Risk Screening Tools Could Potentially Miss HIV-Positive Individuals Who Seek Testing Services: A Secondary Program Data Analysis on the Performance Characteristics of an Adolescent and Adult HIV Risk Screening Tool in Uganda.

Improving HIV testing efficiency saves financial and material resources for health. We conducted a secondary data analysis of routinely collected HIV risk-screening program data in Uganda, from October to November 2019, to determine the performance characteristics of the adolescent and adult HIV risk screening tools in public health facilities. A total of 19,854 clients had been screened for HIV testing eligibility and tested for HIV. The overall positivity rate (cluster-weighted prevalence of HIV) among those screened was 4.5% (95% CI: 4.1-4.8) versus 3.71% (95% CI: 3.06-4.50) among those not screened. The sensitivity and specificity of the risk screening tool were 91% (95% CI: 89-93) and 25% (24.2-26), respectively. With screening, the number needed to test to identify one PLHIV was reduced from 27 to 22. Although risk screening would have led to a 24.5% (4825/19,704) reduction in testing volume, 9.3% (68/732) of PLHIV would have been missed and be misclassified as not eligible for testing. The cost saving per PLHIV identified was minimally reduced by 3% from USD 69 without screening to USD 66.9 with screening. Since the treatment-adjusted prevalence of HIV is dropping globally, overzealous use of risk screening tools to determine who to test or not carries the potential of missing PLHIV due to their limited specificity. We recommend the use of scientifically validated HIV risk screening tools, and a need to explore the use of HIV self-testing as a test for tirage to minimize misclassification of people who seek HIV testing services.

Patient costs for prevention of mother-to-child HIV transmission and antiretroviral therapy services in public health facilities in Zimbabwe.

Zimbabwe has made large strides in addressing HIV. To ensure a continued robust response, a clear understanding of costs associated with its HIV program is critical. We conducted a cross-sectional evaluation in 2017 to estimate the annual average patient cost for accessing Prevention of Mother-To-Child Transmission (PMTCT) services (through antenatal care) and Antiretroviral Treatment (ART) services in Zimbabwe. Twenty sites representing different types of public health facilities in Zimbabwe were included. Data on patient costs were collected through in-person interviews with 414 ART and 424 PMTCT adult patients and through telephone interviews with 38 ART and 47 PMTCT adult patients who had missed their last appointment. The mean and median annual patient costs were examined overall and by service type for all participants and for those who paid any cost. Potential patient costs related to time lost were calculated by multiplying the total time to access services (travel time, waiting time, and clinic visit duration) by potential earnings (US$75 per month assuming 8 hours per day and 5 days per week). Mean annual patient costs for accessing services for the participants was US$20.00 [standard deviation (SD) = US$80.42, median = US$6.00, range = US$0.00-US$12,18.00] for PMTCT and US$18.73 (SD = US$58.54, median = US$8.00, range = US$0.00-US$ 908.00) for ART patients. The mean annual direct medical costs for PMTCT and ART were US$9.78 (SD = US$78.58, median = US$0.00, range = US$0.00-US$ 90) and US$7.49 (SD = US$60.00, median = US$0.00) while mean annual direct non-medical cost for US$10.23 (SD = US$17.35, median = US$4.00) and US$11.23 (SD = US$25.22, median = US$6.00, range = US$0.00-US$ 360.00). The PMTCT and ART costs per visit based on time lost were US$3.53 (US$1.13 to US$8.69) and US$3.43 (US$1.14 to US$8.53), respectively. The mean annual patient costs per person for PMTCT and ART in this evaluation will impact household income since PMTCT and ART services in Zimbabwe are supposed to be free.

Fibrostenotic eosinophilic esophagitis might reflect epithelial lysyl oxidase induction by fibroblast-derived TNF-α.

BACKGROUND: Fibrosis and stricture are major comorbidities in patients with eosinophilic esophagitis (EoE). Lysyl oxidase (LOX), a collagen cross-linking enzyme, has not been investigated in the context of EoE. OBJECTIVE: We investigated regulation of epithelial LOX expression as a novel biomarker and functional effector of fibrostenotic disease conditions associated with EoE. METHODS: LOX expression was analyzed by using RNA-sequencing, PCR assays, and immunostaining in patients with EoE; cytokine-stimulated esophageal 3-dimensional organoids; and fibroblast-epithelial cell coculture, the latter coupled with fluorescence-activated cell sorting. RESULTS: Gene ontology and pathway analyses linked TNF-α and LOX expression in patients with EoE, which was validated in independent sets of patients with fibrostenotic conditions. TNF-α-mediated epithelial LOX upregulation was recapitulated in 3-dimensional organoids and coculture experiments. We find that fibroblast-derived TNF-α stimulates epithelial LOX expression through activation of nuclear factor κB and TGF-ß-mediated signaling. In patients receiver operating characteristic analyses suggested that LOX upregulation indicates disease complications and fibrostenotic conditions in patients with EoE. CONCLUSIONS: There is a novel positive feedback mechanism in epithelial LOX induction through fibroblast-derived TNF-α secretion. Esophageal epithelial LOX might have a role in the development of fibrosis with substantial translational implications.

Preferential Secretion of Thymic Stromal Lymphopoietin (TSLP) by Terminally Differentiated Esophageal Epithelial Cells: Relevance to Eosinophilic Esophagitis (EoE).

Eosinophilic esophagitis (EoE) is a chronic Th2 and food antigen-mediated disease characterized by esophageal eosinophilic infiltration. Thymic stromal lymphopoetin (TSLP), an epithelial derived cytokine which bridges innate and Th2-type adaptive immune responses in other allergic conditions, is overexpressed in esophageal biopsies of EoE subjects. However, the triggers of TSLP expression in the esophageal epithelium are unknown. The objective of the current study was to characterize TSLP expression in human esophageal epithelium in EoE in vivo and to determine the role of food antigens upon epithelial TSLP expression in vitro. Using immunohistochemistry (IHC), we localized TSLP in esophageal biopsies of active EoE (≥15 eos/hpf), inactive EoE (<15 eos/hpf) and non-EoE control subjects, and found that TSLP expression was restricted to the differentiated suprabasal layer of the epithelium in actively inflamed EoE biopsies. Consistent with these results in vivo, inducible TSLP protein secretion was higher in CaCl2 differentiated telomerase-immortalized esophageal epithelial cells (EPC2-hTERT) compared to undifferentiated cells of the basal phenotype, following stimulation with the TLR3 ligand poly(I:C). To determine whether food antigens could directly induce epithelial TSLP secretion, differentiated and undifferentiated primary esophageal epithelial cells from EoE and non-EoE subjects were challenged with food antigens clinically relevant to EoE: Chicken egg ovalbumin (OVA), wheat, and milk proteins beta-lactoglobulin (blg) and beta-casein. Food antigens failed to induce TSLP secretion by undifferentiated cells; in contrast, only OVA induced TSLP secretion in differentiated epithelial cells from both EoE and control cell lines, an effect abolished by budesonide and NF-κb inhibition. Together, our study shows that specific food antigens can trigger innate immune mediated esophageal TSLP secretion, suggesting that esophageal epithelial cells at the barrier surface may play a significant role in the pathogenesis of EoE by regulating TSLP expression.