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The World Health Organization recommends all pregnant women receive screening for gestational diabetes (GDM) with a fasting oral glucose tolerance test (OGTT). However, very few women receive recommended screening in resource-limited countries like India. We implemented a community health worker (CHW)-delivered program to evaluate if home-based, CHW-delivered OGTT would increase GDM screening in a low-resource setting. We conducted a mixed methods study in two urban slum communities in Pune, India. CHWs were trained to deliver home-based, point-of-care fasting OGTT to women in their third trimester of pregnancy. The primary outcome was uptake of CHW-delivered OGTT. Secondary outcomes included GDM prevalence and linkage to GDM care. Individual interviews were conducted with purposively sampled pregnant women, CHWs, and local clinicians to assess barriers and facilitators of this approach. From October 2021-June 2022, 248 eligible pregnant women were identified. Of these, 223 (90%) accepted CHW-delivered OGTT and 31 (14%) were diagnosed with GDM. Thirty (97%) women diagnosed with GDM subsequently sought GDM care; only 10 (33%) received lifestyle counseling or pharmacologic therapy. Qualitative interviews indicated that CHW-delivered testing was considered highly acceptable as home-based testing saved time and was more convenient than clinic-based testing. Inconsistent clinical management of GDM was attributed to providers' lack of time to deliver counseling, and perceptions that low-income populations are not at risk for GDM. Convenience and trust in a CHW-delivered GDM screening program resulted in high access to gold-standard OGTT screening and identification of a high GDM prevalence among pregnant women in two urban slum communities. Appropriate linkage to care was limited by clinician time constraints and misperceptions of GDM risk. CHW-delivered GDM screening and counseling may improve health education and access to preventive healthcare, offloading busy public clinics in high-need, low-resource settings.

Tuberculosis (TB) is the leading cause of death from infection with a single bacterial pathogen. Host macrophages are the primary cell type infected with Mycobacterium tuberculosis (Mtb), the organism that causes TB. Macrophage response pathways are regulated by various factors, including microRNAs (miRNAs) and epigenetic changes that can shape the outcome of infection. Although dysregulation of both miRNAs and DNA methylation have been studied in the context of Mtb infection, studies have not yet investigated how these two processes may jointly co-regulate critical anti-TB pathways in primary human macrophages. In the current study, we integrated genome-wide analyses of miRNA abundance and DNA methylation status with mRNA transcriptomics in Mtb-infected primary human macrophages to decipher which macrophage functions may be subject to control by these two types of regulation. Using in vitro macrophage infection models and next generation sequencing, we found that miRNAs and methylation changes co-regulate important macrophage response processes, including immune cell activation, macrophage metabolism, and AMPK pathway signaling.

Mycobacterium avium complex (MAC) species are the most commonly isolated nontuberculous mycobacteria to cause pulmonary infections worldwide. The lengthy and complicated therapy required to cure lung disease due to MAC is at least in part due to the phenomenon of antibiotic tolerance. In this review, we will define antibiotic tolerance and contrast it with persistence and antibiotic resistance. We will discuss physiologically relevant stress conditions that induce altered metabolism and antibiotic tolerance in mycobacteria. Next, we will review general molecular mechanisms underlying bacterial antibiotic tolerance, particularly those described for MAC and related mycobacteria, including Mycobacterium tuberculosis, with a focus on genes containing significant sequence homology in MAC. An improved understanding of antibiotic tolerance mechanisms can lay the foundation for novel approaches to target antibiotic-tolerant mycobacteria, with the goal of shortening the duration of curative treatment and improving survival in patients with MAC.