Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru

Peru. PLoS ONE 6(11): e27610. doi:10.1371/journal.pone.0027610 Factors Associated with Anti-Tuberculosis Medication Adverse Effects: A Case-Control Study in Lima, Peru Kocfa Chung-Delgado 0 Alejandro Revilla-Montag 0 Sonia Guillen-Bravo 0 Eduardo Velez- 0 Segovia 0 Andrea Soria-Montoya 0 Alexandra Nun ez-Garbin 0 Wilmer Silva-Caso 0 Antonio 0 Madhukar Pai, McGill University, Canada 0 1 School of Medicine, Faculty of Health Sciences, Universidad Peruana de Ciencias Aplicadas, Lima, Peru, 2 Sociedad Cient fica de Estudiantes de Medicina, Universidad Peruana de Ciencias Aplicadas SOCIEMUPC , 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. - Tuberculosis (TB) is considered a global emergency by the World Health Organization (WHO) [1]. Worldwide, about 9.4 million new cases are diagnosed annually and 1.7 million people die due to the infection. Moreover, over a third of the population has a latent infection with possibility of a posterior reactivation. Recently, 440,000 cases of multidrug resistant TB (MDR-TB) have been reported [1]. In Peru, around 35,000 cases of active TB are diagnosed every year, with morbidity and incidence rates of 118 and 103 per 100,000 people, respectively [2]. MDR-TB cases represent 5.3% of the total cases, and about 200 cases of extremely drug-resistant TB (XDR TB) have been reported [3,4]. Usual treatment, according to the Peruvian National Health Strategy for Control and Prevention of Tuberculosis, is based upon DOTS strategy [2,5]. The anti-TB therapy includes a long-time, wide spectrum of drugs depending on the characteristics of the TB infection: new cases, re-infection, relapses, failures, MDR-TB, or XDR-TB. Overall, this situation can predispose patients to develop adverse drug reactions due to the long-time exposition to the anti-TB drugs [6,7]. Anti-TB drug side effects are an inherent risk for patients commencing any type of anti-TB therapy, especially the drugresistant cases. The Peruvian Ministry of Health has notified a side-effects prevalence of 3.3% amongst treated patients [3]. The emergence of side effects may depend on patients characteristics but also on concomitant events during therapy [8], which might determine adherence and, therefore, therapy success. Thus, an appropriate determination of risk factors associated with anti-TB medication adverse reaction is needed. The objective of this study was to assess factors associated with tuberculosis treatment side effects in Lima, Peru, with special emphasis on MDR-TB medication, HIV infection, diabetes, age, and tobacco use, adjusting for potential confounders. Study Design, Setting and Participants A retrospective, case-control study was performed using information from the National Health Strategy for Control and Prevention of Tuberculosis in Lima, Peru. This research used programmatic TB diagnosis, treatment monitoring and outcome data as recorded from the National Strategy for Prevention and Control of Tuberculosis at the San Juan de Miraflores-Villa Maria del Triunfo Health Network, periurban districts located at the south of Lima. Those patients who had completed anti-TB treatment for pulmonary tuberculosis in any health facility of one of the districts aforementioned during 20052010 were considered for this investigation. Patients with XDR-TB were excluded from analysis due to their high probability of adverse effects and the individualization of treatment schemes. Patients with extrapulmonary TB were also excluded from analysis because overall it is not possible to confirm the diagnosis (bacterial and histopathological confirmation), as well as the use of non-TB drugs such as corticoids during the active disease. Variable Definition An adverse reaction was defined as having a harmful and nonintentioned effect due to anti-TB drug administration at an appropriate dose, being reported in clinical records with the respective notification documentation [2]. In the same way, according to clinical records and TB Programme information [3], the following data was extracted for analysisall at the beginning of their respective anti-tuberculosis treatment: MDR-TB medication (yes/no), HIV infection (yes/no), diabetes (yes/no), and current smoking status (yes/no). Other variables included were: anemia (yes/no), defined using hemoglobin levels (,13.0 mg/dL in men and ,12.0 mg/dL in women) [9]; current alcohol use (yes/no); and body mass index (BMI), in kg/m2, defined as normal (18.5#BMI,25), overweight/obese (BMI$25), and underweight (BMI,18.5) [10]. Cases and Control Definition A case was defined as having reported any TB-drug adverse effect (mild, moderate or severe) during 20052010 with the appropriate adverse effect notification and clinical record, both part of the TB Programme report. They must have included at least two more variables of interest, not including sex. A control was defined as those not having reported a side effect, receiving anti-TB therapy during the same time that the case had appeared. Thus, when a case was found, the next 4 controls sequentially commencing treatment at the same time were selected from the TB Programme records. Procedures and Data Collection Routinely, during anti-TB therapy, patients are closely supervised until completion. When any ad (...truncated)