Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania.

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data. We show that the TB epidemic in Dar es Salaam is dominated by multiple MTBC genotypes introduced to Tanzania from different parts of the world during the last 300 years. The most common MTBC genotypes deriving from these introductions exhibited differences in transmission rates and in the duration of the infectious period, but little differences in overall fitness, as measured by the effective reproductive number. Moreover, measures of disease severity and bacterial load indicated no differences in virulence between these genotypes during active TB. Instead, the combination of an early introduction and a high transmission rate accounted for the high prevalence of L3.1.1, the most dominant MTBC genotype in this setting. Yet, a longer co-existence with the host population did not always result in a higher transmission rate, suggesting that distinct life-history traits have evolved in the different MTBC genotypes. Taken together, our results point to bacterial factors as important determinants of the TB epidemic in Dar es Salaam.

Feasibility of an Antiracism Curriculum in an Academic Pulmonary, Critical Care, and Sleep Medicine Division.

Background: Structural health inequities and racism adversely affect patient health and the culture of academic medicine. Formal training to educate fellows and faculty on antiracism is lacking. Objective: Our objective was to design, implement, and assess the feasibility and preliminary efficacy of a year-long antiracism curriculum within a pulmonary, critical care, and sleep medicine division. Methods: This was a pre- and postintervention observational study conducted between July 2020 and June 2021. The curriculum was offered during an allotted educational meeting time slot at a single-center pulmonary, critical care, and sleep medicine division at a large academic institution to fellows and faculty. The curriculum consisted of 13 1-hour virtual interactive workshops delivered by local experts in diversity, equity, and inclusion topics. Surveys assessed knowledge on racism in medicine; opinions, understanding, and comfort surrounding race and racism in medicine; as well as additional questions to solicit feedback on the curriculum itself via visual analog scale and write-in comments. Results: Before initiating the curriculum, 74% (n = 28) of respondents reported interest in an antiracism curriculum, and the majority (95%, n = 36) believed that discrimination affects medical staff and patients. Respondents reported only moderate comfort in talking about race (median, 58; interquartile range 41-70 on visual analog scale 0-100, where 100 is strongly agree with "I feel comfortable talking about race"). The postintervention survey demonstrated stability of the belief of the presence of racial discrimination and a 15% increase in self-directed learning about related topics. Although knowledge related to the use of race in medical algorithms improved, 14% fewer participants reported interest in continuing to engage in a division-wide structured antiracism curriculum. Conclusion: Implementation of a curriculum on justice, equity, diversity, and inclusion within a fellowship program is feasible and addresses an unmet need within graduate medical education.

Latent Tuberculosis Infection Treatment Outcomes in an At-Risk Underserved Population in Rhode Island.

OBJECTIVES: Within the United States (US), significant racial and ethnic disparities exist in the rates of latent TB infection (LTBI) and active TB disease. A disproportionate number of TB disease cases result from untreated LTBI among individuals born outside the US. This study evaluates LTBI treatment outcomes among an underserved, at-risk population in Rhode Island. METHODS: A quantitative retrospective chart review of adult patients with a positive screening test assessed LTBI care cascade outcomes including referral, treatment initiation, and completion. RESULTS: Seventy-four percent of patients found to have positive screening TB tests were born outside of the US; 80% identified as Hispanic or Black and 45% spoke a preferred language other than English. Twenty-one percent of potential candidates for LTBI treatment initiated treatment. CONCLUSIONS: Major gaps were identified in referral success and treatment initiation. Expanding LTBI treatment access into primary care settings could be a solution to improve outcomes and decrease health inequities among at-risk communities.

Primary care providers' and nurses' knowledge, attitudes, and skills regarding latent TB infection testing and treatment: A qualitative study from Rhode Island.

BACKGROUND: Untreated latent tuberculosis infection (LTBI) is a major source of active tuberculosis disease in the United States. In 2016, the United States Preventive Services Task Force (USPSTF) recommended that screening for latent tuberculosis infection among individuals at increased risk be performed as routine preventive care. Traditionally, LTBI management-including both testing and treatment-has been conducted by specialists in the United States. It is believed that knowledge gaps among primary care team members and discomfort with LTBI treatment are significant barriers to LTBI management being conducted in primary care. METHODS AND OBJECTIVES: This qualitative study sought to evaluate the knowledge, attitudes, and skills of primary care team members regarding the LTBI care cascade, and to identify each stepwise barrier limiting primary care teams in following the USPSTF recommendations. RESULTS: We conducted 24 key informant interviews with primary care providers and nurses in Rhode Island. Our results demonstrate that overall, few primary care providers and nurses felt comfortable with LTBI management, and their confidence and comfort decreased throughout the cascade. Participants felt least confident with LTBI treatment and held misconceptions about LTBI testing, such as high cost. Although participants were not confident about LTBI treatment, most were enthusiastic about treating patients if provided additional training. Participants suggested that their lack of knowledge regarding LTBI treatment led to high rates of referral to specialist providers. CONCLUSION: The gaps revealed in this study can inform training curricula for primary care team members in Rhode Island and nationally to shift the USPSTF policy into practice, and, ultimately, contribute to TB elimination in the United States.

Modeling future asthma attributable to fine particulate matter (PM2.5) in a changing climate: a health impact assessment.

Exposure to fine particulate matter (PM2.5) is associated with asthma development as well as asthma exacerbation in children. PM2.5 can be directly emitted or can form in the atmosphere from pollutant precursors. PM2.5 emitted and formed in the atmosphere is influenced by meteorology; future changes in climate may alter the concentration and distribution of PM2.5. Our aim is to estimate the future burden of climate change and PM2.5 on new and exacerbated cases of childhood asthma. Projected concentrations of PM2.5 are based on the Geophysical Fluid Dynamics Laboratory Coupled Model version 3 climate model, the Representative Concentration Pathway 8.5 greenhouse gas scenario, and two air pollution emissions datasets: a 2011 emissions dataset and a 2040 emissions dataset that reflects substantial reductions in emissions of PM2.5 as compared to the 2011 inventory. We estimate additional PM2.5-attributable asthma as well as PM2.5-attributable albuterol inhaler use for four future years (2030, 2050, 2075, and 2095) relative to the year 2000. Exacerbations, regardless of the trigger, are counted as attributable to PM2.5 if the incident disease is attributable to PM2.5. We project 38 thousand (95% CI 36, 39 thousand) additional PM2.5-attributable incident childhood asthma cases and 29 million (95% CI 27, 31 million) additional PM2.5-attributable albuterol inhaler uses per year in 2030, increasing to 200 thousand (95% CI 190, 210 thousand) additional incident cases and 160 million (95% CI 150, 160 million) inhaler uses per year by 2095 relative to 2000 under the 2011 emissions dataset. These additional PM2.5-attributable incident asthma cases and albuterol inhaler use would cost billions of additional U.S. dollars per year by the late century. These outcomes could be mitigated by reducing air pollution emissions.

Incidence and Mortality of Extrapulmonary Tuberculosis in Ukraine: Analysis of National Surveillance Data.

BACKGROUND: Improved understanding of the epidemiology and mortality risk factors of extrapulmonary tuberculosis (EPTB) may facilitate successful diagnosis and management. METHODS: We analyzed national surveillance data from Ukraine to characterize EPTB subtypes (ie, localized in different anatomic sites). We calculated annual reported incidence, stratified by age, sex, and human immunodeficiency virus (HIV) status. Using Cox regression, we estimated mortality risk factors. RESULTS: Between January 2015 and November 2018, 14 062 adults/adolescents (≥15 years) and 417 children (<15 years) had EPTB with or without concomitant pulmonary TB. The most commonly reported EPTB subtypes were pleural, peripheral lymph node, and osteoarticular. Most EPTB subtype notifications peaked at age 30-39 years and were higher in males. In adults/adolescents, most peripheral TB lymphadenitis, central nervous system (CNS) TB, and abdominal TB occurred in those with untreated HIV. CNS TB notifications in people without HIV peaked before age 5 years. Adults/adolescents with CNS TB (adjusted hazard ratio [aHR]: 3.22; 95% CI: 2.89-3.60) and abdominal TB (aHR: 1.83; 95% CI: 1.59-2.11) were more likely to die than those with pulmonary TB. Children with CNS TB were more likely to die (aHR: 88.25; 95% CI: 43.49-179.10) than those with non-CNS TB. Among adults/adolescents, older age and HIV were associated with death. Rifampicin resistance was associated with mortality in pleural, peripheral lymph node, and CNS TB. CONCLUSIONS: We identified the most common EPTB subtypes by age and sex, patterns of EPTB disease by HIV status, and mortality risk factors. These findings can inform diagnosis and care for people with EPTB.

Closing the loop in child TB contact management: completion of TB preventive therapy outcomes in western Kenya.

SETTING: Children especially those <5 years of age exposed to pulmonary tuberculosis (TB) are at a high risk of severe TB disease and death. Isoniazid preventive therapy (IPT) has been shown to decrease disease progression by up to 90%. Kenya, a high TB burden country experiences numerous operational challenges that limit implementation of TB preventive services. IPT completion in child contacts is not routinely reported in Kenya. OBJECTIVE: This study aims to review the child contact management (CCM) cascade and present IPT outcomes across 10 clinics in western Kenya. DESIGN: A retrospective chart review of programmatic data of a TB Reach-funded active, clinic-based CCM strategy. RESULTS: Of 553 child contacts screened, 231 (42%) were reported symptomatic. 74 (13%) of the child contacts were diagnosed with active TB disease. Of those eligible for IPT, 427 (90%) initiated IPT according to TB REACH project data while 249 (58%) were recorded in the IPT register with 49 (11%) recorded as a transfer to other facilities. Of the 249 recorded in the IPT register, 205 (82%) were documented to complete therapy (48% of project initiation children). CONCLUSION: Our evaluation shows gaps in the routine CCM care cascade related to completeness of documentation that require further programmatic monitoring and evaluation to improve CCM outcomes.

Mortality from drug-resistant tuberculosis in high-burden countries comparing routine drug susceptibility testing with whole-genome sequencing: a multicentre cohort study.

BACKGROUND: Drug resistance threatens global tuberculosis control. We aimed to examine mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and whole-genome sequencing (WGS). METHODS: In this multicentre cohort study, we collected pulmonary Mycobacterium tuberculosis isolates and clinical data from individuals with tuberculosis from antiretroviral therapy programmes and tuberculosis clinics in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, Peru, South Africa, and Thailand, stratified by HIV status and drug resistance. Sites tested drug susceptibility using routinely available methods. WGS was done on Illumina HiSeq 2500 in the USA and Switzerland, and TBprofiler was used to analyse the genomes. We included individuals aged 16 years or older with pulmonary tuberculosis (bacteriologically confirmed or clinically diagnosed). We analysed mortality in multivariable logistic regression models adjusted for sex, age, HIV status, history of tuberculosis, and sputum positivity. FINDINGS: Between Sept 1, 2014, and July 4, 2016, of 634 patients included in our previous analysis, we included 582 patients with tuberculosis (median age 33 years [IQR 27-43], 225 [39%] women, and 247 [42%] HIV-positive). Based on WGS, 339 (58%) isolates were pan-susceptible, 35 (6%) monoresistant, 146 (25%) multidrug-resistant, and 24 (4%) pre-extensively drug-resistant (pre-XDR) or XDR. The analysis of mortality was based on 530 patients; 63 (12%) died and 77 (15%) patients received inappropriate treatment. Mortality ranged from 6% (18 of 310) in patients with pan-susceptible tuberculosis to 39% (nine of 23) in patients with pre-XDR or XDR tuberculosis. The adjusted odds ratio for mortality was 4·92 (95% CI 2·47-9·78) among undertreated patients, compared with appropriately treated patients. INTERPRETATION: In seven countries with a high burden of tuberculosis, we observed discrepancies between drug resistance patterns obtained locally and WGS. The underdiagnosis of drug resistance resulted in inappropriate treatment and higher mortality. WGS can provide accurate and detailed drug resistance information required to improve the outcomes of drug-resistant tuberculosis in high-burden settings. Our results support WHO's call for point-of-care tests based on WGS. FUNDING: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, and Swiss National Center for Mycobacteria.

Gender difference in mortality among pulmonary tuberculosis HIV co-infected adults aged 15-49 years in Kenya.

SETTING: Kenya, 2012-2015. OBJECTIVE: To explore whether there is a gender difference in all-cause mortality among smear positive pulmonary tuberculosis (PTB)/ HIV co-infected patients treated for tuberculosis (TB) between 2012 and 2015 in Kenya. DESIGN: Retrospective cohort of 9,026 smear-positive patients aged 15-49 years. All-cause mortality during TB treatment was the outcome of interest. Time to start of antiretroviral therapy (ART) initiation was considered as a proxy for CD4 cell count. Those who took long to start of ART were assumed to have high CD4 cell count. RESULTS: Of the 9,026 observations analysed, 4,567(51%) and 4,459(49%) were women and men, respectively. Overall, out of the 9,026 patients, 8,154 (90%) had their treatment outcome as cured, the mean age in years (SD) was 33.3(7.5) and the mean body mass index (SD) was 18.2(3.4). Men were older (30% men' vs 17% women in those ≥40 years, p = <0.001) and had a lower BMI <18.5 (55.3% men vs 50.6% women, p = <0.001). Men tested later for HIV: 29% (1,317/4,567) of women HIV tested more than 3 months prior to TB treatment, as compared to 20% (912/4,459) men (p<0.001). Mortality was higher in men 11% (471/4,459) compared to women 9% (401/4,567, p = 0.004). There was a 17% reduction in the risk of death among women (adjusted HR 0.83; 95% CI 0.72-0.96; p = 0.013). Survival varied by age-groups, with women having significantly better survival than men, in the age-groups 40 years and over (log-rank p = 0.006). CONCLUSION: Women with sputum positive PTB/HIV co-infection have a significantly lower risk of all-cause mortality during TB treatment compared to men. Men were older, had lower BMI and tested later for HIV than women.

HIV Coinfection Is Associated with Low-Fitness rpoB Variants in Rifampicin-Resistant Mycobacterium tuberculosis.

We analyzed 312 drug-resistant genomes of Mycobacterium tuberculosis isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant M. tuberculosis strains isolated from HIV-coinfected patients carried disproportionally more resistance-conferring mutations in rpoB that are associated with a low fitness in the absence of the drug, suggesting these low-fitness rpoB variants can thrive in the context of reduced host immunity.

Mortality Among People With HIV Treated for Tuberculosis Based on Positive, Negative, or No Bacteriologic Test Results for Tuberculosis: The IeDEA Consortium.

BACKGROUND: In resource-constrained settings, many people with HIV (PWH) are treated for tuberculosis (TB) without bacteriologic testing. Their mortality compared with those with bacteriologic testing is uncertain. METHODS: We conducted an observational cohort study among PWH ≥15 years of age initiating TB treatment at sites affiliated with 4 International epidemiology Databases to Evaluate AIDS consortium regions from 2012 to 2014: Caribbean, Central and South America, and Central, East, and West Africa. The exposure of interest was the TB bacteriologic test status at TB treatment initiation: positive, negative, or no test result. The hazard of death in the 12 months after TB treatment initiation was estimated using a Cox proportional hazard model. Missing covariate values were multiply imputed. RESULTS: In 2091 PWH, median age 36 years, 53% had CD4 counts ≤200 cells/mm3, and 52% were on antiretroviral therapy (ART) at TB treatment initiation. The adjusted hazard of death was higher in patients with no test compared with those with positive test results (hazard ratio [HR], 1.56; 95% confidence interval [CI], 1.08-2.26). The hazard of death was also higher among those with negative compared with positive tests but was not statistically significant (HR, 1.28; 95% CI, 0.91-1.81). Being on ART, having a higher CD4 count, and tertiary facility level were associated with a lower hazard for death. CONCLUSIONS: There was some evidence that PWH treated for TB with no bacteriologic test results were at higher risk of death than those with positive tests. Research is needed to understand the causes of death in PWH treated for TB without bacteriologic testing.

Using artificial intelligence to read chest radiographs for tuberculosis detection: A multi-site evaluation of the diagnostic accuracy of three deep learning systems.

Deep learning (DL) neural networks have only recently been employed to interpret chest radiography (CXR) to screen and triage people for pulmonary tuberculosis (TB). No published studies have compared multiple DL systems and populations. We conducted a retrospective evaluation of three DL systems (CAD4TB, Lunit INSIGHT, and qXR) for detecting TB-associated abnormalities in chest radiographs from outpatients in Nepal and Cameroon. All 1196 individuals received a Xpert MTB/RIF assay and a CXR read by two groups of radiologists and the DL systems. Xpert was used as the reference standard. The area under the curve of the three systems was similar: Lunit (0.94, 95% CI: 0.93-0.96), qXR (0.94, 95% CI: 0.92-0.97) and CAD4TB (0.92, 95% CI: 0.90-0.95). When matching the sensitivity of the radiologists, the specificities of the DL systems were significantly higher except for one. Using DL systems to read CXRs could reduce the number of Xpert MTB/RIF tests needed by 66% while maintaining sensitivity at 95% or better. Using a universal cutoff score resulted different performance in each site, highlighting the need to select scores based on the population screened. These DL systems should be considered by TB programs where human resources are constrained, and automated technology is available.

Tuberculosis: An Epidemic Perpetuated by Health Inequalities.

Tuberculosis (TB) is the leading single-agent infectious disease killer worldwide. The World Health Organization (WHO)'s End TB Strategy aims to achieve tuberculosis (TB) elimination by 2030, and in September 2018, the United Nations General Assembly held a High-Level Meeting on TB to address the urgency of the TB epidemic and the health inequalities that continue to propel it. The meeting endorsed an ambitious, comprehensive approach to the TB epidemic that incorporates universal health coverage and tackles the social determinants of this disease. In this article, we provide an overview of the key strategies promoted in this meeting and introduce work by five Rhode Island-based physicians that align with these goals.

High Rates of Indeterminate TB Tests Among Hospitalized Patients: Can We Optimize Use of Gamma Interferon Release Assays in Tuberculosis?

In the United States, high concern for iatrogenic reactivation to tuberculosis (TB) disease secondary to prescribed immunosuppression has resulted in increased use of the QuantiFERON-TB Gold In-Tube test (QFT-GIT) to screen for Mycobacterium tuberculosis (Mtb) infection. The aim of our study was to determine indications for QFT-GIT testing and risk factors for indeterminate QFT-GIT results. We retrospectively identified patients with QFT-GIT testing over a six-month period in a tertiary care academic health care system and performed a record review. Inpatients were 11 times more likely to have an indeterminate QFT-GIT result than outpatients (95% CI 7.6-16.2). 61.5% inpatient QFT-GITs were ordered during workup of active TB. Providers treating exogenously or endogenously immunosuppressed patients ordered the most QFT-GITs. We highlight the significant limitations of TB screening tests in the inpatient setting and the need to test earlier in those requiring immunosuppressive therapy to avoid indeterminate results.

Global Health-related Training Opportunities. A National Survey of Pulmonary and Critical Care Medicine Fellowship Programs.

Rationale: Clinical and research training opportunities in global health are of increasing interest to medical trainees, but little is known about such opportunities in U.S.-based pulmonary and pulmonary/critical care medicine (PCCM) fellowship programs.Objectives: Summarize currently available global health-related training opportunities and identify potential barriers to implementing global health curricula among U.S.-based PCCM fellowship programs.Methods: We sent a confidential, online, targeted needs assessment to PCCM fellowship program directors and associate program directors. Data collected included program demographics, currently available global health-related clinical and research training opportunities, potential barriers to the implementation of global health-related programmatic content, and perceived interest in global health-related training opportunities by current and/or prospective trainees. To evaluate for nonresponse bias, we performed an online search to identify global health-related training opportunities offered by nonresponding programs.Results: Out of 171 surveyed programs, 63 PCCM fellowship programs (37%) provided survey responses. Most responses (n = 56, 89%) were from combined PCCM training programs; 66% (n = 40) of programs offered at least one component of global health-related clinical or research training. Overall, 27% (n = 17) had a Ruth L. Kirschstein National Research Service Award Institutional Research Training Grant (National Institutes of Health T32), 73% (n = 46) had fewer than 35 faculty members, and 51% (n = 32) had at least one faculty member conducting global health-focused research. Most responding programs (66%, n = 40) offered at least one global health-related educational component. Among programs that would like to offer global health-related training components, the most common barriers included competing priorities for lecture content and a lack of in-division mentors with global health experience, a champion for global health-related activities, and established partnerships outside the United States.Conclusions: PCCM program leaders are interested in offering global health-related training opportunities, but important barriers include lack of mentorship, dedicated fellowship time, and established global partnerships. Future research is needed to better understand global health-related interests and training needs of incoming fellows and to design creative solutions for providing global health-related training across academic institutions with variable global health-related training capacities.

Drug susceptibility testing and mortality in patients treated for tuberculosis in high-burden countries: a multicentre cohort study.

BACKGROUND: Drug resistance is a challenge for the global control of tuberculosis. We examined mortality in patients with tuberculosis from high-burden countries, according to concordance or discordance of results from drug susceptibility testing done locally and in a reference laboratory. METHODS: This multicentre cohort study was done in Côte d'Ivoire, Democratic Republic of the Congo, Kenya, Nigeria, South Africa, Peru, and Thailand. We collected Mycobacterium tuberculosis isolates and clinical data from adult patients aged 16 years or older. Patients were stratified by HIV status and tuberculosis drug resistance. Molecular or phenotypic drug susceptibility testing was done locally and at the Swiss National Center for Mycobacteria, Zurich, Switzerland. We examined mortality during treatment according to drug susceptibility test results and treatment adequacy in multivariable logistic regression models adjusting for sex, age, sputum microscopy, and HIV status. FINDINGS: We obtained M tuberculosis isolates from 871 patients diagnosed between 2013 and 2016. After exclusion of 237 patients, 634 patients with tuberculosis were included in this analysis; the median age was 33·2 years (IQR 26·9-42·5), 239 (38%) were women, 272 (43%) were HIV-positive, and 69 (11%) patients died. Based on the reference laboratory drug susceptibility test, 394 (62%) strains were pan-susceptible, 45 (7%) monoresistant, 163 (26%) multidrug-resistant (MDR), and 30 (5%) had pre-extensively or extensively drug resistant (pre-XDR or XDR) tuberculosis. Results of reference and local laboratories were concordant for 513 (81%) of 634 patients and discordant for 121 (19%) of 634. Overall, sensitivity to detect any resistance was 90·8% (95% CI 86·5-94·2) and specificity 84·3% (80·3-87·7). Mortality ranged from 6% (20 of 336) in patients with pan-susceptible tuberculosis treated according to WHO guidelines to 57% (eight of 14) in patients with resistant strains who were under-treated. In logistic regression models, compared with concordant drug susceptibility test results, the adjusted odds ratio of death was 7·33 (95% CI 2·70-19·95) for patients with discordant results potentially leading to under-treatment. INTERPRETATION: Inaccurate drug susceptibility testing by comparison with a reference standard leads to under-treatment of drug-resistant tuberculosis and increased mortality. Rapid molecular drug susceptibility test of first-line and second-line drugs at diagnosis is required to improve outcomes in patients with MDR tuberculosis and pre-XDR or XDR tuberculosis. FUNDING: National Institutes of Allergy and Infectious Diseases, Swiss National Science Foundation, Swiss National Center for Mycobacteria.

Creating a specialist physician workforce in low-resource settings: reflections and lessons learnt from the East African Training Initiative.

Many African countries have extremely low ratios of physicians to population, and there are very, very few specialists. This leaves most patients without access to specialised care, and importantly also leaves many countries with insufficient expertise to properly evaluate the burden of illness and the needs of the population overall. The challenges to training a specialised physician workforce in resource-limited settings are many, and they go far beyond the (relatively simple) task of transmission of clinical skills. We initiated a capacity-building programme to train pulmonary physicians in Ethiopia, a country of 105 million persons with a high burden of lung disease that had no prior existing training programme in pulmonary medicine. Using volunteer faculty from the USA and Europe, we have provided high-quality training and established a cohort of pulmonary specialists there. We have identified several components of training that go beyond clinical skills development but which we feel are crucial to sustainability. These components include the delineation of viable career pathways that allow professional growth for subspecialist physicians and that support the permanent establishment of a local faculty; the development of important non-clinical skills, including leadership and pedagogical techniques; training in clinical research methodologies; and the development of mechanisms to amplify the impact of a still relatively small number of specialised physicians to address the needs of the population generally. Our programme, the East African Training Initiative, has successfully addressed many of these challenges and we hope that it can be replicated elsewhere.