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.