Long-term outcomes of SARS-CoV-2 variants and other respiratory infections: evidence from the Virus Watch prospective cohort in England.

This study compared the likelihood of long-term sequelae following infection with SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals. Participants (n=5,630) were drawn from Virus Watch, a prospective community cohort investigating SARS-CoV-2 epidemiology in England. Using logistic regression, we compared predicted probabilities of developing long-term symptoms (>2 months) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status. SARS-CoV-2 infection during early variant periods up to Omicron BA.1 was associated with greater probability of long-term sequalae (adjusted predicted probability (PP) range 0.27, 95% CI = 0.22-0.33 to 0.34, 95% CI = 0.25-0.43) compared with later Omicron sub-variants (PP range 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, all post-infection estimates substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00, 0.02 to 0.03, 95% CI 0.01-0.06). Variant was an important predictor of SARS-CoV-2 post-infection sequalae, with recent Omicron sub-variants demonstrating similar probabilities to other contemporaneous ARIs. Further aetiological investigation including between-pathogen comparison is recommended.

Racism, xenophobia, discrimination, and the determination of health.

This Series shows how racism, xenophobia, discrimination, and the structures that support them are detrimental to health. In this first Series paper, we describe the conceptual model used throughout the Series and the underlying principles and definitions. We explore concepts of epistemic injustice, biological experimentation, and misconceptions about race using a historical lens. We focus on the core structural factors of separation and hierarchical power that permeate society and result in the negative health consequences we see. We are at a crucial moment in history, as populist leaders pushing the politics of hate have become more powerful in several countries. These leaders exploit racism, xenophobia, and other forms of discrimination to divide and control populations, with immediate and long-term consequences for both individual and population health. The COVID-19 pandemic and transnational racial justice movements have brought renewed attention to persisting structural racial injustice.

Racism, xenophobia, and discrimination: mapping pathways to health outcomes.

Despite being globally pervasive, racism, xenophobia, and discrimination are not universally recognised determinants of health. We challenge widespread beliefs related to the inevitability of increased mortality and morbidity associated with particular ethnicities and minoritised groups. In refuting that racial categories have a genetic basis and acknowledging that socioeconomic factors offer incomplete explanations in understanding these health disparities, we examine the pathways by which discrimination based on caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour affect health. Discrimination based on these categories, although having many unique historical and cultural contexts, operates in the same way, with overlapping pathways and health effects. We synthesise how such discrimination affects health systems, spatial determination, and communities, and how these processes manifest at the individual level, across the life course, and intergenerationally. We explore how individuals respond to and internalise these complex mechanisms psychologically, behaviourally, and physiologically. The evidence shows that racism, xenophobia, and discrimination affect a range of health outcomes across all ages around the world, and remain embedded within the universal challenges we face, from COVID-19 to the climate emergency.

Confronting the consequences of racism, xenophobia, and discrimination on health and health-care systems.

Racism, xenophobia, and discrimination are key determinants of health and equity and must be addressed for improved health outcomes. We conclude that far broader, deeper, transformative action is needed compared with current measures to tackle adverse effects of racism on health. To challenge the structural drivers of racism and xenophobia, anti-racist action and other wider measures that target determinants should implement an intersectional approach to effectively address the causes and consequences of racism within a population. Structurally, legal instruments and human rights law provide a robust framework to challenge the pervasive drivers of disadvantage linked to caste, ethnicity, Indigeneity, migratory status, race, religion, and skin colour. Actions need to consider the historical, economic, and political contexts in which the effects of racism, xenophobia, and discrimination affect health. We propose several specific actions: a commission that explores how we action the approaches laid out in this paper; building a conversation and a series of events with international multilateral agency stakeholders to raise the issue and profile of racism, xenophobia, and discrimination within health; and using our multiple platforms to build coalitions, expand knowledge, highlight inequities, and advocate for change across the world.

Population health outcomes in Nigeria compared with other west African countries, 1998-2019: a systematic analysis for the Global Burden of Disease Study.

BACKGROUND: Population-level health and mortality data are crucial for evidence-informed policy but scarce in Nigeria. To fill this gap, we undertook a comprehensive assessment of the burden of disease in Nigeria and compared outcomes to other west African countries. METHODS: In this systematic analysis, using data and results of the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, we analysed patterns of mortality, years of life lost (YLLs), years lived with disability (YLDs), life expectancy, healthy life expectancy (HALE), and health system coverage for Nigeria and 15 other west African countries by gender in 1998 and 2019. Estimates of all-age and age-standardised disability-adjusted life-years for 369 diseases and injuries and 87 risk factors are presented for Nigeria. Health expenditure per person and gross domestic product were extracted from the World Bank repository. FINDINGS: Between 1998 and 2019, life expectancy and HALE increased in Nigeria by 18% to 64·3 years (95% uncertainty interval [UI] 62·2-66·6), mortality reduced for all age groups for both male and female individuals, and health expenditure per person increased from the 11th to third highest in west Africa by 2018 (US$18·6 in 2001 to $83·75 in 2018). Nonetheless, relative outcomes remained poor; Nigeria ranked sixth in west Africa for age-standardised mortality, seventh for HALE, tenth for YLLs, 12th for health system coverage, and 14th for YLDs in 2019. Malaria (5176·3 YLLs per 100 000 people, 95% UI 2464·0-9591·1) and neonatal disorders (4818·8 YLLs per 100 000, 3865·9-6064·2) were the leading causes of YLLs in Nigeria in 2019. Nigeria had the fourth-highest under-five mortality rate for male individuals (2491·8 deaths per 100 000, 95% UI 1986·1-3140·1) and female individuals (2117·7 deaths per 100 000, 1756·7-2569·1), but among the lowest mortality for men older than 55 years. There was evidence of a growing non-communicable disease burden facing older Nigerians. INTERPRETATION: Health outcomes remain poor in Nigeria despite higher expenditure since 2001. Better outcomes in countries with equivalent or lower health expenditure suggest health system strengthening and targeted intervention to address unsafe water sources, poor sanitation, malnutrition, and exposure to air pollution could substantially improve population health. FUNDING: The Bill & Melinda Gates Foundation.

Drivers determining tuberculosis disease screening yield in four European screening programmes: a comparative analysis.

BACKGROUND: The World Health Organization End TB Strategy emphasises screening for early diagnosis of tuberculosis (TB) in high-risk groups, including migrants. We analysed key drivers of TB yield differences in four large migrant TB screening programmes to inform TB control planning and feasibility of a European approach. METHODS: We pooled individual TB screening episode data from Italy, the Netherlands, Sweden and the UK, and analysed predictors and interactions for TB case yield using multivariable logistic regression models. RESULTS: Between 2005 and 2018 in 2 302 260 screening episodes among 2 107 016 migrants to four countries, the programmes identified 1658 TB cases (yield 72.0 (95% CI 68.6-75.6) per 100 000). In logistic regression analysis, we found associations between TB screening yield and age (≥55 years: OR 2.91 (95% CI 2.24-3.78)), being an asylum seeker (OR 3.19 (95% CI 1.03-9.83)) or on a settlement visa (OR 1.78 (95% CI 1.57-2.01)), close TB contact (OR 12.25 (95% CI 11.73-12.79)) and higher TB incidence in the country of origin. We demonstrated interactions between migrant typology and age, as well as country of origin. For asylum seekers, the elevated TB risk remained similar above country of origin incidence thresholds of 100 per 100 000. CONCLUSIONS: Key determinants of TB yield included close contact, increasing age, incidence in country of origin and specific migrant groups, including asylum seekers and refugees. For most migrants such as UK students and workers, TB yield significantly increased with levels of incidence in the country of origin. The high, country of origin-independent TB risk in asylum seekers above a 100 per 100 000 threshold could reflect higher transmission and re-activation risk of migration routes, with implications for selecting populations for TB screening.

Previous BCG vaccination is associated with less severe clinical progression of COVID-19.

BACKGROUND: BCG vaccination, originally used to prevent tuberculosis, is known to "train" the immune system to improve defence against viral respiratory infections. We investigated whether a previous BCG vaccination is associated with less severe clinical progression of COVID-19 METHODS: A case-control study comparing the proportion with a BCG vaccine scar (indicating previous vaccination) in cases and controls presenting with COVID-19 to health units in Brazil. Cases were subjects with severe COVID-19 (O2 saturation < 90%, severe respiratory effort, severe pneumonia, severe acute respiratory syndrome, sepsis, and septic shock). Controls had COVID-19 not meeting the definition of "severe" above. Unconditional regression was used to estimate vaccine protection against clinical progression to severe disease, with strict control for age, comorbidity, sex, educational level, race/colour, and municipality. Internal matching and conditional regression were used for sensitivity analysis. RESULTS: BCG was associated with high protection against COVID-19 clinical progression, over 87% (95% CI 74-93%) in subjects aged 60 or less and 35% (95% CI - 44-71%) in older subjects. CONCLUSIONS: This protection may be relevant for public health in settings where COVID-19 vaccine coverage is still low and may have implications for research to identify vaccine candidates for COVID-19 that are broadly protective against mortality from future variants. Further research into the immunomodulatory effects of BCG may inform COVID-19 therapeutic research.

The use of Traditional Medicines for Sexual Enhancement in Northern Nigeria.

BACKGROUND: There is a paucity of information on the use of traditional medicine TM to improve sexual performance. This study aims to assess the prevalence and self-reported adverse effects associated with the use of TM as a sexual enhancer in northern Nigeria. METHODS: The study was a cross-sectional design among adults aged 18 years and above, who are residing in northern Nigeria. A mixed-mode approach was utilized using face-to-face interviews and an online survey. For the online survey, a link to the questionnaire was shared on the social media platforms of the targeted participants. RESULTS: A total of 794 eligible participants completed the survey over the six weeks. Of this number, 508 reported ever using TM for sexual enhancement, with a prevalence of 64% (95% CI: 60.5, 67.3). About 30 (3.8%) reported daily use, 49 (4.9%) weekly, 65 (8.2%) monthly and 473 (59.6%) as when needed. Islamic medicine was the most frequently implicated TM. Most respondents obtained it TM practitioners 213 (26.8%). Participants 164 (20.7%) reported experiencing side effects, mostly headaches 59 (35.9%), and 31 (3.9%) were severe (required hospitalization). Predictors of TM use for sexual enhancement were found to be gender, marital status, number of wives, ethnicity, educational level, and lifestyle. CONCLUSION: The use of TM for sexual enhancement is common among the adult population in northern Nigeria. One out of five of the users reported an adverse event. Therefore, there is a need for improved awareness of the safe use of the TM in the community, especially among females, those with multiple wives, a low education level, and poor lifestyles.

Effect of Nigeria Presidential Task Force on COVID-19 Pandemic, Nigeria.

Nigeria had a confirmed case of COVID-19 on February 28, 2020. On March 17, 2020, the Nigerian Government inaugurated the Presidential Task Force (PTF) on COVID-19 to coordinate the country's multisectoral intergovernmental response. The PTF developed the National COVID-19 Multisectoral Pandemic Response Plan as the blueprint for implementing the response plans. The PTF provided funding, coordination, and governance for the public health response and executed resource mobilization and social welfare support, establishing the framework for containment measures and economic reopening. Despite the challenges of a weak healthcare infrastructure, staff shortages, logistic issues, commodity shortages, currency devaluation, and varying state government cooperation, high-level multisectoral PTF coordination contributed to minimizing the effects of the pandemic through early implementation of mitigation efforts, supported by a strong collaborative partnership with bilateral, multilateral, and private-sector organizations. We describe the lessons learned from the PTF COVID-19 for future multisectoral public health response.

Optima TB: A tool to help optimally allocate tuberculosis spending.

Approximately 85% of tuberculosis (TB) related deaths occur in low- and middle-income countries where health resources are scarce. Effective priority setting is required to maximise the impact of limited budgets. The Optima TB tool has been developed to support analytical capacity and inform evidence-based priority setting processes for TB health benefits package design. This paper outlines the Optima TB framework and how it was applied in Belarus, an upper-middle income country in Eastern Europe with a relatively high burden of TB. Optima TB is a population-based disease transmission model, with programmatic cost functions and an optimisation algorithm. Modelled populations include age-differentiated general populations and higher-risk populations such as people living with HIV. Populations and prospective interventions are defined in consultation with local stakeholders. In partnership with the latter, demographic, epidemiological, programmatic, as well as cost and spending data for these populations and interventions are then collated. An optimisation analysis of TB spending was conducted in Belarus, using program objectives and constraints defined in collaboration with local stakeholders, which included experts, decision makers, funders and organisations involved in service delivery, support and technical assistance. These analyses show that it is possible to improve health impact by redistributing current TB spending in Belarus. Specifically, shifting funding from inpatient- to outpatient-focused care models, and from mass screening to active case finding strategies, could reduce TB prevalence and mortality by up to 45% and 50%, respectively, by 2035. In addition, an optimised allocation of TB spending could lead to a reduction in drug-resistant TB infections by 40% over this period. This would support progress towards national TB targets without additional financial resources. The case study in Belarus demonstrates how reallocations of spending across existing and new interventions could have a substantial impact on TB outcomes. This highlights the potential for Optima TB and similar modelling tools to support evidence-based priority setting.

The impact of SARS-CoV-2 treatment on the cardiovascular system: an updated review.

The coronavirus disease-2019 (COVID-19) pandemic has become a major global health problem. COVID-19 is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and exhibits pulmonary and extrapulmonary effects, including cardiovascular involvement. There are several attempts to identify drugs that could treat COVID-19. Moreover, many patients infected with COVID-19 have underlying diseases, particularly cardiovascular diseases. These patients are more likely to develop severe illnesses and would require optimized treatment strategies. The current study gathered information from various databases, including relevant studies, reviews, trials, or meta-analyses until April 2022 to identify the impact of SARS-CoV-2 treatment on the cardiovascular system. Studies have shown that the prognosis of patients with underlying cardiovascular disease is worsened by COVID-19, with some COVID-19 medications interfering with the cardiovascular system. The COVID-19 treatment strategy should consider many factors and parameters to avoid medication-induced cardiac injury, mainly in elderly patients. Therefore, this article provides a synthesis of evidence on the impact of different COVID-19 medications on the cardiovascular system and related disease conditions.

Leaving no one behind: Older African women's rights to sexual and reproductive health.

Despite growing agreement on the importance of sexual and reproductive health and rights at all stages of human development, the link between ageing and the sexual and reproductive rights of older African women has been an overlooked topic of research and policy formulation. This commentary takes a multidisciplinary approach to highlighting older African women's sexual and reproductive health and rights, identifying extant legislative frameworks, shortcomings, and strategies to improve their implementation. An examination of the legislative frameworks in place demonstrates that they are insufficient for the full implementation of these rights. As a result, a deliberate effort is required to correct historical wrongs and preserve older women's sexual and reproductive health and rights.

Using molecular testing and whole-genome sequencing for tuberculosis diagnosis in a low-burden setting: a cost-effectiveness analysis using transmission-dynamic modelling.

BACKGROUND: Despite progress in TB control in low-burden countries like England and Wales, there are still diagnostic delays. Molecular testing and/or whole-genome sequencing (WGS) provide more rapid diagnosis but their cost-effectiveness is relatively unexplored in low-burden settings. METHODS: An integrated transmission-dynamic health economic model is used to assess the cost-effectiveness of using WGS to replace culture-based drug-sensitivity testing, versus using molecular testing versus combined use of WGS and molecular testing, for routine TB diagnosis. The model accounts for the effects of faster appropriate treatment in reducing transmission, benefiting health and reducing future treatment costs. Cost-effectiveness is assessed using incremental net benefit (INB) over a 10-year horizon with a quality-adjusted life-year valued at £20 000, and discounting at 3.5% per year. RESULTS: WGS shortens the time to drug sensitivity testing and treatment modification where necessary, reducing treatment and hospitalisation costs, with an INB of £7.1 million. Molecular testing shortens the time to TB diagnosis and treatment. Initially, this causes an increase in annual costs of treatment, but averting transmissions and future active TB disease subsequently, resulting in cost savings and health benefits to achieve an INB of £8.6 million (GeneXpert MTB/RIF) or £11.1 million (Xpert-Ultra). Combined use of Xpert-Ultra and WGS is the optimal strategy we consider, with an INB of £16.5 million. CONCLUSION: Routine use of WGS or molecular testing is cost-effective in a low-burden setting, and combined use is the most cost-effective option. Adoption of these technologies can help low-burden countries meet the WHO End TB Strategy milestones, particularly the UK, which still has relatively high TB rates.

Cross-Reactivity of Two SARS-CoV-2 Serological Assays in a Setting Where Malaria Is Endemic.

Accurate SARS-CoV-2 serological assays are critical for COVID-19 serosurveillance. However, previous studies have indicated possible cross-reactivity of these assays, including in areas where malaria is endemic. We tested 213 well-characterized prepandemic samples from Nigeria using two SARS-CoV-2 serological assays, Abbott Architect IgG and Euroimmun NCP IgG assay, both targeting SARS-CoV-2 nucleocapsid protein. To assess antibody binding strength, an avidity assay was performed on these samples and on plasma from SARS-CoV-2 PCR-positive persons. Thirteen (6.1%) of 212 samples run on the Abbott assay and 38 (17.8%) of 213 run on the Euroimmun assay were positive. Anti-Plasmodium IgG levels were significantly higher among false positives for both Abbott and Euroimmun; no association was found with active Plasmodium falciparum infection. An avidity assay using various concentrations of urea wash in the Euroimmun assay reduced loosely bound IgG: of 37 positive/borderline prepandemic samples, 46%, 86%, 89%, and 97% became negative using 2 M, 4 M, 5 M, and 8 M urea washes, respectively. The wash slightly reduced avidity of antibodies from SARS-CoV-2 patients within 28 days of PCR confirmation; thereafter, avidity increased for all urea concentrations except 8 M. This validation found moderate to substantial cross-reactivity on two SARS-CoV-2 serological assays using samples from a setting where malaria is endemic. A simple urea wash appeared to alleviate issues of cross-reactivity.

Quantitative IFN-γ Release Assay and Tuberculin Skin Test Results to Predict Incident Tuberculosis. A Prospective Cohort Study.

Rationale: Development of diagnostic tools with improved predictive value for tuberculosis (TB) is a global research priority.Objectives: We evaluated whether implementing higher diagnostic thresholds than currently recommended for QuantiFERON Gold-in-Tube (QFT-GIT), T-SPOT.TB, and the tuberculin skin test (TST) might improve prediction of incident TB.Methods: Follow-up of a UK cohort of 9,610 adult TB contacts and recent migrants was extended by relinkage to national TB surveillance records (median follow-up 4.7 yr). Incidence rates and rate ratios, sensitivities, specificities, and predictive values for incident TB were calculated according to ordinal strata for quantitative results of QFT-GIT, T-SPOT.TB, and TST (with adjustment for prior bacillus Calmette-Guérin [BCG] vaccination).Measurements and Main Results: For all tests, incidence rates and rate ratios increased with the magnitude of the test result (P < 0.0001). Over 3 years' follow-up, there was a modest increase in positive predictive value with the higher thresholds (3.0% for QFT-GIT ≥0.35 IU/ml vs. 3.6% for ≥4.00 IU/ml; 3.4% for T-SPOT.TB ≥5 spots vs. 5.0% for ≥50 spots; and 3.1% for BCG-adjusted TST ≥5 mm vs. 4.3% for ≥15 mm). As thresholds increased, sensitivity to detect incident TB waned for all tests (61.0% for QFT-GIT ≥0.35 IU/ml vs. 23.2% for ≥4.00 IU/ml; 65.4% for T-SPOT.TB ≥5 spots vs. 27.2% for ≥50 spots; 69.7% for BCG-adjusted TST ≥5 mm vs. 28.1% for ≥15 mm).Conclusions: Implementation of higher thresholds for QFT-GIT, T-SPOT.TB, and TST modestly increases positive predictive value for incident TB, but markedly reduces sensitivity. Novel biomarkers or validated multivariable risk algorithms are required to improve prediction of incident TB.

Current Status of Endoplasmic Reticulum Stress in Type II Diabetes.

The endoplasmic reticulum (ER) plays a multifunctional role in lipid biosynthesis, calcium storage, protein folding, and processing. Thus, maintaining ER homeostasis is essential for cellular functions. Several pathophysiological conditions and pharmacological agents are known to disrupt ER homeostasis, thereby, causing ER stress. The cells react to ER stress by initiating an adaptive signaling process called the unfolded protein response (UPR). However, the ER initiates death signaling pathways when ER stress persists. ER stress is linked to several diseases, such as cancer, obesity, and diabetes. Thus, its regulation can provide possible therapeutic targets for these. Current evidence suggests that chronic hyperglycemia and hyperlipidemia linked to type II diabetes disrupt ER homeostasis, thereby, resulting in irreversible UPR activation and cell death. Despite progress in understanding the pathophysiology of the UPR and ER stress, to date, the mechanisms of ER stress in relation to type II diabetes remain unclear. This review provides up-to-date information regarding the UPR, ER stress mechanisms, insulin dysfunction, oxidative stress, and the therapeutic potential of targeting specific ER stress pathways.

Evaluation of resistance to gastrointestinal helminth nematodes in two naturally infected indigenous Nigerian goat breeds.

Tropical goat breeds often have at least modest resistance to gastrointestinal nematode parasites (GIN), but enhancement of GIN resistance is important for breed improvement. This study compared changes in fecal egg count (FEC), packed cell volume, and body weight in Red Sokoto (RS) and Sahelian (SH) male and female weaner kids and adult goats. The RS is found throughout Nigeria, but the SH is found only in the arid Sahel. Goats were evaluated fortnightly for 20 times (MT) under normal grazing conditions and natural GIN infection over 9.5 months, beginning in the dry season (November) and ending at the end of the subsequent wet season (August). Animals were dewormed at the start of the study and during the rainy season (MT 18). Breed differences in FEC and PCV were not observed in weaners. Weaner females had lower FEC than males but were rapidly re-infected after deworming, perhaps in association with attainment of puberty. Adult SH goats of both sexes had lower FEC than RS goats in MT 8 through 17, suggesting a stronger acquired immune response. The FEC in lactating females of both breeds increased rapidly after deworming, to ≥ 3000 eggs per gram of feces at MT 19 and 20. The optimal time to evaluate GIN resistance in weaners was during the early rainy season, but the decision to focus on the initial high FEC near MT 15 or wait until mobilization of the acquired immune response near MT 17 requires further consideration.

Effectiveness of BCG Vaccination Against Mycobacterium tuberculosis Infection in Adults: A Cross-sectional Analysis of a UK-Based Cohort.

BACKGROUND: BCG appears to reduce acquisition of Mycobacterium tuberculosis infection in children, measured using interferon-gamma release assays (IGRAs). We explored whether BCG vaccination continues to be associated with decreased prevalence of M. tuberculosis infection in adults. METHODS: We conducted a cross-sectional analysis of data from adult contacts of tuberculosis cases participating in a UK cohort study. Vaccine effectiveness (VE) of BCG, ascertained based on presence of a scar or vaccination history, against latent tuberculosis infection (LTBI), measured via IGRA, was assessed using multivariable logistic regression. The effects of age at BCG and time since vaccination were also explored. RESULTS: Of 3453 recent tuberculosis contacts, 27.5% had LTBI. There was strong evidence of an association between BCG and LTBI (adjusted odds ratio = 0.70; 95% confidence interval, .56-.87; P = .0017) yielding a VE of 30%. VE declined with time since vaccination but there was evidence that LTBI prevalence was lower amongst vaccinated individuals even >20 years after vaccination, compared with nonvaccinated participants. CONCLUSIONS: BCG is associated with lower prevalence of LTBI in adult contacts of tuberculosis. These results contribute to growing evidence that suggests BCG may protect against M. tuberculosis infection as well as disease. This has implications for immunization programs, vaccine development, and tuberculosis control efforts worldwide. CLINICAL TRIALS REGISTRATION: NCT01162265.

Blood Transcriptomic Stratification of Short-term Risk in Contacts of Tuberculosis.

BACKGROUND: The highest risk of tuberculosis arises in the first few months after exposure. We reasoned that this risk reflects incipient disease among tuberculosis contacts. Blood transcriptional biomarkers of tuberculosis may predate clinical diagnosis, suggesting they offer improved sensitivity to detect subclinical incipient disease. Therefore, we sought to test the hypothesis that refined blood transcriptional biomarkers of active tuberculosis will improve stratification of short-term disease risk in tuberculosis contacts. METHODS: We combined analysis of previously published blood transcriptomic data with new data from a prospective human immunodeficiency virus (HIV)-negative UK cohort of 333 tuberculosis contacts. We used stability selection as an alternative computational approach to identify an optimal signature for short-term risk of active tuberculosis and evaluated its predictive value in independent cohorts. RESULTS: In a previously published HIV-negative South African case-control study of patients with asymptomatic Mycobacterium tuberculosis infection, a novel 3-gene transcriptional signature comprising BATF2, GBP5, and SCARF1 achieved a positive predictive value (PPV) of 23% for progression to active tuberculosis within 90 days. In a new UK cohort of 333 HIV-negative tuberculosis contacts with a median follow-up of 346 days, this signature achieved a PPV of 50% (95% confidence interval [CI], 15.7-84.3) and negative predictive value of 99.3% (95% CI, 97.5-99.9). By comparison, peripheral blood interferon gamma release assays in the same cohort achieved a PPV of 5.6% (95% CI, 2.1-11.8). CONCLUSIONS: This blood transcriptional signature provides unprecedented opportunities to target therapy among tuberculosis contacts with greatest risk of incident disease.