Outcomes for people with TB by disease severity at presentation.

There is substantial heterogeneity in disease presentation for individuals with TB disease, which may correlate with disease outcomes. We estimated disease outcomes by disease severity at presentation among individuals with TB during the pre-chemotherapy era.We extracted data on people with TB enrolled between 1917 and 1948 in the USA, stratified by three disease severity categories at presentation using the U.S. National Tuberculosis Association diagnostic criteria. These criteria were based largely on radiographic findings ("minimal", "moderately advanced", and "far advanced"). We used Bayesian parametric survival analysis to model the survival distribution overall, and by disease severity and Bayesian logistic regression to estimate the severity-level specific natural recovery odds within 3 years.People with minimal TB at presentation had a 2% (95% CrI 0-11%) probability of TB death within 5 years vs. 40% (95% CrI 15-68) for those with far advanced disease. Individuals with minimal disease had 13.62 times the odds (95% CrI 9.87-19.10) of natural recovery within 3 years vs. those with far advanced disease.Mortality and natural recovery vary by disease severity at presentation. This supports continued work to evaluate individualized (e.g., shortened or longer) regimens based on disease severity at presentation, identified using radiography..

Survival of people with untreated TB: effects of time, geography and setting.

BACKGROUND: An estimated 40% of people who developed TB in 2021 were not diagnosed or treated. Pre-chemotherapy era data are a rich resource on survival of people with untreated TB. We aimed to identify heterogeneities in these data to inform their more precise use.METHODS: We extracted survival data from pre-chemotherapy era papers reporting TB-specific mortality and/or natural recovery data. We used Bayesian parametric survival analysis to model the survival distribution, stratifying by geography (North America vs. Europe), time (pre-1930 vs. post-1930), and setting (sanitoria vs. non-sanitoria).RESULTS: We found 12 studies with TB-specific mortality data. Ten-year survival was 69% in North America (95% CI 54-81) and 36% in Europe (95% CI 10-71). Only 38% (95% CI 18-63) of non-sanitorium individuals survived to 10 years compared to 69% (95% CI 41-87) of sanitoria/hospitalized patients. There were no significant differences between people diagnosed pre-1930 and post-1930 (5-year survival pre-1930: 65%, 95% CI 44-88 vs. post-1930: 72%, 95% CI 41-94).CONCLUSIONS: Mortality and natural recovery risks vary substantially by location and setting. These heterogeneities need to be considered when using pre-chemotherapy data to make inferences about expected survival of people with undiagnosed TB.

Smoked drug use in patients with TB is associated with higher bacterial burden.

BACKGROUND: Smoking of illicit drugs may lead to more rapid TB disease progression or late treatment presentation, yet research on this topic is scant. We examined the association between smoked drug use and bacterial burden among patients newly initiated on drug-susceptible TB (DS-TB) therapy.METHODS: Data from 303 participants initiating DS-TB treatment in the Western Cape Province, South Africa, were analyzed. Smoked drug use was defined as self-reported or biologically verified methamphetamine, methaqualone and/or cannabis use. Proportional hazard and logistic regression models (adjusted for age, sex, HIV status and tobacco use) examined associations between smoked drug use and mycobacterial time to culture positivity (TTP), acid-fast bacilli sputum smear positivity and lung cavitation.RESULTS: People who smoked drugs (PWSD) comprised 54.8% (n = 166) of the cohort. TTP was faster for PWSD (hazard ratio 1.48, 95% CI 1.10-1.97; P = 0.008). Smear positivity was higher among PWSD (OR 2.28, 95% CI 1.22-4.34; P = 0.011). Smoked drug use (OR 1.08, 95% CI 0.62-1.87; P = 0.799) was not associated with increased cavitation.CONCLUSIONS: PWSD had a higher bacterial burden at diagnosis than those who do not smoke drugs. Screening for TB among PWSD in the community may facilitate earlier linkage to TB treatment and reduce community transmission.

QuantiFERON®-TB Gold In-Tube reliability for immigrants with parasitic infections in Boston, USA.

Accurate testing and treatment for latent tuberculous infection is necessary for tuberculosis elimination. Certain parasite infections are associated with increased tuberculin skin test positivity; species-specific effects on QuantiFERON®-TB Gold In-Tube (QGIT) have not been described. To determine whether infection with helminths or protozoa affects QGIT results. We retrospectively analyzed QGIT and parasite testing results for immigrants screened in Boston, MA, USA, from 2012 to 2017. We also prospectively measured cytokines in QGIT supernatants for a subset (n = 68) with 1) helminths, 2) Blastocystis hominis, 3) other protozoa, and 4) no parasites. Of 527 immigrants screened, 141 (26.8%) were QGIT-positive and 229 (43.4%) had parasites detected: 27/527 (5.1%) had helminths and 202/527 (38.3%) protozoa. Cytokine analysis revealed increased interleukin-10 concentrations with protozoa (P = 0.04), and non-significantly higher T-helper 2 concentrations with helminths compared with no parasites. No significant differences emerged in QGIT positivity or interferon-gamma concentrations in any group. Study results support the use of QGIT in parasite-endemic settings. .

Quantifying TB transmission: a systematic review of reproduction number and serial interval estimates for tuberculosis.

Tuberculosis (TB) is the leading global infectious cause of death. Understanding TB transmission is critical to creating policies and monitoring the disease with the end goal of TB elimination. To our knowledge, there has been no systematic review of key transmission parameters for TB. We carried out a systematic review of the published literature to identify studies estimating either of the two key TB transmission parameters: the serial interval (SI) and the reproductive number. We identified five publications that estimated the SI and 56 publications that estimated the reproductive number. The SI estimates from four studies were: 0.57, 1.42, 1.44 and 1.65 years; the fifth paper presented age-specific estimates ranging from 20 to 30 years (for infants <1 year old) to <5 years (for adults). The reproductive number estimates ranged from 0.24 in the Netherlands (during 1933-2007) to 4.3 in China in 2012. We found a limited number of publications and many high TB burden settings were not represented. Certain features of TB dynamics, such as slow transmission, complicated parameter estimation, require novel methods. Additional efforts to estimate these parameters for TB are needed so that we can monitor and evaluate interventions designed to achieve TB elimination.

Sex and age differences in Mycobacterium tuberculosis infection in Brazil.

Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30-87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1-2.2; P = 0.02) and between ages 0-4 and 15-39 years among male contacts (OR 2.7, 95% CI 0.83-8.9 and 1.1, 95% CI 0.99-1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.

Atomic-scale age resolution of planetary events.

Resolving the timing of crustal processes and meteorite impact events is central to understanding the formation, evolution and habitability of planetary bodies. However, identifying multi-stage events from complex planetary materials is highly challenging at the length scales of current isotopic techniques. Here we show that accurate U-Pb isotopic analysis of nanoscale domains of baddeleyite can be achieved by atom probe tomography. Within individual crystals of highly shocked baddeleyite from the Sudbury impact structure, three discrete nanostructural domains have been isolated yielding average 206Pb/238U ages of 2,436±94 Ma (protolith crystallization) from homogenous-Fe domains, 1,852±45 Ma (impact) from clustered-Fe domains and 1,412±56 Ma (tectonic metamorphism) from planar and subgrain boundary structures. Baddeleyite is a common phase in terrestrial, Martian, Lunar and asteroidal materials, meaning this atomic-scale approach holds great potential in establishing a more accurate chronology of the formation and evolution of planetary crusts.

Effect of previous treatment and sputum quality on diagnostic accuracy of Xpert® MTB/RIF.

SETTING: In early studies, Xpert® MTB/RIF accurately detected culture-proven pulmonary tuberculosis (TB). Recent reports have, however, found a lower than expected specificity in previously treated TB patients. OBJECTIVE: To investigate the diagnostic accuracy of Xpert in presumptive pulmonary TB patients in Southwestern Uganda. DESIGN: We obtained demographic and clinical information and collected three sputum samples from each patient for smear microscopy, Xpert and culture. We estimated Xpert sensitivity and specificity against culture, and stratified the analysis by previous treatment and sputum quality status. RESULTS: We analyzed results from 860 presumptive TB patients, including 109 (13%) with a previous history of anti-tuberculosis treatment; 205 (24%) were culture-positive. Xpert specificity was lower (91.8%, 95%CI 84.9-96.2) in previously treated than in new TB patients (97.5%, 95%CI 96.1-98.5; P = 0.01). In an adjusted analysis, patients with culture-, Xpert+ results were more likely to have been previously treated for TB (OR 8.3, 95%CI 2.1-32.0; P = 0.002), and to have mucosalivary sputum (OR 4.1, 95%CI 1.1-14.6; P = 0.03), but were less likely to self-report fever (OR 0.23, 95%CI 0.1-0.7; P = 0.008) than patients with concordant positive results. CONCLUSION: Xpert specificity was lower in previously treated patients with suspected TB. The clinical and programmatic impact of culture-, Xpert+ results requires evaluation in future studies.

Mortality among African American women with sarcoidosis: data from the Black Women's Health Study.

BACKGROUND: Sarcoidosis is a chronic systemic granulomatous disease of unknown etiology that disproportionately affects black females.  Few studies have specifically addressed causes of death in this population. OBJECTIVES: To assess rates and causes of death among women with sarcoidosis in a prospective cohort study of U.S. black women. DESIGN: The Black Women's Health Study is a follow-up study of 59,000 U.S. black women aged 21-69 (median age 38) at entry in 1995.  Data on demographic and lifestyle factors and medical conditions, including sarcoidosis, were obtained through biennial questionnaires.  Deaths and causes of death from 1995 through 2009 among study subjects were identified from National Death Index data. We assessed mortality rates among women with and without a history of sarcoidosis.  Poisson regression models were used to estimate age-adjusted mortality rates. Cox proportional-hazards models were used to estimate hazard ratios for mortality and 95% confidence intervals. RESULTS: A total of 121 deaths occurred among 1,192 women with a history of sarcoidosis and 2813 deaths among women without sarcoidosis.  Mortality was greater at every age among women with sarcoidosis and the overall multivariable-adjusted hazard ratio was 2.44 (95% CI 2.03-2.93, p<0.0001). Of the deaths among women with sarcoidosis, 24.7% were directly attributable to sarcoidosis. CONCLUSIONS: In the Black Women's Health Study, women with sarcoidosis were more than twice as likely to die as women without the disease, with many of the deaths directly attributable to sarcoidosis.  Sarcoidosis is an important cause of premature death among black women with the disease.