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Histoplasmosis is a fungal disease associated with substantial mortality rates among persons with advanced HIV disease. Our systematic review synthesized data on the global prevalence of Histoplasma--caused antigenuria in persons with HIV. We searched PubMed/Medline, Embase, and Scopus databases on January 3, 2023, to identify cross-sectional and cohort studies evaluating Histoplasma antigenuria prevalence among adults with HIV infection. We calculated point estimates and 95% CIs to summarize prevalence. Of 1,294 studies screened, we included 15. We found Histoplasma antigenuria among 581/5,096 (11%; 95% CI 11%-12%) persons with HIV and 483/3,789 persons with advanced HIV disease (13%; 95% CI 12%-14%). Among persons with HIV and symptoms consistent with histoplasmosis, Histoplasma antigenuria prevalence was 14% (95% CI 13%-15%; 502/3,631 participants). We determined that persons with advanced HIV disease, inpatients, and symptomatic persons might benefit from a systematic approach to early detection of histoplasmosis using urine antigen testing.
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Antígenos Fúngicos , Infecciones por VIH , Histoplasma , Histoplasmosis , Humanos , Histoplasmosis/epidemiología , Histoplasmosis/orina , Histoplasmosis/diagnóstico , Histoplasma/inmunología , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Prevalencia , Antígenos Fúngicos/orina , Antígenos Fúngicos/inmunología , América Latina/epidemiología , África/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/epidemiología , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/orinaRESUMEN
People experiencing homelessness balance competing priorities resulting in reduced capacity to meet the care demands of chronic conditions, including Type 2 Diabetes Mellitus (T2DM). Arts-based performances present an avenue to expose others to these challenges. This article describes the process of incorporating qualitative research findings in a community-based participatory theater production to expose audiences to the day-to-day realities of living with T2DM while simultaneously experiencing homelessness. We conducted five focus groups and two individual interviews with people living with T2DM who had experienced homelessness with guidance from a community-engaged research team. We then collaborated with a local theater company to present common themes from these focus groups in a co-created play about the experience of managing T2DM while being homeless. We performed a staged reading of the play and assessed audience members' perceived stigma through a pre- and post-survey to determine if audience engagement within our theatrical production could reduce stigma toward individuals living with diabetes and/or people experiencing homelessness. This theatrical production is titled "Life Heist: Stealing Hope While Surviving Diabetes and Homelessness." Our work illustrates the feasibility and effectiveness of using participatory theater to disseminate qualitative research findings.
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Using data from 67 Ugandan human immunodeficiency virus (HIV) clinics (July 2019-January 2022), we report a 40% (1005/1662) reduction in the number of people with HIV presenting to care after August 2021 compared to prepandemic levels, with a greater proportion presenting with advanced HIV disease (20% vs 16% in the pre-coronavirus disease 2019 period).
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COVID-19 , Infecciones por VIH , Humanos , Uganda/epidemiología , Control de Enfermedades Transmisibles , Infecciones por VIH/epidemiología , VIH , Instituciones de Atención AmbulatoriaRESUMEN
This study aims to evaluate the association between smoking exposure and human papillomavirus (HPV)-related cervical abnormalities among women living with HIV (WLWH). By conducting a systematic review of the current literature, we evaluated the association between current active smoking and/or exposure to secondhand smoke (SHS) and the risk of cervical HPV incidence, prevalence, and clearance, as well as high-grade cervical intraepithelial neoplasm (HGCIN) incidence, prevalence, progression, and regression among WLWH. We conducted the literature search in Ovid Medline, Embase, and Scopus following the PRISMA guidelines. We determined the risk of bias of included studies using the Risk of Bias Assessment Tool for Nonrandomized Studies. Studies with the same effect measure were combined for a pooled estimate. We identified 15 studies that met the inclusion criteria for the final analysis, with a limited number of studies evaluating each study question. Among WLWH, current active smoking is associated with an increased risk of new HPV infections (HR = 1.33, 95% CI 1.10-1.60), HPV prevalence (ORpooled = 1.55, 95% CI 1.26-1.91), HGCIN incidence (HR = 1.5, 95% CI 1.2-2.0), and HGCIN prevalence (PR = 3.69, 95% CI 1.54-8.78). There was no significant association between current active smoking and HPV clearance. We did not identify any study that evaluated the association between SHS exposure and HPV-related cervical abnormalities among WLWH. Active smoking increases the risk of HPV infection and pre-cancer lesion development in WLWH. Considering smoking as an additional risk factor when designing tailored cervical cancer screening programs for WLWH is necessary in high smoking prevalence regions.
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Infecciones por VIH , Infecciones por Papillomavirus , Displasia del Cuello del Útero , Neoplasias del Cuello Uterino , Humanos , Femenino , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/prevención & control , Virus del Papiloma Humano , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Infecciones por Papillomavirus/complicaciones , Detección Precoz del Cáncer , Prevalencia , Fumar/efectos adversos , Fumar/epidemiología , Papillomaviridae , Displasia del Cuello del Útero/patologíaRESUMEN
BACKGROUND: The Visitect CD4 Advanced Disease test (AccuBio, Alva, United Kingdom) is a rapid, semi-quantitative assay that estimates CD4 results above or below 200 cells/µL. We evaluated the performance of the Visitect CD4 assay in semi-urban laboratories in Uganda. METHODS: We performed a pragmatic laboratory validation of the Visitect CD4 platform in four routine HIV clinics in Uganda, nested within a cluster randomized trial evaluating an enhanced package of screening and treatment for persons with advanced HIV disease (NCT05085171). As part of the clinical trial, samples processed on the Visitect CD4 platform were confirmed using another CD4 testing method. We compared the diagnostic performance of the Visitect CD4 platform against the confirmatory method by evaluating the sensitivity, specificity, positive and negative predictive values. RESULTS: Of 1495 venous blood samples that were processed both by the Visitect CD4 test and another confirmatory CD4 platform at clinics in Kampala, Uganda, specificity was 81% (95% CI, 79%-84%) and the positive predictive value was 69% (95% CI, 66%-73%). There were no samples for which the Visitect test was >200 cells/µL and the confirmatory test was ≤200 cells/µL, resulting in a sensitivity of 100%. Among Visitect CD4 tests that were read as <200 cells/µL with confirmatory results >200 cells/µL, the median confirmatory CD4 result was 397 (IQR, 281-590) cells/µL. Specificity varied by clinic ranging from 63% to 99%. CONCLUSIONS: Given variable specificity of the Visitect CD4 Advanced Disease platform, successful implementation will require consideration of clinic context and laboratory staffing.
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In sub-Saharan Africa, an estimated 25% of people with HIV present with advanced HIV and are at high risk of opportunistic infections. Whereas histoplasmosis has occasionally been seen in Uganda, the understanding of the local risk of acute infection is limited. We sought to determine the prevalence of Histoplasma antigenuria using an enzyme immunoassay (EIA, clarus Histoplasma GM EIA, IMMY; Norman, OK, USA) in a cohort of outpatients with advanced HIV disease in Kampala, Uganda. Among the persons with positive urine Histoplasma antigen tests, we assessed their clinical presentation and outcomes. The EIA was run on stored urine samples as per the manufacturer's instructions. Specimens ≥1 EIA units were considered positive. Among the 388 tested urine samples, 4 (1.2%) were positive for Histoplasma antigen. The histoplasmosis prevalence among participants with a CD4 < 100 cells/mcL was 2.5% (4/158). Three of the four participants with a positive Histoplasma antigen test reported systemic symptoms consistent with histoplasmosis. All four participants had a positive urine lipoarabinomannan test and were treated for tuberculosis. By the four-week follow-up visit, all participants were clinically improved, alive, and in care without antifungal therapy. In advanced HIV, the clinical presentations of tuberculosis and histoplasmosis overlap. The value of histoplasmosis screening and pre-emptive treatment is an area of future research.
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Protease-activated receptor 1 (PAR1), a thrombin-responsive G protein-coupled receptor (GPCR), is implicated in promoting metastasis in multiple tumor types, including both sarcomas and carcinomas, but the molecular mechanisms responsible remain largely unknown. We previously discovered that PAR1 stimulation in endothelial cells leads to activation of NF-κB, mediated by a protein complex comprised of CARMA3, Bcl10, and the MALT1 effector protein (CBM complex). Given the strong association between NF-κB and metastasis, we hypothesized that this CBM complex could play a critical role in the PAR1-driven metastatic progression of specific solid tumors. In support of our hypothesis, we demonstrate that PAR1 stimulation results in NF-κB activation in both osteosarcoma and breast cancer, which is suppressed by siRNA-mediated MALT1 knockdown, suggesting that an intact CBM complex is required for the response in both tumor cell types. We identify several metastasis-associated genes that are upregulated in a MALT1-dependent manner after PAR1 stimulation in cancer cells, including those encoding the matrix remodeling protein, MMP9, and the cytokines, IL-1ß and IL-8. Further, exogenous expression of PAR1 in MCF7 breast cancer cells confers highly invasive and metastatic behavior which can be blocked by CRISPR/Cas9-mediated MALT1 knockout. Importantly, we find that PAR1 stimulation induces MALT1 protease activity in both osteosarcoma and breast cancer cells, an activity that is mechanistically linked to NF-κB activation and potentially other responses associated with aggressive phenotype. Several small molecule MALT1 protease inhibitors have recently been described that could therefore represent promising new therapeutics for the prevention and/or treatment of PAR1-driven tumor metastasis.