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.

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.

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.

Women and Lung Disease. Sex Differences and Global Health Disparities.

There is growing evidence that a number of pulmonary diseases affect women differently and with a greater degree of severity than men. The causes for such sex disparity is the focus of this Blue Conference Perspective review, which explores basic cellular and molecular mechanisms, life stages, and clinical outcomes based on environmental, sociocultural, occupational, and infectious scenarios, as well as medical health beliefs. Owing to the breadth of issues related to women and lung disease, we present examples of both basic and clinical concepts that may be the cause for pulmonary disease disparity in women. These examples include those diseases that predominantly affect women, as well as the rising incidence among women for diseases traditionally occurring in men, such as chronic obstructive pulmonary disease. Sociocultural implications of pulmonary disease attributable to biomass burning and infectious diseases among women in low- to middle-income countries are reviewed, as are disparities in respiratory health among sexual minority women in high-income countries. The implications of the use of complementary and alternative medicine by women to influence respiratory disease are examined, and future directions for research on women and respiratory health are provided.

Prevalence of sexually transmitted infections including HIV in street-connected adolescents in western Kenya.

PURPOSE: The objectives of this study were to characterise the sexual health of street-connected adolescents in Eldoret, Kenya, analyse gender disparity of risks, estimate the prevalence of sexually transmitted infections (STIs), and identify factors associated with STIs. METHODS: A cross-sectional study of street-connected adolescents ages 12-21 years was conducted in Eldoret, Kenya. Participants were interviewed and screened for Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, herpes simplex virus-2, syphilis and HIV. Descriptive statistics and logistic regression were used to identify factors associated with having any STI. RESULTS: Of the 200 participants, 81 (41%) were female. 70.4% of females and 60.5% of males reported sexual activity. Of those that participated in at least one STI test, 28% (55/194) had ≥1 positive test, including 56% of females; 14% (28/194) had >1 positive test. Twelve females and zero males (6% overall, 14.8% of females) were HIV positive. Among females, those with HIV infection more frequently reported transactional sex (66.7% vs. 26.1%, p=0.01), drug use (91.7% vs. 56.5%, p=0.02), and reported a prior STI (50.0% vs. 14.7%, p<0.01). Having an adult caregiver was less likely among those with HIV infection (33.3% vs. 71.0%, p=0.04). Transactional sex (AOR 3.02, 95% CI (1.05 to 8.73)), a previous STI (AOR 3.46 95% CI (1.05 to 11.46)) and ≥2 sexual partners (AOR 5.62 95% (1.67 to 18.87)) were associated with having any STI. CONCLUSIONS: Street-connected adolescents in Eldoret, Kenya are engaged in high-risk sexual behaviours and females in particular have a substantial burden of STIs and HIV. There is a need for STI interventions targeted to street-connected youth.

Low correlation between household carbon monoxide and particulate matter concentrations from biomass-related pollution in three resource-poor settings.

Household air pollution from the burning of biomass fuels is recognized as the third greatest contributor to the global burden of disease. Incomplete combustion of biomass fuels releases a complex mixture of carbon monoxide (CO), particulate matter (PM) and other toxins into the household environment. Some investigators have used indoor CO concentrations as a reliable surrogate of indoor PM concentrations; however, the assumption that indoor CO concentration is a reasonable proxy of indoor PM concentration has been a subject of controversy. We sought to describe the relationship between indoor PM2.5 and CO concentrations in 128 households across three resource-poor settings in Peru, Nepal, and Kenya. We simultaneously collected minute-to-minute PM2.5 and CO concentrations within a meter of the open-fire stove for approximately 24h using the EasyLog-USB-CO data logger (Lascar Electronics, Erie, PA) and the personal DataRAM-1000AN (Thermo Fisher Scientific Inc., Waltham, MA), respectively. We also collected information regarding household construction characteristics, and cooking practices of the primary cook. Average 24h indoor PM2.5 and CO concentrations ranged between 615 and 1440 µg/m(3), and between 9.1 and 35.1 ppm, respectively. Minute-to-minute indoor PM2.5 concentrations were in a safe range (<25 µg/m(3)) between 17% and 65% of the time, and exceeded 1000 µg/m(3) between 8% and 21% of the time, whereas indoor CO concentrations were in a safe range (<7 ppm) between 46% and 79% of the time and exceeded 50 ppm between 4%, and 20% of the time. Overall correlations between indoor PM2.5 and CO concentrations were low to moderate (Spearman ρ between 0.59 and 0.83). There was also poor agreement and evidence of proportional bias between observed indoor PM2.5 concentrations vs. those estimated based on indoor CO concentrations, with greater discordance at lower concentrations. Our analysis does not support the notion that indoor CO concentration is a surrogate marker for indoor PM2.5 concentration across all settings. Both are important markers of household air pollution with different health and environmental implications and should therefore be independently measured.

HIV testing in US tuberculosis care settings: a survey of current practice and perceived barriers.

CONTEXT: Extent of and challenges to implementation of the Centers for Disease Control and Prevention (CDC) 2006 recommendation for routine HIV testing have not been reviewed specifically within tuberculosis (TB) care settings. OBJECTIVE: To determine current adherence to the CDC's HIV testing recommendations in TB care settings and identify barriers. DESIGN: An online survey was designed and distributed via Survey Monkey. SETTING: The 2011 National TB Conference attendees, National TB Nurse Controllers, and the CDC's TB-educate mailing list were invited to participate via e-mail. PARTICIPANTS: A total of 153 respondents from US states: 30 physicians, 91 nurses, 19 public health practitioners, and 13 other. MAIN OUTCOME MEASURES: Perceived importance of HIV testing, current HIV testing practices, perceived barriers to HIV testing, and understanding of state HIV testing laws. RESULTS: One hundred forty-one of 153 (92.2%) reported that patients with TB disease were "always" or "almost always" HIV tested; 65 of 153 (42.5%) reported the same for patients with latent TB infection (LTBI). Among those not routinely testing LTBI patients, "patient refusal of test" (53/88; 60.2%), "cost" (41/88; 46.6%), and "prevalence too low to justify" (33/88; 37.5%) were the most commonly identified barriers to opt-out testing. Forty-seven of 59 providers (79.7%) who reported that their state required written consent for HIV testing had incorrect knowledge regarding HIV testing legislation. CONCLUSIONS: Rates of HIV testing are high for patients with TB disease, but fewer than half of providers' care settings routinely test LTBI patients. Knowledge of HIV status is required to appropriately interpret TST results and make decisions regarding treatment in TB infection, since HIV coinfection increases risk of progression to active TB. Lack of HIV testing in LTBI patients represents a missed opportunity to prevent TB disease and its resultant morbidity and mortality. In addition, incorrect knowledge regarding testing legislation was a common problem among our TB providers. Further work is necessary to improve HIV testing rates in patients who have not yet progressed to active TB disease.

Results from early programmatic implementation of Xpert MTB/RIF testing in nine countries.

BACKGROUND: The Xpert MTB/RIF assay has garnered significant interest as a sensitive and rapid diagnostic tool to improve detection of sensitive and drug resistant tuberculosis. However, most existing literature has described the performance of MTB/RIF testing only in study conditions; little information is available on its use in routine case finding. TB REACH is a multi-country initiative focusing on innovative ways to improve case notification. METHODS: We selected a convenience sample of nine TB REACH projects for inclusion to cover a range of implementers, regions and approaches. Standard quarterly reports and machine data from the first 12 months of MTB/RIF implementation in each project were utilized to analyze patient yields, rifampicin resistance, and failed tests. Data was collected from September 2011 to March 2013. A questionnaire was implemented and semi-structured interviews with project staff were conducted to gather information on user experiences and challenges. RESULTS: All projects used MTB/RIF testing for people with suspected TB, as opposed to testing for drug resistance among already diagnosed patients. The projects placed 65 machines (196 modules) in a variety of facilities and employed numerous case-finding strategies and testing algorithms. The projects consumed 47,973 MTB/RIF tests. Of valid tests, 7,195 (16.8%) were positive for MTB. A total of 982 rifampicin resistant results were found (13.6% of positive tests). Of all tests conducted, 10.6% failed. The need for continuous power supply was noted by all projects and most used locally procured solutions. There was considerable heterogeneity in how results were reported and recorded, reflecting the lack of standardized guidance in some countries. CONCLUSIONS: The findings of this study begin to fill the gaps among guidelines, research findings, and real-world implementation of MTB/RIF testing. Testing with Xpert MTB/RIF detected a large number of people with TB that routine services failed to detect. The study demonstrates the versatility and impact of the technology, but also outlines various surmountable barriers to implementation. The study is not representative of all early implementer experiences with MTB/RIF testing but rather provides an overview of the shared issues as well as the many different approaches to programmatic MTB/RIF implementation.

Increasing access to the MDR-TB surveillance programme through a collaborative model in western Kenya.

OBJECTIVE: Kenya, like many resource-constrained countries, has a single mycobacterial laboratory, centrally located in Nairobi, with capacity for drug-susceptibility testing (DST) - the gold standard in diagnosing drug-resistant tuberculosis. We describe and evaluate a novel operational design that attempts to overcome diagnostic delivery barriers. METHODS: Review of the public DST programme identified several barriers limiting access: lack of programme awareness amongst physicians, limited supplies, unreliable transport and no specimen tracking methods. Staff visited 19 clinic sites in western Kenya and trained healthcare providers in regard to the novel diagnostics model. Provincial laboratory registries were reviewed to assess utilization of DST services prior to and after programme modification. RESULTS: Onsite training consisted of the inclusion criteria for re-treatment patients - the high-priority group for DST. Additionally, infrastructural support established a stable supply chain. An existing transport system was adapted to deliver sputum specimens. Task shifting created an accession and tracking system of specimens. During the 24 months post-implementation, the number of re-treatment specimens from the catchment area increased from 9.1 to 23.5 specimens per month. In comparing annual data pre- and post-implementation, the proportion of re-treatment cases receiving DST increased from 24.7% (n = 403) to 32.5% (n = 574) (P < 0.001), and the number of multidrug-resistant (MDR) TB cases increased from 5 to 10 cases. CONCLUSION: The delivery model significantly increased the proportion of re-treatment cases receiving DST. Barriers to accessing the national MDR-TB surveillance programme can be overcome through an operational model based on pragmatic use of existing services from multiple partners.

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.

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.

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.

Impact of immigration on the molecular epidemiology of tuberculosis in Rhode Island.

While foreign-born persons constitute only 11% of the population in the state of Rhode Island, they account for more than 65% of incident tuberculosis (TB) annually. We investigated the molecular-epidemiological differences between foreign-born and U.S.-born TB patients to estimate the degree of recent transmission and identify predictors of clustering. A total of 288 isolates collected from culture-confirmed TB cases in Rhode Island between 1995 and 2004 were fingerprinted by spoligotyping and 12-locus mycobacterial interspersed repetitive units. Of the 288 fingerprinted isolates, 109 (37.8%) belonged to 36 genetic clusters. Our findings demonstrate that U.S.-born patients, Hispanics, Asian/Pacific islanders, and uninsured patients were significantly more likely to be clustered. Recent transmission among the foreign-born population was restricted and occurred mostly locally, within populations originating from the same region. Nevertheless, TB transmission between the foreign-born and U.S.-born population should not be neglected, since 80% of the mixed clusters of foreign- and U.S.-born persons arose from a foreign-born source case. We conclude that timely access to routine screening and treatment for latent TB infection for immigrants is vital for disease elimination in Rhode Island.

Chronic noncommunicable cardiovascular and pulmonary disease in sub-Saharan Africa: an academic model for countering the epidemic.

Noncommunicable diseases are rapidly overtaking infectious, perinatal, nutritional, and maternal diseases as the major causes of worldwide death and disability. It is estimated that, within the next 10 to 15 years, the increasing burden of chronic diseases and the aging of the population will expose the world to an unprecedented burden of chronic diseases. Preventing the potential ramifications of a worldwide epidemic of chronic noncommunicable diseases in a sustainable manner requires coordinated, collaborative efforts. Herein, we present our collaboration's strategic plan to understand, treat, and prevent chronic cardiovascular and pulmonary disease (CVPD) in western Kenya, which builds on a 2-decade partnership between academic universities in North America and Kenya, the Academic Model Providing Access to Healthcare. We emphasize the importance of training Kenyan clinician-investigators who will ultimately lead efforts in CVPD care, education, and research. This penultimate aim will be achieved by our 5 main goals. Our goals include creating an administrative core capable of managing operations, develop clinical and clinical research training curricula, enhancing existing technology infrastructure, and implementing relevant research programs. Leveraging a strong international academic partnership with respective expertise in cardiovascular medicine, pulmonary medicine, and medical informatics, we have undertaken to understand and counter CVPD in Kenya by addressing patient care, teaching, and clinical research.

Tuberculosis among participants in an academic global health medical exchange program.

BACKGROUND: Although individuals from low tuberculosis (TB) burden countries experience an increased risk of TB infection when traveling to high burden countries for medical training or service, the degree of risk has not been well quantified. OBJECTIVE: Improved knowledge will aid development of guidelines for TB screening, pre/post-travel education, and risk reduction. DESIGN: Retrospective survey including questions on demographic characteristics, pre-travel TB counseling, in-country activities, and post-travel TB testing. PARTICIPANTS: Six hundred eight individuals who traveled to Eldoret, Kenya with the Academic Model Providing Access to Healthcare (AMPATH) medical exchange program between July 2004 and June 2009 were invited to complete an online survey in January 2010. MAIN MEASURES: The percentage of participants with a tuberculin skin test (TST) conversion and percentage reporting pre-travel and post-travel counseling and testing for TB were examined. KEY RESULTS: Four hundred thirteen out of 608 (68%) responded with sufficient information to be included in the analysis. Two hundred thirty-nine individuals (58%) reported that TB prevention was discussed in pre-travel preparations. One hundred thirteen (27%) of the survey participants reported "ideal" care [definition: pre-travel TST (within 1 year of travel), pre-travel counseling, and a post-travel TST specifically related to their travel]. Out of 267 participants at risk for TST conversion, 11 (4.1%; 95% CI: 2.2-7.3) had a conversion. TST conversion was not associated with longer duration of stay or participation in direct medical care. CONCLUSIONS: Travelers to TB-endemic areas with international medical exchange programs are at risk for TB infection, regardless of their length of stay or whether or not they participate in direct medical care. Many receive inadequate pre- and post-travel TB counseling and testing. Efforts should be made to improve TB education for program participants.

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.

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.