This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards “pre-elimination” (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Introduction: Rising rates of antimicrobial resistance (AMR) globally continue to pose agrave threat to human health. Low- and middle-income countries (LMICs) are disproportionately affected, partly due to the high burden of communicable diseases. Areas covered: We reviewed current trends in AMR in LMICs and examined the forces driving AMR in those regions. The state of interventions being undertaken to curb AMR across the developing world are discussed, and the impact of the current COVID-19 pandemic on those efforts is explored. Expert opinion: The dynamics that drive AMR in LMICs are inseparable from the political, economic, socio-cultural, and environmental forces that shape these nations. The COVID-19 pandemic has further exacerbated underlying factors that increase AMR. Some progress is being made in implementing surveillance measures in LMICs, but implementation of concrete measures to meaningfully impact AMR rates must address the underlying structural issues that generate and promote AMR. This, in turn, will require large infrastructural investments and significant political will.

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. 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. 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. PROSPERO registration number: CRD42019123269.

Tuberculosis (TB) is a leading cause of morbidity and mortality worldwide, accounting for about 9.6 million new cases and 1.5 million deaths annually. The poorest and socially excluded groups carry the largest burden of disease, which makes it essential to properly address the social determinants of health through poverty reduction measures and targeted interventions on high-risk populations. The spread of multidrug-resistance TB requires special attention and highlights the need to foster research on TB diagnostics, new drugs and vaccines. Although many advances have been made in the fight against TB over the last twenty years, a lot is still needed to achieve global elimination. The new end-TB strategy that was first launched in 2014 by the World Health Organization, is fully in line with the seventeen Sustainable Development Goals that came into effect since January 2016 and sets ambitious goals for the post-2015 agenda. A 90% reduction in TB-related mortality and an 80% decline in TB incidence within 2030 as well as the abolition of catastrophic expenditures for TB-affected people are the main targets of this strategy. Strong government commitment and adequate financing from all countries together with community engagement and appropriate investments in research are necessary in order to reach these objectives.

Antibiotic use drives antibiotic resistance. To systematically review the literature and estimate associations between prior exposure to antibiotics across World Health Organization's (WHO) AWaRe categories (Access, Watch, Reserve) and isolation of critical and high-priority multidrug resistant organisms (MDROs) on the WHO priority pathogen list. Embase, Ovid Medline, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov (from inception to 20/08/2020). Case-control, cohort, or experimental studies that assessed the risk of infection/colonization with MDROs. Inpatients or outpatients of any age and sex. Prior exposure to antibiotics that could be categorized into the AWaRe framework. Tailored design-specific checklists applied to each included study. For each antibiotic/class, crude odds ratios (ORs) were pooled through random-effects meta-analyses, both overall and by MDRO. Heterogeneity was examined. We identified 349 eligible studies. All were observational, prone to bias due to design and lack of adjustment for confounding, and not primarily designed to compare associations across AWaRe categories. We found statistically significant associations between prior exposure to almost all antibiotics/classes across AWaRe categories and colonization/infection with any MDRO. We observed higher ORs for Watch and Reserve antibiotics than with Access antibiotics. First generation cephalosporins (Access) had the least association with any MDRO colonization/infection (58 studies; OR = 1.2 [95% CI: 1.0-1.4]), whereas strongest associations were estimated for linezolid (Reserve) (22 studies; OR = 2.6 [95% CI: 2.1-3.1]), followed by carbapenems (Watch) (237 studies; OR = 2.3 [95% CI: 2.1-2.5]). There was high heterogeneity for all antibiotic/MDRO associations. Optimising use of Access antibiotics is likely to reduce the selection of MDROs and global antibiotic resistance. Despite data limitations, our study offers a strong rationale for further adoption of AWaRe as an important tool to improve antibiotic use globally.