, consumption of legal and illicit drugs, and being indigenous highlight the need to revise the treatment strategies with an inter-institutional approach.

Factores asociados al resultado de tratamiento no exitoso de pacientes con tuberculosis sensible en Paraguay

[RESUMEN]. Objetivo. Determinar los factores asociados con el tratamiento no exitoso en pacientes diagnosticados con tuberculosis (TB) sensible en Paraguay. Métodos. Estudio de cohorte retrospectivo, con datos recolectados del programa nacional entre enero de 2016 y marzo de 2017. Se definió tratamiento no exitoso como pacientes que se perdieron en el seguimiento, fracasaron en el tratamiento o fallecieron. Los factores asociados con tratamiento no exitoso se determinaron con regresión de Poisson; se estimó el riesgo relativo (RR) y el intervalo de confianza de 95% (IC95%) ajustados por región sanitaria. Resultados. Se estudiaron 3 034 casos: 2 189 (72,1%) tuvieron tratamiento exitoso (curados: 1 221 [40,2%], tratamiento completo: 968 [31,9%]) y 845 (27,9%) presentaron tratamiento no exitoso (fracaso: 40 [1,3%], pérdida de seguimiento: 466 [15,4%] y fallecidos: 339 [11,2%]). Los factores asociados a tratamiento no exitoso fueron hombres 1,28 (1,14- 1,42), indígenas 1,30 (1,09- 1,54), sin reporte de área de residencia 1,27 (1,02- 1,57), coinfección TB/VIH 1,97 (1,63- 2,38), adicción a drogas ilícitas 1,38 (1,16- 1,63), consumo de alcohol 1,25 (1,02- 1,52), ser previamente tratado 1,23 (1,10- 1,38) y sin datos de supervisión del tratamiento 4,92 (3,69- 6,56). Como factores protectores se consideran ser persona privada de libertad 0,65 (0,47- 0,89), así como la comorbilidad TB/diabetes 0,80 (0,67- 0,95). Conclusión. Paraguay presenta un alto porcentaje de tratamiento no exitoso en casi todo el país, sin alcanzar la meta propuesta por la Organización Mundial de la Salud. Los factores de riesgo asociados como infección por el virus de la inmunodeficiencia humana (VIH), consumo de drogas licitas e ilícitas y el ser indígena revela que es necesario revisar las estrategias dirigidas con abordaje interinstitucional.

[ABSTRACT]. Objective. To determine the factors associated with the unsuccessful treatment of patients diagnosed with drug-sensitive tuberculosis (TB) in Paraguay. Methods. Retrospective cohort study, with data collected from the national program between January 2016 and March 2017. Unsuccessful treatment was defined as patients who were lost to follow-up, failed treatment, or died. Factors associated with unsuccessful treatment were determined using Poisson regression; the adjusted relative risk (RR) and 95% confidence interval (95% CI) were estimated by health region. Results. A total of 3 034 cases were studied: 2 189 (72.1%) were successfully treated (cured: 1 221 [40.2%], complete treatment: 968 [31.9%]) and 845 (27.9%) were unsuccessfully treated (treatment failure: 40 [1.3%], loss to follow-up: 466 [15.4%] and deaths: 339 [11.2%]). Factors associated with unsuccessful treatment were masculine sex 1.28 (1.14- 1.42), indigenous descent 1.3 (1.09- 1.54), lack of report of area of residence 1.27 (1.02- 1.57), TB/HIV coinfection 1.97 (1, 63- 2.38), illicit drug addiction 1.38 (1.16- 1.63), alcohol consumption 1.25 (1.02- 1.52), previous treatment 1.23 (1.10- 1.38) and lack of treatment monitoring data 4.92 (3.69- 6.56). Being deprived of liberty 0.65 (0.47- 0.89) and TB/diabetes comorbidity 0.80 (0.67- 0.95) were considered protective factors. Conclusion. Paraguay has a high percentage of unsuccessful treatment in almost the entire country, without reaching the target proposed by the World Health Organization. Associated risk factors such as HIV, consumption of legal and illicit drugs, and being indigenous highlight the need to revise the treatment strategies with an inter-institutional approach.

[Clinical-epidemiological characterization of patients with tuberculosis in the Department of Caaguazú, Paraguay. 2014-2017]. / Caracterización clínico-epidemiológica de pacientes con tuberculosis en el Departamento de Caaguazú, Paraguay. 2014 a 2017.

BACKGROUND: Tuberculosis (TB) is one of the ten leading causes of death worldwide. AIM: To characterize the clinical and epidemiological point of view of TB cases reported in the Department of Caaguazú-Paraguay, from 2014 to 2017. METHODS: Observational, descriptive, retrospective study; Population: 659 cases of TB registered in the National Tuberculosis Control Program (NTCP); variables: age, sex, population group, type of TB, TB/HIV coinfection. We procesed database in Excel 2016 © using Stata 14.0®. RESULTS: 63.3% were of male gender, average age: 35.8 years, 39.6% were indigenous and 85.4% were liberty deprived persons known as inmates (LDP), 89.6% had pulmonary TB and 2,4% had TB/HIV coinfection. Incidence rate exceed 21.6/100,000 inhabitants in 2014. Indigenous incidence was 76.5/100,000 inhabitants in 2017, LDP incidence was 2,272.1/ 100,000 inhabitants in 2017. CONCLUSION: The incidence of TB in the Department of Caaguazú is low, mainly affecting men, while TB incidence in indigenous people and LDP was high.

Prevalencia de la comorbilidad tuberculosis y diabetes mellitus en Paraguay, 2016 y 2017

[RESUMEN]. Objetivo. Estimar la prevalencia nacional y regional de la comorbilidad tuberculosis (TB) y diabetes mellitus (DM) e identificar los factores asociados con esta comorbilidad en Paraguay. Métodos. Estudio transversal en pacientes con TB notificada en 2016 y 2017 y registrados en la base de datos del Programa Nacional de Control de la TB. La prevalencia de DM, definida por autonotificación, se estimó en pacientes con TB. Para conocer los factores asociados con la comorbilidad TB-DM se empleó un modelo multivariante de regresión binomial para ajustar las razones de prevalencia (RP) según los errores estándar por el clúster de región sanitaria. Resultados. Entre 2016 y 2017 se notificaron 5 315 casos de TB. La prevalencia de la comorbilidad TB-DM fue 6,3% en 2016, 6,0% en 2017 y 6,2% en ambos años. Fue más alta en Itapúa (9,2%), Alto Paraguay (8,0%), Alto Paraná (7,5%), Central (7,4%) y Asunción (7,2%). La mediana de edad de personas con DM fue más alta que la de las que no tenían DM (55 y 33 años; P < 0,001). Tener una edad mayor de 45 años (RP = 18,3), antecedente de hipertensión arterial (HTA) (RP = 2,17), baciloscopía de diagnóstico de tres cruces (RP 1,98), y antecedente de enfermedad pulmonar obstructiva crónica (EPOC) (RP 1,68) estuvieron asociados con mayor comorbilidad. En cambio, se asociaron con menor comorbilidad pertenecer a la población indígena (RP = 0,26), la infección por el virus de la inmunodeficiencia humana (RP = 0,44), historia de adicción a drogas (RP = 0,49), el sexo masculino (RP = 0,64), y la TB extrapulmonar (RP = 0,75). Conclusiones. La prevalencia de la comorbilidad de TB y DM en Paraguay, por autonotificación, fue 6,2% en el periodo 2016-2017 y varió entre las regiones sanitarias. La edad, el sexo, una alta carga bacilar al diagnóstico y la comorbilidad con HTA y EPOC se asociaron a una mayor comorbilidad. Estos hallazgos permitirán priorizar grupos de población para aumentar rendimiento del cribado, diagnóstico, tratamiento y prevención de la comorbilidad TB-DM en Paraguay.

[ABSTRACT]. Objective. To estimate the national and regional prevalence of tuberculosis (TB) and diabetes mellitus (DM) co-morbidity and identify the factors associated with this co-morbidity in Paraguay. Methods. Cross-sectional study in patients with TB notified in 2016 and 2017 and registered in the database of the National TB Control Program. The prevalence of self-reported DM was estimated in patients with TB. A multivariate binomial regression model was used to know the factors associated with TB-DM co-morbidity to adjust the prevalence ratios (PR) according to standard errors by health region. Results. Between 2016 and 2017, 5 315 cases of TB were reported. The prevalence of TB-DM co-morbidity was 6.3% in 2016, 6.0% in 2017, and 6.2% in both years. It was highest in Itapua (9.2%), Alto Paraguay (8.0%), Alto Parana (7.5%), Central (7.4%) and Asuncion (7.2%). The median age of people with DM was higher than that of those without DM (55 vs 33 years; P < 0.001). Being older than 45 years (RP = 18.3), history of hypertension (RP = 2.17), diagnostic baciloscopy +++ (RP 1.98), and history of chronic obstructive pulmonary disease (COPD) (RP 1.68) were associated with greater co-morbidity. A lower co-morbidity was associated with belonging to the indigenous population (RP = 0.26), human immunodeficiency virus infection (RP = 0.44), history of drug dependence (RP = 0.49), male sex (RP = 0.64), and extrapulmonary TB (RP = 0.75). Conclusions. The prevalence of self-reported co-morbidity of TB-DM in Paraguay was 6.2% in 2016-2017 and varied between health regions. Age, sex, high bacillary burden at diagnosis and co-morbidity with hypertension and COPD were associated with higher co-morbidity. These findings will allow prioritizing population groups to increase screening performance, diagnosis, treatment and prevention of TB-DM co-morbidity in Paraguay.

[RESUMO]. Objetivo. Estimar a prevalência nacional e regional de comorbidade entre tuberculose (TB) e diabetes mellitus (DM) no Paraguai e identificar os fatores associados a essa comorbidade. Métodos. Estudo transversal em pacientes com TB notificados em 2016 e 2017 e cadastrados na base de dados do Programa Nacional de Controle da TB. A prevalência de DM, definida por autorrelato, foi estimada em pacientes com TB. Para conhecer os fatores associados à comorbidade TB-DM, foi utilizado um modelo de regressão binomial multivariada para ajustar as razões de prevalência (RP) de acordo com os erros padrão do cluster da região de saúde. Resultados. Em 2016 e 2017 foram notificados 5 315 casos de TB. A prevalência de comorbidade TB-DM foi de 6,3% em 2016, 6,0% em 2017 e 6,2% para o período dos 2 anos. As prevalências mais altas foram observadas em Itapúa (9,2%), Alto Paraguai (8,0%), Alto Paraná (7,5%), Central (7,4%) e Assunção (7,2%). A mediana de idade foi mais alta em pessoas com DM do que naquelas sem DM (55 e 33 anos; P <0,001). Ter idade superior a 45 anos (RP = 18,3), história de hipertensão arterial (HAS) (RP = 2,17), baciloscopia diagnóstica (+++) (RP = 1,98) e história de doença pulmonar obstrutiva crônica (DPOC) (RP = 1,68) foram associados a maior comorbidade. Por sua vez, pertencer à população indígena (RP = 0,26), infecção pelo vírus da imunodeficiência humana (RP = 0,44), histórico de dependência de drogas (RP = 0,49), sexo masculino (RP = 0,64) e TB extrapulmonar (RP = 0,75) estiveram associados a menor comorbidade. Conclusões. A prevalência de comorbidade TB-DM no Paraguai, determinada a partir de autorrelato, foi de 6,2% no período 2016-2017 e variou entre as regiões de saúde. Idade, sexo, alta carga bacilar no diagnóstico e comorbidade com HAS e DPOC foram fatores associados a maior comorbidade. Esses achados permitirão priorizar grupos populacionais para aumentar o desempenho da triagem, diagnóstico, tratamento e prevenção da comorbidade TB-DM no Paraguai.

Factores asociados a la mortalidad por tuberculosis en Paraguay, 2015-2016

[RESUMEN]. Objetivo. Describir las características sociodemográficas y clínico-epidemiológicas y determinar los factores asociados a la mortalidad de personas con diagnóstico de tuberculosis en Paraguay. Métodos. Investigación operativa con un diseño de cohortes retrospectivo de los casos diagnosticados con TB en Paraguay entre 2015-2016. Se utilizó la base datos del Programa Nacional de Control de Tuberculosis. Para determinar los factores asociados con mortalidad se utilizaron pruebas chi cuadrado y riesgo relativo (RR) con un intervalo de confianza de 95% (IC95%); además, se ajustó un modelo de regresión múltiple de Poisson robusto. Se utilizó un nivel de significación de 5%. Resultados. Se estudiaron 5 141 casos de TB, de los cuales 11,5% fallecieron, los factores que aumentan el riesgo de muerte fueron: sexo masculino (RR: 1,26 IC; 95%: 1,1-1,50), infección con virus de la inmunodeficiencia humana (VIH) (RR: 4,78; IC 95%: 4,04-5,65) y enfermedad pulmonar obstructiva crónica (RR: 1,70; IC 95%: 1,19-2,42). Como factor protector se identificó ser persona privada de la libertad (RR: 0,37 IC 95%: 0,24-0,61). Conclusiones. El mayor riesgo de muerte lo presentan los hombres y las personas con coinfección TB/VIH y el menor riesgo, las personas privadas de la libertad. Es necesario mejorar el diagnóstico y seguimiento a los casos de TB, con la efectiva implementación del tratamiento directamente observado (TDO) así como el manejo oportuno de enfermedades asociadas como VIH y enfermedad pulmonar obstructica crónica (EPOC).

[ABSTRACT]. Objective. To describe the socio-demographic and clinical-epidemiological characteristics and to determine the factors associated with the mortality of people diagnosed with tuberculosis (TB) in Paraguay. Methods. Operational research with a retrospective cohort design of cases diagnosed with TB in Paraguay between 2015-2016. The database of the National Tuberculosis Control Program was used. Chi-square and relative risk (RR) tests with a 95% confidence interval (95% CI) were used to determine the factors associated with mortality; in addition, a robust Poisson multiple regression model was adjusted. A significance level of 5% was used. Results. Five hundred and forty-one cases of TB were studied, of which 11.5% died. The factors increasing the risk of death were male sex (RR 1.26; 95% CI 1.1-1.50), infection with human immunodeficiency virus (RR 4.78; 95% CI 4.04-5.65) and chronic obstructive pulmonary disease (RR 1.70; 95% CI 1.19-2.42). Being deprived of one’s liberty was a protective factor (RR 0.37; 95% CI 0.24-0.61). Conclusions. The highest risk of death is presented by men and people with TB/HIV coinfection and the lowest risk is presented by people deprived of liberty. There is a need to improve diagnosis and follow-up of TB cases, with effective implementation of directly observed treatment (DOTS) and timely management of associated diseases such as HIV and chronic obstructive pulmonary disease.

[RESUMO]. Objetivo. Descrever as características sociodemográficas e clínico-epidemiológicas e determinar os fatores associados à mortalidade de pessoas diagnosticadas com tuberculose (TB) no Paraguai. Métodos. Pesquisa operacional com desenho de coorte retrospectivo de casos diagnosticados com TB no Paraguai entre 2015-2016. Foi utilizada a base de dados do Programa Nacional de Controle da Tuberculose. Testes de qui-quadrado e risco relativo (RR) com intervalo de confiança de 95% (IC95%) foram utilizados para determinar os fatores associados à mortalidade; além disso, um robusto modelo de regressão múltipla de Poisson foi ajustado. Foi utilizado nível de significância de 5%. Resultados. Foram estudados quinhentos e quarenta e um casos de TB, dos quais 11,5% morreram. Os fatores que aumentaram o risco de morte foram sexo masculino (RR 1,26; IC95% 1,1-1,50), infecção por vírus da imunodeficiência humana (RR 4,78; IC95% 4,04-5,65) e doença pulmonar obstrutiva crônica (RR 1,70; 95 % CI 1,19-2,42). Ser privado de liberdade foi um fator protetor (RR 0,37; IC 95% 0,24-0,61). Conclusões O maior risco de morte é apresentado por homens e pessoas com co-infecção TB / HIV e o menor risco é apresentado por pessoas privadas de liberdade. É necessário melhorar o diagnóstico e o acompanhamento dos casos de TB, com a implementação efetiva do tratamento diretamente observado (DOTS) e o gerenciamento oportuno de doenças associadas, como o HIV e a doença pulmonar obstrutiva crônica.