Improving measurement of tuberculosis care cascades to enhance people-centred care.

Care cascades represent the proportion of people reaching milestones in care for a disease and are widely used to track progress towards global targets for HIV and other diseases. Despite recent progress in estimating care cascades for tuberculosis (TB) disease, they have not been routinely applied at national and subnational levels, representing a lost opportunity for public health impact. As researchers who have estimated TB care cascades in high-incidence countries (India, Madagascar, Nigeria, Peru, South Africa, and Zambia), we describe the utility of care cascades and identify measurement challenges, including the lack of population-based disease burden data and electronic data capture, the under-reporting of people with TB navigating fragmented and privatised health systems, the heterogeneity of TB tests, and the lack of post-treatment follow-up. We outline an agenda for rectifying these gaps and argue that improving care cascade measurement is crucial to enhancing people-centred care and achieving the End TB goals.

Funders: The missing link in equitable global health research?

Global health research is mired by inequities, some of which are linked to current approaches to research funding. The role of funders and donors in achieving greater equity in global health research needs to be clearly defined. Imbalances of power and resources between high income countries (HICs) and low- and middle-income countries (LMICs) is such that many funding approaches do not centre the role of LMIC researchers in shaping global health research priorities and agenda. Relative to need, there is also disparity in financial investment by LMIC governments in health research. These imbalances put at a disadvantage LMIC health professionals and researchers who are at forefront of global health practice. Whilst many LMICs do not have the means (due to geopolitical, historical, and economic reasons) for direct investment, if those with means were to invest more of their own funds in health research, it may help LMICs become more self-sufficient and shift some of the power imbalances. Funders and donors in HICs should address inequities in their approach to research funding and proactively identify mechanisms that assure greater equity-including via direct funding to LMIC researchers and direct funding to build local LMIC-based, led, and run knowledge infrastructures. To collectively shape a new approach to global health research funding, it is essential that funders and donors are part of the conversation. This article provides a way to bring funders and donors into the conversation on equity in global health research.

One year of COVID-19 and its impact on private provider engagement for TB: A rapid assessment of intermediary NGOs in seven high TB burden countries.

The COVID-19 pandemic has impacted health systems and health programs across the world. For tuberculosis (TB), it is predicted to set back progress by at least twelve years. Public private mix (PPM)has made a vital contribution to reach End TB targets with a ten-fold rise in TB notifications from private providers between 2012 and 2019. This is due in large part to the efforts of intermediary agencies, which aggregate demand from private providers. The COVID-19 pandemic has put these gains at risk over the past year. In this rapid assessment, representatives of 15 intermediary agencies from seven countries that are considered the highest priority for PPM in TB care (the Big Seven) share their views on the impact of COVID-19 on their programs, the private providers operating under their PPM schemes, and their private TB clients. All intermediaries reported a drop in TB testing and notifications, and the closure of some private practices. While travel restrictions and the fear of contracting COVID-19 were the main contributing factors, there were also unanticipated expenses for private providers, which were transferred to patients via increased prices. Intermediaries also had their routine activities disrupted and had to shift tasks and budgets to meet the new needs. However, the intermediaries and their partners rapidly adapted, including an increased use of digital tools, patient-centric services, and ancillary support for private providers. Despite many setbacks, the COVID-19 pandemic has underlined the importance of effective private sector engagement. The robust approach to fight COVID-19 has shown the possibilities for ending TB with a similar approach, augmented by the digital revolution around treatment and diagnostics and the push to decentralize health services.

Computer-aided X-ray screening for tuberculosis and HIV testing among adults with cough in Malawi (the PROSPECT study): A randomised trial and cost-effectiveness analysis.

BACKGROUND: Suboptimal tuberculosis (TB) diagnostics and HIV contribute to the high global burden of TB. We investigated costs and yield from systematic HIV-TB screening, including computer-aided digital chest X-ray (DCXR-CAD). METHODS AND FINDINGS: In this open, three-arm randomised trial, adults (≥18 years) with cough attending acute primary services in Malawi were randomised (1:1:1) to standard of care (SOC); oral HIV testing (HIV screening) and linkage to care; or HIV testing and linkage to care plus DCXR-CAD with sputum Xpert for high CAD4TBv5 scores (HIV-TB screening). Participants and study staff were not blinded to intervention allocation, but investigator blinding was maintained until final analysis. The primary outcome was time to TB treatment. Secondary outcomes included proportion with same-day TB treatment; prevalence of undiagnosed/untreated bacteriologically confirmed TB on day 56; and undiagnosed/untreated HIV. Analysis was done on an intention-to-treat basis. Cost-effectiveness analysis used a health-provider perspective. Between 15 November 2018 and 27 November 2019, 8,236 were screened for eligibility, with 473, 492, and 497 randomly allocated to SOC, HIV, and HIV-TB screening arms; 53 (11%), 52 (9%), and 47 (9%) were lost to follow-up, respectively. At 56 days, TB treatment had been started in 5 (1.1%) SOC, 8 (1.6%) HIV screening, and 15 (3.0%) HIV-TB screening participants. Median (IQR) time to TB treatment was 11 (6.5 to 38), 6 (1 to 22), and 1 (0 to 3) days (hazard ratio for HIV-TB versus SOC: 2.86, 1.04 to 7.87), with same-day treatment of 0/5 (0%) SOC, 1/8 (12.5%) HIV, and 6/15 (40.0%) HIV-TB screening arm TB patients (p = 0.03). At day 56, 2 SOC (0.5%), 4 HIV (1.0%), and 2 HIV-TB (0.5%) participants had undiagnosed microbiologically confirmed TB. HIV screening reduced the proportion with undiagnosed or untreated HIV from 10 (2.7%) in the SOC arm to 2 (0.5%) in the HIV screening arm (risk ratio [RR]: 0.18, 0.04 to 0.83), and 1 (0.2%) in the HIV-TB screening arm (RR: 0.09, 0.01 to 0.71). Incremental costs were US$3.58 and US$19.92 per participant screened for HIV and HIV-TB; the probability of cost-effectiveness at a US$1,200/quality-adjusted life year (QALY) threshold was 83.9% and 0%. Main limitations were the lower than anticipated prevalence of TB and short participant follow-up period; cost and quality of life benefits of this screening approach may accrue over a longer time horizon. CONCLUSIONS: DCXR-CAD with universal HIV screening significantly increased the timeliness and completeness of HIV and TB diagnosis. If implemented at scale, this has potential to rapidly and efficiently improve TB and HIV diagnosis and treatment. TRIAL REGISTRATION: clinicaltrials.gov NCT03519425.

Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred. METHODS AND FINDINGS: We performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches. CONCLUSIONS: A significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Addressing power asymmetries in global health: Imperatives in the wake of the COVID-19 pandemic.

Seye Abimbola and co-authors argue for a transformation in global health research and practice in the post-COVID-19 world.

Commentary: Lessons from the COVID-19 global health response to inform TB case finding.

The coronavirus disease 2019 (COVID-19) has emerged as a serious threat to global public health, demanding urgent action and causing unprecedented worldwide change in a short space of time. This disease has devastated economies, infringed on individual freedoms, and taken an unprecedented toll on healthcare systems worldwide. As of 1 April 2020, over a million cases of COVID-19 have been reported in 204 countries and territories, resulting in more than 51,000 deaths. Yet, against the backdrop of the COVID-19 pandemic, lies an older, insidious disease with a much greater mortality. Tuberculosis (TB) is the leading cause of death by a single infectious agent and remains a potent threat to millions of people around the world. We discuss the differences between the two pandemics at present, consider the potential impact of COVID-19 on TB case management, and explore the opportunities that the COVID-19 response presents for advancing TB prevention and control now and in future.

Antibiotic prescription practices in primary care in low- and middle-income countries: A systematic review and meta-analysis.

BACKGROUND: The widespread use of antibiotics plays a major role in the development and spread of antimicrobial resistance. However, important knowledge gaps still exist regarding the extent of their use in low- and middle-income countries (LMICs), particularly at the primary care level. We performed a systematic review and meta-analysis of studies conducted in primary care in LMICs to estimate the prevalence of antibiotic prescriptions as well as the proportion of such prescriptions that are inappropriate. METHODS AND FINDINGS: We searched PubMed, Embase, Global Health, and CENTRAL for articles published between 1 January 2010 and 4 April 2019 without language restrictions. We subsequently updated our search on PubMed only to capture publications up to 11 March 2020. Studies conducted in LMICs (defined as per the World Bank criteria) reporting data on medicine use in primary care were included. Three reviewers independently screened citations by title and abstract, whereas the full-text evaluation of all selected records was performed by 2 reviewers, who also conducted data extraction and quality assessment. A modified version of a tool developed by Hoy and colleagues was utilized to evaluate the risk of bias of each included study. Meta-analyses using random-effects models were performed to identify the proportion of patients receiving antibiotics. The WHO Access, Watch, and Reserve (AWaRe) framework was used to classify prescribed antibiotics. We identified 48 studies from 27 LMICs, mostly conducted in the public sector and in urban areas, and predominantly based on medical records abstraction and/or drug prescription audits. The pooled prevalence proportion of antibiotic prescribing was 52% (95% CI: 51%-53%), with a prediction interval of 44%-60%. Individual studies' estimates were consistent across settings. Only 9 studies assessed rationality, and the proportion of inappropriate prescription among patients with various conditions ranged from 8% to 100%. Among 16 studies in 15 countries that reported details on prescribed antibiotics, Access-group antibiotics accounted for more than 60% of the total in 12 countries. The interpretation of pooled estimates is limited by the considerable between-study heterogeneity. Also, most of the available studies suffer from methodological issues and report insufficient details to assess appropriateness of prescription. CONCLUSIONS: Antibiotics are highly prescribed in primary care across LMICs. Although a subset of studies reported a high proportion of inappropriate use, the true extent could not be assessed due to methodological limitations. Yet, our findings highlight the need for urgent action to improve prescription practices, starting from the integration of WHO treatment recommendations and the AWaRe classification into national guidelines. TRIAL REGISTRATION: PROSPERO registration number: CRD42019123269.

Informing decision-making for universal access to quality tuberculosis diagnosis in India: an economic-epidemiological model.

BACKGROUND: India and many other high-burden countries have committed to providing universal access to high-quality diagnosis and drug susceptibility testing (DST) for tuberculosis (TB), but the most cost-effective approach to achieve this goal remains uncertain. Centralized testing at district-level hub facilities with a supporting sample transport network can generate economies of scale, but decentralization to the peripheral level may provide faster diagnosis and reduce losses to follow-up (LTFU). METHODS: We generated functions to evaluate the costs of centralized and decentralized molecular testing for tuberculosis with Xpert MTB/RIF (Xpert), a WHO-endorsed test which can be performed at centralized and decentralized levels. We merged the cost estimates with an agent-based simulation of TB transmission in a hypothetical representative region in India to assess the impact and cost-effectiveness of each strategy. RESULTS: Compared against centralized Xpert testing, decentralization was most favorable when testing volume at decentralized facilities and pre-treatment LTFU were high, and specimen transport network was exclusively established for TB. Assuming equal quality of centralized and decentralized testing, decentralization was cost-saving, saving a median $338,000 (interquartile simulation range [IQR] - $222,000; $889,000) per 20 million people over 10 years, in the most cost-favorable scenario. In the most cost-unfavorable scenario, decentralized testing would cost a median $3161 [IQR $2412; $4731] per disability-adjusted life year averted relative to centralized testing. CONCLUSIONS: Decentralization of Xpert testing is likely to be cost-saving or cost-effective in most settings to which these simulation results might generalize. More decentralized testing is more cost-effective in settings with moderate-to-high peripheral testing volumes, high existing clinical LTFU, inability to share specimen transport costs with other disease entities, and ability to ensure high-quality peripheral Xpert testing. Decision-makers should assess these factors when deciding whether to decentralize molecular testing for tuberculosis.

Tuberculosis.

Tuberculosis remains the leading cause of death from an infectious disease among adults worldwide, with more than 10 million people becoming newly sick from tuberculosis each year. Advances in diagnosis, including the use of rapid molecular testing and whole-genome sequencing in both sputum and non-sputum samples, could change this situation. Although little has changed in the treatment of drug-susceptible tuberculosis, data on increased efficacy with new and repurposed drugs have led WHO to recommend all-oral therapy for drug-resistant tuberculosis for the first time ever in 2018. Studies have shown that shorter latent tuberculosis prevention regimens containing rifampicin or rifapentine are as effective as longer, isoniazid-based regimens, and there is a promising vaccine candidate to prevent the progression of infection to the disease. But new tools alone are not sufficient. Advances must be made in providing high-quality, people-centred care for tuberculosis. Renewed political will, coupled with improved access to quality care, could relegate the morbidity, mortality, and stigma long associated with tuberculosis, to the past.