Africa

Youth FORWARD: Capacity Building in Alternate Delivery Platforms and Implementation Models for Bringing Evidence-Based Behavioral Interventions to Scale for Youth Facing Adversity in West Africa by BOSTON COLLEGE (The Research University TRU)

HANSEN, NATHAN B

 

Youth FORWARD (Youth Functioning and Organizational Success for West African Regional Development) will establish an implementation science hub in West Africa with a dual mission: (a) to accelerate scaling up innovative and sustainable delivery of evidence-based mental health interventions for youth exposed to violence and other forms of adversity across a range of delivery settings; and (b) to serve as a global hub for capacity building in mental health services research on children, youth and families facing adversity and to conduct implementation science on the delivery of evidence-based mental health services via alternate delivery systems such as youth employment programs in West Africa. Youth FORWARD will establish partnerships that leverage the expertise and resources of the Harvard T.H. Chan School of Public Health, University of Georgia College of Public Health, CARITAS, World Bank, the governments of Sierra Leone and Liberia, and a network of youth service providers and universities. A proposed Scale-Up Study will use a hybrid implementation- effectiveness trial design across N=24 youth employment programs to evaluate an innovative approach to training and supervision?Interagency Collaborative Teams (ICTs)?and their influence on integration, fidelity, cost and sustainment of a quality mental health intervention?the Youth Readiness Intervention (YRI)?into a national youth employment program?the Youth Employment Scheme (YES). The concurrent effectiveness trial will assess youth mental health, emotion regulation, functioning and economic self-sufficiency among N=960 Sierra Leonean male and female youth aged 15-24 over time to determine effects of the YRI when implemented under this new delivery platform. Guided by the EPIS implementation model, qualitative data on attitudes towards mental health and barriers and facilitators to the integration of mental health services into youth employment programs will be collected. A Capacity Building Core will build sustainable capacity to conduct and apply mental health services and implementation research by fostering exchange and mutual learning between sites, through the development and delivery of innovative and locally relevant training and technical assistance programs for stakeholders including West African faculty, students, government partners, and NGO leaders. Links between the Scale-Up Study and Capacity Building Core will provide opportunities for on-the-job learning in quantitative and qualitative research to increase capacity for implementation science. These capacity building efforts will accelerate the scale up of evidence-based mental health programs to address the treatment gap in West Africa and will help government stakeholders make greater use of the evidence-base in policy and program development and evaluation methods to measure program effectiveness. .

 

Africa

The Health and Poverty Effects of a Large-scale Cookstove Initiative in Rwanda by UNIV OF NORTH CAROLINA CHAPEL HILL (The Research University TRU)

HANDA, SUDHANSHU

 

DESCRIPTION (provided by applicant): This project will evaluate the impact of a private sector cookstove and fuel distribution intervention on exposure to airborne pollutants, health and poverty. Inyenyeri, a private social entrepreneurship venture, will provide free cookstoves to over 50,000 households in Western Rwanda and implement a fuel pellet business over the next three years. We will build a randomized control trial 1) to assess the impact of this intervention on exposure to carbon monoxide, particulate matter (PM) and polycyclic aromatic hydrocarbons (PAH) of the primary household cook, and 2) to model the dose-response relationship between exposure and cardiovascular disease risk. We will conduct exposure monitoring and health assessments six times over two years in 180 households, one-third of which we will randomized out to the control arm. We will conduct a socioeconomic survey in a sample of 1,400 households at baseline, 12 and 24 months to measure consumption, health, time use, and emissions exposure to model the impact of cookstove adoption on time allocation, income generating activities, school enrollment and household poverty.

 

Africa

The effect of poverty; stress and immune function on health across the life-course by UNIV OF NORTH CAROLINA CHAPEL HILL (The Research University TRU)

HANDA, SUDHANSHU

 

AbstractThis project will assess the medium-term impact of a large-scale national anti-poverty program on disease andhealth risk of mature adults (age 45+) and young adults (age 20-26). We build on a longitudinal randomizedcontrol trial designed to evaluate the impact of an unconditional cash transfer program in a low-income setting.A fourth wave of data on the study population will include new measures of immune response, disease risk,and cognitive capacity. Combing these measures with information from previous waves, including the pre-intervention period, will allow us to map out the biological, behavioral and economic pathways through which acash transfer program influences health at two points in the life-cycle.Specifically, we will exploit the exogenous change in income evoked by random assignment to early-entrytreatment condition to estimate the causal effect of income poverty on immune function, and the role of stressin mediating this relationship. We will also estimate the causal effect of the cash transfer on a range ofindicators of disease risk. Half the young adults in our sample were exposed to the cash transfer during theircritical adolescence years, allowing us to estimate the impact of the cash on their disease risk. By providingestimates for both mature and younger adults, we can observe whether the hypothesized relationship varyacross the life-course. The proposal addresses the National Institute of Ageing’s Goal B to `better understandthe effects of personal, interpersonal, and societal factors on ageing, including mechanisms through whichthese factors exert their effects.’ Within Goal B, the proposal responds to objective B1: `Illuminate the pathwaysby which social, psychological, economic, and behavioral factors affect health in middle-aged and older adults.’

 

Africa

Promoting HIV health behaviors among pregnant couples in Zambia using an adaptive relationship strengthening intervention by UNIVERSITY OF COLORADO DENVER (The Research University TRU)

HAMPANDA, KAREN MARIE

 

PROJECT SUMMARY/ABSTRACTCandidate: I am a behavioral health researcher with expertise in the social determinants of HIV, with a particularemphasis on prevention of mother-to-child transmission (PMTCT) in sub-Saharan Africa. My long-term careergoal is to be a tenure-track professor in a school of public health with a robust research portfolio focused onfamily-based HIV prevention and treatment strategies. My prior training and experiences have enabled me toconduct rigorous research on the social and behavioral aspects of HIV in various global settings. However, tobecome a top investigator in my field capable of securing R01 funding, I require additional training andmentorship in intervention design and evaluation. The K99/R00 Pathway to Independence Award is a logicalprogression from my previous research and training. Under the mentorship of an exceptional team ofresearchers, I will focus my training phase of the award on career development activities that facilitate mytransition to an independent behavioral HIV investigator capable of leading intervention trials in resource limitedsettings. Mentored Phase Research (K99, years 1-2): The effectiveness of PMTCT programs is dependent onoptimizing pregnant and postpartum women?s adherence to antiretroviral therapy (ART) and sustainedengagement in care. In high HIV prevalence settings of sub-Saharan Africa, such as Zambia, women are lost-to-follow up at alarming rates across the cascade of care. Contextual factors, such as relationship dynamics withmale partners (relationship satisfaction, communication, conflict resolution), are a long-overlooked influence inwomen?s PMTCT-related health behaviors. Couples counseling interventions in the region have provensuccessful in strengthening relationships and promoting some HIV prevention behaviors, such couples HIVtesting. In order to test if a couples counseling approach can extend to PMTCT outcomes in Zambia, I willrefine a couples counseling intervention for HIV-positive pregnant women and their male partners (Aim 1). Theintervention is based on elements of my mentors? successful couples counseling models and uses a uniqueadaptive design. I will refine the content and delivery of the proposed intervention through qualitative interviewsand focus groups with HIV-positive pregnant women, their male partners, and service providers, while engagingstakeholders and building my research capacity in this setting. Independent Phase Research (R00, Years 3-5): I will implement a single-site randomized controlled trial of the couples counseling intervention (n=238couples; 119 per arm) and assess service utilization and PMTCT outcome indicators, including women?s viralload at 9 months postpartum, self-reported ART adherence, and retention in PMTCT care (Aim 2). I will alsoestablish the effect of the intervention on intra- and inter-personal mechanisms I hypothesize to be on the causalpathway influencing PMTCT outcomes (Aim 3) through behavioral surveys at baseline, 3 and 9 monthspostpartum. Future Directions: Findings from this study will provide evidence of the preliminary efficacy of thecouples counseling intervention to promote PMTCT adherence and retention, which will be used to develop alarger multi-site R01 trial with longer-term HIV outcomes.

 

Africa

Summer Institute in Statistics and Modeling in Infectious Diseases by UNIVERSITY OF WASHINGTON (The Research University TRU)

HALLORAN, M ELIZABETH

 

ABSTRACTThe overall goal of the annual Summer Institute in Statistics and Modeling in InfectiousDiseases (SISMID) at the University of Washington is to educate the next generation ofresearchers in a broad range of state-of-the-art quantitative methods for infectiousdisease research. Courses for skill development: SISMID is a collection of 16 2.5-daymodules offered over 2.5 weeks in July on a variety of topics relevant to researcheducation in statistics, modeling and computational methods applied to infectiousdiseases. Most participants take on average three modules per year. SISMID has beenheld each summer since 2009. This proposal requests funds for 2020-2024. The 2020SISMID proposes to offer the following: 1. Probability and Statistical Inference; 2.Mathematical Models of Infectious Diseases; 3. Introduction to R; 4. Causal Inference; 5.Evolutionary Dynamics and Molecular Epidemiology of Viruses; 6. Stochastic EpidemicModels with Inference; 7. Markov chain Monte Carlo I; 8. Microbiome Data Analysis; 9.Pathogen Evolution, Selection, and Immunity; 10. Simulation-based Inference forEpidemiologic Dynamics; 11. Statistics and Modeling with Novel Data Streams; 12.Infectious Diseases, Immunology, Within Host Models; 13. Markov chain Monte Carlo IIfor Infectious Diseases; 14. Spatial Statistics in Epidemiology and Public Health; 15.Contact Network Epidemiology: 16. Reconstructing Transmission with Genomic Data.The instructors are drawn from the University of Washington and other academicinstitutions in the USA and Europe, and industry. Instructor mentors will be assigned torecipients of support through this grant and put into email contact before SISMID. Theywill meet together during SISMID. Research experiences will include teams working onongoing projects and using innovative methods for reproducible research. This NIAIDResearch Education Program (R25) will allow us to provide graduate students andpostdoctoral fellows approximately 350 modules per year without charge and 100 partialtravel awards.

 

Africa

Partnership in Education Training and Research Advancement (PETRA) by COLLEGE OF HEALTH SCIS UNIV OF ZIMBABWE (The Research University TRU)

HAKIM, JAMES GITA

 

This proposal is to establish the Partnership for Education Training and Research Enhancement (PETRA)as a consortium of four Zimbabwean University faculties and departments of health professions educationin collaboration with two United States Universities to pursue a program of health professions educationand research capacity initiatives. The Zimbabwean Universities are University of Zimbabwe, College ofHealth Sciences, National University of Science and Technology, Midlands State University and AfricaUniversity. The USA universities are; University of Colorado Denver and Stanford University. The healtheducation focus is inter-professional education and collaborative practice (IPE/CP). The research focus isdissemination and implementation science research (DIS). These are new areas of education and researchat the Consortium institutions. The innovation in PETRA is to bring together these four university levelhealth education training institutions in the country in a coordinated and integrated program to promotethese new education and research models in Zimbabwe. The rationale for IPE/CP is that there aresynergies, advantages and complementarities in various health professionals working in teams thatcollaborate and respect each other. IPE/CP training of faculty will enable capacitation in being able tofacilitate teaching sessions in IPE/CP. We have planned demonstration projects in antiretroviral therapyclinics and at a stroke unit to provide experiential learning of the model. In DIS, faculty will also receivetraining alongside the usual training in research methodology and scholars will be selected to pursuemultidisciplinary projects with a focus on DIS in HIV/AIDS research questions. Utilization of informationcommunication technology platforms will be used in multimodal and blended models to deliver the PETRAprogram. Robust communication and outreach will ensure that all stakeholders are made aware of PETRAinitiatives which can be leveraged for wider circulation and implementation. We have targeted working withthe Ministries of Health and Higher Education and Community Service Organizations.

 

Africa

Role of African Trypanosome Extracellular Vesicles in Infection and Pathogenesis by UNIVERSITY OF GEORGIA (The Research University TRU)

HAJDUK, STEPHEN L

 

Intercellular communication between parasites and with host cells provides mechanisms for parasitedevelopment, immune evasion and disease pathology. Bloodstream African trypanosomes producemembranous nanotubes (NTs) that originate from the flagellar membrane and disassociate into freeextracellular vesicles (EVs). Trypanosome EVs contain several flagellar proteins that contribute tovirulence in the mammalian host including calflagin, adenylate cyclase (GRESAG4),glycosylphosphatidylinositol phospholipase C (GPI-PLC), calreticulin and metacaspase 4. In addition,the human sleeping sickness parasite Trypanosoma brucei rhodesiense produces EVs that containthe serum resistance associated protein (SRA) a virulence factor necessary for human infectivity. Wehave shown that T. b. rhodesiense EVs transfer SRA to non-human infectious trypanosomes allowingevasion of human innate immunity. Morphological and biophysical studies have shown thattrypanosome EVs can also fuse with phosphatidylcholine liposomes, the trypanosome flagellar pocketand mammalian erythrocytes. Trypanosome EV fusion with erythrocytes alters the physical propertiesof erythrocytes increasing membrane rigidity resulting in rapid erythrocyte clearance and anemia. Theproposed studies will extend these initial findings and address several fundamental questions aboutthe function of membrane NTs and EVs. 1) Are EVs produced during trypanosome infection and if sowhat is the rate of production and does EV cargo change during the course of infection? 2) Do EVsdeliver quorum-sensing molecules that trigger differentiation of BF trypanosomes? 3) Does the NT/EVpathway provide an efflux mechanism to rid human sleeping sickness parasites of trypanosome lyticfactors (TLF)? 4) Do EVs deliver trypanosome effector molecules that modulate production of thecytokine, tumor necrosis factor-?, in myeloid cells? 5) Does the fusion of trypanosome EVs with hosterythrocytes result in erythrophagocytosis and anemia? 6) What trypanosome proteins are necessaryfor EVs fusion to membranes? Together the proposed studies will result in a better understanding ofthe role of trypanosome EVs in cell-cell communication and pathogenesis associated by Africantrypanosomiasis. We anticipate these studies will lead to the development of new diagnostic tools andoffer novel strategies to combat anemia in human sleeping sickness and Nagana. 

 

Africa

The Genetic Basis of Aggressive Prostate Cancer: The Role of Rare Variation by UNIVERSITY OF SOUTHERN CALIFORNIA (The Research University TRU)

HAIMAN, CHRISTOPHER ALAN

 

? DESCRIPTION (provided by applicant): Prostate cancer (PCa) is the most common cancer in men with 220,000 new cases and 27,000 deaths estimated this year in the U.S. The vast majority of these deaths occur among the approximately 10-15% of cases diagnosed with aggressive PCa. There are few known risk factors for PCa beyond age, African descent and a family history of PCa, and there are no risk factors that can determine which men will develop aggressive versus non-aggressive disease. Multiple lines of evidence indicate a substantial heritable component of aggressive PCa. Over the past decade, genome-wide association studies (GWAS) have identified over 100 common susceptibility loci that collectively account for 33% of the familial risk of PCa. These loci contribute equally to risk of aggressive and non-aggressive disease which suggests they play a role in the very early stages of PCa tumor evolution. Recent sequencing studies have revealed rare coding variants (well under 1%) in genes such as BRCA1/2 and other DNA repair pathway genes that convey larger risks (3-5 fold) of aggressive PCa relative to non-aggressive disease. These observations suggest that the allelic architecture of aggressive disease may be quite different than overall PCa, and highlight the need for larger efforts focused on rare genetic variation (<1%). This spectrum of variation represents ~80% of all genetic variation in the human genome and is not adequately surveyed through GWAS. In this study, we will apply a multi-staged approach to reveal genes harboring rare variants that are associated with aggressive PCa. Whole-exome sequencing (Aim 1a) of 2,000 aggressive cases and 2,000 non-aggressive cases of European ancestry will be conducted followed by rare variant analysis of single sites and gene burden testing to identify novel susceptibility loci/genes for aggressive disease. We will validate the most significantly associated genes (~500) through targeted sequencing in an additional 7,500 aggressive and 7,500 non-aggressive cases (Aim 1b). Next, we will investigate the clinical predictive utility of the genes/variants identified in 2,300 cases in the STHM3 trial who are undergoing biopsy based on PSA and genetic risk score stratification (Aim 2). Last, we will examine whether the genes identified in Aim 1 contribute to the greater risk of aggressive PCa in 4,000 men of African ancestry (Aim 3). Through this tiered approach we expect to significantly advance knowledge of aggressive PCa etiology and health disparities as well as guide the development of early detection and prognostic strategies for the subset of men who are most susceptible to this fatal form of disease.

 

Africa

Interventions to reduce alcohol use and increase adherence to TB preventive therapy among HIV/TB co-infected drinkers (DIPT 1/2) by UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (The Research University TRU)

HAHN, JUDITH ALISSA

 

ABSTRACTTB is the leading cause of death among persons with HIV worldwide. Globally, approximately 25% of personswith HIV are heavy drinkers, and heavy alcohol use is associated with a 3-fold higher risk of TB diseasecompared to no alcohol use, thus HIV-infected persons who drink alcohol are at high risk for TB. Six months ofisoniazid (INH) preventive therapy (IPT) reduces TB incidence and mortality by 30-50% above the positiveimpact of antiretroviral therapy (ART). However, INH can be toxic to the liver, and thus many heavy alcoholusers in resource-limited settings such as east Africa are not offered IPT. In addition, heavy alcohol users havepoorer ART adherence and data suggest decreased IPT adherence as well. Thus interventions are needed toboth decrease alcohol use and increase IPT adherence, and thereby reduce INH toxicity, TB morbidity andmortality in this high-risk population. The use of incentives to promote healthy behavior has been shown to bea highly effective approach for reducing substance use and for improving adherence to HIV and TB regimensin high-income countries. Reducing alcohol use may create a window for safe and effective IPT use bydecreasing hepatotoxicity and increasing IPT adherence; however, additional interventions for IPT adherencemay be needed. The use of incentives conditional on reduced alcohol use or increased INH adherence inresource-limited settings has been previously limited by the lack of reliable, rapid tests for these behaviors.Recent technological advances allow for point of care (POC) urine testing for recent alcohol use with an ethylglucuronide (EtG) dipstick that is positive for 3 days after heavy drinking, and INH pill-taking using theIsoScreen urine test to test for 24-hour INH ingestion, thereby creating an opportunity to test incentive-basedinterventions during IPT among heavy drinkers. We propose leveraging two established cohorts of personswith HIV in Uganda for a randomized 2×2 factorial trial among HIV/TB co-infected adults with heavy alcoholuse (n=800 persons. 400 each U01 cohort). Aim 1 is to determine whether economic incentives contingent onreduced alcohol use assessed by POC EtG tests conducted at INH refill visits reduces heavy alcohol use oversix months of IPT compared to the control. Aim 2 is to determine whether economic incentives contingent onINH positive POC urine tests at these visits compared to the control increases IPT adherence over six months.Aim 3 is to examine the longer-term impact of the intervention on HIV virologic suppression, and examinemediators of an effect. Primary outcomes will be self-reported heavy alcohol use augmented byphosphatidylethanol (PEth) concentrations, and INH adherence, measured using medication event monitoringsystem (MEMS), with additional measurements of pill ingestion by INH levels in hair samples. Using incentive-based interventions to reduce alcohol use and increase medication safety in low-income settings is novel. Thisstudy to optimize IPT in HIV/TB co-infected drinkers will provide new information on low-cost strategies toreduce alcohol use and increase IPT adherence in low-income countries.

 

Africa

Interventions to reduce alcohol use and increase adherence to TB preventive therapy among HIV/TB co-infected drinkers (DIPT 1/2) by UNIVERSITY OF CALIFORNIA, SAN FRANCISCO (The Research University TRU)

HAHN, JUDITH ALISSA

 

Project summary/abstractTB is the leading cause of death among persons with HIV worldwide, and HIV-infected drinkers are at veryhigh risk for TB disease and mortality; receipt of six months of isoniazid (INH) preventive therapy (IPT) reducesTB morbidity and mortality by 30-50% above the benefit of antiretroviral therapy (ART), however, INH can betoxic to the liver. Thus, interventions to reduce alcohol use are needed to decrease INH toxicity during IPTamong HIV/TB infected drinkers. It is also well established that heavy drinkers have poorer ART adherence,and there is growing evidence of reduced IPT adherence in drinkers. However, interventions to reduce drinkinghave had limited impact on ART adherence, and further interventions to increase IPT adherence amongHIV/TB infected drinkers are likely needed. The use of incentives to promote healthy behavior is a highlyeffective approach for reducing substance use and for improving adherence to HIV and TB regimens inresource-rich settings. Economic incentives to reduce alcohol use may create a window for safe and effectiveIPT use over six months by decreasing hepatotoxicity. Decreases in alcohol use may also improve IPTadherence, or additional incentives for IPT adherence may be needed. Such strategies to reduce alcohol usehave not been studied in low-income countries and the effectiveness of incentives to optimize IPT in HIV/TBco-infected drinkers is unknown. The DIPT Study is a factorial design randomized controlled trial that aims totest interventions for reduced drinking and increased medication adherence to safely and effectively providetuberculosis (TB) preventive therapy to HIV/TB co-infected drinkers in sub-Saharan Africa. The study utilizesbehavioral theory to provide economic incentives for reduced drinking and isoniazid (INH) adherencemeasured by point-of-care tests. The study outcomes are (1) reduced heavy drinking during the 6-months ofINH, (2) increased isoniazid (INH; the drug used to prevent active TB) pill taking, and (3) increased viralsuppression over 12 months, in the intervention arms compared to the control. As far as we are aware, this isthe first study to examine the use of economic incentives to reduce alcohol use and to increase medicationadherence in HIV-infected drinkers in sub-Saharan Africa, so the findings from this study will be seminal. TheDIPT Study will collect outcome data, including objective biologic measures of alcohol use, INH adherence,and HIV viral suppression, and quantitative data on potential mediators and moderators of the effects; there isno current budget for qualitative data collection. Therefore, we propose a qualitative study with a subset ofDIPT participants in order to deepen our understanding of how economic incentives for decreased drinking andincreased INH adherence among HIV/TB co-infected drinkers are perceived to impact these outcomes, andtheir collateral effects on HIV risk taking, interpersonal relationships and violence, and economic well-being.

 

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