Realizing the "40 by 2022" Commitment from the United Nations High-Level Meeting on the Fight to End Tuberculosis: What Will It Take to Meet Rapid Diagnostic Testing Needs?

The potential gains from full adoption of World Health Organization (WHO)-recommended rapid diagnostics (WRDs) for tuberculosis (TB) are significant, but there is no current analysis of the additional investment needed to reach this goal. We sought to estimate the necessary investment in instruments, tests, and money, using Xpert MTB/RIF (Xpert), which detects Mycobacterium tuberculosis (MTB) and tests for resistance to rifampicin (RIF), as an example. An existing calculator for TB diagnostic needs was adapted to estimate the Xpert needs for a group of 24 countries with high TB burdens. This analysis assumed that countries will achieve the case-finding commitments agreed to at the recent United Nations High-Level Meeting on the Fight to End Tuberculosis, and that countries would adopt the WHO-recommended algorithm in which all people with signs and symptoms of TB receive an Xpert test. When compared to the current investments in these countries, this baseline model revealed that countries would require a 4-fold increase in the number of Xpert modules and a 6-fold increase in the number of Xpert test cartridges per year to meet their full testing needs. The incremental cost of the additional instruments for these countries would total approximately US$474 million, plus an incremental cost each year of cartridges of approximately $586 million, or a 5-fold increase over current investments. A sensitivity analysis revealed a variety of possible changes under alternative scenarios, but most of these changes either do not meet the global goals, are unrealistic, or would result in even greater investment needs. These findings suggest that a major investment is needed in WRD capacity to implement the recommended diagnostic algorithm for TB and reach the case-finding commitments by 2022.

Quality of TB services assessment: The unique contribution of patient and provider perspectives in identifying and addressing gaps in the quality of TB services.

Ambitious efforts to detect and treat tuberculosis (TB) are required to reduce the burden of disease in low resource settings, and the provision of high quality TB services is critical to reaching global TB targets. The quality of TB services assessment (QTSA) is a facility-based approach aimed at identifying gaps in TB services and prioritizing interventions to improve care across multiple countries with high TB burden. Randomly sampled facilities are assessed with standardized instruments to collect data on structures, processes, and outcomes of TB care, with adaption for local diagnostic and treatment algorithms. The sampling strategy is modified to ensure representation of all levels of the health system where TB services are provided, as well as inclusion of private sector or other facility types relevant to the context. Instruments include a facility audit, provider and patient interviews, and a review of TB registers. A recent QTSA in the Philippines generated important data on provider and patient perspectives on quality of care, showing that providers are more likely to report that they counseled current TB patients on key aspects of TB diagnosis and treatment than patients are to report having received the information. These comparisons highlight areas where refresher training or interpersonal communication and counseling skills may be needed.

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study.

BACKGROUND: In many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis. METHODS: Population-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing. FINDINGS: Isolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87-94) for rpoB (rifampicin resistance), 86% (74-93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39-68) for pncA (pyrazinamide resistance), 85% (77-91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81-92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing. INTERPRETATION: Genetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation. FUNDING: Bill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.

Tuberculosis in pregnancy: an estimate of the global burden of disease.

BACKGROUND: The estimated number of maternal deaths in 2013 worldwide was 289 000, a 45% reduction from 1990. Non-obstetric causes such as infectious diseases including tuberculosis now account for 28% of maternal deaths. In 2013, 3·3 million cases of tuberculosis were estimated to occur in women globally. During pregnancy, tuberculosis is associated with poor outcomes, including increased mortality in both the neonate and the pregnant woman. The aim of our study was to estimate the burden of tuberculosis disease among pregnant women, and to describe how maternal care services could be used as a platform to improve case detection. METHODS: We used publicly accessible country-level estimates of the total population, distribution of the total population by age and sex, crude birth rate, estimated prevalence of active tuberculosis, and case notification data by age and sex to estimate the number of pregnant women with active tuberculosis for 217 countries. We then used indicators of health system access and tuberculosis diagnostic test performance obtained from published literature to determine how many of these cases could ultimately be detected. FINDINGS: We estimated that 216 500 (95% uncertainty range 192 100-247 000) active tuberculosis cases existed in pregnant women globally in 2011. The greatest burdens were in the WHO African region with 89 400 cases and the WHO South East Asian region with 67 500 cases in pregnant women. Chest radiography or Xpert RIF/MTB, delivered through maternal care services, were estimated to detect as many as 114 100 and 120 300 tuberculosis cases, respectively.

Evaluation of community-based interventions to improve TB case detection in a rural district of Tanzania.

In Tanzania, people with tuberculosis (TB) commonly self-medicate or visit traditional healers before seeking formal medical care. Between 2009 and 2011, we piloted a community-based project in Kisarawe District to improve TB case notification. The project trained 15 traditional healers and 15 pharmacists to identify and refer individuals with TB symptoms to diagnostic facilities. In addition, the project trained 2 community members to collect and fix sputum from symptomatic individuals onto slides, which they then delivered by bicycle to the nearest diagnostic facility. To determine effectiveness, we analyzed routine case detection data and referrals from traditional healers and pharmacists and conducted a cross-sectional survey of recently diagnosed smear-positive TB patients (N = 150) to understand their treatment-seeking behavior. From 2009 to 2011, smear-positive TB case notification increased by 68% in Kisarawe District, from 28/100,000 to 47/100,000, even while TB case notification nationally stayed the same (at approximately 14/100,000). The traditional healers and pharmacists referred 434 people with presumptive TB to diagnostic facilities, 419 of whom (97%) went to the facilities; of those who went to facilities for testing, 104 people (25%) were diagnosed with TB. The percentage of new TB case notifications that were referred through the network ranged from 38% to 70% per reporting quarter. Sputum fixers collected and delivered specimens from 178 individuals, 17 of whom (10%) were diagnosed with TB. Almost 60% of surveyed smear-positive TB patients first visited a pharmacist or traditional healer before seeking care at a diagnostic facility. These results prompted scale up of community interventions to 9 more districts in 2011 and to another 26 districts in 2013. Establishing referral networks that bring TB information and services closer to community members can contribute to improved TB case notification.

The impact of the African Youth Alliance program on the sexual behavior of young people in Uganda.

This study evaluates the impact of the African Youth Alliance (AYA) program on the sexual behavior of young people aged 17-22 in Uganda. Between 2000 and 2005, the comprehensive multicomponent AYA program implemented behavior-change communication and youth-friendly clinical services, and it coordinated policy and advocacy. The program provided institutional capacity building and established coordination mechanisms between agencies that implemented programs for young people. The analysis of findings from both a self-reported exposure design and a static group comparison design indicated that AYA had a positive impact on sexual behavior among young females but not among young males. AYA-exposed girls were at least 13 percentage points more likely to report having used a condom at last sex, at least 10 percentage points more likely to report that they had consistently used condoms with their current partner, at least 10 percentage points more likely to have used contraceptives at last sex, and 13 percentage points more likely to have had fewer sex partners during the past 12 months, compared with girls who were not exposed to the AYA program. Scaling up the AYA program in Uganda could, therefore, be expected to improve significantly the sexual and reproductive health of young women. Effective strategies for promoting safer sexual behaviors among boys and young men must be identified, however.