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Item Caring for Adolescents and Young Adults With Tuberculosis or at Risk of Tuberculosis: Consensus Statement From an International Expert Panel(Elsevier, 2023) Chiang, Silvia S.; Waterous, Patricia M.; Atieno, Vivian Faith; Bernays, Sarah; Bondarenko, Yaroslava; Cruz, Andrea T.; de Oliveira, Márcia C. B.; Del Castillo Barrientos, Hernán; Enimil, Anthony; Ferlazzo, Gabriella; Ferrand, Rashida Abbas; Furin, Jennifer; Hoddinott, Graeme; Isaakidis, Petros; Kranzer, Katharina; Maleche-Obimbo, Elizabeth; Mansoor, Homa; Marais, Ben J.; Mohr-Holland, Erika; Morales, Mabel; Nguyen, Anh Phuong; Oliyo, Joshua Ochieng; Sant'Anna, Clemax Couto; Sawyer, Susan M.; Schaaf, H. Simon; Seddon, James A.; Sharma, Sangeeta; Skrahina, Alena; Starke, Jeffrey R.; Triasih, Rina; Tsogt, Bazarragchaa; Welch, Henry; Enane, Leslie A.; Pediatrics, School of MedicineBackground: Despite being a preventable and treatable disease, tuberculosis (TB) is a leading cause of death among young people globally. Each year, an estimated 1.8 million adolescents and young adults (AYAs; 10–24 years old) develop TB. In 2019, an estimated 161,000 AYAs died of the disease. AYAs have unique developmental, psychosocial, and healthcare needs, but these needs have been neglected in both TB care and research agendas. In order to improve outcomes in this age group, the specific needs of AYAs must be considered and addressed. Methods: Through a consensus process, an international panel of 34 clinicians, researchers, TB survivors, and advocates with expertise in child/adolescent TB and/or adolescent health proposed interventions for optimizing AYA engagement in TB care. The process consisted of reviewing the literature on TB in AYAs; identifying and discussing priority areas; and drafting and revising proposed interventions until consensus, defined a priori, was reached. Results: The panel acknowledged the dearth of evidence on best practices for identifying and managing AYAs with TB. The final consensus statement, based on expert opinion, proposes nine interventions to reform current practices that may harm AYA health and well-being, and nine interventions to establish high-quality AYA-centered TB services. Conclusion: AYA-specific interventions for TB care and research are critical for improving outcomes in this age group. In the absence of evidence on best practices, this consensus statement from an international group of experts can help address the needs of AYA with TB or at risk for TB.Item Certificate of merit posted in every grocery and meat market in the city.(Indiana State Board of Health, 1909-04)A certificate of food safety to advertise a free tuberculosis clinic.Item Cottage at tuberculosis treatment facility in Danville, Indiana.(Indiana State Board of Health, 1908-05)A near view of the cottages at the Rockwood Tuberculosis Sanitorium.Item Demonstration of patient in window-tent(Indiana State Board of Health, 1906-12) Kny-Scheerer CompanyDr. S.A. Knopf's window-tent in position with patient in bed looking through the celluloid window into the room but breathing outdoor air only.Item Design and implementation of a global site assessment survey among HIV clinics participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) research consortium(Public Library of Science, 2023) Brazier, Ellen; Maruri, Fernanda; Wester, C. William; Musick, Beverly; Freeman, Aimee; Parcesepe, Angela; Hossmann, Stefanie; Christ, Benedikt; Kimmel, April; Humphrey, John; Freeman, Esther; Enane, Leslie A.; Lancaster, Kathryn E.; Ballif, Marie; Golub, Jonathan E.; Nash, Denis; Duda, Stephany N.; International epidemiology Databases to Evaluate AIDS (IeDEA) consortium; Medicine, School of MedicineIntroduction: Timely descriptions of HIV service characteristics and their evolution over time across diverse settings are important for monitoring the scale-up of evidence-based program strategies, understanding the implementation landscape, and examining service delivery factors that influence HIV care outcomes. Methods: The International epidemiology Databases to Evaluate AIDS (IeDEA) consortium undertakes periodic cross-sectional surveys on service availability and care at participating HIV treatment sites to characterize trends and inform the scientific agenda for HIV care and implementation science communities. IeDEA's 2020 general site assessment survey was developed through a consultative, 18-month process that engaged diverse researchers in identifying content from previous surveys that should be retained for longitudinal analyses and in developing expanded and new content to address gaps in the literature. An iterative review process was undertaken to standardize the format of new survey questions and align them with best practices in survey design and measurement and lessons learned through prior IeDEA site assessment surveys. Results: The survey questionnaire developed through this process included eight content domains covered in prior surveys (patient population, staffing and community linkages, HIV testing and diagnosis, new patient care, treatment monitoring and retention, routine HIV care and screening, pharmacy, record-keeping and patient tracing), along with expanded content related to antiretroviral therapy (differentiated service delivery and roll-out of dolutegravir-based regimens); mental health and substance use disorders; care for pregnant/postpartum women and HIV-exposed infants; tuberculosis preventive therapy; and pediatric/adolescent tuberculosis care; and new content related to Kaposi's sarcoma diagnostics, the impact of COVID-19 on service delivery, and structural barriers to HIV care. The survey was distributed to 238 HIV treatment sites in late 2020, with a 95% response rate. Conclusion: IeDEA's approach for site survey development has broad relevance for HIV research networks and other priority health conditions.Item Diversity-Oriented Synthesis for Novel, Selective and Drug-like Inhibitors for a Phosphatase from Mycobacterium Tuberculosis(Royal Society of Chemistry, 2014-10) He, Rongjun; Bai, Yunpeng; Yu, Zhi-Hong; Wu, Li; Gunawan, Andrea Michelle; Zhang, Zhong-Yin; Department of Biochemistry & Molecular Biology, IU School of MedicineMycobacterium protein tyrosine phosphatase B (mPTPB) is a potential drug target of Tuberculosis (TB). Small molecule inhibitors of mPTPB could be a treatment to overcome emerging TB drug resistance. Using a Diversity-Oriented Synthesis (DOS) strategy, we successfully developed a salicylic acid based and drug-like mPTPB inhibitor with an IC50 of 2 μM and >20-fold specificity over many human PTPs, making it an excellent lead molecule for anti-TB drug discovery. In addition, DOS generated bicyclic salicylic acids are also promising starting points for acquiring inhibitors targeting other PTPs.Item DNA Testing Reveals the Putative Identity of JB55, a 19th Century Vampire Buried in Griswold, Connecticut(MDPI, 2019-08-22) Daniels-Higginbotham, Jennifer; Gorden, Erin M.; Farmer, Stephanie K.; Spatola, Brian; Damann, Franklin; Bellantoni, Nicholas; Gagnon, Katie S.; de la Puente, Maria; Xavier, Catarina; Walsh, Susan; Parson, Walther; McMahon, Timothy P.; Marshall, Charla; Biology, School of ScienceIn 1990 in Griswold, Connecticut, archaeologists excavated a burial found in a "skull and crossbones" orientation. The lid of the 19th century coffin had brass tacks that spelled "JB55", the initials of the person lying there and age at death. JB55 had evidence of chronic pulmonary infection, perhaps tuberculosis. It is possible that JB55 was deemed a vampire due to his disease, and therefore had to be "killed" by mutilating his corpse. In an attempt to reveal the identity of JB55, DNA testing was performed. Ancestry informative single nucleotide polymorphism (SNP) analysis using the Precision ID Ancestry Panel indicated European ancestry. A full Y-chromosomal short tandem repeat (Y-STR) profile was obtained, belonging to haplogroup R1b. When the Y-STR profile was searched in the publicly accessible FamilyTreeDNA R1b Project website, the two closest matches had the surname "Barber". A search of historical records led to a death notice mentioning John Barber, whose son Nathan Barber was buried in Griswold in 1826. The description of Nathan Barber closely fits the burial of "NB13," found near JB55. By applying modern forensic DNA tools to a historical mystery, the identity of JB55 as John Barber, the 19th century Connecticut vampire, has been revealed.Item Do clinical decision-support reminders for medical providers improve isoniazid preventative therapy prescription rates among HIV-positive adults? Study protocol for a randomized controlled trial(BioMed Central, 2015-04-09) Green, Eric P.; Catalani, Caricia; Diero, Lameck; Carter, E. Jane; Gardner, Adrian; Ndwiga, Charity; Keny, Aggrey; Owiti, Philip; Israelski, Dennis; Biondich, Paul; Department of Medicine, IU School of MedicineBACKGROUND: This document describes a research protocol for a study designed to estimate the impact of implementing a reminder system for medical providers on the use of isoniazid preventative therapy (IPT) for adults living with HIV in western Kenya. People living with HIV have a 5% to 10% annual risk of developing active tuberculosis (TB) once infected with TB bacilli, compared to a 5% lifetime risk in HIV-negative people with latent TB infection. Moreover, people living with HIV have a 20-fold higher risk of dying from TB. A growing body of literature suggests that IPT reduces overall TB incidence and is therefore of considerable benefit to patients and the larger community. However, in 2009, of the estimated 33 million people living with HIV, only 1.7 million (5%) were screened for TB, and about 85,000 (0.2%) were offered IPT. METHODS/DESIGN: This study will examine the use of clinical decision-support reminders to improve rates of initiation of preventative treatment in a TB/HIV co-morbid population living in a TB endemic area. This will be a pragmatic, parallel-group, cluster-randomized superiority trial with a 1:1 allocation to treatment ratio. For the trial, 20 public medical facilities that use clinical summary sheets generated from an electronic medical records system will participate as clusters. All HIV-positive adult patients who complete an initial encounter at a study cluster and at least one return encounter during the study period will be included in the study cohort. The primary endpoint will be IPT prescription at 3 months post the initial encounter. We will conduct both individual-level and cluster-level analyses. Due to the nature of the intervention, the trial will not be blinded. This study will contribute to the growing evidence base for the use of electronic health interventions in low-resource settings to promote high-quality clinical care, health system optimization and positive patient outcomes. Trial registration ClinicalTrials.gov NCT01934309, registered 29 August 2013.Item Exploring Dual-Targeting GroEL/ES & PtpB Inhibitors as a New Antibiotic Strategy for Tuberculosis(2019-05) Washburn, J. Alex; Johnson, Steven M.; Georgiadis, Millie M.; Hoang, Quyen Q.Current Mycobacterium tuberculosis (Mtb) treatments suffer from an increase in antibiotic resistance strains and the lack of efficacy against latent state tuberculosis, thus novel approaches targeting different mechanisms of action are needed. One strategy to target Mtb is to target protein homeostasis pathways by inhibiting molecular chaperones, in particular, GroEL/ES (HSP60/10) chaperonin systems. Mtb has two homologs of GroEL, of which GroEL1 is not essential, but is important for cytokine-dependent granuloma formation, and GroEL2 is essential for survival and the likely canonical housekeeping chaperonin. Another strategy to target Mtb is to target the protein tyrosine phosphatase B (PtpB) virulence factor that Mtb secretes into host cells to help evade immune responses. Thus, we envisioned that this analog series might also be capable of inhibiting Mtb PtpB along with GroEL. By developing compound 1 inhibitors that could act on all of GroEL1, GroEL2, and PtpB, we could have an antibiotic candidate that targets all stages of tuberculosis: actively replicating bacteria, bacteria evading host cell immune response, and granuloma formation in latent disease. In the Johnson lab, previous studies explored GroEL/ES inhibitors, with compound 1 being one of the most potent inhibitors, inhibiting both Trypanosoma brucei and Staphylococcus aureus proliferation. In the present study, we have screened previously developed compound 1 analogs, as well as a series of newly synthesized analogs that we term “half-molecules”. In this study, our results indicated two potential avenues to explore for future research. The first is a series of carboxyl-bearing compound 1 inhibitors, compounds 2m-o, 2m-m, and 2m-p, which act solely on Mtb PtpB phosphatase activity without inhibiting GroEL. The second is a series of compound 1 inhibitors (e.g. 20R and 20L) that are able to inhibit both the PtpB phosphatase and GroEL/ES chaperonin system. Thus, this exploratory study showed the possibility of pursuing such a polypharmacological antibiotic strategy against Mtb infections and with further optimization, such dual-targeting GroEL/ES and PtpB inhibitors could be effective against all stages of tuberculosis.Item Global emerging resistance in pediatric infections with TB, HIV, and gram-negative pathogens(Taylor & Francis, 2021-02) Enane, Leslie A.; Christenson, John C.; Pediatrics, School of MedicineInfants, children and adolescents are at risk of life-threatening, antimicrobial-resistant infections. Global burdens of drug-resistant TB, HIV and gram-negative pathogens have a particular impact on paediatric age groups, necessitating a paediatric-focused agenda to address emerging resistance. Dedicated approaches are needed to find, successfully treat and prevent resistant infections in paediatric populations worldwide. Challenges include the diagnosis and identification of resistant infections, limited access to novel antimicrobials or to paediatric-friendly formulations, limited access to research and clinical trials and implementation challenges related to prevention and successful completion of treatment. In this review, the particular complexities of emerging resistance in TB, HIV and gram-negative pathogens in children, with attention to both clinical and public health challenges, are highlighted. Key principles of a paediatric-focused agenda to address antimicrobial resistance are outlined. They include quality of care, increasing equitable access to key diagnostics, expanding antimicrobial stewardship and infection prevention across global settings, and health system strengthening. Increased access to research studies, including clinical trials, is needed. Further study and implementation of care models and strategies for child- or adolescent-centred management of infections such as HIV and TB can critically improve outcome and avoid development of resistance. As the current global pandemic of a novel coronavirus, SARS-CoV-2, threatens to disrupt health systems and services for vulnerable populations, this is a critical time to mitigate against a potential surge in the incidence of resistant infections.