Newton Fund Research Articles

Investigating the effect of England's smoke-free private vehicle regulation on changes in tobacco smoke exposure and respiratory disease in children: a quasi-experimental study

Comprehensive tobacco control policies can help to protect children from tobacco smoke exposure and associated adverse respiratory health consequences. We investigated the impact of England's 2015 regulation that prohibits smoking in a private vehicle with children present on changes in environmental tobacco smoke exposure and respiratory health in children. In this quasi-experimental study, we used repeated cross-sectional, nationally representative data from the Health Survey for England from Jan 1, 2008, to Dec 31, 2017, of children aged up to 15 years. We did interrupted time series logistic or ordinal regression analyses to assess changes in prevalence of self-reported respiratory conditions, prevalence of self-reported childhood tobacco smoke exposure (children aged 8-15 years only), and salivary cotinine levels (children aged 2 years or older) before and after implementation of the smoke-free private vehicle regulation on Oct 1, 2015. Children who were considered active smokers were excluded from the analyses of salivary cotinine levels. Our primary outcome of interest was self-reported current wheezing or asthma, defined as having medicines prescribed for these conditions. Analyses were adjusted for underlying time trends, quarter of year, sex, age, Index of Multiple Deprivation quintile, and urbanisation level. 21 096 children aged 0-15 years were included in our dataset. Implementation of the smoke-free private vehicle regulation was not associated with a demonstrable change in self-reported current wheezing or asthma (adjusted odds ratio 0·81, 95% CI 0·62-1·05; p=0·108; assessed in 13 369 children), respiratory conditions (1·02, 0·80-1·29; p=0·892; assessed in 17 006 children), or respiratory conditions probably affecting stamina, breathing, or fatigue (0·75, 0·47-1·19; p=0·220; assessed in 12 386 children). Self-reported tobacco smoke exposure and salivary cotinine levels generally decreased over the study period. There was no additional change in self-reported tobacco smoke exposure in cars among children aged 8-15 years following the legislation (0·77, 0·51-1·17; p=0·222; assessed in 5399 children). We observed a relative increase in the odds of children having detectable salivary cotinine levels post legislation (1·36, 1·09-1·71; p=0·0074; assessed in 7858 children) and levels were also higher (1·30, 1·04-1·62; p=0·020; ordinal variable). Despite introduction of the regulation, one in 20 children still reported being regularly exposed to tobacco smoke in cars and one in three still had detectable salivary cotinine levels. We found no demonstrable association between the implementation of England's smoke-free private vehicle regulation and changes in children's self-reported tobacco smoke exposure or respiratory health. There is an urgent need to develop more effective approaches to protect children from tobacco smoke in various places, including in private vehicles. Netherlands Lung Foundation, Erasmus MC, Farr Institute, Health Data Research UK, Asthma UK Centre for Applied Research, Academy of Medical Sciences, and Newton Fund.

Sustainable Aquaculture Futures

Sustainable Aquaculture Futures

HIV Exposure Without Infection Impacts Early Language Development: Outcomes from a South African Birth Cohort Study

Background: Whereas HIV infection is known to cause developmental delay, effects of HIV and antiretroviral drugs (ARVs) in HIV-exposed uninfected (HEU) children are unclear. We compared developmental outcomes of HEU and HIV-unexposed uninfected (HUU) children during their first 2 years of life in the South African population-based Drakenstein Child Health cohort study. Methods: Between 2012-2015, pregnant women were enrolled antenatally in a peri-urban setting. Mothers and children received HIV testing and ARVs per local guidelines. Developmental assessments were conducted blinded to HIV/ARV status, using the Bayley-III Scales of Infant and Toddler Development(BSID-III). Of 1143 live births, 1065(93%) children were in follow-up at 6 months and 1000(87%) at 24 months excluding two HIV-infected children. 260(24%) randomly selected children (61 HEU, 199 HUU) had BSID-III assessments at 6 months and 732(73%)(168 HEU, 564 HUU) at 24 months. All HEU children were exposed to ARVs (88% to maternal triple antiretroviral therapy). Outcomes were similar for HEU and HUU children at 6 months (p>0·10). At 24 months, HEU children scored lower than HUU in receptive language (adjusted difference -1·03, 95% confidence interval[CI] -1·69 to -0·37) and expressive language (-1·17, 95%CI -2·09 to -0·24); in contrast, cognitive, fine and gross motor domains were similar (all p>0·24). Corresponding to this, HEU children had higher proportions of developmental delay (score<-2SD) compared to HUU in receptive (14%vs7%, adjusted odds ratio[aOR] 1·96, 95%CI 1·09 to 3·52) and expressive language(11%vs6%, aOR 2·14, 95%CI 1·11 to 4·15). Interpretation: We found uninfected children exposed to maternal HIV and ARVs had two-fold increased odds of receptive and expressive language delay at two years. Given almost a quarter of South African children are HIV-exposed, and the importance of language in society, further long-term work to understand developmental outcomes of HEU children is needed. Funding Statement: The study was funded by the Bill & Melinda Gates Foundation [OPP 1017641]. Additional support for HJZ, DJS and KAD was provided by the South African Medical Research Council. CJW is supported by the Wellcome Trust through a Research Training Fellowship [203525/Z/16/Z]. KAD is additionally supported by the NRF, an Academy of Medical Sciences Newton Advanced Fellowship (NAF002/1001) funded by the UK Government’s Newton Fund, by NIAAA via (R21AA023887), by the Collaborative Initiative on Fetal Alcohol Spectrum Disorders (CIFASD) developmental grant (U24 AA014811), and by the US Brain and Behaviour Foundation Independent Investigator grant (24467). AMR is additionally supported by the UK Medical Research Council (MRC) and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement which is also part of the EDCTP2 programme supported by the European Union grant reference (MR/R010161/1). WB is supported by the SAMRC National Health Scholars programme. Declaration of Interests: The authors state: No conflicts of interest. Ethics Approval Statement: The study was approved by the Faculty of Health Sciences, Human Research Ethics Committee, University of Cape Town (401/2009 and 044/2017) and the London School of Hygiene & Tropical Medicine Observational/Interventions Research Ethics committee (11903).

Connecting Museums: a case study in leadership, innovation and education in university science museums leading internationalisation projects

This article reports on Connecting Museums: leadership, innovation and education in Science Museums, an international conference involving three university museums: Museu de Ciências e Tecnologia da Pontifícia Universidade Católica do Rio Grande do Sul (MCT-PUCRS), the Great North Museum: Hancock (GNM), at Newcastle University (NU), and the Oxford University Museum of Natural History (OUMNH). The partnership started with a project to develop a joint exhibition on the theme of evolution organised by MCT-PUCRS and GNM, supported by the British Council’s Newton Fund (Institutional Skills 2016). The two museums shared the project at the UK University Museums Group (UMG) conference in 2016, where it came to the attention of colleagues at OUMNH. Following the UMG conference, the leadership and education teams of the three museums opened a dialogue to exchange knowledge and experience on leadership, innovation and education in science museums. This culminated in the first Connecting Museums conference in Porto Alegre, Brazil in October 2017. The conference was attended by 81 professionals, researchers, undergraduate and graduate students with interests in museology, the natural sciences and related areas. *** Connecting Museums: um estudo de caso sobre liderança, inovação e educação em museus de ciências universitários liderando projetos de internacionalização ***Este artigo constitui-se de um relato sobre o Connecting Museums: liderança, inovação e educação em Museus de Ciências, uma conferência internacional envolvendo três museus universitários: o Museu de Ciências e Tecnologia da Pontifícia Universidade Católica do Rio Grande do Sul (MCT-PUCRS), o Great North Museum: Hancock (GNM), da Newcastle University (NU) e o Oxford University Museum of Natural History (OUMNH). A parceria entre as instituições iniciou-se a partir de um projeto para o desenvolvimento de uma exposição conjunta, organizada pelo MCT-PUCRS e pelo GNM financiada pelo Newton Fund por meio do edital Institutional Skills 2016 promovido pelo British Council. Os dois museus apresentaram o projeto na conferência do University Museum Group (UMG) em 2016 no Reino Unido, despertando a atenção de colegas do OUMNH. Após a conferência, as equipes de gestão e de educação dos três museus iniciaram um diálogo que culminou na troca de conhecimentos e experiências nas áreas de liderança, inovação e educação em museus de ciências. Este diálogo resultou na primeira edição da conferência Connecting Museums em Porto Alegre, Brasil, em outubro de 2017. Participaram do evento 81 profissionais, entre pesquisadores e alunos de graduação e pós-graduação, cujo interesse estava relacionado à museologia, ciências naturais e áreas correlatas.Palavras-chave: Museus de ciência. Liderança. Inovação. Educação em ciências. Internacionalização.

Overview of the Optimal Smart Energy Coordination for Microgrid Applications

This work was supported in part by the Southern African Systems Analysis Center (SASAC), in part by the South Africa National Research Foundation (NRF), in part by the Newton Fund | British Council, and in part by the University of Pretoria; the rst author thanks them for their sponsorships.

1387. Phase I Study to Evaluate the Safety and Pharmacokinetics (PK) of Single and Multiple Ascending Doses (SAD/MAD) of Intravenous (IV) Minocycline in Healthy Adult Subjects

BackgroundCarbapenem-resistant Acinetobacter baumannii infections are defined by the WHO as a critical threat. IV minocycline is approved in the United States for treatment of Acinetobacter infections at doses up to 200 mg BID. This study investigated safety and PK of single and multiple doses of IV minocycline, including doses higher than approved in the United States.MethodsThis was a randomized, double blind, placebo-controlled, SAD/MAD study of 6 doses (100–600 mg) of IV minocycline. Healthy adult subjects received a single dose of minocycline or placebo on Day 1, and 15 doses BID starting on Day 4. Safety was assessed throughout the study. Serial blood and urine samples were collected for PK assessment.ResultsSixty-nine healthy subjects were randomized, 49 were included in the PK analysis. No serious adverse events (AEs) occurred; 55 subjects (79.9%) reported study drug-related AEs; dizziness 40 (58.0%) and nausea 34 (49.3%) were the most common. All related AEs were mild except for seven subjects with moderate nausea and/or dizziness. Dosing in the 400 mg cohort was discontinued due to AEs, therefore MAD escalation was stopped. Subsequent cohorts were escalated for SAD and loading dose only.SAD Mean (SD) PK ParametersDose (mg)100200300400500600 N 888889Cmax (mg/L)0.99 (0.2)1.89 (0.4)3.35 (1.2)4.93 (1.8)4.36 (0.9)7.03 (2.4) T 1/2 (h)11.05 (2.1)13.70 (2.3)16.62 (3.9)17.55 (2.1)14.44 (2.7)17.27 (3.6)AUC0-∞(mg*h/L)9.73 (1.4)25.90 (6.9)39.16 (13.8)63.64 (18.2)53.76 (20.3)83.00 (29.4)Cl (L/h)10.48 (1.8)8.21 (2.2)8.28 (2.1)6.71 (1.7)10.25 (3.0)8.07 (2.8)Vss (L)156 (36.7)148 (36.6)158 (45.4)142 (38.0)179 (46.5)153 (52.8)AUC, area under the drug concentration–time curve; Cmax, maximum observed drug concentration; T1/2, half-life; Cl, plasma clearance; Vss, volume of distribution at steady state. N, number of subjects.ConclusionSingle IV doses of minocycline up to 600 mg were tolerated reasonably well, but the maximum tolerated multi-dose was 300 mg BID. Most common AEs were mild nausea and dizziness with evidence of increasing incidence but not increasing severity with increasing dose. Exposure increased in a dose proportional fashion with exception of the 500 mg dose. The dosage regimen selected for further studies will be a 600 mg loading dose followed by 300 mg BID.Disclosures O. A. Cornely, Innovative Medicines Initiative Joint Undertaking: Grant Investigator, Grant recipient. A. MacGowan, Merck: Commercial grant, Research support; Paratek: Commercial grant, Research support; VenatoRx: Commercial grant, Research support; Bayer: Commercial grant, Research support; Achaogen: Commercial grant, Research support; AiCuris: Collaborator and Commercial grant, Grant recipient and Research support; Polyphor: Commercial grant, Research support; Pfizer: Commercial grant, Research support; Roche: Commercial grant, Research support; Melinta: Industrial partner, Research support; MedImmune (AZ): Industrial partner (IMI), Research support; NIHR England: Grant Investigator, Grant recipient; MRC (UK): Grant Investigator, Grant recipient; Innovate UK: Grant Investigator, Grant recipient. Newton Fund (FCO): Grant Investigator, Grant recipient. S. K. Cammarata, Melinta Therapeutics, Inc.: Employee, Salary. K. Fusaro, Melinta Therapeutics: Employee, Salary. J. S. Loutit, The Medicines Company: Employee and Shareholder, Salary

Editorial and News

Editorial and News

"You Travel Faster Alone, but Further Together": Learning From a Cross Country Research Collaboration From a British Council Newton Fund Grant.

Providing universal health coverage (UHC) through better maternal, neonatal, child and adolescent health (MNCAH) can benefit both parties through North–South research collaborations. This paper describes lessons learned from bringing together early career researchers, tutors, consultants and mentors from the United Kingdom, Kenya, and South Africa to work in multi-disciplinary teams in a capacity-building workshop in Johannesburg, co-ordinated by senior researchers from the three partner countries. We recruited early career researchers and research users from a range of sectors and institutions in the participating countries and offered networking sessions, plenary lectures, group activities and discussions. To encourage bonding and accommodate cross-cultural and cross-disciplinary partners, we asked participants to respond to questions relating to research priorities and interventions in order to allocate them into multidisciplinary and cross-country teams. A follow up meeting took place in London six months later. Over the five day initial workshop, discussions informed the development of four draft research proposals. Intellectual collaboration, friendship and respect were engendered to sustain future collaborations, and we were able to identify factors which might assist capacity-building funders and organizers in future. This was a modestly funded brief intervention, with a follow-up made possible through the careful stewardship of resources and volunteerism. Having low and middle-income countries in the driving seat was a major benefit but not without logistic and financial challenges. Lessons learned and follow-up are described along with recommendations for future funding of partnerships schemes.

The DARA Big Data Project

AbstractThe DARA Big Data project is a flagship UK Newton Fund &amp; GCRF program in partnership with the South African Department of Science &amp; Technology (DST). DARA Big Data provides bursaries for students from the partner countries of the African VLBI Network (AVN), namely Botswana, Ghana, Kenya, Madagascar, Mauritius, Mozambique, Namibia and Zambia, to study for MSc(R) and PhD degrees at universities in South Africa and the UK. These degrees are in the three data intensive DARA Big Data focus areas of astrophysics, health data and sustainable agriculture. The project also provides training courses in machine learning, big data techniques and data intensive methodologies as part of the Big Data Africa initiative.

ZEB1 REGULATES MULTIPLE ASPECTS OF ENDOTHELIAL QUIESCENCE DURING VASCULAR REMODELLING

Generation of new blood vessels is essential for vascular remodeling in exercise to provide greater blood flow to developing muscles. As blood vessels grow, the sprouting endothelial tips need to recognise each other, and move from a motile, angiogenic phenotype to a maturing, quiescent phenotype,, form tubes and allow blood flow to occur and regulate their development. They grow in response to cytokine signalling such as VEGF and other angiogenic factors, but they mature as a consequence of cell contact and flow. As they do so, they change their metabolic state from growing, glycolytic, to quiescent oxidative metabolism. The mechanisms behind the transcriptional control of this phenotype are unknown, but recent work has demonstrated the dynamic interplay between ‘quiescence’ factors (such as FOXO1 expression) and expression of glycolytic enzymes such as PFKFB3 through c‐MYC. We investigated potential drivers of this process and identified Zeb1 (a transcription factor with known functions in cancer progression) to be expressed by quiescent (non‐angiogenic) endothelial cells and reduced in angiogenic endothelial cells in the developing murine retina. In vitro analyses demonstrates that Zeb1 is expressed by confluent monolayers of Human Vein Umbilical Cord Endothelial cells (HUVECs) but is downregulated in actively growing cells. Zeb1 knockdown promotes an angiogenic EC phenotype: including enhanced PFKFB3, c‐myc and VEGFR2 and reduced FOXO1, Tie2 and VE‐cadherin expression. Consistently, Zeb1 knockdown EC were metabolically more active (both through oxidative and glycolytic pathways). Furthermore, loss of Zeb1 promoted EC migration and proliferation in vitro. In vivo shRNA knockdown of Zeb1 led to altered vessel formation and hypercellularity. In conclusion, Zeb1 appears to be linked to key quiescence regulating signaling pathways and furthermore regulates aspects of these pathways. Zeb1 expression appears to be a critical component for endothelial cells to generate functional vasculatures that can support enhanced muscle blood flow, by its control of FOXO1, PFKFB3 and Myc.Support or Funding InformationThis work was supported by the British Heart Foundation (grant PG/11/67/29067), the University of Nottingham Cancer Research Priority Area, and the Medical Research Council Newton Fund (MR/N01247X/1)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

IEEE Radio and Antenna Days of the Indian Ocean (IEEE RADIO 2017)

EDITOR’S FOREWORDProfessor Weng Cho Chew, IEEE Antennas and Propagation Society (APS) President-Elect 2018, officially opened the fifth edition of the 2017 IEEE Radio and Antenna Days of the Indian Ocean (IEEE RADIO 2017) international conference that was held at the Protea Hotel by Marriott Cape Sea Point, Cape Town, South Africa from 25th to 28th September 2017. The conference was organized by the Radio Society (Mauritius) and financially sponsored by IEEE APS. IEEE RADIO 2017 was also technically co-sponsored by Union Radio Scientifique Internationale (URSI) and IEEE Region 8.The local organizing committee comprised researchers from Centrale Supélec, France, Université de La Réunion, University of Mauritius and Square Kilometre Array (SKA) Africa. We are grateful to SKA Africa, Newton Fund, Development in Africa for Radio Astronomy (DARA), Mobile & Wireless Forum (MWF) and Computer Simulation Technology (CST) for providing financial sponsorship for the conference.

New Paradigms to Help Solve the Global Aquaculture Disease Crisis.

The authors (GDS, KS) acknowledge funding administered by the British Council under the Newton Fund Researcher Links Programme, for a UK-Thailand bilateral workshop entitled Scientific, technological and social solutions for sustainable aquaculture in Thailand: a key player in global aquatic food supply, Bangkok, March 2016. Further funding support is acknowledged from the European Commission (EC) and the UK Department for Environment, Food and Rural Affairs (Defra) under contracts C6928 and FB002 (to GDS and DB); from the Royal Society under a University Research Fellowship (to BAPW); and to the Agricultural Research Development Agency (ARDA) and National Research Council of Thailand (NRCT) (to KS, TWF, and OI). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Outcomes, infectiousness, and transmission dynamics of patients with extensively drug-resistant tuberculosis and home-discharged patients with programmatically incurable tuberculosis: a prospective cohort study

The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies. In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179). Between Oct 1, 2008, and Oct 31, 2012, we enrolled and followed up 273 patients for a median of 20·3 months (IQR 9·6-27·8). 203 (74%) had programmatically incurable tuberculosis and unfavourable outcomes (treatment failure, relapse, default, or death despite treatment with a regimen based on capreomycin, aminosalicylic acid, or both). 172 (63%) patients were discharged home, of whom 104 (60%) had an unfavourable outcome. 54 (31%) home-discharged patients had failed treatment, with a median time to death after discharge of 9·9 months (IQR 4·2-17·4). 35 (20%) home-discharged cases were smear-positive at discharge. Using CASS, six (23%) of 26 home-discharged cases with data available expectorated infectious culture-positive cough aerosols in the respirable range (<5 μm), and most reported inter-person contact with suboptimal protective mask usage. WGS identified 17 (19%) of the 90 patients (with available sequence data) that were discharged home before the diagnosis of 20 downstream cases of extensively drug-resistant tuberculosis with almost identical sequencing profiles suggestive of community-based transmission (five or fewer single nucleotide polymorphisms different and with identical resistance-encoding mutations for 14 drugs). 11 (55%) of these downstream cases had HIV co-infection and ten (50%) had died by the end of the study. 22 (56%) of 39 isolates in patients discharged home after treatment failure were resistant to eight or more drugs. However, five (16%) of 31 isolates were susceptible to rifabutin and more than 90% were likely to be sensitive to linezolid, bedaquiline, and delamanid. More than half of the patients with programmatically incurable tuberculosis were discharged into the community where they remained for an average of 16 months, were at risk of expectorating infectious cough aerosols, and posed a threat of transmission of extensively drug-resistant tuberculosis. Urgent action, including appropriate containment strategies, is needed to address this situation. Access to delamanid, bedaquiline, linezolid, and rifabutin, when appropriate, must be accelerated along with comprehensive drug susceptibility testing. UK Medical Research Council, South African Medical Research Council, South African National Research Foundation, European & Developing Countries Clinical Trials Partnership, Oppenheimer Foundation, Newton Fund, Biotechnology and Biological Sciences Research Council, King Abdullah University of Science & Technology.

The Atmospheric Circulation Reconstructions over the Earth (ACRE) initiative ACRE China workshop: Recovery, digitization, and analysis of pre‐mid‐twentieth century climate observational data in East Asia workshop on 23–24 August, Beijing, China

AbstractThis commentary discusses a recent workshop designed to explore the extant historic instrumental record of weather observations for China, East Asia, and the China Seas region; to uncover new sources of observations; and to work on joint initiatives for their recovery and inclusion in open access data sets. The workshop was funded by the UK Newton Fund's Climate Science for Service Partnership China. It was organized by the Atmospheric Circulation Reconstructions over the Earth China, the China Meteorological Administration (CMA), the Beijing Climate Centre, and the China University of Geosciences (Wuhan) and held at CMA offices in Beijing.

POSTNATAL CARE IN BRAZIL: OPPORTUNITIES AND CHALLENGES

ABSTRACT Aim: in this paper the authors described the experience in proposition and realization of a workshop in a partnership between UK and Brazilian researchers. The aim was plan out a strategy for the successful implementation of interventions to improve the health and wellbeing of women's postnatal care in Brazil. Method: this is an experience report about the implementation of that workshop. It was held in the Universidade Federal de Santa Catarina, from 7 to 10 March 2016, under the auspices of the British Council Researcher Links Scheme, funded through the Newton Fund and Brazilian Council of the State Foundations of Research, Sciences and Innovation represented in Santa Catarina by Foundation for Research and Innovation of Santa Catarina. Results: during the workshop were presented health and social care experiences of women in Brazil from pregnancy through to the months after birth, integrated review of social technology in health, the importance of specific public health initiatives and good health surveillance in a country as large and multi-cultured as Brazil. It was also carried out a meeting between health professionals and women and their partners who had received postnatal care. Each day we worked in small groups to identify the research areas that we were interested in moving forward with as a Brazil-UK research network. Conclusions: a number of perceived opportunities and challenges were identified during the workshop from researchers, practitioners, parents and policy makers. The success of social technology interventions depends on their appropriate introduction within Brazil's social and healthcare context.

Chemotherapy and survival of tubercle bacilli in lung tissue assessed by postmortem cultures

The emergence of programmatically incurable tuberculosis threatens to destabilise control efforts. The aim of this study was to collect prospective patient-level data to inform treatment and containment strategies.In a prospective cohort study, 273 South African patients with extensively drug-resistant tuberculosis, or resistance beyond extensively drug-resistant tuberculosis, were followed up over a period of 6 years. Transmission dynamics, infectiousness, and drug susceptibility were analysed in a subset of patients from the Western Cape using whole-genome sequencing (WGS; n=149), a cough aerosol sampling system (CASS; n=26), and phenotypic testing for 18 drugs (n=179).Between Oct 1, 2008, and Oct 31, 2012, we enrolled and followed up 273 patients for a median of 20·3 months (IQR 9·6–27·8). 203 (74%) had programmatically incurable tuberculosis and unfavourable outcomes (treatment failure, relapse, default, or death despite treatment with a regimen based on capreomycin, aminosalicylic acid, or both). 172 (63%) patients were discharged home, of whom 104 (60%) had an unfavourable outcome. 54 (31%) home-discharged patients had failed treatment, with a median time to death after discharge of 9·9 months (IQR 4·2–17·4). 35 (20%) home-discharged cases were smear-positive at discharge. Using CASS, six (23%) of 26 home-discharged cases with data available expectorated infectious culture-positive cough aerosols in the respirable range (<5 μm), and most reported inter-person contact with suboptimal protective mask usage. WGS identified 17 (19%) of the 90 patients (with available sequence data) that were discharged home before the diagnosis of 20 downstream cases of extensively drug-resistant tuberculosis with almost identical sequencing profiles suggestive of community-based transmission (five or fewer single nucleotide polymorphisms different and with identical resistance-encoding mutations for 14 drugs). 11 (55%) of these downstream cases had HIV co-infection and ten (50%) had died by the end of the study. 22 (56%) of 39 isolates in patients discharged home after treatment failure were resistant to eight or more drugs. However, five (16%) of 31 isolates were susceptible to rifabutin and more than 90% were likely to be sensitive to linezolid, bedaquiline, and delamanid.More than half of the patients with programmatically incurable tuberculosis were discharged into the community where they remained for an average of 16 months, were at risk of expectorating infectious cough aerosols, and posed a threat of transmission of extensively drug-resistant tuberculosis. Urgent action, including appropriate containment strategies, is needed to address this situation. Access to delamanid, bedaquiline, linezolid, and rifabutin, when appropriate, must be accelerated along with comprehensive drug susceptibility testing.UK Medical Research Council, South African Medical Research Council, South African National Research Foundation, European & Developing Countries Clinical Trials Partnership, Oppenheimer Foundation, Newton Fund, Biotechnology and Biological Sciences Research Council, King Abdullah University of Science & Technology.