Antibody Duration After Infection From SARS-CoV-2 in the Texas Coronavirus Antibody Response Survey.

Understanding the duration of antibodies to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus that causes COVID-19 is important to controlling the current pandemic. Participants from the Texas Coronavirus Antibody Response Survey (Texas CARES) with at least 1 nucleocapsid protein antibody test were selected for a longitudinal analysis of antibody duration. A linear mixed model was fit to data from participants (n = 4553) with 1 to 3 antibody tests over 11 months (1 October 2020 to 16 September 2021), and models fit showed that expected antibody response after COVID-19 infection robustly increases for 100 days postinfection, and predicts individuals may remain antibody positive from natural infection beyond 500 days depending on age, body mass index, smoking or vaping use, and disease severity (hospitalized or not; symptomatic or not).

Financing Benefits and Barriers to Routine HIV Screening in Clinical Settings in the United States: A Scoping Review.

The Centers for Disease Control and Prevention recommends everyone between 13-64 years be tested for HIV at least once as a routine procedure. Routine HIV screening is reimbursable by Medicare, Medicaid, expanded Medicaid, and most commercial insurance plans. Yet, scaling-up HIV routine screening remains a challenge. We conducted a scoping review for studies on financial benefits and barriers associated with HIV screening in clinical settings in the U.S. to inform an evidence-based strategy to scale-up routine HIV screening. We searched Ovid MEDLINE®, Cochrane, and Scopus for studies published between 2006-2020 in English. The search identified 383 Citations; we screened 220 and excluded 163 (outside the time limit, irrelevant, or outside the U.S.). Of the 220 screened articles, we included 35 and disqualified 155 (did not meet the eligibility criteria). We organized eligible articles under two themes: financial benefits/barriers of routine HIV screening in healthcare settings (9 articles); and Cost-effectiveness of routine screening in healthcare settings (26 articles). The review concluded drawing recommendations in three areas: (1) Finance: Incentivize healthcare providers/systems for implementing HIV routine screening and/or separate its reimbursement from bundle payments; (2) Personnel: Encourage nurse-initiated HIV screening programs in primary care settings and educate providers on CDC recommendations; and (3) Approach: Use opt-out approach.

Commentary: Texas Has a Secret Weapon Against Cancer.

Cancer is the No. 2 cause of death in Texas and across the United States. The good news is that things change, and we can be active agents in making sure that they change for the better. The Cancer Prevention and Research Institute of Texas (CPRIT) was established by a voter-supported constitutional amendment in 2007. It is a unique Texas resource, and is now second only to the National Institutes of Health in overall cancer research funding. On Nov. 5, voters will have the opportunity to extend CPRIT's important work for an additional 10 years and $3 billion. If approved, Texas will continue to lead the nation and the world in the fight against cancer. If the new funding is not approved, far too much of this important work will end. Reauthorization of CPRIT would do more than keep the ball rolling; it would save lives.

Building a health communication brand for University of Texas System tobacco control.

Objective: Despite declining cigarette smoking rates in the US, there is a continued need for tobacco prevention education campaigns to reach young adults. Recognizing the need for improved tobacco control messaging, the University of Texas (UT) System engaged The University of Texas at Austin Center for Health Communication to develop a brand and message that would strengthen tobacco control efforts at its 14 institutions. Methods: This article describes the iterative process involved in creating a brand for tobacco control, including an environmental scan, identifying potential message themes, and creating and refining logos. Results: This article highlights the process of developing a system-wide tobacco control brand. Specifically, the process included coordinating an interdisciplinary team with content and design experts, and presenting ideas to stakeholders for serial feedback and refinement, among others. Conclusions: Ultimately, this project offers a model for other systems of higher education interested in pursuing similar initiatives.

Maternal risk factor index and cesarean delivery among women with nulliparous, term, singleton, vertex deliveries, Texas, 2015.

BACKGROUND: Cesarean delivery accounts for over one-third of the ~400 000 annual births in Texas, with first-time cesarean accounting for 20% of the overall cesareans. We examined associations of maternal medical comorbidities with cesarean delivery among nulliparous, term, singleton, vertex (NTSV) deliveries in Texas. METHODS: Nulliparous, term, singleton, vertex deliveries to women aged 15-49 years were identified using the 2015 Texas birth file (Center for Health Statistics, Texas Department of State Health Services). A risk factor index was constructed (score range 0-4), including preexisting/gestational diabetes mellitus, preexisting/gestational hypertension/eclampsia, infertility treatment, smoking during pregnancy, and prepregnancy overweight/obesity, and categorized as 0, 1, 2, and 3+ based on the number of risk factors present. Multivariable logistic regression analyses were conducted to examine associations between the categorized risk factor index and cesarean delivery, overall and by maternal race and ethnicity. RESULTS: Among the 114 535 NTSV deliveries in Texas in 2015, 27.2% were by cesarean. The most prevalent maternal risk among all deliveries was prepregnancy overweight/obesity (42.4%). The odds of cesarean delivery increased significantly with increasing number of risk factors [one risk factor: 1.72 (95% CI 1.67-1.78); two risk factors: 2.58 (95% CI 2.46-2.71); and three or more risk factors: 3.91 (95% CI 3.45-4.44)]. DISCUSSION: In Texas in 2015, nearly half of NTSV deliveries had at least one maternal risk factor and the odds of cesarean delivery were significantly elevated for women with a higher risk index score. The findings from this study highlight the need for intervening during the preconception and interconception period as intrapartum care practices have an important influence on birth outcomes.

The principal sigma factor sigA mediates enhanced growth of Mycobacterium tuberculosis in vivo.

The ability of Mycobacterium tuberculosis to grow in macrophages is central to its pathogenicity. We found previously that the widespread 210 strain of M. tuberculosis grew more rapidly than other strains in human macrophages. Because principal sigma factors influence virulence in some bacteria, we analysed mRNA expression of the principal sigma factor, sigA, in M. tuberculosis isolates during growth in human macrophages. Isolates of the 210 strain had higher sigA mRNA levels and higher intracellular growth rates, compared with other clinical strains and the laboratory strain H37Rv. SigA was also upregulated in the 210 isolate TB294 during growth in macrophages, compared with growth in broth. In contrast, H37Rv sigA mRNA levels did not change under these conditions. Overexpression of sigA enhanced growth of recombinant M. tuberculosis in macrophages and in lungs of mice after aerosol infection, whereas recombinant strains expressing antisense transcripts to sigA showed decreased growth in both models. In the presence of superoxide, sense sigA transformants showed greater resistance than vector controls, and the antisense sigA transformant did not grow. We conclude that M. tuberculosis sigA modulates the expression of genes that contribute to virulence, enhancing growth in human macrophages and during the early phases of pulmonary infection in vivo. This effect may be mediated in part by increased resistance to reactive oxygen intermediates.

Spectrum of manifestations of Mycobacterium tuberculosis infection in primates infected with SIV.

To characterize the manifestations of coinfection with M. tuberculosis and SIV infection, we studied 12 SIV-infected rhesus monkeys, six of which were infected intrabronchially with a low dose of Mycobacterium tuberculosis H37Rv. In the six coinfected animals, M. tuberculosis antigen-stimulated lung and blood cells produced high concentrations of IFN-gamma but not IL-4 8-16 weeks after infection. Of the three coinfected animals with high levels of plasma viremia, two developed disseminated tuberculosis and the other died of bacterial peritonitis. Of three coinfected animals with moderate levels of plasma viremia, two had no clinical or radiographic evidence of tuberculosis or progressive SIV infection for 6 months after infection. At neuropsy, pulmonary granulomata were observed and acid-fast organisms or M. tuberculosis were present. These clinical, immunologic and pathologic findings are consistent with those in humans with latent tuberculosis infection (LTBI), and suggest that a model of LTBI in SIV-infected primates can be developed. Such a model will permit delineation of the immunologic and microbial factors that characterize LTBI in HIV-infected persons.

The Mycobacterium tuberculosis 19-kilodalton lipoprotein inhibits gamma interferon-regulated HLA-DR and Fc gamma R1 on human macrophages through Toll-like receptor 2.

Mycobacterium tuberculosis survives in macrophages in the face of acquired CD4(+) T-cell immunity, which controls but does not eliminate the organism. Gamma interferon (IFN-gamma) has a central role in host defenses against M. tuberculosis by activating macrophages and regulating major histocompatibility complex class II (MHC-II) antigen (Ag) processing. M. tuberculosis interferes with IFN-gamma receptor (IFN-gamma R) signaling in macrophages, but the molecules responsible for this inhibition are poorly defined. This study determined that the 19-kDa lipoprotein from M. tuberculosis inhibits IFN-gamma-regulated HLA-DR protein and mRNA expression in human macrophages. Inhibition of HLA-DR expression was associated with decreased processing and presentation of soluble protein Ags and M. tuberculosis bacilli to MHC-II-restricted T cells. Inhibition of HLA-DR required prolonged exposure to 19-kDa lipoprotein and was blocked with a monoclonal antibody specific for Toll-like receptor 2 (TLR-2). The 19-kDa lipoprotein also inhibited IFN-gamma-induced expression of Fc gamma RI. Thus, M. tuberculosis, through 19-kDa lipoprotein activation of TLR-2, inhibits IFN-gamma R signaling in human macrophages, resulting in decreased MHC-II Ag processing and recognition by MHC-II-restricted CD4 T cells. These findings provide a mechanism for M. tuberculosis persistence in macrophages.

The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium.

We used human tuberculosis as a model to investigate the role of NK cytotoxic mechanisms in the immune response to intracellular infection. Freshly isolated NK cells and NK cell lines from healthy donors lysed Mycobacterium tuberculosis-infected monocytes to a greater extent than uninfected monocytes. Lysis of infected monocytes was associated with increased expression of mRNA for the NKp46 receptor, but not the NKp44 receptor. Antisera to NKp46 markedly inhibited lysis of infected monocytes. NK cell-mediated lysis was not due to reduced expression of MHC class I molecules on the surface of infected monocytes or to enhanced production of IL-18 or IFN-gamma. NK cell lytic activity against M. tuberculosis-infected monocytes and NKp46 mRNA expression were reduced in tuberculosis patients with ineffective immunity to M. tuberculosis compared with findings in healthy donors. These observations suggest that 1) the NKp46 receptor participates in NK cell-mediated lysis of cells infected with an intracellular pathogen, and 2) the reduced functional capacity of NK cells is associated with severe manifestations of infectious disease.

Reduced expression of nuclear cyclic adenosine 5'-monophosphate response element-binding proteins and IFN-gamma promoter function in disease due to an intracellular pathogen.

Mycobacterium tuberculosis-induced IFN-gamma protein and mRNA expression have been shown to be reduced in tuberculosis patients, compared with healthy tuberculin reactors. To determine whether this decrease was associated with reduced activity of the IFN-gamma promoter, we first studied binding of nuclear proteins to the radiolabeled proximal IFN-gamma promoter (-71 to -40 bp), using EMSAs with nuclear extracts of freshly isolated peripheral blood T cells. Nuclear extracts of T cells from most tuberculosis patients showed markedly reduced expression of proteins that bind to the proximal IFN-gamma promoter, compared with findings in nuclear extracts of T cells from healthy tuberculin reactors. These DNA-binding complexes contained CREB proteins, based on competitive EMSAs, supershift assays, and Western blotting with an anti-CREB Ab. Transient transfection of PBLs with a luciferase reporter construct under the control of the IFN-gamma promoter revealed reduced IFN-gamma promoter activity in tuberculosis patients. Transient transfection of Jurkat cells with a dominant-negative CREB repressor plasmid reduced IFN-gamma promoter activity. These data suggest that reduced expression of CREB nuclear proteins in tuberculosis patients results in decreased IFN-gamma promoter activity and reduced IFN-gamma production.