Sustained effect of isoniazid preventive therapy among household contacts in Brazil.

BACKGROUND: Isoniazid preventive therapy (IPT) is highly effective in preventing TB disease; however, its long-term benefit in household contacts (HHCs) of infectious TB cases is unclear.METHODS: We conducted a retrospective analysis of two household contact studies in Vitoria, ES, Brazil, between 2008 and 2015. Households with smear-positive, culture-proven TB disease were enrolled. Eligible HHCs with tuberculin skin test (TST) indurations of ≥10 mm were referred to local TB clinics and IPT was started according to national guidelines. We reviewed the national dataset information system in January 2020 to identify HHCs with a diagnosis of TB disease. Time to event and Cox proportional regression analysis were conducted to identify factors associated with TB disease.RESULTS: Of the 1097 HHCs enrolled, 654 (60%) had TST ≥10 mm; 160 (24%) initiated IPT, of whom 115 (71.9%) completed IPT, which accounts for an overall completion rate of 18% among the population at risk; 42 (6%) TB cases were identified. IPT was associated with a 71% decrease in TB disease rates (HR 0.29, 95% CI 0.10-0.82; P = 0.02) among HHCs with TST ≥10 mm. IPT effect was sustained, as TB cases in HHCs without IPT occurred along the 7.9-year follow-up, whereas all four TB cases in HHCs with IPT were diagnosed within the first 3 years after exposureCONCLUSION: Isoniazid provides long-term protection for TB disease in household contacts of culture-proven TB cases.

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.

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.

Expression, regulation and clinical relevance of the ATPase inhibitory factor 1 in human cancers.

Recent findings in colon cancer cells indicate that inhibition of the mitochondrial H(+)-adenosine triphosphate (ATP) synthase by the ATPase inhibitory factor 1 (IF1) promotes aerobic glycolysis and a reactive oxygen species (ROS)-mediated signal that enhances proliferation and cell survival. Herein, we have studied the expression, biological relevance, mechanism of regulation and potential clinical impact of IF1 in some prevalent human carcinomas. We show that IF1 is highly overexpressed in most (>90%) of the colon (n=64), lung (n=30), breast (n=129) and ovarian (n=10) carcinomas studied as assessed by different approaches in independent cohorts of cancer patients. The expression of IF1 in the corresponding normal tissues is negligible. By contrast, the endometrium, stomach and kidney show high expression of IF1 in the normal tissue revealing subtle differences by carcinogenesis. The overexpression of IF1 also promotes the activation of aerobic glycolysis and a concurrent ROS signal in mitochondria of the lung, breast and ovarian cancer cells mimicking the activity of oligomycin. IF1-mediated ROS signaling activates cell-type specific adaptive responses aimed at preventing death in these cell lines. Remarkably, regulation of IF1 expression in the colon, lung, breast and ovarian carcinomas is exerted at post-transcriptional levels. We demonstrate that IF1 is a short-lived protein (t1/2 ∼100 min) strongly implicating translation and/or protein stabilization as main drivers of metabolic reprogramming and cell survival in these human cancers. Analysis of tumor expression of IF1 in cohorts of breast and colon cancer patients revealed its relevance as a predictive marker for clinical outcome, emphasizing the high potential of IF1 as therapeutic target.

Tuberculosis in household contacts of infectious cases in Kampala, Uganda.

Tuberculosis remains a serious threat to public health, especially in sub-Saharan Africa. To determine the host and environmental factors responsible for tuberculosis in African households, the authors performed a prospective cohort study of 1,206 household contacts of 302 index cases with tuberculosis enrolled in Uganda between 1995 and 1999. All contacts were systematically evaluated for active tuberculosis and risk factors for active disease. Among the 1,206 household contacts, 76 secondary cases (6%) of tuberculosis were identified. Of these cases, 51 were identified in the baseline evaluation, and 25 developed during follow-up. Compared with index cases, secondary cases presented more often with minimal disease. The risk for secondary tuberculosis was greater among young children than adults (10% vs. 1.9%) and among human immunodeficiency virus-seropositive than -seronegative contacts (23% vs. 3.3%). Host risk factors could not be completely separated from the effects of environmental risk factors, suggesting that a household may represent a complex system of interacting risks for tuberculosis.

Thyroid cancer. Survival in 148 cases followed for 10 years or more.

One hundred forty-eight patients with differentiated carcinoma of the thyroid treated between May 1954 and April 1973 are presented. There were 89 papillary and 59 follicular carcinomas. They were classified according to Woolner criteria. Treatment consisted of surgery I-131 and thyroid hormone. Recurrences occurred in 8.7% of the patients, and lethality at the end of the observation period was 3.3%. The impact of histologic type, extent of the primary, and age of the patient at the time of treatment on prognosis were studied. The data were submitted to statistical analysis. This study revealed that these factors are determinant on prognosis. Best survival rates were observed in patients 40 years of age or younger at the time of treatment, in patients with intrathyroid papillary carcinomas, and in patients with noninvasive follicular carcinomas.