Lydia Holtgrewe

Identifying case-finding strategies to reduce tuberculosis (TB) incidence in high-burden countries requires better knowledge of the disease burden in key contributing populations and settings. To inform South Africa’s National Tuberculosis Strategic Plan 2023–2028, we conducted a systematic review of active TB disease and latent TB infection (LTBI) prevalence and incidence in underserved populations, defined as those living in informal settlements, townships, or impoverished communities. We identified articles published from January 2010 to December 2023, assessed study quality, and conducted a meta-analysis to estimate pooled TB and LTBI prevalence stratified by HIV status. We calculated prevalence ratios for underserved populations compared to the overall South African population. The search yielded 726 unique citations. We identified 22 studies reporting TB prevalence (n = 12), TB incidence (n = 5), LTBI prevalence (n = 5), and/or LTBI incidence (n = 2) eligible for the review, including six high-quality studies. Meta-analysis demonstrated a high prevalence of TB disease among persons living without HIV (2.7% 95% CI 0.1 to 8.5%) and persons living with HIV (PLWH) (22.7%, 95% CI 15.8 to 30.4%), but heterogeneity was high (I² = 95.5% and 92.3%, p-value2 = 14.6%, p-value = 0.31), and lower among PLWH (33%, 95% CI 22.6 to 44.4%) based on one study. Compared to the national average, underserved populations of persons living without HIV had a 4-fold higher TB prevalence and a 3.3-fold higher LTBI prevalence. Underserved PLWH had a 31-fold higher TB prevalence than the national average, but similar LTBI prevalence as measured in one study. Our findings illustrate that underserved populations in South Africa have a substantially higher TB and LTBI prevalence than the general population, making targeted TB interventions potentially beneficial. More research is needed to explore the heterogeneous TB epidemiology in South Africa.

Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are crucial to bridge the TB diagnostic gap. Leveraging recent advancements in COVID-19 diagnostics, we explored adapting commercially available POC SARS-CoV-2 tests for TB diagnosis in line with the World Health Organization (WHO) target product profiles (TPPs). A scoping review was conducted following PRISMA-ScR guidelines to systematically map POC antigen and molecular SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings. Data were gathered from PubMed/MEDLINE, bioRxiv, medRxiv, publicly accessible in vitro diagnostic test databases, and developer websites up to 23 November 2022. Data on developer attributes, operational characteristics, pricing, clinical performance, and regulatory status were charted using standardized data extraction forms and evaluated with a standardized scorecard. A narrative synthesis of the data is presented. Our search yielded 2003 reports, with 408 meeting eligibility criteria. Among these, we identified 66 commercialized devices: 22 near-POC antigen tests, 1 POC molecular test, 31 near-POC molecular tests, and 12 low-complexity molecular tests potentially adaptable for TB. The highest-scoring SARS-CoV-2 diagnostic tests were the near-POC antigen platform LumiraDx (Roche, Basel, Switzerland), the POC molecular test Lucira Check-It (Pfizer, New York, NY, USA), the near-POC molecular test Visby (Visby, San Jose, CA, USA), and the low-complexity molecular platform Idylla (Biocartis, Lausanne, Switzerland). We highlight a diverse landscape of commercially available diagnostic tests suitable for potential adaptation to peripheral TB testing. This work aims to bolster global TB initiatives by fostering stakeholder collaboration, leveraging SARS-CoV-2 diagnostic technologies for TB, and uncovering new commercial avenues to tackle longstanding challenges in TB diagnosis.

Introduction: Rapid and accurate point-of-care (POC) tuberculosis (TB) diagnostics are a key priority to close the TB diagnostic gap of 3.1 million people without a diagnosis. Leveraging the recent surge in COVID-19 diagnostic innovation, we explored the potential adaptation of commercially available SARS-CoV-2 tests for TB diagnosis, aligning with World Health Organization (WHO) target product profiles (TPPs). Methods: A scoping review was conducted following PRISMA-ScR guidelines to systematically map commercially available POC molecular and antigen SARS-CoV-2 diagnostic tests potentially meeting the TPPs for TB diagnostic tests for peripheral settings. Data were gathered from PubMed/MEDLINE, bioRxiv, and medRxiv, along with publicly accessible in vitro diagnostic test databases, and developer websites, up to November 23, 2022. Data on developer and test attributes, operational characteristics, pricing, and clinical performance were charted using standardized data extraction forms. Each identified test was evaluated using a standardized scorecard. A narrative synthesis of the charted data is presented. Results: Our database search yielded 2,003 studies, from which 408 were considered eligible. Among these, we identified 58 commercialized diagnostic devices, including 17 near-POC antigen tests, one POC molecular test, 29 near-POC molecular tests, and 11 low-complexity molecular tests. We summarized the detailed characteristics, regulatory status, and clinical performance data of these tests. The LumiraDx (Roche, Switzerland) emerged as the highest- scoring near-POC antigen platform, while Visby (Visby, USA) was the highest-performing near-POC molecular platform. The Lucira Check-It (Pfizer, USA) was noted as the sole POC molecular test. The Idylla ^TM (Biocartis, Switzerland) was identified as the leading low- complexity molecular test. Discussion: We highlight a diverse landscape of commercially available diagnostic tests suitable for potential adaptation to TB POC testing. This work aims to bolster global TB initiatives by fostering stakeholder collaboration, leveraging COVID-19 diagnostic technologies for TB diagnosis, and uncovering new commercial avenues to tackle longstanding challenges in TB diagnosis.

Sprue-like enteropathy (SLE) is a clinical syndrome similar to celiac disease and has been associated with the use of various angiotensin receptor blockers (ARBs), a class of medications frequently used in the management of hypertension. Currently, there has only been one documented case report which has observed this occurrence with the use of the ARB candesartan. A 90-year-old female patient presented with chronic diarrhea and weight loss of unclear etiology. Diagnostic esophagogastroduodenoscopy and ileocolonoscopy were macroscopically unremarkable, but histological samples revealed complete villous atrophy, chronic mucosal inflammation, and intraepithelial T-lymphocytic infiltration. However, serological studies could not confirm celiac disease as a cause for the patient’s symptoms of malabsorption. After exclusion of other intestinal inflammation etiologies with noted ongoing candesartan use, the diagnosis of SLE was made, and candesartan therapy was discontinued. Additionally, we decided to initiate a lactose-free diet. Clinical remission was achieved without any recurrences. Candesartan is a commonly prescribed therapeutic agent in the treatment of hypertension. Our case underlines the importance of considering it as a potential cause for unexplained symptoms of malabsorption.

Introduction In 2014, the WHO published high-priority target product profiles (TPPs) for new tuberculosis (TB) diagnostics to align end-user needs with test targets and specifications; nevertheless, no TB test meets these targets to date. The COVID-19-driven momentum in the diagnostics world offers an opportunity to address the long-standing lack of innovation in the field of TB diagnostics. This scoping review aims to summarise point-of-care (POC) molecular and antigen tests for COVID-19 diagnosis that, when applied to TB, potentially meet WHO TPPs. This summary of currently available innovative diagnostic tools will guide the development of novel TB diagnostics toward the WHO-set targets. Methods and analysis We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension Scoping Reviews recommendations. MEDLINE (via PubMed), bioRxiv, MedRxiv and other publicly available in vitro diagnostic test databases were searched on 23 November 2022. POC antigen or molecular tests developed for SARS-CoV-2 detection that meet the eligibility criteria will be included in the review. Developer description, test description, operation characteristics, pricing information, performance and commercialisation status of diagnostic tests identified will be extracted using a predefined standardised data extraction form. Two reviewers will independently perform the screening and data extraction. A narrative synthesis of the final data will be provided. Ethics and dissemination No ethical approval is required because individual patient data will not be included. The findings will be published in open-access scientific journals.

The doctors of the future need to be empowered to deliver healthcare sustainably while protecting their patients' health in the context of a degrading environment. This study aimed to objectively review the extent and nature of the teaching of planetary health and sustainability topics in UK medical education. A multi-centre national review of the timetabled teaching sessions in medical courses in the UK during the academic year 2020/2021 against the General Medical Council's adopted 'Educating for Sustainable Healthcare - Priority Learning Outcomes'. Medical students were recruited and reviewed the entirety of their own institution's online teaching materials associated with core teaching sessions using a standardised data collection tool. Learning outcome coverage and estimated teaching time were calculated and used to rank participating medical schools. 45% of eligible UK medical schools were included in the study. The extent of teaching varied considerably amongst courses. Mean coverage of the 13 learning outcomes was 9.9 (SD:2.5) with a mean estimated teaching time of 140 min (SD:139). Courses with dedicated planetary health and sustainability sessions ranked best. There is large disparity in the education that medical students receive on these topics. Teaching may not adequately prioritise sustainability or reflect advances in planetary health knowledge.[Box: see text].