Risk of developing active tuberculosis following tuberculosis screening and preventive therapy for Tibetan refugee children and adolescents in India: An impact assessment.

BACKGROUND: Tuberculosis (TB) rates among Tibetan refugee children and adolescents attending boarding schools in India are extremely high. We undertook a comprehensive case finding and TB preventive treatment (TPT) program in 7 schools in the Zero TB Kids project. We aimed to measure the TB infection and disease burden and investigate the risk of TB disease in children and adults who did and did not receive TPT in the schools. METHODS AND FINDINGS: A mobile team annually screened children and staff for TB at the 7 boarding schools in Himachal Pradesh, India, using symptom criteria, radiography, molecular diagnostics, and tuberculin skin tests. TB infection (TBI) was treated with short-course regimens of isoniazid and rifampin or rifampin. TB disease was treated according to Tibetan and Indian guidelines. Between April 2017 and December 2019, 6,582 schoolchildren (median age 14 [IQR 11-16] years) and 807 staff (median age 40 [IQR 33-48] years) were enrolled. Fifty-one percent of the students and 58% of the staff were females. Over 13,161 person-years of follow-up in schoolchildren (median follow-up 2.3 years) and 1,800 person-years of follow-up in staff (median follow-up 2.5 years), 69 TB episodes occurred in schoolchildren and 4 TB episodes occurred in staff, yielding annual incidence rates of 524/100,000 (95% CI 414-663/100,000) person-years and 256/100,000 (95% CI 96-683/100,000) person-years, respectively. Of 1,412 schoolchildren diagnosed with TBI, 1,192 received TPT. Schoolchildren who received TPT had 79% lower risk of TB disease (adjusted hazard ratio [aHR] 0.21; 95% CI 0.07-0.69; p = 0.010) compared to non-recipients, the primary study outcome. Protection was greater in recent contacts (aHR 0.07; 95% CI 0.01-0.42; p = 0.004), the secondary study outcome. The prevalence of recent contacts was 28% (1,843/6,582). Two different TPT regimens were used (3HR and 4R), and both were apparently effective. No staff receiving TPT developed TB. Overall, between 2017 and 2019, TB disease incidence decreased by 87%, from 837/100,000 (95% CI 604-1,129/100,000) person-years to 110/100,000 (95% CI 36-255/100,000) person-years (p < 0.001), and TBI prevalence decreased by 42% from 19% (95% CI 18%-20%) to 11% (95% CI 10%-12%) (p < 0.001). A limitation of our study is that TB incidence could be influenced by secular trends during the study period. CONCLUSIONS: In this study, following implementation of a school-wide TB screening and preventive treatment program, we observed a significant reduction in the burden of TB disease and TBI in children and adolescents. The benefit of TPT was particularly marked for recent TB contacts. This initiative may serve as a model for TB detection and prevention in children and adolescents in other communities affected by TB.

Free Clinic Patients' Perceptions and Barriers to Applying for Health Insurance After Implementation of the Affordable Care Act.

Despite implementation of the Affordable Care Act (ACA), many Americans remain uninsured and receive care in free clinics. It is unknown what free clinic attendees in Pennsylvania know about health insurance expansion or what they perceive as barriers in enrolling in health insurance. The objective of this study was to assess the perceptions and experiences of free clinic patients from southwestern Pennsylvania when applying for health insurance after implementation of the ACA. We designed and implemented a survey of patients at three free clinics within Allegheny County, Pennsylvania from September 2016 to February 2017. Our survey included 22-items, 7 sociodemographic questions and 15 questions regarding the patient's health status and their perspectives related to obtaining health insurance. Data was obtained from 203 patient surveys; 110 (55.3%) of the respondents were men and 99 (48.8%) were African American. There were 48 respondents (24.1%) who did not report any income at the time of the study, and of those that did report an income, 92 (46.2%) respondents reported an income below 133% of the federal poverty level. The main barriers patients faced when applying for health insurance were: (1) lack of knowledge about health insurance (n = 127, 58.1%), (2) cost of health coverage (n = 85, 41.9%), (3) lack of resources (n = 83, 40.4%), and (4) lack of enrollment documentation (n = 43, 23.8%). Significant work is needed to better educate patients about their eligibility and options for health insurance. Free clinics can play a key role in eliminating barriers to health insurance enrollment.

Tuberculosis and hepatic steatosis are prevalent liver pathology findings among HIV-infected patients in South Africa.

Liver disease epidemiology in sub-Saharan Africa has shifted as a result of HIV and the increased use of antiretroviral therapy leading to a need for updated data on common causes of liver disease. We retrospectively reviewed records from all hospitalized patients who had liver biopsy at a single hospital in South Africa from 2001 to 2009 and compared diagnosis by HIV status. During the period of study 262 patients had liver biopsy, 108 (41%) were HIV-infected, 25 (10%) were HIV-sero-negative, and 129 (49%) had unknown or unrecorded HIV status. Overall 81% of biopsies provided additional diagnostic data. Malignancy was the most common finding reported on 56 (21%) biopsies followed by granuloma or TB, hepatic steatosis, and fibrosis or cirrhosis. HIV-infected patients were more likely to have granulomas and steatosis. Half of patients with granulomas were already on TB treatment, suggesting paradoxical reactions or drug induced liver injury may have been important causes of liver inflammation among these patients. We note that TB, paradoxical reactions during TB treatment, possible drug induced liver injury, and hepatic steatosis are important causes of liver pathology among HIV-infected hospitalized patients with unclear etiology of liver disease after initial assessment. Among HIV sero-negative patients, malignancy was the major cause of liver disease. Our findings re-enforce the importance of TB as a diagnosis among HIV-infected individuals.

Active tuberculosis case-finding among pregnant women presenting to antenatal clinics in Soweto, South Africa.

BACKGROUND: Human immunodeficiency virus (HIV) and tuberculosis (TB) are among the leading causes of death among women of reproductive age worldwide. TB is a significant cause of maternal morbidity. Detection of TB during pregnancy could provide substantial benefits to women and their children. METHODS: This was a cross-sectional implementation research study of integrating active TB case-finding into existing antenatal and prevention of mother-to-child transmission services in six clinics in Soweto, South Africa. All pregnant women 18 years of age or older presenting for routine care to these public clinics were screened for symptoms of active TB, cough for 2 weeks or longer, sputum production, fevers, night sweats, or weight loss, regardless of their HIV status. Participants with any symptom of active TB were asked to provide a sputum specimen for smear microscopy, mycobacterial culture and drug-susceptibility testing. RESULTS: Between December 2008 and July 2009, 3963 pregnant women were enrolled and screened for TB, of whom 1454 (36.7%) were HIV-seropositive. Any symptom of TB was reported by 23.1% of HIV-seropositive and 13.8% of HIV-seronegative women (P < 0.01). Active pulmonary TB was diagnosed in 10 of 1454 HIV-seropositve women (688 per 100,000) and 5 of 2483 HIV-seronegative women (201 per 100,000, P = 0.03). The median CD4⁺ T-cell count among HIV-seropositive women with TB was similar to that of HIV-seropositive women without TB (352 versus 333 cells/µL, P = 0.85). CONCLUSIONS: There is a high burden of active TB among HIV-seropositive pregnant women. TB screening and provision of isoniazid preventive therapy and antiretroviral therapy should be integrated with prevention of mother-to-child transmission services.

Synthesis, activity, and pharmacophore development for isatin-beta-thiosemicarbazones with selective activity toward multidrug-resistant cells.

We have recently identified a new class of compounds that selectively kill cells that express P-glycoprotein (P-gp, MDR1), the ATPase efflux pump that confers multidrug resistance on cancer cells. Several isatin-beta-thiosemicarbazones from our initial study have been validated and a range of analogues synthesized and tested. A number demonstrated improved MDR1-selective activity over the lead, NSC73306 (1). Pharmacophores for cytotoxicity and MDR1 selectivity were generated to delineate the structural features required for activity. The MDR1-selective pharmacophore highlights the importance of aromatic/hydrophobic features at the N4 position of the thiosemicarbazone and the reliance on the isatin moiety as key bioisosteric contributors. Additionally, a quantitative structure-activity relationship (QSAR) model that yielded a cross-validated correlation coefficient of 0.85 effectively predicts the cytotoxicity of untested thiosemicarbazones. Together, the models serve as effective approaches for predicting structures with MDR1-selective activity and aid in directing the search for the mechanism of action of 1.