BackgroundAn estimated 32,000 children develop multidrug-resistant tuberculosis (MDR-TB; Mycobacterium tuberculosis resistant to isoniazid and rifampin) each year. Little is known about the optimal treatment for these children.Methods and findingsTo inform the pediatric aspects of the revised World Health Organization (WHO) MDR-TB treatment guidelines, we performed a systematic review and individual patient data (IPD) meta-analysis, describing treatment outcomes in children treated for MDR-TB. To identify eligible reports we searched PubMed, LILACS, Embase, The Cochrane Library, PsychINFO, and BioMedCentral databases through 1 October 2014. To identify unpublished data, we reviewed conference abstracts, contacted experts in the field, and requested data through other routes, including at national and international conferences and through organizations working in pediatric MDR-TB. A cohort was eligible for inclusion if it included a minimum of three children (aged <15 years) who were treated for bacteriologically confirmed or clinically diagnosed MDR-TB, and if treatment outcomes were reported. The search yielded 2,772 reports; after review, 33 studies were eligible for inclusion, with IPD provided for 28 of these. All data were from published or unpublished observational cohorts. We analyzed demographic, clinical, and treatment factors as predictors of treatment outcome. In order to obtain adjusted estimates, we used a random-effects multivariable logistic regression (random intercept and random slope, unless specified otherwise) adjusted for the following covariates: age, sex, HIV infection, malnutrition, severe extrapulmonary disease, or the presence of severe disease on chest radiograph. We analyzed data from 975 children from 18 countries; 731 (75%) had bacteriologically confirmed and 244 (25%) had clinically diagnosed MDR-TB. The median age was 7.1 years. Of 910 (93%) children with documented HIV status, 359 (39%) were infected with HIV. When compared to clinically diagnosed patients, children with confirmed MDR-TB were more likely to be older, to be infected with HIV, to be malnourished, and to have severe tuberculosis (TB) on chest radiograph (p < 0.001 for all characteristics). Overall, 764 of 975 (78%) had a successful treatment outcome at the conclusion of therapy: 548/731 (75%) of confirmed and 216/244 (89%) of clinically diagnosed children (absolute difference 14%, 95% confidence interval [CI] 8%–19%, p < 0.001). Treatment was successful in only 56% of children with bacteriologically confirmed TB who were infected with HIV who did not receive any antiretroviral treatment (ART) during MDR-TB therapy, compared to 82% in children infected with HIV who received ART during MDR-TB therapy (absolute difference 26%, 95% CI 5%–48%, p = 0.006). In children with confirmed MDR-TB, the use of second-line injectable agents and high-dose isoniazid (15–20 mg/kg/day) were associated with treatment success (adjusted odds ratio [aOR] 2.9, 95% CI 1.0–8.3, p = 0.041 and aOR 5.9, 95% CI 1.7–20.5, p = 0.007, respectively). ...

Global HIV program stakeholders, including the US President’s Emergency Plan for AIDS Relief (PEPFAR), are undertaking efforts to ensure that eligible people living with HIV (PLHIV) receiving antiretroviral treatment (ART) receive a course of TB preventive treatment (TPT). In PEPFAR programming, this effort may require providing TPT not only to newly diagnosed PLHIV as part of HIV care initiation, but also to treatment-experienced PLHIV stable on ART who may not have been previously offered TPT. TPT scale-up is occurring at the same time as a trend to provide more person-centered HIV care through differentiated service delivery (DSD). In DSD, PLHIV stable on ART may receive less frequent clinical follow-up or receive care outside the traditional clinic-based model. The misalignment between traditional delivery of TPT and care delivery in innovative DSD may require adaptations to TPT delivery practices for PLHIV. Adaptations include components of planning and operationalization of TPT in DSD, such as determination of TPT eligibility and TPT initiation, and clinical management of PLHIV while on TPT. A key adaptation is alignment of timing and location for TPT and ART prescribing, monitoring, and dispensing. Conceptual examples of TPT delivery in DSD may help program managers operationalize TPT in HIV care.

Objective To describe outcomes of HIV-infected pediatric patients with drug-resistant tuberculosis (DR TB). Methods Demographic, clinical, and laboratory data from pediatric patient charts treated for DR TB during 2005–2008 were collected retrospectively from five MDR TB hospitals in South Africa. Data were summarized and Pearson’s chi-squared test or Fisher’s exact test were used to assess differences in variables of interest by HIV status. A time-to-event analysis was conducted using days from start of treatment to death. Variables of interest were first assessed using the Kaplan-Meier method. Cox proportional hazard models were fit to estimate crude and adjusted hazard ratios. Results Of 423 eligible participants, 398 (95%) had culture-confirmed DR-TB and 238 (56%) were HIV-infected. A total of 54% were underweight, 42% were male and median age was 10.7 years (IQR: 5.5–15.3). Of the 423 participants, 245 (58%) were successfully treated, 69 (16%) died, treatment failed in 3 (1%), 36 (9%) were lost to follow-up, and 70 (17%) were still on treatment, transferred or had unknown outcomes. Time to death differed by HIV status (p=0.008), sex (p<0.001), year of TB diagnosis (p=0.05) and weight status (p=0.002). Over the two-year risk period, the adjusted rate of death was 2-fold higher among participants with HIV compared to HIV-negative participants (aHR=2.28; 95% CI: 1.11, 4.68). Conclusions Male, underweight, and HIV-infected children with DR TB were more likely to experience death when compared to other children with DR TB within this study population.

Objective: To describe the implementation and utilization of the Xpert ® MTB/RIF (Xpert) assay to diagnose tuberculosis (TB) among people living with the human immunodeficiency virus/acquired immune-deficiency syndrome (HIV/AIDS, PLHA) in Cambodia. Design: Following the rollout of Xpert, an evaluation was conducted in four provinces of Cambodia from March to December 2012 to determine the utilization, performance, and turnaround time (TAT) of Xpert among PLHA. Data were collected from paper-based patient registers. Results: Of 497 PLHA with a positive TB symptom screen, 357 (72%) were tested with smear microscopy, and 250 (50%) with Xpert; 25 (10%) PLHA tested with Xpert were positive for TB and none were rifampicin-resistant. The utilization of Xpert increased from 23% to 75%, with a median TAT of 1 day. Across districts, utilization ranged from zero to 85%, while the TAT ranged from zero to 22 days. Conclusion: While early data show increasing utilization of Xpert for PLHA with a positive symptom screen, most patients underwent smear microscopy as an initial diagnostic test. Training delays and challenges associated with specimen referral may have contributed to variability in Xpert uptake and TAT, particularly for sites without onsite Xpert testing. Enhanced programmatic support, particularly for specimen referral and results reporting, may facilitate appropriate utilization.