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Introduction: This study evaluates the performance of individual and combinations tests used for pediatric tuberculosis diagnosis at a reference center. Materials and Methods: Diagnostic test outcomes from children with presumed pulmonary tuberculosis evaluated from January 2005 - July 2010 were compared to a standard diagnosis made by an expert panel of physicians. Results: Presence of at least one sign/symptom, history of contact, or abnormal chest X-ray (aCXR) individually showed the highest sensitivity (85.7%). While the combination of history of contact, at least one sign/symptom, positive tuberculin skin test, and aCXR had low sensitivity of 20%, but the specificity and a positive predictive value were 100%, respectively. The combination of tests used in the International Union Against Tuberculosis and Lung Disease and the Brazilian Ministry of Health systems showed sensitivity of 28.6% and 71.4% and specificity of 95.8% and 97.0%, respectively. Conclusions: In the absence of a gold standard, the combination of clinical history, tuberculin skin test, and aCXR, as well as the Brazilian scoring system serve as simple, low-cost approach that can be used for pediatric TB diagnosis by first-contact care providers.

Abstract Tuberculosis is the leading cause of death among people living with HIV (PLH). Preventive tuberculosis therapy reduces mortality in PLH, especially in those with a positive tuberculin skin test (TST). New, more specific technologies for detecting latent tuberculosis infection (LTBI) are now commercially available. We sought to analyse the cost-effectiveness of four different strategies for the diagnosis of LTBI in PLH in Brazil, from the Brazilian public health care system perspective. We developed a Markov state-transition model comparing four strategies for the diagnosis of LTBI over 20 years. The strategies consisted of TST with the currently used protein purified derivative (PPD RT 23), two novel skin tests using recombinant allergens (Diaskintest [Generium Pharmaceutical, Moscow, Russia] and EC [Zhifei Longcom Biologic Pharmacy Co., Anhui, China]), and the QuantiFERON-TB-Gold-Plus (Qiagen, Hilden, Germany). The main outcome was cost (in 2020 US dollars) per quality-adjusted life years (QALY). For the base case scenario, the Diaskintest was dominant over all other examined strategies. The cost saving estimate per QALY was US $1375. In sensitivity analyses, the Diaskintest and other newer tests remained cost-saving compared to TST. For PLH, TST could be replaced by more specific tests in Brazil, considering the current national recommendations.

ABSTRACT Background: Rapid molecular methods such as the line probe assay (LPA) and Xpert® MTB/RIF assay (Xpert) have been recommended by the World Health Organization for drug-resistant tuberculosis (DR-TB) diagnosis. We conducted an interventional trial in DR-TB reference centers in Brazil to evaluate the impact of the use of LPA and Xpert. Methods: Patients with DR-TB were eligible if their drug susceptibility testing results were available to the treating physician at the time of consultation. The standard reference MGITTM 960 was compared with Xpert (arm 1) and LPA (arm 2). Effectiveness was considered as the start of the appropriate TB regimen that matched drug susceptibility testing (DST) and the proportions of culture conversion and favorable treatment outcomes after 6 months. Results: A higher rate of empirical treatment was observed with MGIT alone than with the Xpert assay (97.0% vs. 45.0%) and LPA (98.2% vs. 67.5%). Patients started appropriate TB treatment more quickly than those in the MGIT group (median 15.0 vs. 40.5 days; p

OBJECTIVES/SPECIFIC AIMS: Previous research suggests that weight loss during early TB treatment (first two months of anti-TB therapy) is a predictor of poor tuberculosis (TB) treatment outcomes among HIV-negative populations, but the relationship has not been well studied in the context of HIV. We examined the association between HIV and weight change during the first two months of anti-tuberculosis treatment, and also assessed the effects of HIV and early weight change on tuberculosis (TB) treatment outcomes. METHODS/STUDY POPULATION: Adults with culture-confirmed, drug-susceptible, pulmonary TB, regardless of HIV status, were enrolled into the Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil cohort and followed on standard anti-TB therapy. For the primary analysis, we compared weight change in persons living with HIV (PLWH) and HIV-negative patients between baseline and two months using multivariable bootstrapped quantile regression and modified Poisson regression. For secondary analysis, we examined the separate effects of HIV and weight change on poor TB treatment outcome (treatment failure, TB recurrence, or death) using Cox proportional hazards regression. RESULTS/ANTICIPATED RESULTS: Among 323 participants, 45 (14%) were HIV-positive. On average, PLWH lost 0.7% (interquartile range (IQR): −5.1%, 4.4%) of their baseline body weight between baseline and two months; those without HIV gained 3.5% (IQR: 0.8%, 6.7%). After adjusting for age, sex, and baseline BMI, PLWH lost 4.1% (95% confidence interval (CI): −6.5%, −1.6%) more weight during the first two months of anti-TB treatment than HIV-negative individuals. HIV infection was associated with weight loss ≥5% (adjusted odds ratio = 9.3; 95% CI: 4.2-20.6). Regarding the secondary analysis, 14 patients had a poor TB treatment outcome: 2 treatment failures, 4 cases of recurrent TB, and 8 deaths. PLWH and patients who lost ≥5% weight had significantly increased risk of poor TB treatment outcome with hazard ratios of 8.77 (95% CI: 2.96-25.94) and 4.09 (95% CI: 1.11-15.14), respectively. DISCUSSION/SIGNIFICANCE OF IMPACT: Our results suggest that HIV is associated with weight loss during early TB treatment, and both HIV and early weight loss were associated with poor treatment outcome. Future research should examine the potential etiologies of these findings and identify the types of interventions that would best promote weight gain during TB treatment, especially among PLWH, in order to prevent poor TB treatment outcomes.

OBJECTIVES/SPECIFIC AIMS: QuantiFERON-TB Gold In-Tube (QFT) conversion from negative to positive, is regarded as a marker of recent latent tuberculosis infection and may be predictive of incident active tuberculosis (TB) disease. However, it remains unclear how conversion is influenced by individual and environmental factors, including the infectiousness of the source case to whom the contact was exposed. We aimed to examine the effect of infectiousness of TB in the source case, as measured by presence of cavitation on chest X-ray, on the incidence of QFT conversion among close contacts of the pulmonary TB index case, after adjusting for potential confounding by contact and source case characteristics. METHODS/STUDY POPULATION: The Regional Prospective Observational Research for Tuberculosis (RePORT)-Brazil is an ongoing prospective cohort study that enrolls close contacts of culture-confirmed pulmonary TB patients and follows them for 24 months for development of active TB. Demographic, clinical, and diagnostic information are obtained at baseline and during follow-up at clinical visits and by telephone. QFT testing is performed at baseline and repeated after 6 months if the baseline QFT is negative. A positive IFN-γ value is defined as >0.35 IU/mL, as recommended by the manufacturer and the CDC, and QFT conversion is defined as a negative QFT at baseline followed by a positive QFT at 6 months. RESULTS/ANTICIPATED RESULTS: Among 260 enrolled contacts with nonpositive baseline QFT results and 6 months of follow-up, 198 (76%) were retested with QFT 6 months after enrollment. Of those retested, 26 (13%) converted to positive. Presence of any cavitation in the source case, based on chest radiography, was significantly associated with QFT-conversion (ORunadjusted=2.4, 95% CI: 1.0–5.7). Additional univariate analyses revealed that QFT conversion was associated with black and brown race (compared with white race) of the contact, current smoking and current alcohol use in the source case. After adjusting for potential confounders (age, sex, and race of the contact and current smoking of the source case), the association between source case cavitation and QFT conversion remained (ORadjusted=2.5 95% CI: 1.0–6.2). As of December 6, 2017, none of the QFT-retested contacts had developed active TB, with a median follow-up of 12.3 months (IQR: 7.1–13.1). We anticipate that ongoing enrollment and follow-up may yield cases of active TB; future analyses will provide greater precision for examining predictors of QFT-conversion and its association with incident TB. DISCUSSION/SIGNIFICANCE OF IMPACT: Our preliminary results agree with published literature suggesting the infectiousness of TB in the index case is a predictor of incident LTBI. Along with recent LTBI, immune suppression, HIV co-infection, and type 2 diabetes are considered risk factors for progression to active TB disease. Because only a small proportion of persons progress from LTBI to active TB disease, it is not appropriate to treat all persons with LTBI. Thus, more research is needed to identify groups at highest risk for QFT-conversion and incident TB disease, so these groups can be targeted for TB prevention, interventions, and facilitate a decline in TB incidence and mortality.

Abstract This article reviews tuberculosis control actions performed over the last decade, at a global level. The perspectives for the fulfillment of the goals of the new Global Tuberculosis Elimination Plan are described, where the insertion of social protection (Pillar 2) and research (Pillar 3) will play an innovative and strategic role, especially in high-burden countries, like Brazil.