1-Year Incidence of Tuberculosis Infection and Disease Among Household Contacts of Rifampin- and Multidrug-Resistant Tuberculosis.

BACKGROUND: Tuberculosis infection (TBI) and TB disease (TBD) incidence remains poorly described following household contact (HHC) rifampin-/multidrug-resistant TB exposure. We sought to characterize TBI and TBD incidence at 1 year in HHCs and to evaluate TB preventive treatment (TPT) use in high-risk groups. METHODS: We previously conducted a cross-sectional study of HHCs with rifampin-/multidrug-resistant TB in 8 high-burden countries and reassessed TBI (interferon-gamma release assay, HHCs aged ≥5 years) and TBD (HHCs all ages) at 1 year. Incidence was estimated across age and risk groups (<5 years; ≥5 years, diagnosed with human immunodeficiency virus [HIV]; ≥5 years, not diagnosed with HIV/unknown, baseline TBI-positive) by logistic or log-binomial regression fitted using generalized estimating equations. RESULTS: Of 1016 HHCs, 850 (83.7%) from 247 households were assessed (median, 51.4 weeks). Among 242 HHCs, 52 tested interferon-gamma release assay-positive, yielding a 1-year 21.6% (95% confidence interval [CI], 16.7-27.4) TBI cumulative incidence. Sixteen of 742 HHCs developed confirmed (n = 5), probable (n = 3), or possible (n = 8) TBD, yielding a 2.3% (95% CI, 1.4-3.8) 1-year cumulative incidence (1.1%; 95% CI, .5-2.2 for confirmed/probable TBD). TBD relative risk was 11.5-fold (95% CI, 1.7-78.7), 10.4-fold (95% CI, 2.4-45.6), and 2.9-fold (95% CI, .5-17.8) higher in age <5 years, diagnosed with HIV, and baseline TBI high-risk groups, respectively, vs the not high-risk group (P = .0015). By 1 year, 4% (21 of 553) of high-risk HHCs had received TPT. CONCLUSIONS: TBI and TBD incidence continued through 1 year in rifampin-/multidrug-resistant TB HHCs. Low TPT coverage emphasizes the need for evidence-based prevention and scale-up, particularly among high-risk groups.

Epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples, Ecuador, 2018.

Objective: To compare the epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples in Ecuador. Methods: A secondary analysis was done of data on bacteria isolated from inpatient and outpatient samples. Data were taken from the 2018 national antimicrobial resistance surveillance database of the National Reference Center for Antimicrobial Resistance. The variables included were: age, sex, inpatient versus outpatient setting, type of specimen, bacterial species identified, pattern of resistance to antibiotics, and geographic area. Results: Data from 57 305 bacterial isolates were included in the study: 48.8% were from hospitalized patients, 55.7% were from women, and 60.1% were from patients older than 45 years. Urine (42.9%) and blood (12.4%) were the most common clinical samples. Overall, 77.1% of bacterial isolates were gram-negative (83% and 71% in outpatients and inpatients, respectively). The most common gram-positive and gram-negative species were Staphylococcus aureus and Escherichia coli, respectively. Antimicrobial resistance levels were high (up to 80% for some antimicrobial drugs), and were higher in hospitalized patients compared with outpatients. A variety of carbapenemases were found to confer resistance to carbapenems (antibiotics of last resort) in gram-negative bacteria. Conclusions: The study findings provide an important baseline on antimicrobial resistance in Ecuador. This will allow the strengthening of guidelines of the surveillance system, the creation of public policies for standardization of laboratory methodologies, the proper handling of information, and the development of empirical therapy guidelines based on local epidemiology.

Epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples, Ecuador, 2018

[ABSTRACT]. Objective. To compare the epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples in Ecuador. Methods. A secondary analysis was done of data on bacteria isolated from inpatient and outpatient samples. Data were taken from the 2018 national antimicrobial resistance surveillance database of the National Refer- ence Center for Antimicrobial Resistance. The variables included were: age, sex, inpatient versus outpatient setting, type of specimen, bacterial species identified, pattern of resistance to antibiotics, and geographic area. Results. Data from 57 305 bacterial isolates were included in the study: 48.8% were from hospitalized patients, 55.7% were from women, and 60.1% were from patients older than 45 years. Urine (42.9%) and blood (12.4%) were the most common clinical samples. Overall, 77.1% of bacterial isolates were gram-negative (83% and 71% in outpatients and inpatients, respectively). The most common gram-positive and gram-negative species were Staphylococcus aureus and Escherichia coli, respectively. Antimicrobial resistance levels were high (up to 80% for some antimicrobial drugs), and were higher in hospitalized patients compared with outpatients. A variety of carbapenemases were found to confer resistance to carbapenems (antibiotics of last resort) in gram-negative bacteria. Conclusions. The study findings provide an important baseline on antimicrobial resistance in Ecuador. This will allow the strengthening of guidelines of the surveillance system, the creation of public policies for stan- dardization of laboratory methodologies, the proper handling of information, and the development of empirical therapy guidelines based on local epidemiology.

[RESUMEN]. Objetivo. Comparar las características epidemiológicas de la resistencia a los antimicrobianos en cepas bacterianas aisladas de muestras de pacientes de servicios hospitalarios y ambulatorios en Ecuador. Métodos. Se realizó un análisis secundario de los datos sobre cepas bacterianas aisladas en muestras de pacientes de servicios hospitalarios y ambulatorios. Se recogieron los datos de la base de datos nacional del 2018 para la vigilancia de la resistencia a los antimicrobianos del Centro de Referencia Nacional para la Resis- tencia a los Antimicrobianos. Las variables incluidas fueron: edad, sexo, entorno hospitalario frente a entorno ambulatorio, tipo de muestra, especies bacterianas detectadas, patrón de resistencia a los antibióticos y zona geográfica. Resultados. En el estudio se incluyeron datos de 57 305 cepas aislamientos bacterianos: 48,8% fueron de pacientes hospitalizados, 55,7% fueron de mujeres y 60,1% fueron de pacientes mayores de 45 años. La orina (42,9%) y la sangre (12,4%) fueron las muestras clínicas más comunes. En general, 77,1% de las cepas bac- terianas aisladas fueron gramnegativas (83% y 71% en pacientes de servicios ambulatorios y hospitalarios, respectivamente). Las especies grampositivas y gramnegativas más comunes fueron Staphylococcus aureus y Escherichia coli, respectivamente. Los niveles de resistencia a los antimicrobianos fueron elevados (hasta 80% en el caso de algunos fármacos antimicrobianos) y fueron más elevados en los pacientes de servicios hospitalarios en comparación con los pacientes de servicios ambulatorios. Se encontró que una variedad de carbapenemasas confiere resistencia a los carbapenémicos (antibióticos de último recurso) en bacterias gramnegativas. Conclusiones. Los resultados del estudio proporcionan una línea de base importante sobre la resistencia a los antimicrobianos en Ecuador, que permitirá el fortalecimiento de las directrices del sistema de vigilancia, la creación de políticas públicas para la estandarización de los métodos de laboratorio, una adecuada gestión de la información y la elaboración de orientaciones de tratamiento empírico basadas en las características epidemiológicas locales.

[RESUMO]. Objetivo. Comparar a epidemiologia da resistência aos antimicrobianos em bactérias isoladas de amostras hospitalares e ambulatoriais no Equador. Métodos. Foi feita uma análise secundária de dados sobre bactérias isoladas de amostras hospitalares e ambulatoriais. Os dados foram obtidos do banco de dados nacional de vigilância da resistência aos antimi- crobianos de 2018 do Centro Nacional de Referência para a Resistência aos Antimicrobianos. As variáveis incluídas foram: idade, sexo, ambiente hospitalar versus ambiente ambulatorial, tipo de espécime, espécies bacterianas identificadas, padrão de resistência a antibióticos e área geográfica. Resultados. Foram incluídos no estudo os dados de 57 305 isolados bacterianos: 48,8% eram de pacientes hospitalizados, 55,7% eram de mulheres e 60,1% eram de pacientes com mais de 45 anos. As amostras clínicas mais comuns foram urina (42,9%) e sangue (12,4%). No total, 77,1% dos isolados bacterianos eram gram-negativos (83% e 71% em pacientes ambulatoriais e pacientes internados, respectivamente). As espécies gram-positivas e gram-negativas mais comuns foram Staphylococcus aureus e Escherichia coli, respectivamente. Os níveis de resistência aos antimicrobianos foram elevados (até 80% para alguns antimi- crobianos) e foram mais elevados em pacientes hospitalizados em comparação com pacientes ambulatoriais. Foram encontradas várias carbapenemases que conferem resistência aos carbapenêmicos (antibióticos de último recurso) em bactérias gram-negativas. Conclusões. Os resultados do estudo fornecem uma importante linha de base sobre a resistência aos anti- microbianos no Equador. Isto permitirá o fortalecimento das diretrizes do sistema de vigilância, a criação de políticas públicas para padronização de metodologias laboratoriais, o manejo adequado de informações e o desenvolvimento de diretrizes para a antibioticoterapia empírica com base na epidemiologia local.

Epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples, Ecuador, 2018 / Características epidemiológicas de la resistencia antimicrobiana en cepas bacterianas aisladas en pacientes de servicios hospitalarios y ambulatorios de Ecuador, 2018 / Epidemiologia da resistência aos antimicrobianos em bactérias isoladas de amostras hospitalares e ambulatoriais no Equador, 2018

ABSTRACT Objective. To compare the epidemiology of antimicrobial resistance in bacteria isolated from inpatient and outpatient samples in Ecuador. Methods. A secondary analysis was done of data on bacteria isolated from inpatient and outpatient samples. Data were taken from the 2018 national antimicrobial resistance surveillance database of the National Reference Center for Antimicrobial Resistance. The variables included were: age, sex, inpatient versus outpatient setting, type of specimen, bacterial species identified, pattern of resistance to antibiotics, and geographic area. Results. Data from 57 305 bacterial isolates were included in the study: 48.8% were from hospitalized patients, 55.7% were from women, and 60.1% were from patients older than 45 years. Urine (42.9%) and blood (12.4%) were the most common clinical samples. Overall, 77.1% of bacterial isolates were gram-negative (83% and 71% in outpatients and inpatients, respectively). The most common gram-positive and gram-negative species were Staphylococcus aureus and Escherichia coli, respectively. Antimicrobial resistance levels were high (up to 80% for some antimicrobial drugs), and were higher in hospitalized patients compared with outpatients. A variety of carbapenemases were found to confer resistance to carbapenems (antibiotics of last resort) in gram-negative bacteria. Conclusions. The study findings provide an important baseline on antimicrobial resistance in Ecuador. This will allow the strengthening of guidelines of the surveillance system, the creation of public policies for standardization of laboratory methodologies, the proper handling of information, and the development of empirical therapy guidelines based on local epidemiology.

RESUMEN Objetivo. Comparar las características epidemiológicas de la resistencia a los antimicrobianos en cepas bacterianas aisladas de muestras de pacientes de servicios hospitalarios y ambulatorios en Ecuador. Métodos. Se realizó un análisis secundario de los datos sobre cepas bacterianas aisladas en muestras de pacientes de servicios hospitalarios y ambulatorios. Se recogieron los datos de la base de datos nacional del 2018 para la vigilancia de la resistencia a los antimicrobianos del Centro de Referencia Nacional para la Resistencia a los Antimicrobianos. Las variables incluidas fueron: edad, sexo, entorno hospitalario frente a entorno ambulatorio, tipo de muestra, especies bacterianas detectadas, patrón de resistencia a los antibióticos y zona geográfica. Resultados. En el estudio se incluyeron datos de 57 305 cepas aislamientos bacterianos: 48,8% fueron de pacientes hospitalizados, 55,7% fueron de mujeres y 60,1% fueron de pacientes mayores de 45 años. La orina (42,9%) y la sangre (12,4%) fueron las muestras clínicas más comunes. En general, 77,1% de las cepas bacterianas aisladas fueron gramnegativas (83% y 71% en pacientes de servicios ambulatorios y hospitalarios, respectivamente). Las especies grampositivas y gramnegativas más comunes fueron Staphylococcus aureus y Escherichia coli, respectivamente. Los niveles de resistencia a los antimicrobianos fueron elevados (hasta 80% en el caso de algunos fármacos antimicrobianos) y fueron más elevados en los pacientes de servicios hospitalarios en comparación con los pacientes de servicios ambulatorios. Se encontró que una variedad de carbapenemasas confiere resistencia a los carbapenémicos (antibióticos de último recurso) en bacterias gramnegativas. Conclusiones. Los resultados del estudio proporcionan una línea de base importante sobre la resistencia a los antimicrobianos en Ecuador, que permitirá el fortalecimiento de las directrices del sistema de vigilancia, la creación de políticas públicas para la estandarización de los métodos de laboratorio, una adecuada gestión de la información y la elaboración de orientaciones de tratamiento empírico basadas en las características epidemiológicas locales.

RESUMO Objetivo. Comparar a epidemiologia da resistência aos antimicrobianos em bactérias isoladas de amostras hospitalares e ambulatoriais no Equador. Métodos. Foi feita uma análise secundária de dados sobre bactérias isoladas de amostras hospitalares e ambulatoriais. Os dados foram obtidos do banco de dados nacional de vigilância da resistência aos antimicrobianos de 2018 do Centro Nacional de Referência para a Resistência aos Antimicrobianos. As variáveis incluídas foram: idade, sexo, ambiente hospitalar versus ambiente ambulatorial, tipo de espécime, espécies bacterianas identificadas, padrão de resistência a antibióticos e área geográfica. Resultados. Foram incluídos no estudo os dados de 57 305 isolados bacterianos: 48,8% eram de pacientes hospitalizados, 55,7% eram de mulheres e 60,1% eram de pacientes com mais de 45 anos. As amostras clínicas mais comuns foram urina (42,9%) e sangue (12,4%). No total, 77,1% dos isolados bacterianos eram gram-negativos (83% e 71% em pacientes ambulatoriais e pacientes internados, respectivamente). As espécies gram-positivas e gram-negativas mais comuns foram Staphylococcus aureus e Escherichia coli, respectivamente. Os níveis de resistência aos antimicrobianos foram elevados (até 80% para alguns antimicrobianos) e foram mais elevados em pacientes hospitalizados em comparação com pacientes ambulatoriais. Foram encontradas várias carbapenemases que conferem resistência aos carbapenêmicos (antibióticos de último recurso) em bactérias gram-negativas. Conclusões. Os resultados do estudo fornecem uma importante linha de base sobre a resistência aos antimicrobianos no Equador. Isto permitirá o fortalecimento das diretrizes do sistema de vigilância, a criação de políticas públicas para padronização de metodologias laboratoriais, o manejo adequado de informações e o desenvolvimento de diretrizes para a antibioticoterapia empírica com base na epidemiologia local.

High Prevalence of Tuberculosis Infection and Disease in Child Household Contacts of Adults With Rifampin-resistant Tuberculosis.

BACKGROUND: Household contact (HHC) investigation is an important strategy to identify individuals with tuberculosis (TB) exposure, infection and disease, including those who may benefit from tuberculosis preventive therapy (TPT). Data in children exposed to rifampin-resistant TB are limited. METHODS: In preparation for and to inform the feasibility of an interventional trial, HHC of adults with pulmonary rifampin-resistant TB from high TB-burden countries were evaluated in a cross-sectional study. Using interferon-gamma release assay and study-specific and 2015 international consensus definitions of intrathoracic TB in children, we evaluated the prevalence and predictors of TB infection and disease in child (<15 years) HHCs. RESULTS: Of 303 child HHCs, median age (range) 7 years (0-14), 57% [95% confidence interval (CI): 50%-64%] had a positive interferon-gamma release assay result (TB infected). TB infection was associated with the index case smoking (P = 0.034), being the parent or sleeping in the same room (P = 0.002) and the child HHC being age ≥5 years and having attended school (P = 0.013). Four had study-defined confirmed TB and 9 had probable TB, a prevalence of 4.3% (95% CI: 2.6%-7.1%). Using the international consensus definitions, 4 had confirmed TB and 49 had unconfirmed TB, a prevalence of 17.2% (95% CI: 12.9%-22.4%). Twenty (7%) children had received TPT. CONCLUSIONS: The prevalence of TB infection and disease was high in child HHC exposed to rifampin-resistant TB. Few children had routinely received TPT. High-quality evidence is needed to inform strong recommendations for and access to TPT in children exposed to TB resistant to rifampin.

Allelic and genotypic frequencies of NAT2, CYP2E1, and AADAC genes in a cohort of Peruvian tuberculosis patients.

BACKGROUND: We determined the frequency of genetic polymorphisms in three anti-TB drug metabolic proteins previously reported: N-acetyltransferase 2 (NAT2), cytochrome P450 2E1 (CYP2E1), and arylacetamide deacetylase (AADAC) within a Peruvian population in a cohort of TB patients. METHODS: We genotyped SNPs rs1041983, rs1801280, rs1799929, rs1799930, rs1208, and rs1799931 for NAT2; rs3813867 and rs2031920 for CYP2E1; and rs1803155 for AADAC in 395 participants completed their antituberculosis treatment. RESULTS: Seventy-four percent of the participants are carriers of slow metabolizer genotypes: NAT2*5, NAT2*6, and NAT2*7, which increase the sensitivity of INH at low doses and increase the risk of drug-induced liver injuries. Sixty-four percent are homozygous for the wild-type CYP2E1*1A allele, which could increase the risk of hepatotoxicity. However, 16% had a NAT2 fast metabolizer phenotype which could increase the risk of acquiring resistance to INH, thereby increasing the risk of multidrug-resistant (MDR) or treatment failure. The frequency of rs1803155 (AADAC*2 allele) was higher (99.9%) in Peruvians than in European American, African American, Japanese, and Korean populations. CONCLUSIONS: This high prevalence of slow metabolizers for isoniazid in the Peruvian population should be further studied and considered to help individualize drug regimens, especially in countries with a great genetic diversity like Peru. These data will help the Peruvian National Tuberculosis Control Program develop new strategies for therapies.

Resistance to Mycobacterium tuberculosis Infection Among Household Contacts: A Multinational Study.

BACKGROUND: Some contacts of patients with tuberculosis remain negative on tests for tuberculosis infection, despite prolonged exposure, suggesting they might be resistant to Mycobacterium tuberculosis infection. The objective of this multinational study was to estimate the proportion of household contacts resistant to M. tuberculosis (resisters). METHODS: We conducted a longitudinal study enrolling index patients enrolled in treatment for pulmonary multidrug- or rifampin-resistant tuberculosis and their household contacts. Contacts were tested for tuberculosis infection with a tuberculin skin test (TST) and interferon-gamma release assay (IGRA) at baseline and after 1 year. Exposure was quantified based on index patients' infectiousness, index patient and household contact interaction, and age. We explored multiple definitions of resistance to tuberculosis infection by varying TST negativity cutoffs (0 vs <5 mm), classification of missing test results, and exposure level. RESULTS: In total, 1016 contacts were evaluated from 284 households; 572 contacts aged ≥5 years had TST and longitudinal IGRA results available. And 77 (13%) or 71 (12%) contacts were classified as resisters with a <5 mm or 0 mm TST threshold, respectively. Among 263 highly exposed contacts, 29 (11%) or 26 (10%) were classified as resisters using TST cutoffs of <5 mm and 0 mm, respectively. The prevalence of resisters did not differ substantially by sex, age, human immunodeficiency virus (HIV) coinfection, or comorbid conditions. CONCLUSIONS: At least 10% of household contacts can be classified as resistant to tuberculosis infection, depending on the definition used, including those with high exposure. Further studies to understand genetic or immunologic mechanisms underlying the resister phenotype may inform novel strategies for therapeutics and vaccines.

Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial.

BACKGROUND: Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). METHODS: As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. RESULTS: Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. CONCLUSIONS: RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

Factores de riesgo asociados a mortalidad en pacientes adultos con neumonía por SARS- CoV-2 en un hospital público de Lima, Perú / Risk factors for in-hospital mortality in SARS-CoV-2 pneumonia adult patients from Lima, Peru

RESUMEN Objetivo: describir los principales factores asociados a la mortalidad en una cohorte de pacientes hospitalizados por neumonía por SARS-CoV-2 en un hospital público de Lima, Perú. Materiales y métodos: estudio de cohorte retrospectivo con muestreo no aleatorio por conveniencia. Se incluyó pacientes adultos con sospecha clínica o confirmados para SARS-CoV-2 con pruebas rápidas y/o moleculares. Se identificaron variables demográficas, clínicas, de laboratorio, tomográficas y de tratamiento. Se emplearon técnicas de estadística descriptiva, análisis bivariado y de regresión de Poisson para determinar el riesgo relativo (RR) ajustado. Resultados: se incluyó 122 pacientes, 70,5% del sexo masculino, edad promedio de 55,8 años, con antecedentes de obesidad (25,4%) e hipertensión arterial (HTA 13,1%). El análisis multivariado de los factores clínicos identificó que la edad (RR ajustado [RRa] 1,03; IC 95%: 1,00-1,06, p=0,021), el índice de masa corporal (IMC, RRa 1,03; IC 95%: 1,01-1,05; p=0,006), la HTA (RRa 1,68; IC 95%: 1,09-2,56; p=0,017), el índice de PaO2/FiO2 (RRa 0,99; IC 95%: 0,99-1,00; p<0,001), la exposición a lopinavir/ritonavir (RRa 0,83; IC 95%: 0,76-0,91; p<0,001), y corticoides sistémicos (RRa 1,18; IC 95%: 1,09-1,27; p<0,001) estuvieron asociados a la mortalidad de manera significativa. Conclusiones: la edad, IMC, HTA, índice PaO2/FiO2, y la exposición a corticoides y LPV/r estuvieron asociadas a la mortalidad en pacientes hospitalizados por neumonía por SARS-CoV-2.

ABSTRACT Objective: this study aimed to describe the main factors associated to mortality in a cohort of patients hospitalized with SARS-CoV-2 pneumonia in a public hospital in Lima, Peru. Materials and methods: this was a retrospective cohort study, with a non-random convenience sampling. Adult patients with confirmed/suspicious SARS-CoV-2 pneumonia with rapid and/ or molecular tests were included. Demographic, clinical, laboratory, tomographic and treatment variables were identified. Descriptive statistics, bivariate analysis, and Poisson regression techniques were used to determine the adjusted relative risk (aRR). Results: 122 patients were included, 70.5% were male, with a mean age of 55.8 years, with a history of obesity (25.4%) and high blood pressure (HBP, 13.1%). The multivariate analysis of clinical factors identified that age (aRR 1.03; 95% CI: 1,00- 1.06; p=0.021), body mass index (BMI; aRR 1.03; 95% CI: 1.01-1.05; p=0.006), HBP (aRR 1.68; 95% CI: 1.09-2.56; p=0.017), PaO2/FiO2 index (aRR 0.99; 95% CI: 0.99-1.00; p<0.001), exposure to lopinavir/ritonavir (LPV/r; aRR 0.83; 95% CI: 0.76-0.91; p <0.001), and systemic corticosteroids (aRR 1.18; 95% CI: 1.09-1.27; p<0.001) were significantly associated with mortality. Conclusions : Age, BMI, HBP, PaO2/FiO2 index, and exposure to corticosteroids and LPV/r were associated with mortality in our cohort of patients hospitalized with SARS-CoV-2 pneumonia.

Clasificación clínica y tratamiento temprano de la COVID-19. Reporte de casos del Hospital de Emergencias Villa El Salvador, Lima-Perú / Clinical classification and early therapy for COVID-19. Cases reported from Hospital de Emergencias Villa el Salvador, Lima-Peru

RESUMEN La enfermedad producida por el SARS-CoV-2 constituye una pandemia declarada con alta contagiosidad y letalidad en grupos de riesgo. En menos de tres meses la humanidad ha tenido que lidiar con este virus sin saber mucho de su patogenia y tratamiento. Se presentan cinco casos atendidos en el Hospital de Emergencias Villa El Salvador (HEVES) en Lima, Perú. Se destaca la importancia de la clasificación clínica en cuatro estadios: leve, moderado, severo y crítico y revisamos el tratamiento antiviral, inmunomodulador y antitrombótico consecuente a tal clasificación. La terapia antiviral con hidroxicloroquina y azitromicina obtuvo resultados favorables en cuatro casos: sobre todo, cuando se inició en los primeros días de enfermedad. Sin embargo, su eficacia es aún controversial y se esperan resultados de ensayos clínicos aleatorizados. Mientras tanto, su uso en fase temprana de la enfermedad, en estadios leves o moderados, debería mantenerse.

ABSTRACT The disease caused by SARS-CoV-2 is a pandemic characterized for being highly contagious and lethal in groups at risk. In less than three months, mankind had to fight against this virus without knowing its pathogenicity and therapy. We present the experience with five cases seen in the Hospital de Emergencias Villa el Salvador in Lima, Peru, and we emphasize the importance of the clinical classification of the disease in four stages: mild, moderate, severe, and critical. We reviewed the current antiviral, immunomodulatory, and antithrombotic therapy approaches. Antiviral therapy using hydroxichloroquine and azithromycin led to favorable outcomes in four cases, particularly when it was early instituted. Nonetheless, its efficacy is still controversial and results from randomized clinical trials are eagerly awaited. Meanwhile, its use during the early phases of mild or moderate disease should be maintained.

Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study.

BACKGROUND: Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. METHODS: In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. RESULTS: From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22-49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07-3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23-3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33-15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29-4.06]). CONCLUSIONS: The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

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.

Pérdida en el seguimiento de pacientes tratados por tuberculosis resistente a rifampicina o multidrogorresistente en Ecuador

[RESUMEN]. Objetivo. Determinar la incidencia de pérdida en el seguimiento (PEES) en pacientes tratados por tuberculosis (TB) resistente a rifampicina o multidrogorresistente (TB-RR/MDR) y los factores asociados a esta condición de egreso en Ecuador. Métodos. Estudio de cohorte retrospectivo de pacientes con TB-RR/MDR tratados con el esquema de 18 a 24 meses de la Organización Mundial de la Salud en 2014 y 2015 notificados al Ministerio de Salud del Ecuador. Se determinó la incidencia de PEES y se compararon las características clínicas y epidemiológicas de los casos egresados como PEES versus los egresados como éxito de tratamiento. Se analizó la sobrevida con regresión de Cox para evaluar factores asociados a PEES. Resultados. De 328 casos, 270 (82,3%) fueron analizados porque tuvieron condición de egreso notificada. El egreso como PEES fue 39,6% y el éxito de tratamiento 50,4%. Los factores de riesgo asociados a PEES fueron: antecedente de egreso como PEES en episodio previo de TB, cociente de riesgos instantáneos (HR, por sus siglas en inglés): 2,96 (1,53-5,73), P < 0,001; adicción al alcohol o drogas, HR: 2,82 (1,10-7,23), P = 0,031 y tener diagnóstico por la prueba Xpert® (TB-RR), HR: 1,53 (1,0-2,35), P = 0,048. Del total de PEES, 43% ocurrió después de nueve meses de tratamiento. Conclusión. La incidencia de PEES en pacientes con TB-RR/MDR en Ecuador está por encima del promedio en la Región de las Américas. Los tres factores identificados refuerzan la implementación de regímenes acortados y atención centrada en el paciente, siguiendo la Estrategia Fin a la Tuberculosis.

[ABSTRACT]. Objective. Determine the incidence of loss to follow-up (LTFU) in patients treated for rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (RR/MDR-TB), and the factors associated with this discharge status in Ecuador. Methods. Retrospective cohort study of patients with RR/MDR-TB who followed the World Health Organization’s 18-24-month treatment regimen in 2014 and 2015, as reported by the Ministry of Health of Ecuador. The incidence of LTFU was determined, and clinical and epidemiological manifestations of cases discharged as LTFU were compared with those discharged as successfully treated. Survival was analyzed with Cox regression in order to evaluate factors associated with LTFU. Results. Of 328 cases, 270 (82.3%) were analyzed because they had a reported discharge status. Discharge as LTFU accounted for 39.6% of cases, and as successfully treated, 50.4%. The risk factors associated with LTFU were: previous discharge as LTFU in a previous TB episode [hazard ratio (HR): 2.96 (1.53-5.73), P < 0.001]; addiction to alcohol or drugs [HR: 2.82 (1.10-7.23), P = 0.031]; and having an Xpert® diagnosis (TBRR) [HR: 1.53 (1.0-2.35), P = 0.048]. Of the total LTFU, 43% occurred after nine months of treatment. Conclusion. The incidence of LTFU in patients with RR/MDR-TB in Ecuador is above the average for the Region of the Americas. The three identified factors support implementation of shorter regimens and patient-centered care, in line with the End TB Strategy.

[RESUMO]. Objetivo. Determinar o percentual de perda de seguimento de pacientes tratados para tuberculose resistente à rifampicina (TB-RR) ou tuberculose multirresistente a medicamentos (TB-MR) e os fatores associados à interrupção do tratamento no Equador. Métodos. Estudo de coorte retrospectivo de casos de pacientes com TB-RR/TB-MR tratados em 2014 e 2015 com o esquema farmacológico de 18 a 24 meses de duração da Organização Mundial da Saúde (OMS) que foram notificados ao Ministério da Saúde do Equador. Foi determinado o percentual de perda de seguimento e foram comparadas as características clínicas e epidemiológicas dos casos de interrupção do tratamento por perda de seguimento e daqueles com alta por sucesso no tratamento. Uma análise da sobrevida com o modelo de regressão de Cox foi realizada para avaliar os fatores associados à perda de seguimento. Resultados. De 328 casos registrados, 270 (82,3%) foram incluídos na análise por terem tido sua interrupção ou alta notificadas. Houve interrupção por perda de seguimento em 39,6% dos casos e alta por sucesso no tratamento em 50,4%. Os fatores de risco associados à perda de seguimento foram: história de perda de seguimento em tratamento anterior de TB, razão de riscos (hazard ratio, HR) 2,96 (1,53–5,73, P < 0,001); consumo excessivo de álcool ou drogas, HR 2,82 (1,10–7,23, P = 0,031); e diagnóstico de tuberculose pelo teste Xpert® (TB-RR), HR 1,53 (1,0–2,35, P = 0,048). A perda de seguimento ocorreu após nove meses de tratamento em 43% dos casos. Conclusão. O percentual de perda de seguimento de pacientes com TB-RR/TB-MR no Equador está acima da média da Região das Américas. Os três fatores identificados no estudo reforçam ser necessário implementar esquemas de tratamento mais curtos e prestar atenção centrada no paciente, segundo as recomendações da Estratégia pelo Fim da Tuberculose.

[Loss to follow-up in patients treated for multidrug-resistant tuberculosis in EcuadorA Perda de seguimento de pacientes tratados para tuberculose multirresistente a medicamentos no Equador]. / Pérdida en el seguimiento de pacientes tratados por tuberculosis resistente a rifampicina o multidrogorresistente en Ecuador.

OBJECTIVE: Determine the incidence of loss to follow-up (LTFU) in patients treated for rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant tuberculosis (RR/MDR-TB), and the factors associated with this discharge status in Ecuador. METHODS: Retrospective cohort study of patients with RR/MDR-TB who followed the World Health Organization's 18-24-month treatment regimen in 2014 and 2015, as reported by the Ministry of Health of Ecuador. The incidence of LTFU was determined, and clinical and epidemiological manifestations of cases discharged as LTFU were compared with those discharged as successfully treated. Survival was analyzed with Cox regression in order to evaluate factors associated with LTFU. RESULTS: Of 328 cases, 270 (82.3%) were analyzed because they had a reported discharge status. Discharge as LTFU accounted for 39.6% of cases, and as successfully treated, 50.4%. The risk factors associated with LTFU were: previous discharge as LTFU in a previous TB episode [hazard ratio (HR): 2.96 (1.53-5.73), P < 0.001]; addiction to alcohol or drugs [HR: 2.82 (1.10-7.23), P = 0.031]; and having an Xpert® diagnosis (TB-RR) [HR: 1.53 (1.0-2.35), P = 0.048]. Of the total LTFU, 43% occurred after nine months of treatment. CONCLUSION: The incidence of LTFU in patients with RR/MDR-TB in Ecuador is above the average for the Region of the Americas. The three identified factors support implementation of shorter regimens and patient-centered care, in line with the End TB Strategy.

OBJETIVO: Determinar o percentual de perda de seguimento de pacientes tratados para tuberculose resistente à rifampicina (TB-RR) ou tuberculose multirresistente a medicamentos (TB-MR) e os fatores associados à interrupção do tratamento no Equador. MÉTODOS: Estudo de coorte retrospectivo de casos de pacientes com TB-RR/TB-MR tratados em 2014 e 2015 com o esquema farmacológico de 18 a 24 meses de duração da Organização Mundial da Saúde (OMS) que foram notificados ao Ministério da Saúde do Equador. Foi determinado o percentual de perda de seguimento e foram comparadas as características clínicas e epidemiológicas dos casos de interrupção do tratamento por perda de seguimento e daqueles com alta por sucesso no tratamento. Uma análise da sobrevida com o modelo de regressão de Cox foi realizada para avaliar os fatores associados à perda de seguimento. RESULTADOS: De 328 casos registrados, 270 (82,3%) foram incluídos na análise por terem tido sua interrupção ou alta notificadas. Houve interrupção por perda de seguimento em 39,6% dos casos e alta por sucesso no tratamento em 50,4%. Os fatores de risco associados à perda de seguimento foram: história de perda de seguimento em tratamento anterior de TB, razão de riscos (hazard ratio, HR) 2,96 (1,53­5,73, P < 0,001); consumo excessivo de álcool ou drogas, HR 2,82 (1,10­7,23, P = 0,031); e diagnóstico de tuberculose pelo teste Xpert® (TB-RR), HR 1,53 (1,0­2,35, P = 0,048). A perda de seguimento ocorreu após nove meses de tratamento em 43% dos casos. CONCLUSÃO: O percentual de perda de seguimento de pacientes com TB-RR/TB-MR no Equador está acima da média da Região das Américas. Os três fatores identificados no estudo reforçam ser necessário implementar esquemas de tratamento mais curtos e prestar atenção centrada no paciente, segundo as recomendações da Estratégia pelo Fim da Tuberculose.

[Prevalence of comorbidity tuberculosis and diabetes mellitus in Paraguay, 2016 and 2017Prevalência de comorbidade tuberculose-diabetes mellitus no Paraguai, 2016 e 2017]. / Prevalencia de la comorbilidad tuberculosis y diabetes mellitus en Paraguay, 2016 y 2017.

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.

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.

Treatment outcomes for isoniazid-monoresistant tuberculosis in Peru, 2012-2014.

BACKGROUND: Resistance to isoniazid is the most common form of drug-resistance in tuberculosis. However only a tiny proportion of TB patients in the world have access to isoniazid drug susceptibility testing-the widely implemented Xpert MTB/RIF technology only tests for resistance to rifampicin. Patients with isoniazid mono resistance that is not identified at baseline are treated with a standard regimen that effectively results in rifampicin mono-therapy during the latter four months of the six month treatment course, exposing remaining viable organisms to a single agent and greatly increasing the risk of development of multi drug-resistant TB. Unusually, Peru has pioneered universal pre-treatment drug susceptibility testing with methods that identify isoniazid resistance and has thus identified a large number of individuals requiring tailored therapy. Since 2010, treatment in Peru for isoniazid-resistant tuberculosis without multidrug-resistant tuberculosis (Hr-TB) has been with a standardized nine-month regimen of levofloxacin, rifampicin, ethambutol and pyrazinamide. The objectives of this study were to evaluate the outcomes of treatment for patients with Hr-TB initiating treatment with this regimen between January 2012 and December 2014 and to determine factors affecting these outcomes. METHODS: Retrospective cross-sectional study; case data were obtained from the national registry of drug-resistant tuberculosis. Patients diagnosed with isoniazid resistant TB without resistance to rifampicin, pyrazinamide, ethambutol and quinolones as determined by either a rapid drug susceptibility testing (DST) (nitrate reductase test, MODS, Genotype MTBDRplus) or by the proportion method were included. FINDINGS: A total of 947 cases were evaluated (a further 403 without treatment end date were excluded), with treatment success in 77.2% (731 cases), loss to follow-up in 19.7% (186 cases), treatment failure in 1.2% (12 cases), and death in 1.9% (18 cases). Unfavorable outcomes were associated in multivariate analysis with male gender (OR 0.50, 95% CI 0.34-0.72, p<0.05), lack of rapid DST (OR 0.67, 95% CI 0.50-0.91, p = 0.01), additional use of an injectable second-line anti-tuberculous drug (OR 0.46, 95% CI 0.31-0.70, p<0.05), and treatment initiation in 2014 (OR 0.77, 95% CI 0.62-0.94, p = 0.01). INTERPRETATION: The treatment regimen implemented in Peru for isoniazid resistant TB is effective for TB cure and is not improved by addition of an injectable second-line agent. Access to rapid DST and treatment adherence need to be strengthened to increase favorable results.

[Tuberculosis in Peru: epidemiological situation, progress and challenges for its control]. / Tubersulosis en el Perú: situación epidemiológica, avances y desafíos para su control.

Tuberculosis (TB) is the first cause of death by an infectious agent in the world, the incidence in the population is declining very slowly and drug resistance is currently considered an international crisis. In Peru, the recent TB Prevention and Control Act in Peru (Law 30287) declares the fight against TB of national interest. In recent years, the Ministry of Health's (MINSA) National Health Strategy for the Prevention and Control of Tuberculosis (ESNPCT) has achieved significant progress in the control of this disease; however, challenges still remain to be addressed. This article reviews the epidemiological situation of TB in Peru, systematizes the progress achieved during the management of the ESNPCT >team between the years 2011 and 2015 from the biomedical approach, public management and social determinants of health, also posing challenges to achieving TB control under law 30287 and the "End of TB" strategy of the World Health Organization (WHO).

La tuberculosis (TB) es la primera causa de muerte por un agente infeccioso en el mundo, la incidencia en la población viene disminuyendo muy lentamente y la resistencia a los medicamentos es actualmente considerada como una crisis internacional. En el Perú, la reciente Ley de Prevención y Control de la TB en el Perú (Ley 30287), declara de interés nacional la lucha contra la TB. En los últimos años, la Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis (ESNPCT) del Ministerio de Salud (MINSA), ha obtenido avances significativos en el control de esta enfermedad; sin embargo, aún persisten desafíos que deben ser abordados. El presente artículo revisa la situación epidemiológica de la TB en el Perú, sistematiza los avances logrados durante la gestión del equipo de la ESNPCT entre los años 2011 y 2015 desde el abordaje biomédico, de gestión pública y en las determinantes sociales de la salud, además, plantea desafíos para lograr el control de la TB, en el marco de la Ley 30287 y la estrategia "Fin de la TB" de la Organización Mundial de la Salud (OMS).

The paradigm shift to end tuberculosis. Are we ready to assume the changes?

INTRODUCTION: Tuberculosis (TB) is the number one infectious disease killer and exemplifies the most neglected of them. Drug-susceptible TB presents with high mortality especially in atypical forms, disproportionally affecting immunosuppressed and vulnerable populations. The drug-resistant TB (DR-TB) epidemic, a world crisis, is sustained and increased through person-to-person transmission in households and the community. TB diagnostics and treatment in recent years are highly evolving fields. New rapid molecular tests are changing the perspectives in diagnosis and resistance screening. Also, new drugs and shorter regimens for DR-TB are appearing. For the first time in recent history, a large number of randomized control trials are incoming. Areas covered: This article reviews most TB advances including new diagnostic tests, drugs, and regimens and outlines upcoming drug trials while disclosing the potential gaps the in development of patient-centered systems and current organizational challenges leading to a delay in the uptake of these innovations. Expert commentary: Innovations are occurring, but not many are implemented on a wide scale in developing countries. TB health systems and staff are not getting updated in parallel. More efforts and funds are needed not only to implement current novelties but also to research for future solutions to eliminate TB.

Tubersulosis en el Perú: situación epidemiológica, avances y desafíos para su control / Tuberculosis in Peru: epidemiological situation, progress and challenges for its control

RESUMEN La tuberculosis (TB) es la primera causa de muerte por un agente infeccioso en el mundo, la incidencia en la población viene disminuyendo muy lentamente y la resistencia a los medicamentos es actualmente considerada como una crisis internacional. En el Perú, la reciente Ley de Prevención y Control de la TB en el Perú (Ley 30287), declara de interés nacional la lucha contra la TB. En los últimos años, la Estrategia Sanitaria Nacional de Prevención y Control de la Tuberculosis (ESNPCT) del Ministerio de Salud (MINSA), ha obtenido avances significativos en el control de esta enfermedad; sin embargo, aún persisten desafíos que deben ser abordados. El presente artículo revisa la situación epidemiológica de la TB en el Perú, sistematiza los avances logrados durante la gestión del equipo de la ESNPCT entre los años 2011 y 2015 desde el abordaje biomédico, de gestión pública y en las determinantes sociales de la salud, además, plantea desafíos para lograr el control de la TB, en el marco de la Ley 30287 y la estrategia "Fin de la TB" de la Organización Mundial de la Salud (OMS).

ABSTRACT Tuberculosis (TB) is the first cause of death by an infectious agent in the world, the incidence in the population is declining very slowly and drug resistance is currently considered an international crisis. In Peru, the recent TB Prevention and Control Act in Peru (Law 30287) declares the fight against TB of national interest. In recent years, the Ministry of Health's (MINSA) National Health Strategy for the Prevention and Control of Tuberculosis (ESNPCT) has achieved significant progress in the control of this disease; however, challenges still remain to be addressed. This article reviews the epidemiological situation of TB in Peru, systematizes the progress achieved during the management of the ESNPCT >team between the years 2011 and 2015 from the biomedical approach, public management and social determinants of health, also posing challenges to achieving TB control under law 30287 and the "End of TB" strategy of the World Health Organization (WHO).