Tuberculosis Preventive Treatment Update - U.S. President's Emergency Plan for AIDS Relief, 36 Countries, 2016-2023.

Tuberculosis (TB) is the leading cause of death among persons with HIV. In 2022, an estimated 167,000 TB-related deaths occurred globally among persons with HIV. TB preventive treatment (TPT) helps prevent TB disease and is recommended for persons at high risk for developing TB, including those with HIV. TPT, when taken with antiretroviral treatment (ART), can reduce TB-attributable deaths among persons with HIV. In 2018, the U.S. President's Emergency Plan for AIDS Relief (PEPFAR) program committed to offer one course of TPT to all eligible clients receiving ART. This analysis describes trends in TPT initiation and completion among PEPFAR-supported programs in 36 countries in Africa, Central and South America, and Asia during fiscal years (FYs) 2017-2023. Overall, TPT initiation rates peaked in FY19, a possible sign of programmatic saturation. TPT initiation among clients who had been on ART <6 months reached 59%, and overall completion rates up to 87% were reported. Approximately 13 million persons with HIV have completed TPT since FY17, but widespread adoption of shorter regimens, patient-centered approaches, and electronic medical record systems might be needed to ensure full TPT coverage. Through PEPFAR's partnership with national HIV programs, TPT has become the standard of care for persons with HIV.

Bidirectional screening and testing for TB and COVID-19 among outpatient department attendees: outcome of an initial intervention in Ghana.

BACKGROUND: Tuberculosis (TB) remains a major public health threat in Ghana. The impact of COVID-19 resulted in a 15% decline of TB case notification in 2020 compared to 2019. To mitigate the impact on TB services, the Ghana National Tuberculosis Programme (NTP) introduced the bidirectional screening and testing for TB and COVID-19 in 2021. OBJECTIVE: To evaluate the yield of bidirectional screening and testing for TB and COVID-19 among facility attendees in the Greater Accra region. METHOD: We used secondary data obtained from the initial implementation stage of the bidirectional testing for TB and COVID-19 among COVID-19 and/or TB presumed cases in five health facilities in the Greater Accra Region from January to March 2021. To mitigate the impact of COVID-19 on TB services and accelerate TB case detection, the NTP of Ghana introduced bidirectional screening and testing for TB and COVID-19 in Greater Accra Region before scaling up at national level. RESULTS: A total of 208 presumed TB or COVID-19 cases were identified: 113 were tested for COVID-19 only, and 94 were tested for both TB and COVID-19, 1 was tested for TB only. Among presumed cases tested for COVID-19, 9.7% (95% CI, 5.6-13.7%) were tested positive. Whilst among the total presumed tested for TB, 13.7% (95% CI, 6.8-20.6%) were confirmed to have TB. Among the total 94 presumed cases tested for both TB and COVID-19, 11.7% (95% CI, 5.2-18.2%) were confirmed to have TB and 13.8% (95% CI, 6.9-20.8%) participants were COVID-19 positive and one participant (1.1%) had both COVID-19 and TB. CONCLUSION: Bidirectional screening and testing for TB and COVID-19 shows significant potential for improving overall case detection for the two diseases. The bidirectional screening and testing could be applicable to address a similar respiratory epidemic in the future that might have a masking effect on the response to TB disease.

QuantiFERON-TB Gold plus testing for the detection of LTBI among health care workers in major TB hospitals of the Northern Kyrgyz Republic.

BACKGROUND: Health care workers (HCW) are at increased risk of TB infection due to their close contact with infected patients with active TB. The objectives of the study were (1) to assess the prevalence of LTBI among HCW in the Northern Kyrgyz Republic, and (2) to determine the association of LTBI with job positions or departments. METHODS: HCWs from four TB hospitals in the Northern Kyrgyz Republic were tested with the interferon-gamma release assay (IGRA) Quantiferon-TB Gold plus (QFT) for the detection of an immune response to TB as marker of TB infection. Age was controlled for as a confounder. Univariate and multivariable analysis were performed using logistic regression to assess the association of the risk factors (job position, and department) with having a QTF positive result. Firth's penalized-likelihood estimates were used to account for the small-sample size. Pairwise comparisons using the Bonferroni correction (conservative) and comparisons without adjusting for multiple comparisons (unadjusted) were used to identify the categories where differences occurred. RESULTS: QFT yielded valid results for 404 HCW, with 189 (46.7%) having a positive test. In the National Tuberculosis Center there was an increased odds to have a positive QFT test for the position of physician (OR = 8.7, 95%, CI = 1.2-60.5, p = 0.03) and laboratory staff (OR = 19.8, 95% CI = 2.9-135.4, p < 0.01) when administration staff was used as the baseline. When comparing departments for all hospitals combined, laboratories (OR 7.65; 95%CI 2.3-24.9; p < 0.001), smear negative TB (OR 5.90; 95%CI 1.6-21.8; p = 0.008), surgery (OR 3.79; 95%CI 1.3-11.4; p = 0.018), and outpatient clinics (OR 3.80; 95%CI 1.1-13.0; p = 0.03) had higher odds of a positive QFT result than the admin department. Fifteen of the 49 HCW with follow-up tests converted from negative to positive at follow-up testing. CONCLUSIONS: This is the first report on prevalence and risk factors of LTBI for HCW in the Kyrgyz republic, and results indicate there may be an increased risk for LTBI among physicians and laboratory personnel. Further research should investigate gaps of infection control measures particularly for physicians and laboratory staff and lead to further improvement of policies.

Effectiveness and safety of fully oral modified shorter treatment regimen for multidrug-resistant tuberculosis in Georgia, 2019-2020.

Tuberculosis treatment is challenging, especially among people with drug-resistant forms of tuberculosis. The introduction of fully oral modified short treatment regimen has a great potential to shorten duration of treatment, improve safety and ultimately increase treatment success rate. In 2019 Georgia has piloted the modified fully oral shorter treatment regimen in a routine programmatic condition. Our study aimed to evaluate effectiveness and safety of the modified shorter treatment regimen in Georgia among the first 25 consecutively enrolled patients with rifampicin-resistant tuberculosis with proven sensitivity to fluoroquinolone and without prior exposure to second-line tuberculosis drugs. Regimen consisted of 9-month daily administration of bedaquilline, linezolid, levofloxacin, clofazimine and cycloserine. Study patients were enrolled between March-August 2019. We used a national electronic surveillance system, medical records and active TB drug-safety monitoring and management database to extract study related data. The mean age of the study participants was 48 years, 68% were male, 8% were HIV positive, 16% had diabetes and 12% tested positive for hepatitis C infection. The median time to culture conversion among 16 patients who were culture positive at treatment initiation was 1.0 (95% CI: 1.0-2.0) month. Of those, by the end of treatment 15 patients converted to negative. Out of the 25 patients in the study cohort 22 (88%) had successful treatment outcome, one patient (4%) died and two (8%) were lost to follow up. The regimen was largely well tolerated. Three patients (12%) experienced serious adverse events, of which in two cases were possibly related to TB drugs in the regimen. Seven patients developed adverse events of interest in eight instances, including musculoskeletal (twice), psychiatric, gastrointestinal disorders, hepatotoxicity, peripheral neuropathy, cardiotoxicity and myelosuppression (once each). In four patients (16%) the duration of the treatment was extended beyond nine months due to insufficient radiological improvements. Our findings demonstrate that good treatment outcomes are achievable in people with fluoroquinolone-sensitive tuberculosis within routine programmatic conditions using fully oral modified short treatment regimen. The extensive use of fully oral modified shorter treatment regimen in Georgia and other high priority countries in the World Health Organization European Region is warranted.

Tuberculosis Preventive Treatment Scale-Up Among Antiretroviral Therapy Patients - 16 Countries Supported by the U.S. President's Emergency Plan for AIDS Relief, 2017-2019.

Tuberculosis (TB) is the leading cause of death among persons living with human immunodeficiency virus (HIV) infection. In 2018, an estimated 251,000 persons living with HIV infection died from TB, accounting for one third of all HIV-related deaths and one sixth of all TB deaths (1). TB preventive treatment (TPT) is recommended by the World Health Organization (WHO) for persons living with HIV infection without active TB disease (i.e., adults with a negative clinical symptom screen for cough, fever, night sweats, or weight loss; and children with a negative clinical screen for cough, fever, contact with a person with TB, or poor weight gain) and either without* a tuberculin skin test result or with a known positive result (2). TPT decreases morbidity and mortality among persons living with HIV infection, independent of antiretroviral therapy (ART) (3); however, in 2017, fewer than 1 million of the estimated 21.3 million ART patients started TPT worldwide. Most patients receiving TPT were treated with 6 months of daily isoniazid (1,4). This report summarizes data on TB symptom screening and TPT initiation and completion among ART patients in 16 countries supported by the U.S. President's Emergency Plan for AIDS† Relief (PEPFAR) during April 1, 2017-March 31, 2019. During this period, these 16 countries accounted for approximately 90% of PEPFAR-supported ART patients. During April 1, 2017-September 30, 2018, TB symptom screening increased from 54% to 84%. Overall, nearly 2 million ART patients initiated TPT, and 60% completed treatment during October 1, 2017-March 31, 2019. Although TPT initiations increased substantially, completion among those who initiated TPT increased only from 55% to 66%. In addition to continuing gains in initiation, improving retention after initiation and identifying barriers to TPT completion are important to increase TPT scale-up and reduce global TB mortality.

Implementing contact tracing for tuberculosis in Kyrgyz Republic and risk factors for positivity using QuantiFERON-TB Gold plus.

BACKGROUND: Effective active case finding (ACF) activities are essential for early identification of new cases of active tuberculosis (TB) and latent TB infection (LTBI). Accurate diagnostics as well as the ability to identify contacts at high risk of infection are essential for ACF, and have not been systematically reported from Central Asia. The objective was to implement a pilot ACF program to determine the prevalence and risk factors for LTBI and active TB among contacts of individuals with TB in Kyrgyz Republic using Quantiferon-TB Gold plus (QuantiFERON). METHODS: An enhanced ACF project in the Kyrgyz Republic was implemented in which close and household (home) contacts of TB patients from the Issyk-Kul Oblast TB Center were visited at home. QuantiFERON and the tuberculin skin test (TST) alongside clinical and bacteriological examination were used to identify LTBI and active TB cases among contacts. The association for QuantiFERON positivity and risk factors were analysed and compared to TST results. RESULTS: Implementation of ACF with QuantiFERON involved close collaboration with the national sanitary and epidemiological services (SES) and laboratories in the Kyrgyz Republic. From 67 index cases, 296 contacts were enrolled of whom 253 had QuantiFERON or TST results; of those 103 contacts had LTBI (positive TST or IGRA), and four (1.4%) active TB cases were detected. Index case smear microscopy (OR 1.76) and high household density (OR 1.97) were significant risk factors for QuantiFERON positivity for all contacts. When stratified by age, association with smear positivity disappeared for children below 15 years. TST was not associated with any risk factor. CONCLUSIONS: This is the first time that ACF activities have been reported for Central Asia, and provide insight for implementation of effective ACF in the region. These ACF activities using QuantiFERON led to increase in the detection of LTBI and active cases, prior to patients seeking treatment. Household density should be taken into consideration as an important risk factor for the stratification of future ACF activities.

Feasibility of district wide screening of health care workers for tuberculosis in Zambia.

BACKGROUND: Many health care workers (HCWs) are at increased risk for tuberculosis (TB). The World Health Organization (WHO) recommends screening HCWs for TB in high burden settings but this is often not implemented in countries with a high TB incidence. We assessed the feasibility of TB screening among HCWs, including participation rate and yield, as part of a project introducing facility specific TB interventions. METHODS: This study had a cross-sectional design. HCWs (including paid staff and community volunteers) from 13 clinics and two hospitals in the Ndola district of Zambia participated. HCWs were screened by a designated person in their own facility. The agreed screening algorithm for HCWs included annual symptom screening, with sputum smear, culture (or Xpert) and chest x-ray offered to HCWs with at least one TB symptom, i.e. those with presumptive TB. RESULTS: A total of 1011 out of 1619 (62%) staff and 71 out of 138 (51%) community volunteers were screened within one year, total 1082/1757 (62%). Five percent (52/1082) of those screened were presumptive TB patients. Seventy-three percent (38/52) of presumptive TB patients received all diagnostic tests according to the agreed algorithm. Eighteen out of 1757 staff and volunteers combined were diagnosed with TB within a calendar year, showing a notified TB incidence of 1%. At least five of them were diagnosed during the screening appointment (0.5% of those screened). One of the 18 HCWs died of TB. Seventy-six percent (822/1082) of screened HCWs indicated that they already knew their HIV status. Screening was considered feasible if confidentiality can be guaranteed although challenges such as the time required for screening and sample transport were reported. CONCLUSIONS: It is feasible to conduct and implement screening programs for TB among HCWs in hospitals and clinics, and the notified incidence and yield is high. Advocacy is needed to educate managers and HCWs on the importance of screening and the implementation of locally relevant screening algorithms. It is essential to ensure access to TB infection control, diagnostics, treatment and confidential registration for HCW.

The global impact of COVID-19 on tuberculosis: A thematic scoping review, 2020-2023.

BACKGROUND: This thematic scoping review of publications sought to understand the global impact of COVID-19 on tuberculosis (TB), interpret the scope of resonating themes, and offer policy recommendations to stimulate TB recovery and future pandemic preparedness. DATA SOURCES: Publications were captured from three search engines, PubMed, EBSCO, and Google Scholar, and applicable websites written in English from January 1, 2020, to April 30, 2023. STUDY SELECTION: Our scoping review was limited to publications detailing the impact of COVID-19 on TB. Original research, reviews, letters, and editorials describing the deleterious and harmful--yet sometimes positive--impact of COVID-19 (sole exposure) on TB (sole outcome) were included. The objective was to methodically categorize the impacts into themes through a comprehensive review of selected studies to provide significant health policy guidance. DATA EXTRACTION: Two authors independently screened citations and full texts, while the third arbitrated when consensus was not met. All three performed data extraction. DATA SYNTHESIS/RESULTS: Of 1,755 screened publications, 176 (10%) covering 39 countries over 41 months met the inclusion criteria. By independently using a data extraction instrument, the three authors identified ten principal themes from each publication. These themes were later finalized through a consensus decision. The themes encompassed TB's care cascade, patient-centered care, psychosocial issues, and health services: 1) case-finding and notification (n = 45; 26%); 2) diagnosis and laboratory systems (n = 19; 10.7%) 3) prevention, treatment, and care (n = 22; 12.2%); 4) telemedicine/telehealth (n = 12; 6.8%); 5) social determinants of health (n = 14; 8%); 6) airborne infection prevention and control (n = 8; 4.6%); 7) health system strengthening (n = 22; 13%); 8) mental health (n = 13; 7.4%); 9) stigma (n = 11; 6.3%); and 10) health education (n = 10; 5.7%). LIMITATIONS: Heterogeneity of publications within themes. CONCLUSIONS: We identified ten globally generalizable themes of COVID-19's impact on TB. The impact and lessons learned from the themed analysis propelled us to draft public health policy recommendations to direct evidence-informed guidance that strengthens comprehensive global responses, recovery for TB, and future airborne pandemic preparedness.

PASS to End TB in Europe: Accelerated efforts on prevention and systematic screening to end tuberculosis in the WHO European Region by 2030.

OBJECTIVES: Outline the objectives, methods, and initial stages of the Prevention and Systematic Screening (PASS) initiative, a complimentary element of the innovative new approach of technical assistance mechanisms of WHO and its partners to countries aligned to the Regional TB Action Plan to End TB in the European Region by 2030. DESIGN: To provide an objective and critical overview of the existing landscape on TB epidemic in the WHO European Region (the European Region) and ii) identify the strategic significance of proactive measures aimed at approaching TB pre-elimination in the Region. RESULTS: Interventions primarily include systematic screening for TB disease and treatment for TB infection (TBI). CONCLUSIONS: PASS to End TB is an exemplary initiative of how technical and funding partners are joining hands to support national health programmes to work towards global commitments to curb major public health challenges like TB.

Meeting the 2030 END TB goals in the wake of COVID-19: A modelling study of countries in the USAID TB portfolio.

Progress towards the 2030 End TB goals has seen severe setbacks due to disruptions arising from the COVID-19 pandemic. For governments and international partner organizations supporting the global TB response, there is a need to assess what level of effort is now needed to reach these goals. Using mathematical modelling, we addressed this question for the countries being supported by the United States Agency for International Development (USAID). We aggregated the 24 countries in the USAID portfolio into three geographical country groups: South Asia; sub-Saharan Africa; and Central Asian Republics/Europe (CAR/EU). From 2023 onwards we modelled a combination of interventions acting at different stages of the care cascade, including improved diagnostics; reducing the patient care seeking delay; and the rollout of a disease-preventing vaccine from 2025 onwards. We found that in all three country groups, meeting the End TB goals by 2030 will require a combination of interventions acting at stages of the TB care cascade. Specific priorities may depend on country settings, for example with public-private mix playing an important role in countries in South Asia and elsewhere. When a vaccine becomes available, its required coverage to meet the 2030 goals will vary by setting, depending on the amount of preventive therapy that has already been implemented. Monitoring the number-needed-to-test to identify 1 person with TB in community settings can provide a useful measure of progress towards the End TB goals.

Strengthening the Operational Research Capacity of National Tuberculosis Control Programs: Necessity or Luxury?

'How to get research into practice: first get practice into research [...].

Tuberculosis Notification Trends and Treatment Outcomes in Penitentiary and Civilian Health Care Sectors in the WHO European Region.

SETTING: Tuberculosis (TB) morbidity in penitentiary sectors is one of the major barriers to ending TB in the World Health Organization (WHO) European Region. OBJECTIVES AND DESIGN: a comparative analysis of TB notification rates during 2014-2018 and of treatment outcomes in the civilian and penitentiary sectors in the WHO European Region, with an assessment of risks of developing TB among people experience incarceration. RESULTS: in the WHO European Region, incident TB rates in inmates were 4-24 times higher than in the civilian population. In 12 eastern Europe and central Asia (EECA) countries, inmates compared to civilians had higher relative risks of developing TB (RR = 25) than in the rest of the region (RR = 11), with the highest rates reported in inmates in Azerbaijan, Kazakhstan, Kyrgyzstan, Republic of Moldova, Russian Federation, and Ukraine. The average annual change in TB notification rates between 2014 and 2018 was -7.0% in the civilian sector and -10.9% in the penitentiary sector. A total of 15 countries achieved treatment success rates of over 85% for new penitentiary sector TB patients, the target for the WHO European Region. In 10 countries, there were no significant differences in treatment outcomes between civilian and penitentiary sectors. CONCLUSION: 42 out of 53 (79%) WHO European Region countries reported TB data for the selected time periods. Most countries in the region achieved a substantial decline in TB burden in prisons, which indicates the effectiveness of recent interventions in correctional institutions. Nevertheless, people who experience incarceration remain an at-risk population for acquiring infection, developing active disease and unfavourable treatment outcomes. Therefore, TB prevention and care practices in inmates need to be improved.

Collect Once, Use Many Times: Attaining Unified Metrics for Tuberculosis Preventive Treatment for People Living With HIV.

The World Health Organization (WHO) recommends providing tuberculosis preventive treatment (TPT) to all persons living with HIV and to all household contacts of persons with bacteriologically confirmed pulmonary tuberculosis disease. Regrettably, the absence of a harmonized data collection and management approach to TPT indicators has contributed to programmatic challenges at local, national, and global levels. However, in April 2020, the WHO launched the Consolidated HIV Strategic Information Guidelines, with an updated set of priority indicators. These guidelines recommend that Ministries of Health collect, report, and use data on TPT completion in addition to TPT initiation. Both indicators are reflected in the WHO's list of 15 core indicators for program management and are also required by the US President's Emergency Plan for AIDS Relief's Monitoring, Evaluation, and Reporting (MER) guidance. Although not perfectly harmonized, both frameworks now share essential indicator characteristics. Aligned indicators are necessary for robust strategic and operational planning, resource allocation, and data communication. "Collect once, use many times" is a best practice for strategic information management. Building harmonized and sustainable health systems will enable countries to successfully maintain essential HIV, tuberculosis, and other health services while combatting new health threats.

Turning threats into opportunities: how to implement and advance quality TB services for people with HIV during the COVID-19 pandemic and beyond.

INTRODUCTION: Until COVID-19, tuberculosis (TB) was the leading infectious disease killer globally, disproportionally affecting people with HIV. The COVID-19 pandemic is threatening the gains made in the fight against both diseases. DISCUSSION: Although crucial guidance has been released on how to maintain TB and HIV services during the pandemic, it is acknowledged that what was considered normal service pre-pandemic needs to improve to ensure that we rebuild person-centred, inclusive and quality healthcare services. The threat that the pandemic may reverse gains in the response to TB and HIV may be turned into an opportunity by pivoting to using proven differentiated service delivery approaches and innovative technologies that can be used to maintain care during the pandemic and accelerate improved service delivery in the long term. Models of care should be convenient, supportive and sufficiently differentiated to avoid burdensome clinic visits for medication pick-ups or directly observed treatments. Additionally, the pandemic has highlighted the chronic and short-sighted lack of investment in health systems and the need to prioritize research and development to close the gaps in TB diagnosis, treatment and prevention, especially for children and people with HIV. Most importantly, TB-affected communities and civil society must be supported to lead the planning, implementation and monitoring of TB and HIV services, especially in the time of COVID-19 where services have been disrupted, and to report on legal, policy and gender-related barriers to access experienced by affected people. This will help to ensure that TB services are held accountable by affected communities for delivering equitable access to quality, affordable and non-discriminatory services during and beyond the pandemic. CONCLUSIONS: Successfully reaching the related targets of ending TB and AIDS as public health threats by 2030 requires rebuilding of stronger, more inclusive health systems by advancing equitable access to quality TB services, including for people with HIV, both during and after the COVID-19 pandemic. Moreover, services must be rights-based, community-led and community-based, to ensure that no one is left behind.

Implementation of whole genome sequencing for tuberculosis diagnostics in a low-middle income, high MDR-TB burden country.

Whole genome sequencing (WGS) is revolutionary for diagnostics of TB and its mutations associated with drug-resistances, but its uptake in low- and middle-income countries is hindered by concerns of implementation feasibility. Here, we provide a proof of concept for its successful implementation in such a setting. WGS was implemented in the Kyrgyz Republic. We estimated needs of up to 55 TB-WGS per week and chose the MiSeq platform (Illumina, USA) because of its capacity of up to 60 TB-WGS per week. The project's timeline was completed in 93-weeks. Costs of large equipment and accompanying costs were 222,065 USD and 8462 USD, respectively. The first 174 WGS costed 277 USD per sequence, but this was skewed by training inefficiencies. Based on real prices and presuming optimal utilization of WGS capacities, WGS costs could drop to 167 and 141 USD per WGS using MiSeq Reagent Kits v2 (500-cycles) and v3 (600-cycles), respectively. Five trainings were required to prepare the staff for autonomous WGS which cost 48,250 USD. External assessment confirmed excellent performance of WGS by the Kyrgyz laboratory in an interlaboratory comparison of 30 M. tuberculosis genomes showing complete agreeance of results.

Drug-resistant tuberculosis in eastern Europe and central Asia: a time-series analysis of routine surveillance data.

BACKGROUND: Among all WHO regions, the WHO European Region has the highest proportion of drug-resistant tuberculosis among new and retreated cases. The 18 high-priority countries in eastern Europe and central Asia account for 85% of the tuberculosis incidence and more than 90% of drug-resistant tuberculosis cases emerging in the region. We aimed to analyse time-series trends in notification rates of drug-resistant tuberculosis among new tuberculosis cases in the 18 high-priority countries in the WHO European Region. METHODS: We used country data stored in WHO's global tuberculosis database. For each country, we calculated annual notification rates per 100 000 population of new tuberculosis cases and of drug-resistant tuberculosis among new cases reported from Jan 1, 2000, to Dec 31, 2017. We computed annual percentage changes of notification rates and identified time-points of significant change in trends using the joinpoint regression method. FINDINGS: All 17 countries with data (no data available from Turkmenistan) showed a significant decline in new tuberculosis notification rates in the most recent years since the last joinpoint if one was identified. Notification rates of drug-resistant tuberculosis showed diverse trends, with substantial year-to-year variation. In the most recent years, notification rates of drug-resistant tuberculosis among new tuberculosis cases were decreasing in two countries (Estonia and Latvia), increasing in eight countries (Azerbaijan, Kyrgyzstan, Moldova [Republic of Moldova], Romania, Russia [Russian Federation], Tajikistan, Ukraine, and Uzbekistan), and stable in seven countries (Armenia, Belarus, Bulgaria, Georgia, Kazakhstan, Lithuania, and Turkey). INTERPRETATION: Our findings suggest that countries in the WHO European Region are more successful in controlling drug-susceptible tuberculosis than drug-resistant forms, and as a result, the proportion of drug-resistant strains among newly notified patients with tuberculosis is increasing in many settings. Two countries showed that it is possible to decrease incidence of both drug-susceptible and drug-resistant tuberculosis. If no additional efforts are made in prevention and care of patients with drug-resistant tuberculosis, further decline of the tuberculosis burden will be halted. Further studies are needed to investigate the success stories and document the most effective interventions to reach the target to end tuberculosis by 2030. FUNDING: United States Agency for International Development.

The potential impact of the COVID-19 pandemic on the tuberculosis epidemic a modelling analysis.

BACKGROUND: Routine services for tuberculosis (TB) are being disrupted by stringent lockdowns against the novel SARS-CoV-2 virus. We sought to estimate the potential long-term epidemiological impact of such disruptions on TB burden in high-burden countries, and how this negative impact could be mitigated. METHODS: We adapted mathematical models of TB transmission in three high-burden countries (India, Kenya and Ukraine) to incorporate lockdown-associated disruptions in the TB care cascade. The anticipated level of disruption reflected consensus from a rapid expert consultation. We modelled the impact of these disruptions on TB incidence and mortality over the next five years, and also considered potential interventions to curtail this impact. FINDINGS: Even temporary disruptions can cause long-term increases in TB incidence and mortality. If lockdown-related disruptions cause a temporary 50% reduction in TB transmission, we estimated that a 3-month suspension of TB services, followed by 10 months to restore to normal, would cause, over the next 5 years, an additional 1⋅19 million TB cases (Crl 1⋅06-1⋅33) and 361,000 TB deaths (CrI 333-394 thousand) in India, 24,700 (16,100-44,700) TB cases and 12,500 deaths (8.8-17.8 thousand) in Kenya, and 4,350 (826-6,540) cases and 1,340 deaths (815-1,980) in Ukraine. The principal driver of these adverse impacts is the accumulation of undetected TB during a lockdown. We demonstrate how long term increases in TB burden could be averted in the short term through supplementary "catch-up" TB case detection and treatment, once restrictions are eased. INTERPRETATION: Lockdown-related disruptions can cause long-lasting increases in TB burden, but these negative effects can be mitigated with rapid restoration of TB services, and targeted interventions that are implemented as soon as restrictions are lifted. FUNDING: USAID and Stop TB Partnership.

New opportunities in tuberculosis prevention: implications for people living with HIV.

INTRODUCTION: Tuberculosis (TB) is a leading cause of mortality among people living with HIV (PLHIV). An invigorated global END TB Strategy seeks to increase efforts in scaling up TB preventive therapy (TPT) as a central intervention for HIV programmes in an effort to contribute to a 90% reduction in TB incidence and 95% reduction in mortality by 2035. TPT in PLHIV should be part of a comprehensive approach to reduce TB transmission, illness and death that also includes TB active case-finding and prompt, effective and timely initiation of anti-TB therapy among PLHIV. However, the use and implementation of preventive strategies has remained deplorably inadequate and today TB prevention among PLHIV has become an urgent priority globally. DISCUSSION: We present a summary of the current and novel TPT regimens, including current evidence of use with antiretroviral regimens (ART). We review challenges and opportunities to scale-up TB prevention within HIV programmes, including the use of differentiated care approaches and demand creation for effective TB/HIV services delivery. TB preventive vaccines and diagnostics, including optimal algorithms, while important topics, are outside of the focus of this commentary. CONCLUSIONS: A number of new tools and strategies to make TPT a standard of care in HIV programmes have become available. The new TPT regimens are safe and effective and can be used with current ART, with attention being paid to potential drug-drug interactions between rifamycins and some classes of antiretrovirals. More research and development is needed to optimize TPT for small children, pregnant women and drug-resistant TB (DR-TB). Effective programmatic scale-up can be supported through context-adapted demand creation strategies and the inclusion of TPT in client-centred services, such as differentiated service delivery (DSD) models. Robust collaboration between the HIV and TB programmes represents a unique opportunity to ensure that TB, a preventable and curable condition, is no longer the number one cause of death in PLHIV.