Tuberculosis presentation and outcomes in older Hispanic adults from Tamaulipas, Mexico.

Older people are at high risk of developing and dying from pulmonary infections like tuberculosis (TB), but there are few studies among them, particularly in Hispanics. To address these gaps, we sought to identify host factors associated with TB and adverse treatment outcomes in older Hispanics by conducting a cross-sectional study of TB surveillance data from Tamaulipas, Mexico (2006-2013; n = 8381). Multivariable logistic regressions were assessed for older adults (OA ≥65 years) when compared to young (YA, 18-39 years) and middle-aged adults (40-64 years). We found that the OA had features associated with a less complicated TB (e.g., lower prevalence of extra-pulmonary TB and less likely to abandon treatment or have drug resistant TB), and yet, were more likely to die during TB treatment (adj-OR 3.9, 95% 2.5, 5.25). Among the OA, excess alcohol use and low body mass index increased their odds of death during TB treatment, while a higher number of reported contacts (social support) was protective. Diabetes was not associated with adverse outcomes in OA. Although older age is a predictor of death during TB disease, OA are not prioritized by the World Health Organization for latent TB infection screening and treatment during contact investigations. With safer, short-course latent TB infection treatment available, we propose the inclusion of OA as a high-risk group in latent TB management guidelines.

Tuberculosis Outbreak Associated With Delayed Diagnosis and Long Infectious Periods in Rural Arkansas, 2010-2018.

OBJECTIVES: During 2010-2018, the Arkansas Department of Health reported 21 genotype-matched cases of tuberculosis (TB) among residents of a rural county in Arkansas with a low incidence of TB and in nearby counties. The Arkansas Department of Health and the Centers for Disease Control and Prevention investigated to determine the extent of TB transmission and provide recommendations for TB control. METHODS: We reviewed medical and public health records, interviewed patients, and reviewed patients' social media posts to describe patient characteristics, identify epidemiologic links, and establish likely chains of transmission. RESULTS: We identified 21 cases; 11 reported during 2010-2013 and 10 during 2016-2018. All case patients were US-born non-Hispanic Black people. Eighteen case patients had the outbreak genotype, and 3 clinically diagnosed (non-culture-confirmed) case patients had epidemiologic links to patients with the outbreak genotype. Social media reviews revealed epidemiologic links among 10 case patients not previously disclosed during interviews. Eight case patients (38%) had ≥1 health care visit during their infectious period, and 7 patients had estimated infectious periods of >12 months. CONCLUSIONS: Delayed diagnoses and prolonged infectiousness led to TB transmission in this rural community. TB education and awareness is critical to reducing transmission, morbidity, and mortality, especially in areas where health care providers have limited TB experience. Use of social media can help elucidate people at risk, especially when traditional TB investigation techniques are insufficient.

Active screening for tuberculosis in high-incidence Inuit communities in Canada: a cost-effectiveness analysis.

BACKGROUND: Active screening for tuberculosis (TB) involves systematic detection of previously undiagnosed TB disease or latent TB infection (LTBI). It may be an important step toward elimination of TB among Inuit in Canada. We aimed to evaluate the cost-effectiveness of community-wide active screening for TB infection and disease in 2 Inuit communities in Nunavik. METHODS: We incorporated screening data from the 2 communities into a decision analysis model. We predicted TB-related health outcomes over a 20-year time frame, beginning in 2019. We assessed the cost-effectiveness of active screening in the presence of varying outbreak frequency and intensity. We also considered scenarios involving variation in timing, impact and uptake of screening programs. RESULTS: Given a single large outbreak in 2019, we estimated that 1 round of active screening reduced TB disease by 13% (95% uncertainty range -3% to 27%) and was cost saving compared with no screening, over 20 years. In the presence of simulated large outbreaks every 3 years thereafter, a single round of active screening was cost saving, as was biennial active screening. Compared with a single round, we also determined that biennial active screening reduced TB disease by 59% (95% uncertainty range 52% to 63%) and was estimated to cost Can$6430 (95% uncertainty range -$29 131 to $13 658 in 2019 Can$) per additional active TB case prevented. With smaller outbreaks or improved rates of treatment initiation and completion for people with LTBI, we determined that biennial active screening remained reasonably cost-effective compared with no active screening. INTERPRETATION: Active screening is a potentially cost-saving approach to reducing disease burden in Inuit communities that have frequent TB outbreaks.

Against settler colonial iatrogenesis: Inuit resistance to treatment in Indian Hospitals in Canada.

Canada's program to examine, transfer and treat Indigenous and Inuit peoples with tuberculosis in Indian Hospitals (ca. 1936 and 1969) has generally been framed by official narratives of population health, benevolence, and care. However, letters written by Inuit patients in Indian hospitals and their kin, and which were addressed to government officials and translated by government employees, challenge this assumption. By focusing on the harmful effects of the segregation and long-term detainment of Inuit peoples away from their communities, the letters theorize TB treatment as multiply harmful and iatrogenic. The letters also showcase how Inuit peoples resisted Indian Hospital treatment and articulated the need for care and treatment to occur within a network of intimate relations, rather than in distant sanatoriums.

Molecular Typing of Mycobacterium tuberculosis Strains in Gifu Prefecture, Japan, Using Variable Number Tandem Repeat Analysis.

To investigate the molecular epidemiological characteristics of Mycobacterium tuberculosis strains collected from patients in Gifu Prefecture, Japan, 483 M. tuberculosis clinical isolates were analyzed using Japan Anti-Tuberculosis Association (JATA) 18-variable number tandem repeats (VNTR) between 2015 and 2019. To evaluate the lineage of M. tuberculosis strains, JATA18-VNTR profiles were applied to a maximum a posteriori method. The results revealed that the ancient Beijing subfamily, accounting for 57.3% (277/483) of the strains was the most prevalent M. tuberculosis strain. Furthermore, 18 clusters (GC-1-18) were found by minimum spanning tree analysis. The proportion of clustering strains was 9.9% (48/483), and epidemiological links to these clusters were unclear without GC-6 and GC-18. Meanwhile, interestingly, VNTR profiles of GC-7-9 and GC-14 were indistinguishable from the regional epidemic strains of Nagoya City, which has a strong socioeconomic relationship with Gifu Prefecture, but did not match the nationwide epidemic strains. This study suggests that coordinated analyses within the prefectures with strong socioeconomic relationships are important.

The 1918 influenza pandemic did not accelerate tuberculosis mortality decline in early-20th century Newfoundland: Investigating historical and social explanations.

OBJECTIVES: The selective mortality hypothesis of tuberculosis after the 1918 influenza pandemic, laid out by Noymer and colleagues, suggests that acute exposure or pre-existing infection with tuberculosis (TB) increased the probability of pneumonia and influenza (P&I) mortality during the 1918 influenza pandemic, leading to a hastened decline of TB mortality in post-pandemic years. This study describes cultural determinants of the post-pandemic TB mortality patterns in Newfoundland and evaluates whether there is support for this observation. MATERIALS AND METHODS: Death records and historical documents from the Provincial Archives of Newfoundland and Labrador were used to calculate age-standardized island-wide and sex-based TB mortality, as well as region-level TB mortality, for 1900-1939. The Joinpoint Regression Program (version 4.8.0.1) was used to estimate statistically significant changes in mortality rates. RESULTS: Island-wide, females had consistently higher TB mortality for the duration of the study period and a significant shift to lower TB mortality beginning in 1928. There was no similar predicted significant decline for males. On the regional level, no models predicted a significant decline after the 1918 influenza pandemic, except for the West, where significant decline was predicted in the late-1930s. DISCUSSION: Although there was no significant decline in TB mortality observed immediately post-pandemic, as has been shown for other Western nations, the female post-pandemic pattern suggests a decline much later. The general lack of significant decrease in TB mortality rate is likely due to Newfoundland's poor nutrition and lack of centralized healthcare rather than a biological interaction between P&I and TB.

Assortative social mixing and sex disparities in tuberculosis burden.

Globally, men have higher tuberculosis (TB) burden but the mechanisms underlying this sex disparity are not fully understood. Recent surveys of social mixing patterns have established moderate preferential within-sex mixing in many settings. This assortative mixing could amplify differences from other causes. We explored the impact of assortative mixing and factors differentially affecting disease progression and detection using a sex-stratified deterministic TB transmission model. We explored the influence of assortativity at disease-free and endemic equilibria, finding stronger effects during invasion and on increasing male:female prevalence (M:F) ratios than overall prevalence. Variance-based sensitivity analysis of endemic equilibria identified differential progression as the most important driver of M:F ratio uncertainty. We fitted our model to prevalence and notification data in exemplar settings within a fully Bayesian framework. For our high M:F setting, random mixing reduced equilibrium M:F ratios by 12% (95% CrI 0-30%). Equalizing male case detection there led to a 20% (95% CrI 11-31%) reduction in M:F ratio over 10 years-insufficient to eliminate sex disparities. However, this potentially achievable improvement was associated with a meaningful 8% (95% CrI 4-14%) reduction in total TB prevalence over this time frame.

Tuberculosis - United States, 2020.

Tuberculosis (TB) disease incidence has decreased steadily since 1993 (1), a result of decades of work by local TB programs to detect, treat, and prevent TB disease and transmission. During 2020, a total of 7,163 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC), a relative reduction of 20%, compared with the number of cases reported during 2019.* TB incidence per 100,000 persons was 2.2 during 2020, compared with 2.7 during 2019. Since 2010, TB incidence has decreased by an average of 2%-3% annually (1). Pandemic mitigation efforts and reduced travel might have contributed to the reported decrease. The magnitude and breadth of the decrease suggest potentially missed or delayed TB diagnoses. Health care providers should consider TB disease when evaluating patients with signs and symptoms consistent with TB (e.g., cough of >2 weeks in duration, unintentional weight loss, and hemoptysis), especially when diagnostic tests are negative for SARS-CoV-2, the virus that causes COVID-19. In addition, members of the public should be encouraged to follow up with their health care providers for any respiratory illness that persists or returns after initial treatment. The steep, unexpected decline in TB cases raises concerns of missed cases, and further work is in progress to better understand factors associated with the decline.

A population approach of rifampicin pharmacogenetics and pharmacokinetics in Mexican patients with tuberculosis.

The aim of this study was to develop a population pharmacokinetic model of rifampicin (RMP) in Mexican patients with tuberculosis (TB) to evaluate the influence of anthropometric and clinical covariates, as well as genotypic variants associated with MDR1 and OATP1B1 transporters. A prospective study approved by Research Ethics Committee was performed at Hospital Central in San Luis Potosí, Mexico. TB patients under DOTS scheme and who signed informed consent were consecutively included. Anthropometric and clinical information was retrieved from medical records. Single nucleotide polymorphisms in MDR1 (C3435T) and SLCO1B1 (A388G and T521C) genes were evaluated. RMP plasma concentrations and time data were assessed with NONMEM software. A total of 71 Mexican TB patients from 18 to 72 years old were included for RMP quantification from 0.3 to 12 h after dose; 329 and 97 plasma concentrations were available for model development and validation, respectively. Sequential process includes a typical lag time of 0.25 h prior to absorption start with a Ka of 1.24 h-1 and a zero-order absorption of 0.62 h to characterize the gradual increase in RMP plasma concentrations. Final model includes total body weight in volume of distribution (0.7 L/kg, CV = 26.8%) and a total clearance of 5.96 L/h (CV = 38.5%). Bioavailability was modified according to time under treatment and generic formulation administration. In conclusion, a population pharmacokinetic model was developed to describe the variability in RMP plasma concentrations in Mexican TB patients. Genetic variants evaluated did not showed significant influence on pharmacokinetic parameters. Final model will allow therapeutic drug monitoring at early stages.

Modeling the Impact of Recommendations for Primary Care-Based Screening for Latent Tuberculosis Infection in California.

OBJECTIVE: Targeted testing and treatment of persons with latent tuberculosis infection (LTBI) is a critical component of the US tuberculosis (TB) elimination strategy. In January 2016, the California Department of Public Health issued a tool and user guide for TB risk assessment (California tool) and guidance for LTBI testing, and in September 2016, the US Preventive Services Task Force (USPSTF) issued recommendations for LTBI testing in primary care settings. We estimated the epidemiologic effect of adherence to both recommendations in California. METHODS: We used an individual-based Markov micro-simulation model to estimate the number of cases of TB disease expected through 2026 with baseline LTBI strategies compared with implementation of the USPSTF or California tool guidance. We estimated the risk of LTBI by age and country of origin, the probability of being in a targeted population, and the probability of presenting for primary care based on available data. We assumed 100% adherence to testing guidance but imperfect adherence to treatment. RESULTS: Implementation of USPSTF and California tool guidance would result in nearly identical numbers of tests administered and cases of TB disease prevented. Perfect adherence to either recommendation would result in approximately 7000 cases of TB disease averted (40% reduction compared with baseline) by 2026. Almost all of this decline would be driven by a reduction in the number of cases among non-US-born persons. CONCLUSIONS: By focusing on the non-US-born population, adherence to LTBI testing strategies recommended by the USPSTF and the California tool could substantially reduce the burden of TB disease in California in the next decade.

Polymorphisms of TLR2, TLR4 and TOLLIP and tuberculosis in two independent studies.

Genetic polymorphisms for tuberculosis (TB) susceptibility have been researched by some studies, but few have studied multiple innate immunity genes associated with TB. Evidence suggests that the toll-like receptor 2, 4 (TLR2, TLR4) and toll interacting protein (TOLLIP) may be associated with TB susceptibility. In this self-validated study, we explored the association between common single nucleotide polymorphisms (SNPs) of TLR2, TLR4 and TOLLIP in the Chinese Han and Tibetan populations. A SNPscan™ method was used to genotype SNPs in the three genes. Multiple logistic regression adjusted by sex and age was used to detect the association between SNPs and TB. In TLR2, rs1898830 was associated with decreased risk against TB in the Chinese Han population, which was validated in the Tibetan population. In TLR4, rs11536889 was a protective factor for TB in the Tibetan population, but not in the Han population. Additionally, in the Tibetan population, we also found that the frequency of genotypes of TOLLIP rs11536889 differs significantly between TB patients and controls. We found rs1898830 in TLR2 was associated with TB susceptibility in both Chinese Han and Tibetan populations while rs11536889 in TLR4 and rs3750920 in TOLLIP were protective factors against TB in the Tibetan population.

Social determinants, ethical issues and future challenge of tuberculosis in a pluralistic society: the example of Israel.

Tuberculosis is a very serious respiratory infectious disease, caused by the bacillus Mycobacterium tuberculosis, which generates a relevant societal and clinical burden. It has always represented a permanent concern and a public health challenge over the course of human history, because of its severe epidemiological, and economic-financial implications. The present review aims at over-viewing the impact of tuberculosis on the Israeli healthcare system, its temporal trend and evolution, stratified according to ethnicities and minorities, the need of establishing new facilities and implementing screening techniques, public health strategies and diagnostic tests, following massive immigration waves from countries characterized by a high incidence rate of tuberculosis during the fifties-sixties until the nineties, and the policies implemented by the Israeli government in the control, management and treatment of tuberculosis, as well as the role played by Israeli prominent scientists in discovering new druggable targets and finding bioactive compounds and bio-molecules in the fight against tuberculosis. Israel represents a unique, living laboratory in which features of developed and developing countries mix together. This country as a case-study of immigrant, pluralistic society underlines the importance of adopting a culturally-sensitive community intervention approach. The understanding of the subtle interplay between race/ethnic host and pathogen factors, including the role of gene variations and polymorphisms can pave the way for a personalized treatment and management of tuberculosis patients, contributing to the development of new tools for targeted tuberculosis therapeutics, immunodiagnostics and vaccination products.

DISSEMINATED BACILLUS-CALMETTE-GUÉRIN INFECTIONS AND PRIMARY IMMUNODEFICIENCY DISORDERS IN SINGAPORE: A SINGLE CENTER 15-YEAR RETROSPECTIVE REVIEW.

BACKGROUND: Disseminated Bacillus Calmette-Guérin (BCG) disease (BCGosis) is a classical feature of children with primary immunodeficiency disorders (PIDs). METHODS: A 15-year retrospective review was conducted in KK Women's and Children's Hospital in Singapore, from January 2003 to October 2017. RESULTS: Ten patients were identified, the majority male (60.0%). The median age at presentation of symptoms of BCG infections was 3.8 (0.8 - 7.4) months. All the patients had likely underlying PIDS - four with Severe Combined Immunodeficiency (SCID), three with Mendelian Susceptibility to Mycobacterial Diseases (MSMD), one with Anhidrotic Ectodermal Dysplasia with Primary Immunodeficiency (EDA-ID), one with combined immunodeficiency (CID), and one with STAT-1 gain-of-function mutation. Definitive BCGosis was confirmed in all patients by the identification of Mycobacterium bovis subsp BCG from microbiological cultures. The susceptibility profiles of Mycobacterium bovis subsp BCG are as follows: Rifampicin (88.9%), Isoniazid (44.47%), Ethambutol (100.0%), Streptomycin (100.0%), Kanamycin (100.0%), Ethionamide (25.0%), and Ofloxacin (100.0%). Four patients (40.0%) received a three-drug regimen. Five patients (50.0%) underwent hematopoietic stem cell transplant (HSCT), of which three (60%) have recovered. Overall mortality was 50.0%. CONCLUSION: Disseminated BCG disease (BCGosis) should prompt immunology evaluation to determine the diagnosis of the immune defect. A three-drug regimen is adequate for treatment if the patient undergoes early HSCT.

A review of health and wellness studies involving Inuit of Manitoba and Nunavut.

The purpose of this review is to summarise past Inuit health and wellness studies in Manitoba and the Kivalliq region of Nunavut to provide a snapshot of the types of studies available and identify the gaps in knowledge. Research to date has largely been disease-based and often provides comparisons between Indigenous and non-Indigenous people. Distinct Inuit experiences are rarely written about from an Inuit perspective. However, Inuit Tapiriit Kanatami, the national organisation of Inuit in Canada, and Pauktuutit Inuit Women of Canada have been leaders in strengths-based community research and publications that address priorities determined by the Inuit, including the 2018 Inuit Tapiriit Kanatami document National Inuit Strategy on Research (132).

Tuberculosis - United States, 2019.

Since 1989, the United States has pursued a goal of eliminating tuberculosis (TB) through a strategy of rapidly identifying and treating cases and evaluating exposed contacts to limit secondary cases resulting from recent TB transmission (1). This strategy has been highly effective in reducing U.S. TB incidence (2), but the pace of decline has significantly slowed in recent years (2.2% average annual decline during 2012-2017 compared with 6.7% during 2007-2012) (3). For this report, provisional 2019 data reported to CDC's National Tuberculosis Surveillance System were analyzed to determine TB incidence overall and for selected subpopulations and these results were compared with those from previous years. During 2019, a total of 8,920 new cases were provisionally reported in the United States, representing a 1.1% decrease from 2018.* TB incidence decreased to 2.7 cases per 100,000 persons, a 1.6% decrease from 2018. Non-U.S.-born persons had a TB rate 15.5 times greater than the rate among U.S.-born persons. The U.S. TB case count and rate are the lowest ever reported, but the pace of decline remains slow. In recent years, approximately 80% of U.S. TB cases have been attributed to reactivation of latent TB infection (LTBI) acquired years in the past, often outside the United States (2). An expanded TB elimination strategy for this new decade should leverage existing health care resources, including primary care providers, to identify and treat persons with LTBI, without diverting public health resources from the continued need to limit TB transmission within the United States. Partnerships with health care providers, including private providers, are essential for this strategy's success.

Pulmonary vs. extra-pulmonary tuberculosis hospitalizations in the US [1998-2014].

BACKGROUND: Few studies have explored the relative burden and trends in pulmonary (PTB) vs. extra-pulmonary (EPTB) tuberculosis in the United States using a nationally representative sample. METHODS: This study examined trends in hospitalization rates, length-of-stay (LOS), in-hospital mortality and inflation-adjusted charges, for PTB vs. EPTB using the Nationwide/National Inpatient Sample (NIS) from 1998 to 2014. Descriptive and multivariable analyses (linear, negative binomial and logistic) were utilized adjusting for demographics, co-morbidity and hospital characteristics. RESULTS: During the study period there were a survey-adjusted, estimated 258,631 PTB (75.5%), 76,476 EPTB (22.3%) and 7552 concurrent PTB and EPTB (2.2%) discharges. Whites accounted for 27.6% of PTB, 21.9% of EPTB and 17.6% of concurrent discharges; and self-pay or no insurance accounted for 22.2%, 18.4%, and 25.9%, respectively. EPTB was more common among blacks (22.5%), and combined TB more common among Hispanics (24.8%). Mean LOS was 11.4 days, 13.2 days, and 19.5 days; with mean nominal charges of $48,031, $62,255, and $89,364 for PTB, EPTB and combined TB respectively. Inpatient mortality for all three groups was approximately 5.7%. Miliary TB and TB of meninges and central nervous system were positively associated with mortality (odds ratios of 2.44 and 2.11, respectively), as was alcohol abuse (OR 1.21). Trend analyses showed decreased hospitalizations for all TB types, no change in LOS trends, decreased mortality for PTB and ETB and increased charges for PTB and ETB from 1998 to 2014. Increased utilization, higher charges and higher risk of mortality (to some extent) among the EPTB cases warrant improved methods for screening, diagnosis and treatment. CONCLUSION: Though rates of TB hospitalization are declining, EPTB is becoming relatively more common and is more costly compared to pulmonary TB. Screening methods that focus on identification of ETB contrary to current practice guidelines are needed to aid ETB case finding.