BACKGROUND: For settings with low tuberculosis incidence, disease elimination is a long-term goal. We investigated pathways to tuberculosis pre-elimination (incidence <1·0 cases per 100 000 people) and elimination (incidence <0·1 cases per 100 000 people) in the USA, where incidence was estimated at 2·9 per 100 000 people in 2023. METHODS: Using a mathematical modelling framework, we simulated how US tuberculosis incidence could be affected by changes in tuberculosis services in the countries of origin for future migrants to the USA, as well as changes in tuberculosis services inside the USA. To do so, we used a linked set of transmission dynamic models, calibrated to demographic and epidemiological data for each setting. We constructed intervention scenarios representing improvements in tuberculosis services internationally and within the USA, individually and in combination, plus a base-case scenario representing continuation of current services. We simulated health and economic outcomes until 2100, using a Bayesian approach to quantify uncertainty in these outcomes. FINDINGS: Under the base-case scenario, US tuberculosis incidence was projected to decline to 1·8 cases per 100 000 (95% uncertainty interval [UI] 1·5-2·1) in the total population by 2050. Intervention scenarios produced substantial reductions in tuberculosis incidence, with the combination of all domestic and international interventions projected to achieve pre-elimination by 2033 (95% UI 2031-2037). Compared with the base-case scenario, this combination of interventions could avert 101 000 tuberculosis cases (95% UI 84 000-120 000) and 13 300 tuberculosis deaths (95% UI 10 500-16 300) in the USA from 2025 to 2050. Tuberculosis elimination was not projected before 2100. INTERPRETATION: Strengthening tuberculosis services domestically, promoting the development of more effective technologies and interventions, and supporting tuberculosis programmes in countries with a high tuberculosis burden are key strategies for accelerating progress towards tuberculosis elimination in the USA. FUNDING: US Centers for Disease Control and Prevention.

RATIONALE: Most United States residents who develop tuberculosis were born abroad, and US TB incidence is increasingly driven by infection risks in other countries. OBJECTIVES: To estimate the potential impact of effective global TB control on health and economic outcomes in the United States. METHODS: We estimated outcomes using linked mathematical models of TB epidemiology in the United States and migrants' birth countries. A base-case scenario extrapolated country-specific TB incidence trends. We compared this to scenarios in which countries achieve 90% TB incidence reductions between 2015 and 2035, as targeted by the Global End TB Strategy ("effective global TB control"). We also considered pessimistic scenarios of flat TB incidence trends in individual countries. MEASUREMENTS AND MAIN RESULTS: We estimated TB cases, TB deaths, costs, and the total economic burden of TB in the US. Compared to the base-case, effective global TB control would avert 40,000 (95% uncertainty interval: 29,000-55,000) TB cases in the United States over 2020-2035. TB incidence rates in 2035 would be 43% (34-54) lower than the base-case, and 49% (44-55) lower than in 2020. Summed over 2020-2035, this represents $0.8 (0.6-1.0) billion dollars in averted healthcare costs and $2.5 (1.7-3.6) billion in productivity gains. The total US economic burden of TB (including the value of averted TB deaths) would be 21% (16-28) lower ($18 (8-32) billion). CONCLUSIONS: In addition to producing major health benefits for high-burden countries, strengthened efforts to achieve effective global TB control could produce substantial health and economic benefits for the United States.

BACKGROUND: In sub-Saharan Africa, patients with advanced HIV experience high mortality during the first few months of antiretroviral therapy (ART), largely attributable to tuberculosis (TB). We evaluated the cost-effectiveness of TB diagnostic strategies to reduce this early mortality. METHODS: We developed a decision analytic model to estimate the incremental cost, deaths averted, and cost-effectiveness of 3 TB diagnostic algorithms. The model base case represents current practice (symptoms screening, sputum smear, and chest radiography) in many resource-limited countries in sub-Saharan Africa. We compared the current practice with World Health Organization (WHO)-recommended practice with culture and WHO-recommended practice with the Xpert mycobacterium tuberculosis and resistance to rifampicin test and considered relevant medical costs from a health system perspective using the timeframe of the first 6 months of ART. We conducted univariate and probabilistic sensitivity analyses on all parameters in the model. RESULTS: When considering TB diagnosis and treatment and ART costs, the cost per patient was $850 for current practice, $809 for the algorithm with Xpert test, and $879 for the algorithm with culture. Our results showed that both WHO-recommended algorithms avert more deaths among TB cases than does the current practice. The algorithm with Xpert test was least costly at reducing early mortality compared with the current practice. Sensitivity analyses indicated that cost-effectiveness findings were stable. CONCLUSIONS: Our analysis showed that culture or Xpert were cost-effective at reducing early mortality during the first 6 months of ART compared with the current practice. Thus, our findings provide support for ongoing efforts to expand TB diagnostic capacity.

The articles by Nicholas et al1 and Petit et al2 in this issue of the Journal of Acquired Immune Deficiency Syndromes report on the incidence of tuberculosis (TB) before and after the initiation of highly active antiretroviral therapy in high and low-TB-prevalence settings. | The TB incidence rate reported by Nicholas et al1 was high (13 per 100 person-years) during the first 3 months of antiretroviral therapy (ART) in a multicountry African cohort. Petit et al also found high TB incidence (4 per 1000 person-years) during the first 6 months of ART in a low-TB-prevalence setting cohort in the United States. Multiple studies in countries with a high TB burden have consistently documented high rates of TB during the very early months of ART.3-8 This high TB incidence during the early phase of ART is, at least in part, the result of unmasking of subclinical TB during the initial rapid restoration of immune response.9,10 However, suboptimal TB case finding due to the use of poorly sensitive TB screening and diagnostic tools before the initiation of ART is also a contributory factor for this reported high TB incidence. Nicholas et al used respiratory symptoms lasting for a duration of ≥2 weeks as the sole screening criterion to identify TB suspects. This TB screening approach has been shown to have a low sensitivity and likely to miss a large proportion of prevalent cases at the time of ART initiation.11,12 Many of the cases identified as incident TB cases during the first 3 months of ART could have been identified before the initiation of ART with the use of a more sensitive TB-screening tool. The World Health Organization (WHO) recommends that people living with HIV (PLHIV) in resource-constrained settings should be actively screened for TB using an evidence-based symptom screening tool (any one of current cough, fever, night sweats, or weight loss) and that the identified TB suspect should be further evaluated.13 In addition to using a less sensitive TB-screening tool, Nicholas et al used sputum smear microscopy and chest radiography for the diagnosis of TB. These diagnostic tests have a low sensitivity to detect culture-positive TB among HIV-infected individuals and might have missed some prevalent TB cases at the initiation of ART.14

BACKGROUND: The World Health Organization recommends the screening of all people living with HIV for tuberculosis (TB) disease, followed by TB treatment, or isoniazid preventive therapy (IPT) when TB is excluded. However, the difficulty of reliably excluding TB disease has severely limited TB screening and IPT uptake in resource-limited settings. We conducted an individual participant data meta-analysis of primary studies, aiming to identify a sensitive TB screening rule. METHODS AND FINDINGS: We identified 12 studies that had systematically collected sputum specimens regardless of signs or symptoms, at least one mycobacterial culture, clinical symptoms, and HIV and TB disease status. Bivariate random-effects meta-analysis and the hierarchical summary relative operating characteristic curves were used to evaluate the screening performance of all combinations of variables of interest. TB disease was diagnosed in 557 (5.8%) of 9,626 people living with HIV. The primary analysis included 8,148 people living with HIV who could be evaluated on five symptoms from nine of the 12 studies. The median age was 34 years. The best performing rule was the presence of any one of: current cough (any duration), fever, night sweats, or weight loss. The overall sensitivity of this rule was 78.9% (95% confidence interval [CI] 58.3%-90.9%) and specificity was 49.6% (95% CI 29.2%-70.1%). Its sensitivity increased to 90.1% (95% CI 76.3%-96.2%) among participants selected from clinical settings and to 88.0% (95% CI 76.1%-94.4%) among those who were not previously screened for TB. Negative predictive value was 97.7% (95% CI 97.4%-98.0%) and 90.0% (95% CI 88.6%-91.3%) at 5% and 20% prevalence of TB among people living with HIV, respectively. Abnormal chest radiographic findings increased the sensitivity of the rule by 11.7% (90.6% versus 78.9%) with a reduction of specificity by 10.7% (49.6% versus 38.9%). CONCLUSIONS: Absence of all of current cough, fever, night sweats, and weight loss can identify a subset of people living with HIV who have a very low probability of having TB disease. A simplified screening rule using any one of these symptoms can be used in resource-constrained settings to identify people living with HIV in need of further diagnostic assessment for TB. Use of this algorithm should result in earlier TB diagnosis and treatment, and should allow for substantial scale-up of IPT.

OBJECTIVE: To measure progress in implementing co-trimoxazole prophylaxis (CTXp) (trimethoprim plus sulfamethoxazole) and isoniazid preventive therapy (IPT) policy recommendations, identify barriers to the development of national policies and pinpoint challenges to implementation. METHODS: In 2007 we conducted by e-mail a cross-sectional survey of World Health Organization (WHO) HIV/AIDS programme officers in 69 selected countries having a high burden of infection with HIV or HIV-associated tuberculosis (TB). The specially-designed, self-administered questionnaire contained items covering national policies for CTXp and IPT in people living with HIV, current level of implementation and barriers to developing or implementing these policies. FINDINGS: The 41 (59%) respondent countries, representing all WHO regions, comprised 85% of the global burden of HIV-associated TB and 82% of the global burden of HIV infection. Thirty-eight countries (93%) had an established national policy for CTXp, but only 66% of them (25/38) had achieved nationwide implementation. For IPT, 21 of 41 countries (51%) had a national policy but only 28% of them (6/21) had achieved nationwide implementation. Despite significant progress in the development of CTXp policy, the limited availability of co-trimoxazole for this indication and inadequate systems to manage drug supply impeded nationwide implementation. Inadequate intensified tuberculosis case-finding and concerns regarding isoniazid resistance were challenges to the development and implementation of national IPT policies. CONCLUSION: Despite progress in implementing WHO-recommended CTXp and IPT policies, these interventions remain underused. Urgent steps are required to facilitate the development and implementation of these policies.

BACKGROUND: High attack rates among vaccinated young adults reported during the 2006 mumps outbreak in the United States heightened concerns regarding mumps vaccine failure. METHODS: Serum specimens from university students and staff were tested for mumps immunoglobulin (Ig) G by enzyme immunoassay (EIA). A subset of participants vaccinated for < or =5 years and > or =15 years were tested by neutralizing antibody (NA) assay. Persons seronegative by EIA were offered a third dose of measles-mumps-rubella vaccine (MMR3), and serum specimens were obtained 7-10 days and 2-3 months after its administration. RESULTS: Overall, 94% (95% confidence interval [CI], 91%-96%) of the 440 participants were seropositive. No differences existed in seropositivity rates by sex, age, age at receipt of the second dose of MMR vaccine (MMR2), or time since receipt of MMR2 (P = .568). The geometric mean titer (GMT) of NA among persons vaccinated with MMR2 during the previous 1-5 years was 97 (95% CI, 64-148), whereas, among those vaccinated > or =15 years before blood collection, the GMT was 58 (95% CI, 44-76) (P = .065). After MMR3, 82% (14/17) and 91% (10/11) seroconverted in 7-10 days and 2-3 months, respectively. CONCLUSIONS: Lower levels of NA observed among persons who received MMR2 > or =15 years ago demonstrates antibody decay over time. MMR3 vaccination of most seronegative persons marked the capacity to mount an anamnestic response.