Mortality among MDR-TB cases: comparison with drug-susceptible tuberculosis and associated factors.

BACKGROUND: An increase in multidrug-resistant tuberculosis (MDR-TB) cases is evident worldwide. Its management implies a complex treatment, high costs, more toxic anti-tuberculosis drug use, longer treatment time and increased treatment failure and mortality. The aims of this study were to compare mortality between MDR and drug-susceptible cases of tuberculosis, and to determine risk factors associated with mortality among MDR-TB cases. METHODS AND RESULTS: A retrospective cohort study was performed using data from clinical records of the National Strategy for Prevention and Control of Tuberculosis in Lima, Peru. In the first objective, MDR-TB, compared to drug-susceptible cases, was the main exposure variable and time to death, censored at 180 days, the outcome of interest. For the second objective, different variables obtained from clinical records were assessed as potential risk factors for death among MDR-TB cases. Cox regression analysis was used to determine hazard ratios (HR) and 95% confidence intervals (95%CI). A total of 1,232 patients were analyzed: mean age 30.9 ±14.0 years, 60.0% were males. 61 patients (5.0%) died during treatment, whereas the MDR-TB prevalence was 19.2%. MDR-TB increased the risk of death during treatment (HR = 7.5; IC95%: 4.1-13.4) when compared to presumed drug-susceptible cases after controlling for potential confounders. Education level (p = 0.01), previous TB episodes (p<0.001), diabetes history (p<0.001) and HIV infection (p = 0.04) were factors associated with mortality among MDR-TB cases. CONCLUSIONS: MDR-TB is associated with an increased risk of death during treatment. Lower education, greater number of previous TB episodes, diabetes history, and HIV infection were independently associated with mortality among MDR-TB cases. New strategies for appropriate MDR-TB detection and management should be implemented, including drug sensitivity tests, diabetes and HIV screening, as well as guarantee for a complete adherence to therapy.

Weight variation over time and its relevance among multidrug-resistant tuberculosis patients.

OBJECTIVES: We aimed to assess the variation in patient body weight over time according to the treatment outcome among multidrug-resistant tuberculosis (MDR-TB) cases. METHODS: This was a retrospective cohort study. The data of patients commencing MDR-TB therapy were analyzed. Data were collected from different public TB treatment facilities located in peri-urban areas to the south of Lima, Peru. The outcome was patient body weight (kilograms) from treatment commencement, measured monthly. A random effects model was fitted using robust standard errors to calculate 95% confidence intervals. RESULTS: Of a total of 1242 TB cases, 243 (19.6%) were MDR-TB. Only 201 cases were included in the analysis; 127 (63.2%) were males and the mean patient age was 33.6 (standard deviation 16.2) years. Weight changes over time among the patients who were cured differed from changes in those who died during therapy (p<0.001). Weight curve divergence was important at the end of the third, fourth, and fifth treatment months: on average, the weight difference was 2.18kg (p<0.001), 3.27kg (p=0.007), and 3.58kg (p=0.03), respectively, when cured patients were compared to those who died. CONCLUSIONS: Our results show that weight variation during treatment can be a useful surrogate for the treatment outcome, specifically death during therapy. MDR-TB patients with weight loss should be followed more closely, as they are at greater risk of death.

Refractory thrombocytopenia responds to octreotide treatment in a case of evans syndrome with gastric neuroendocrine tumor.

A 37-year-old woman with history of Evans Syndrome with poor response to high-dose corticoid treatment presented to the emergency department with gastrointestinal and vaginal bleeding. The patient was later diagnosed with severe thrombocytopenia and a stage G1, well-differentiated gastric neuroendocrine tumor, confirmed by a biopsy. A total gastrectomy was performed to eradicate the tumor. After being treated with a total splenectomy for her Evans Syndrome with no clinical or laboratory improvement, she began regular treatment with octreotide on the basis of a possible hepatic metastasis. Days after the initiation of the octreotide, an increase in the platelet count was evidenced by laboratory findings, from 2,000 platelets/mm(3) to 109,000 platelets/mm(3). Weeks later, the hepatic metastasis is discarded by a negative octreotide-body scan, and the octreotide treatment was interrupted. Immediately after the drug interruption, a progressive and evident descent in the platelet count was evidenced (4000 platelets/mm(3)). The present case report highlights the possible association between octreotide treatment and a severe thrombocytopenia resistant to conventional treatment.

[Medical students at risk: prevalence and incidence of tuberculin skin test conversion]. / Estudiantes de medicina en riesgo: prevalencia e incidencia de conversión de PPD.

INTRODUCTION: One third of the world population is affected by latent tuberculosis, with 9.4 million new cases; medical students have 2 to 50 times the probability of acquiring the infection. OBJECTIVES: Establish the baseline prevalence of positive tuberculin skin test (TST) at the beginning of medical studies and determine the incidence and variables associated with TST conversion in medical students. MATERIALS AND METHODS: Secondary analysis of a historical cohort (2007-2010) of medical students in a private Peruvian university. The TST conversion was evaluated. A binomial regression analysis was applied for each associated variable. RESULTS: 707 medical students were included, of whom 219 (31%) were male. The basal prevalence of reactive TST was 14.4%. Significant associations were found with the year of university entry of 2007-08 (p = 0.007) and a history of tuberculosis (p = 0.02). With a total of 822 person-years, the incidence of conversion was 2.92 cases per 100 person-years (CI95%: 1.96-4.36). The TST conversion was associated with the year of university entry (RR = 2,55; IC95%: 1,06-6,30) and a body mass index > 25 kg/m² (RR = 0,16; IC95%: 0,01-0,97). No association was detected with gender, tobacco or alcohol use. CONCLUSIONS: There is evidence of a high basal prevalence of latent tuberculosis infection in medical students. The incidence rate is within expected values and high in comparison with the general population. People with BMI > 25 kg/m² have protection against a latent infection. In medical students, more attention should be paid to biosecurity.

Estudiantes de medicina en riesgo: prevalencia e incidencia de conversión de PPD / Medical students at risk: prevalence and incidence of tuberculin skin test conversion

Introduction: One third of the world population is affected by latent tuberculosis, with 9.4 million new cases; medical students have 2 to 50 times the probability of acquiring the infection. Objectives: Establish the baseline prevalence of positive tuberculin skin test (TST) at the beginning of medical studies and determine the incidence and variables associated with TST conversion in medical students. Materials and Methods: Secondary analysis of a historical cohort (2007-2010) of medical students in a private Peruvian university. The TST conversion was evaluated. A binomial regression analysis was applied for each associated variable. Results: 707 medical students were included, of whom 219 (31%) were male. The basal prevalence of reactive TST was 14.4%. Significant associations were found with the year of university entry of 2007-08 (p = 0.007) and a history of tuberculosis (p = 0.02). With a total of 822 person-years, the incidence of conversion was 2.92 cases per 100 person-years (CI95%: 1.96-4.36). The TST conversion was associated with the year of university entry (RR = 2,55; IC95%: 1,06-6,30) and a body mass index > 25 kg/m² (RR = 0,16; IC95%: 0,01-0,97). No association was detected with gender, tobacco or alcohol use. Conclusions: There is evidence of a high basal prevalence of latent tuberculosis infection in medical students. The incidence rate is within expected values and high in comparison with the general population. People with BMI > 25 kg/m² have protection against a latent infection. In medical students, more attention should be paid to biosecurity.

Introducción: Un tercio de la población mundial presenta una infección tuberculosa latente, con 9,4 millones de casos nuevos reportados en el 2009; los estudiantes de medicina tienen de 2 a 50 veces más probabilidad de adquirir la infección. Objetivos: Establecer la prevalencia de PPD positivo basal al inicio de la carrera médica y determinar la incidencia y los factores asociados a la conversión de PPD en alumnos de medicina. Materiales y Métodos: Análisis secundario de datos de una cohorte histórica (2007-2010) involucrando alumnos de medicina de una universidad privada en Perú. Se evaluó la conversión de PPD. Se aplicó un análisis de regresión binomial para cada variable de interés. Resultados: 707 estudiantes fueron seguidos, de ellos 219 (31%) fueron hombres. La prevalencia basal de PPD positivo fue 14,4%. Se encontró asociación significativa con el año de ingreso 2007-08 (p = 0,007) y antecedente de tuberculosis anterior (p = 0,02). Con un total de 822 personas-año, la incidencia de conversión fue de 2,92 por 100 personas-año (IC95%: 1,96-4,36). En el modelo bivariado, el año de ingreso a la carrera y el IMC > 25 kg/m² estuvieron asociados con conversión de PPD. Sin embargo, en el modelo multivariado, sólo el año de ingreso mostró asociación estadísticamente significativa (RR = 2,53; IC95%: 1,11-5,76). Conclusiones: Existe una prevalencia basal elevada de infección latente en alumnos de medicina. La tasa de incidencia está dentro de los valores esperados y previamente reportados. Se recomienda prestar más atención a las medidas de bioseguridad y prevención en estudiantes de medicina.

Factors associated with anti-tuberculosis medication adverse effects: a case-control study in Lima, Peru.

BACKGROUND: Long-term exposure to anti-tuberculosis medication increases risk of adverse drug reactions and toxicity. The objective of this investigation was to determine factors associated with anti-tuberculosis adverse drug reactions in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age and tobacco use. METHODOLOGY AND RESULTS: A case-control study was performed using information from Peruvian TB Programme. A case was defined as having reported an anti-TB adverse drug reaction during 2005-2010 with appropriate notification on clinical records. Controls were defined as not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Crude, and age- and sex-adjusted models were calculated using odds ratios (OR) and 95% confidence intervals (95%CI). A multivariable model was created to look for independent factors associated with side effect from anti-TB therapy. A total of 720 patients (144 cases and 576 controls) were analyzed. In our multivariable model, age, especially those over 40 years (OR = 3.93; 95%CI: 1.65-9.35), overweight/obesity (OR = 2.13; 95%CI: 1.17-3.89), anemia (OR = 2.10; IC95%: 1.13-3.92), MDR-TB medication (OR = 11.1; 95%CI: 6.29-19.6), and smoking (OR = 2.00; 95%CI: 1.03-3.87) were independently associated with adverse drug reactions. CONCLUSIONS: Old age, anemia, MDR-TB medication, overweight/obesity status, and smoking history are independent risk factors associated with anti-tuberculosis adverse drug reactions. Patients with these risk factors should be monitored during the anti-TB therapy. A comprehensive clinical history and additional medical exams, including hematocrit and HIV-ELISA, might be useful to identify these patients.