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Incomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued transmission in the community, as well as treatment failure, relapse, and development or amplification of drug resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes. We systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions. When compared with DOT alone, self-administered therapy (SAT) was associated with lower rates of treatment success (CS: risk ratio [RR] 0.81, 95% CI 0.73-0.89; RCT: RR 0.94, 95% CI 0.89-0.98), adherence (CS: RR 0.83, 95% CI 0.75-0.93), and sputum smear conversion (RCT: RR 0.92, 95% CI 0.87-0.98) as well as higher rates of development of drug resistance (CS: RR 4.19, 95% CI 2.34-7.49). When compared to DOT provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: RR 0.86, 95% CI 0.79-0.94). DOT delivery in the community versus at the clinic was associated with a higher rate of treatment success (CS: RR 1.08, 95% CI 1.01-1.15) and sputum conversion at the end of two months (CS: RR 1.05, 95% CI 1.02-1.08) as well as lower rates of treatment failure (CS: RR 0.56, 95% CI 0.33-0.95) and loss to follow-up (CS: RR 0.63, 95% CI 0.40-0.98). Medication monitors improved adherence and treatment success and VOT was comparable with DOT. SMS reminders led to a higher treatment completion rate in one RCT and were associated with higher rates of cure and sputum conversion when used in combination with medication monitors. TB treatment outcomes improved when patient education, healthcare provider education, incentives and enablers, psychological interventions, reminders and tracers, or mobile digital technologies were employed. Our findings are limited by the heterogeneity of the included studies and lack of standardized research methodology on adherence interventions. TB treatment outcomes are improved with the use of adherence interventions, such as patient education and counseling, incentives and enablers, psychological interventions, reminders and tracers, and digital health technologies. Trained healthcare providers as well as community delivery provides patient-centered DOT options that both enhance adherence and improve treatment outcomes as compared to unsupervised, SAT alone.

Background Contact investigation, the systematic evaluation of individuals in close contact with an infectious tuberculosis (TB) patient, is a key active case-finding strategy for global TB control. Better estimates of the yield of contact investigation can guide strategies to reduce the number of underreported and underdiagnosed TB cases, approximately three million cases per year globally. A systematic review (Prospero ID # CRD42019133380) and meta-analysis was conducted to update and enhance the estimates of the yield of TB contact investigation in low- and middle-income countries (LMIC). Pubmed, Web of Science, Embase and the WHO Global Index Medicus were searched for peer-reviewed studies (published between January 2006–April 2019); studies reporting the number of active TB or latent tuberculosis infection (LTBI) found through contact investigation were included. Pooled data were meta-analyzed using a random effects model and risk of bias was assessed. Results Of 1,644 unique citations obtained from database searches, 110 studies met eligibility criteria for descriptive data synthesis and 95 for meta-analysis. The pooled yields of contact investigation activities for different outcomes were: secondary cases of all active TB (defined as those bacteriologically confirmed or clinically diagnosed) 2.87% (2.61–3.14, I 2 97.79%), bacteriologically confirmed active TB 2.04% (1.77–2.31, I 2 98.06%), and LTBI 43.83% (38.11–49.55, I 2 99.36%). Yields are interpreted as the percent of contacts screened who are diagnosed with active TB as a result of TB contact investigation activities. Pooled estimates were substantially heterogenous (I 2  ≥ 75%). Conclusions This study provides methodologically rigorous and up-to-date estimates for the yield of TB contact investigation activities in low- and middle-income countries (LMIC). While the data are heterogenous, these findings can inform strategic and programmatic planning for scale up of TB contact investigation activities.

Respiratory isolation of inpatients during evaluation for TB is a slow and costly process in low-burden settings. Xpert MTB/RIF (Xpert) is a novel molecular test for tuberculosis (TB) that is faster and more sensitive but substantially more expensive than smear microscopy. No previous studies have examined the costs of molecular testing as a replacement for smear microscopy in this setting. We conducted an incremental cost-benefit analysis comparing the use of a single negative Xpert versus two negative sputum smears to release consecutive adult inpatients with presumed TB from respiratory isolation at an urban public hospital in the United States. We estimated all health-system costs and patient outcomes related to Xpert implementation, diagnostic evaluation, isolation, hospitalization, and treatment. We performed sensitivity and probabilistic uncertainty analyses to determine at what threshold the Xpert strategy would become cost-saving. Among a hypothetical cohort of 234 individuals undergoing evaluation for presumed active TB annually, 6.4% had culture-positive TB. Compared to smear microscopy, Xpert reduced isolation bed utilization from an average of 2.7 to 1.4 days per patient, leading to a 48% reduction in total annual isolation bed usage from 632 to 328 bed-days. Xpert saved an average of $2,278 (95% uncertainty range $1582-4570) per admission, or $533,520 per year, compared with smear microscopy. Molecular testing for TB could provide substantial savings to hospitals in high-income countries by reducing respiratory isolation usage and overall length of stay.

Community active case finding (ACF) for tuberculosis was widely implemented in Europe and North America between 1940 and 1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening. Case notifications for 1950 to 1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNRs) during and after a mass screening intervention implemented over 5 weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11 March 1957 to 12 April 1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950 to 1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI] [1.81, 2.11]) and 35% decline in the year after (RR: 0.65, 95% UI [0.59, 0.71]). Post-intervention (1958 to 1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95% UI [0.69, 0.85]), and there were an estimated 4,599 (95% UI [3,641, 5,683]) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined in young children (0 to 5 years) with the intervention. Limitations include the lack of data in historical reports on microbiological testing for tuberculosis, and uncertainty in contributory effects of other contemporaneous interventions including slum clearances, introduction of BCG vaccination programmes, and the ending of postwar food rationing. A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) likely resulted in a major and sustained reduction in tuberculosis case notifications. Synthesis of evidence from other historical tuberculosis screening programmes is needed to confirm findings from Glasgow and to provide insights into ongoing efforts to successfully implement ACF interventions in today's high tuberculosis burden countries and with new screening tools and technologies.

Background Studies of the quality of tuberculosis (TB) diagnostic evaluation of patients in high burden countries have generally shown poor adherence to international or national guidelines. Health worker perspectives on barriers to improving TB diagnostic evaluation are critical for developing clinic-level interventions to improve guideline implementation. Methods We conducted structured, in-depth interviews with staff at six district-level health centers in Uganda to elicit their perceptions regarding barriers to TB evaluation. Interviews were transcribed, coded with a standardized framework, and analyzed to identify emergent themes. We used thematic analysis to develop a logic model depicting health system and contextual barriers to recommended TB evaluation practices. To identify possible clinic-level interventions to improve TB evaluation, we categorized findings into predisposing, enabling, and reinforcing factors as described by the PRECEDE model, focusing on potentially modifiable behaviors at the clinic-level. Results We interviewed 22 health center staff between February 2010 and November 2011. Participants identified key health system barriers hindering TB evaluation, including: stock-outs of drugs/supplies, inadequate space and infrastructure, lack of training, high workload, low staff motivation, and poor coordination of health center services. Contextual barrier challenges to TB evaluation were also reported, including the time and costs borne by patients to seek and complete TB evaluation, poor health literacy, and stigma against patients with TB. These contextual barriers interacted with health system barriers to contribute to sub-standard TB evaluation. Examples of intervention strategies that could address these barriers and are related to PRECEDE model components include: assigned mentors/peer coaching for new staff (targets predisposing factor of low motivation and need for support to conduct job duties); facilitated workshops to implement same day microscopy (targets enabling factor of patient barriers to completing TB evaluation), and recognition/incentives for good TB screening practices (targets low motivation and self-efficacy). Conclusions Our findings suggest that health system and contextual barriers work together to impede TB diagnosis at health centers and, if not addressed, could hinder TB case detection efforts. Qualitative research that improves understanding of the barriers facing TB providers is critical to developing targeted interventions to improve TB care.

IntroductionThere are limited published data on how countries carry out screening for tuberculosis (TB) disease and what the perceived challenges are for implementing screening from a country perspective. Understanding these factors are important to enable better planning and support for the roll-out of appropriate screening interventions.MethodsWe conducted a cross-sectional survey of national TB programmes from countries reporting >1000 TB cases annually.ResultsSixty of 123 countries responded, representing 82% of the global TB burden. Only 35% of countries had a policy to screen for TB in all four key risk groups identified by WHO, 66% carried out all six WHO-recommended steps to implement screening and 39% collected all seven of the WHO-recommended data points for monitoring activity. Although 68% of countries planned to increase CXR-based screening, 90% reported at least one significant barrier to implementing this, and 20% were not aware of computer-aided detection (CAD) software technology.ConclusionAlthough chest X-ray and CAD use are expanding and hold promise as tools to find people with TB, many programmes do not have adequate access to them. While global policy is in place that recommends the use of these tools, efforts should be made to support countries tackling these barriers.

The clinical impact of Xpert MTB/RIF for tuberculosis (TB) diagnosis in high HIV-prevalence settings is unknown. To determine the diagnostic accuracy and impact of Xpert MTB/RIF among high-risk TB suspects. WE PROSPECTIVELY ENROLLED CONSECUTIVE, HOSPITALIZED, UGANDAN TB SUSPECTS IN TWO PHASES: baseline phase in which Xpert MTB/RIF results were not reported to clinicians and an implementation phase in which results were reported. We determined the diagnostic accuracy of Xpert MTB/RIF in reference to culture (solid and liquid) and compared patient outcomes by study phase. 477 patients were included (baseline phase 287, implementation phase 190). Xpert MTB/RIF had high sensitivity (187/237, 79%, 95% CI: 73-84%) and specificity (190/199, 96%, 95% CI: 92-98%) for culture-positive TB overall, but sensitivity was lower (34/81, 42%, 95% CI: 31-54%) among smear-negative TB cases. Xpert MTB/RIF reduced median days-to-TB detection for all TB cases (1 [IQR 0-26] vs. 0 [IQR 0-1], p<0.001), and for smear-negative TB (35 [IQR 22-55] vs. 22 [IQR 0-33], p=0.001). However, median days-to-TB treatment was similar for all TB cases (1 [IQR 0-5] vs. 0 [IQR 0-2], p=0.06) and for smear-negative TB (7 [IQR 3-53] vs. 6 [IQR 1-61], p=0.78). Two-month mortality was also similar between study phases among 252 TB cases (17% vs. 14%, difference +3%, 95% CI: -21% to +27%, p=0.80), and among 87 smear-negative TB cases (28% vs. 22%, difference +6%, 95% CI: -34 to +46%, p=0.77). Xpert MTB/RIF facilitated more accurate and earlier TB diagnosis, leading to a higher proportion of TB suspects with a confirmed TB diagnosis prior to hospital discharge in a high HIV/low MDR TB prevalence setting. However, our study did not detect a decrease in two-month mortality following implementation of Xpert MTB/RIF possibly because of insufficient powering, differences in empiric TB treatment rates, and disease severity between study phases.

Background Interferon-gamma release assays may be used as an alternative to the tuberculin skin test for detection of M. tuberculosis infection. However, the risk of active tuberculosis disease following screening using interferon-gamma release assays in immigrants is not well defined. To address these uncertainties, we determined the incidence rates of active tuberculosis disease in a cohort of high-risk immigrants with Class B TB screened with interferon-gamma release assays (IGRAs) upon arrival in the United States. Methods Using a retrospective cohort design, we enrolled recent U.S. immigrants with Class B TB who were screened with an IGRA (QuantiFERON ® Gold or Gold In-Tube Assay) at the San Francisco Department of Public Health Tuberculosis Control Clinic from January 2005 through December 2010. We reviewed records from the Tuberculosis Control Patient Management Database and from the California Department of Public Health Tuberculosis Case Registry to determine incident cases of active tuberculosis disease through February 2015. Results Of 1233 eligible immigrants with IGRA screening at baseline, 81 (6.6 %) were diagnosed with active tuberculosis disease as a result of their initial evaluation. Of the remaining 1152 participants without active tuberculosis disease at baseline, 513 tested IGRA-positive and 639 tested IGRA-negative. Seven participants developed incident active tuberculosis disease over 7730 person-years of follow-up, for an incidence rate of 91 per 100,000 person-years (95 % CI 43–190). Five IGRA-positive and two IGRA-negative participants developed active tuberculosis disease (incidence rates 139 per 100,000 person-years (95 % CI 58–335) and 48 per 100,000 person-years (95 % CI 12–193), respectively) for an unadjusted incidence rate ratio of 2.9 (95 % CI 0.5–30, p  = 0.21). IGRA test results had a negative predictive value of 99.7 % but a positive predictive value of only 0.97 %. Conclusions Among high-risk immigrants without active tuberculosis disease at the time of entry into the United States, risk of progression to active tuberculosis disease was higher in IGRA-positive participants compared with IGRA-negative participants. However, these findings did not reach statistical significance, and a positive IGRA at enrollment had a poor predictive value for progressing to active tuberculosis disease. Additional research is needed to identify biomarkers and develop clinical algorithms that can better predict progression to active tuberculosis disease among U.S. immigrants.

Background Tuberculosis (TB) remains a significant public health challenge in the Western Pacific Region, which accounts for approximately 20% of the global TB burden. Despite effective diagnostic tools and treatment, many individuals with TB remain undiagnosed or unreported, particularly in high-burden countries. Systematic screening is a key strategy for identifying cases early and reducing transmission. This study presents a situational analysis of TB screening policies, practices, and challenges across seven high-burden countries in the region: Cambodia, China, Lao PDR, Mongolia, Papua New Guinea, the Philippines, and Viet Nam. Main body Data were collected through questionnaires, follow-up discussions, and a regional workshop involving National TB Programme representatives and WHO staff. Most countries have national guidelines for systematic screening, prioritising high-risk groups, like people living with HIV and household contacts. Common screening tools include symptom screening, chest X-rays, and WHO-recommended rapid molecular diagnostics. Although asymptomatic TB is increasingly recognised, symptom screening remains the primary initial tool. Chest X-rays with computer-aided detection technologies are available in most countries, but are often limited to donor-funded projects. Screening is conducted through routine healthcare visits, scheduled checks for specific populations (e.g., prisoners, older adults), and ad hoc campaigns. Implementation varies due to resource and infrastructure limitations. While integration with other health services and community-based approaches shows promise, these remain underutilised. Key challenges include limited funding, workforce shortages, low provider awareness, and stigma. The COVID-19 pandemic disrupted TB services, underscoring the need for resilient health systems. Conclusion Improving systematic TB screening requires scaling up sensitive diagnostic tools, decentralising implementation, and strengthening community engagement. Sustainable financing, robust health systems, and multi-sectoral collaboration are critical to reaching the “missing millions” and achieving the End TB goals. This analysis underscores the need for targeted, evidence-based strategies to enhance screening coverage and effectiveness across diverse epidemiological and resource settings.

Background Tuberculosis preventive treatment (TPT) can avert progression from infection to disease, yet scale-up across the World Health Organization Western Pacific Region is patchy. To guide acceleration, we assessed progress, challenges and responses in seven high-burden countries—Cambodia, China, Lao People’s Democratic Republic (PDR), Mongolia, Papua New Guinea, the Philippines and Viet Nam—drawing on 2015–2023 programme data, structured questionnaires, follow-up interviews and a regional validation workshop. Main body Six of the seven countries have issued national TPT guidelines and five now offer shorter rifapentine- or rifampicin-based regimens. The number of people started on TPT rose sharply in most settings, driven by household contacts aged ≥ 5 years in Cambodia, Mongolia and the Philippines and by people living with HIV in Lao PDR and Papua New Guinea. However, coverage of children under five and other high-risk groups remains low. Cascade analysis revealed major attrition between screening and TPT initiation. Key obstacles, viewed through a socio-ecological lens, include: individual complacency, fear of adverse events and limited provider confidence; stigma and consent barriers in migrant households; intermittent staff training, medicine stock-outs and weak digital tools; long journeys to health facilities; and policy–practice gaps such as the absence of child-friendly formulations and non-notification of tuberculosis infection. Countries and partners endorsed a tiered package combining patient-centred counselling, mobile reminders, shorter paediatric regimens, stigma-reduction campaigns and remote e-consent. Health systems will reinforce staff training, digital supply-chain and adherence tools, while decentralised one-stop outreach and community health-workers extend coverage. A multisector task force will fast-track paediatric fixed-dose registration, make infection notifiable and absorb preventive treatment costs into national budgets and insurance schemes. Conclusions The introduction of shorter regimens and rising enrolment confirm that rapid gains are achievable, yet wide disparities persist across age groups, risk categories and care-cascade stages. Implementing the agreed client, community, institutional and policy interventions—backed by integrated governance and sustainable domestic funding—can convert TPT from a promising guideline into a routine, life-saving component of primary health care throughout the Western Pacific Region.