Aggressive Regimens for Multidrug-Resistant Tuberculosis Decrease All-Cause Mortality

Rationale: A better understanding of the composition of optimal treatment regimens for multidrug-resistant tuberculosis (MDR-TB) is essential for expanding universal access to effective treatment and for developing new therapies for MDR-TB. Analysis of observational data may inform the definition of an optimized regimen. Objectives: This study assessed the impact of an aggressive regimen–one containing at least five likely effective drugs, including a fluoroquinolone and injectable–on treatment outcomes in a large MDR-TB patient cohort. Methods: This was a retrospective cohort study of patients treated in a national outpatient program in Peru between 1999 and 2002. We examined the association between receiving an aggressive regimen and the rate of death. Measurements and Main Results: In total, 669 patients were treated with individualized regimens for laboratory-confirmed MDR-TB. Isolates were resistant to a mean of 5.4 (SD 1.7) drugs. Cure or completion was achieved in 66.1% (442) of patients; death occurred in 20.8% (139). Patients who received an aggressive regimen were less likely to die (crude hazard ratio [HR]: 0.62; 95% CI: 0.44,0.89), compared to those who did not receive such a regimen. This association held in analyses adjusted for comorbidities and indicators of severity (adjusted HR: 0.63; 95% CI: 0.43,0.93). Conclusions: The aggressive regimen is a robust predictor of MDR-TB treatment outcome. TB policy makers and program directors should consider this standard as they design and implement regimens for patients with drug-resistant disease. Furthermore, the aggressive regimen should be considered the standard background regimen when designing randomized trials of treatment for drug-resistant TB

Impact of HIV on mortality among patients treated for tuberculosis in Lima, Peru: a prospective cohort study

Background: Human immunodeficiency virus (HIV)-associated tuberculosis deaths have decreased worldwide over the past decade. We sought to evaluate the effect of HIV status on tuberculosis mortality among patients undergoing treatment for tuberculosis in Lima, Peru, a low HIV prevalence setting. Methods: We conducted a prospective cohort study of patients treated for tuberculosis between 2005 and 2008 in two adjacent health regions in Lima, Peru (Lima Ciudad and Lima Este). We constructed a multivariate Cox proportional hazards model to evaluate the effect of HIV status on mortality during tuberculosis treatment. Results: Of 1701 participants treated for tuberculosis, 136 (8.0 %) died during tuberculosis treatment. HIV-positive patients constituted 11.0 % of the cohort and contributed to 34.6 % of all deaths. HIV-positive patients were significantly more likely to die (25.1 vs. 5.9 %, P < 0.001) and less likely to be cured (28.3 vs. 39.4 %, P = 0.003). On multivariate analysis, positive HIV status (hazard ratio [HR] = 6.06; 95 % confidence interval [CI], 3.96–9.27), unemployment (HR = 2.24; 95 % CI, 1.55–3.25), and sputum acid-fast bacilli smear positivity (HR = 1.91; 95 % CI, 1.10–3.31) were significantly associated with a higher hazard of death. Conclusions: We demonstrate that positive HIV status was a strong predictor of mortality among patients treated for tuberculosis in the early years after Peru started providing free antiretroviral therapy. As HIV diagnosis and antiretroviral therapy provision are more widely implemented for tuberculosis patients in Peru, future operational research should document the changing profile of HIV-associated tuberculosis mortality

CASITA: a controlled pilot study of community-based family coaching to stimulate early child development in Lima, Peru

Objective: To determine whether the 3-month, community-based early stimulation coaching and social support intervention ‘CASITA’, delivered by community health workers, could improve early child development and caregiver-child interaction in a resource-limited district in Lima, Peru. Design: A controlled two-arm proof-of-concept study. Setting: Six neighbourhood health posts in Carabayllo, a mixed rural/urban district in Lima. Sessions were held in homes and community centres. Participants Children aged 6–24 months who screened positive for risk of neurodevelopmental delay (using validated developmental delay tool) and poverty (using progress out of poverty tool) were enrolled with their caregivers. Dyads with children born >21 days early were excluded. Intervention 12-week parenting/support intervention plus nutritional support (n=41) or nutrition alone (n=19). Outcome measures Development and home environment differences and mean changes from baseline to 3 months postintervention were evaluated using age-adjusted z-scores on the Extended Ages and Stages Questionnaire (EASQ) and the Home Observation Measurement of the Environment (HOME) scores, respectively. Results: Development in CASITA improved significantly in all EASQ domains, whereas the control group’s z-scores did not improve significantly in any domain. The mean adjusted difference (MAD) in change in EASQ age-adjusted z-scores between the two study arms was 1.39 (95% CI 0.55 to 2.22); Cohen’s d effect size of 0.87 (95% CI 0.23 to 1.50). Likewise, intervention significantly improved global HOME scores versus control group (MAD change of 6.33 (95% CI 2.12 to 10.55); Cohen’s d of 0.85 (95% CI 0.28 to 1.41)). Conclusions: An evidence-based early intervention delivered weekly during 3 months by a community health worker significantly improved children’s communication, motor and personal/social development in this proof-of-concept study

Understanding HIV Risk Behavior among Tuberculosis Patients with Alcohol Use Disorders in Tomsk, Russian Federation.

Russian Federation's (RF) HIV epidemic is the fastest growing of any country. This study explores factors associated with high HIV risk behavior in tuberculosis (TB) patients with alcohol use disorders in Tomsk, RF. This analysis was nested within the Integrated Management of Physician-delivered Alcohol Care for TB Patients (IMPACT, trial number NCT00675961) randomized controlled study of integrating alcohol treatment into TB treatment in Tomsk. Demographics, HIV risk behavior (defined as participant report of high-risk intravenous drug use and/or multiple sexual partners with inconsistent condom use in the last six months), clinical data, alcohol use, depression and psychosocial factors were collected from 196 participants (161 male and 35 female) at baseline. Forty-six participants (23.5%) endorsed HIV risk behavior at baseline. Incarceration history(Odds Ratio (OR)3.93, 95% confidence interval (CI) 1.95, 7.95), age under 41 (OR:2.97, CI:1.46, 6.04), drug addiction(OR: 3.60 CI:1.10, 11.77), history of a sexually transmitted disease(STD)(OR 2.00 CI:1.02, 3.90), low social capital (OR:2.81 CI:0.99, 8.03) and heavier alcohol use (OR:2.56 CI: 1.02, 6.46) were significantly more likely to be associated with HIV risk behavior at baseline. In adjusted analysis, age under 41(OR: 4.93, CI: 2.10, 11.58), incarceration history(OR: 3.56 CI:1.55, 8.17) and STD history (OR: 3.48, CI: 1.5, 8.10) continued to be significantly associated with HIV risk behavior. Understanding HIV transmission dynamics in Russia remains an urgent priority to inform strategies to address the epidemic. Larger studies addressing sex differences in risks and barriers to protective behavior are needed

Factors associated with HIV high risk behavior at baseline among study participants, Tomsk, Russian Federation (n = 196).

<p>Factors associated with HIV high risk behavior at baseline among study participants, Tomsk, Russian Federation (n = 196).</p

Comprehensive treatment of extensively drug-resistant tuberculosis

BACKGROUND: Extensively drug-resistant tuberculosis has been reported in 45 countries, including countries with limited resources and a high burden of tuberculosis. We describe the management of extensively drug-resistant tuberculosis and treatment outcomes among patients who were referred for individualized outpatient therapy in Peru. METHODS: A total of 810 patients were referred for free individualized therapy, including drug treatment, resective surgery, adverse-event management, and nutritional and psychosocial support. We tested isolates from 651 patients for extensively drug-resistant tuberculosis and developed regimens that included five or more drugs to which the infecting isolate was not resistant. RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis. The patients with extensively drug-resistant tuberculosis had undergone more treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9 vs. 3.2+/-1.6; P\u3c0.001) and had isolates that were resistant to more drugs (number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P\u3c0.001). None of the patients with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency virus (HIV). Patients with extensively drug-resistant tuberculosis received daily, supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine, an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%) completed treatment or were cured, as compared with 400 patients (66.3%) with multidrug-resistant tuberculosis (P=0.36). CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative patients through outpatient treatment, even in those who have received multiple prior courses of therapy for tuberculosis

Multivariable, time-varying Cox proportional hazards analysis of aggressive regimen and time to death.

<p>Multivariable, time-varying Cox proportional hazards analysis of aggressive regimen and time to death.</p