FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences Grants

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

The HIV research agenda in Kenya and sub-Saharan Africa (SSA) is far-reaching. Much of it has been developed and carried out in partnership with institutions in the United States, Canada, and Europe, leading to gains in local capacity in terms infrastructure and professional development of scientists and physicians. One important domain where capacity building still lags behind is biostatistics and quantitative sciences: There is a shortage of African biostatisticians available to work on international research teams, and many HIV research programs in SSA continue to rely on their partners from the Global North for implementation of advanced methods for design and analysis. Although the past 5 years have seen substantial advances in research and educational capacity, many leading universities in SSA are only beginning to develop graduate-level training in statistics for health research. Statistics training in Kenya has typically been theoretical in nature, with applied work focusing primarily on biometry and agricultural statistics. Moi University, the second largest in Kenya, is typical in this regard. During Phase 1 of this training program, Moi began the process of implementing a graduate biostatistics curriculum. However there are only two faculty at Moi with PhD in biostatistics, highlighting the need for expansion of expertise among current faculty and development of potential new faculty members. At the College of Health Sciences, there continues to be high demand for masters-level statisticians to engage in externally funded research. Finally, the small number of African statisticians with advanced training working in HIV research centers in SSA tend to be geographically isolated from their peers, limiting opportunities for professional development and exchange of ideas. The proposed training program will respond to these needs by launching Phase 2 of a partnership between Moi and Brown Universities. The program will expand research and curricular capacity in HIV-related biostatistics and advanced quantitative methods at Moi and lay the foundation for sustainable growth in this field by accomplishing the following Specific Aims: (1) provide masters-level training at Brown (2 trainees, 2 years each), PhD training in a sandwich program at Moi and Brown (2 trainees, 4 years each), and postdoctoral training at Brown and Moi (2 trainees, 2 years each; (2) facilitate revision and expansion of the biostatistics curriculum at Moi through faculty development and faculty fellowships (4 trainees, 1 year each); (3) continue an annual workshop on advanced biostatistical methods at Moi that will offer short-term training and ongoing professional development activities for faculty members and professionals throughout SSA; and (4) lay the groundwork for a Center for Health Data Science on the campus of Moi University. This proposal builds directly upon the accomplishments and experiences from Phase 1 of the partnership, which provided training to 6 Kenyan statisticians; 4 masters students, 1 faculty fellow and 1 research fellow. Four of the six trainees are working at Moi or AMPATH in Eldoret, and one is pursuing a PhD in biostatistics.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Eastern Nigeria Research Ethics Training (ENRICH) Program Administrative Supplement. Project summary The Eastern Nigeria Research Ethics Training (ENRICH) Program a successful collaboration between the University of Maryland School of Medicine and the Center for Bioethics and Research, Nigeria has trained 17 MSc Bioethics and 14 MPH with Bioethics Concentration trainees since inception in 2021. The program has also offered 14,446 short-term online CBR- BRANY-CITI trainings and 48 3-months long diploma trainings in research ethics. In total, we have trained 15 health research ethics committees and strengthened them to become registered ethics committee in Nigeria. During this administrative supplement period, the program would sustain the momentum and 3 MSc Bioethics, 6 MPH with Bioethics concertation trainees, sustain access to online short-term bioethics training and strategize on curriculum revision to align with the America First Global Health strategy and new NIH and USG priorities.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Neuromyelitis optica (NMO) is an autoantibody-mediated disease of the central nervous system, predominantly affecting women and disproportionately people of African descent. The diagnosis of NMO is contingent upon the accurate detection of the aquaporin-4 (AQP4) antibody, the disease's sensitive and specific biomarker. The availability, accessibility, and affordability of the AQP4 antibody test is low in low- and middle-income countries. Most patients with NMO do not have access to the test globally. Moreover, neuroimmunological disorders have traditionally, but erroneously, been considered to be rare in Black patients, with costly diagnostic tests and even more costly treatments, leading to limited expertise being built in lowest income African settings. Recently, new advances in autoantibody detection using low-cost techniques have emerged, allowing our team to detect the AQP4 antibody from small blood samples that are collected by the patient onto a filter paper-based test and mailed to the processing laboratory. This method allows patients far from reference laboratories to collect a dried blood sample and learn their diagnosis. These samples can be tested from warm temperatures, stored at room temperature, and last months and still be processed successfully. When processed at the Mayo Clinic Laboratories, dried blood spots have a high sensitivity and moderately high specificity for AQP4 detection. The most immediate value for a point of care AQP4 test is in lowest income settings where laboratory capacity is limited and antibody testing is not the current standard of care. In this study, a collaborative team from Massachusetts General Hospital, Mayo Clinic Rochester, and the Ignace Hospital in Guinea with three rural Guinean sites - Dubreka, Fouricariah, and Kindia - will focus on capacity building for neuroimmunological diagnosis and management in the West African Republic of Guinea. The team will test the point of care dried blood spot test in phenotypically-enriched cohorts at highest likelihood of having AQP4 antibody positive NMO in Guinea and estimate point prevalence of NMO in these cohorts. The well-defined subcohort of AQP4+ NMO patients will serve as a base for future clinical trials for the Guinean investigators. The study team will leverage their deep and established expertise to elevate the status of neuroimmunological disease expertise in West Africa. The team will also establish a workflow for testing at the point of care for complex and devastating neuroimmunological diseases, a process that can be eventually scaled for other point of care tests in remote, rural, and/or resource-limited settings.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Project Abstract Alzheimer’s Disease and Alzheimer’s Disease-Related Dementias (AD/ADRD) affect 51 million people worldwide, a prevalence expected to triple by 2050. Two-thirds of those with AD/ADRD live in low- and middle- income countries (LMICs) where the greatest growth in AD/ADRD prevalence is expected, but where services to diagnose and manage this condition are scarce and data regarding dementia burden are limited. Although the Lancet Commission on Dementia, Prevention, Intervention, and Care has identified 14 modifiable risk factors that contribute to 45% of AD/ADRD cases worldwide, there are limited data regarding the prevalence and role of these modifiable risk factors in LMICs. Thus, interventions targeting these factors may have limited impact on AD/ADRD risk in LMIC settings. This proposal’s overall objective is to assess the prevalence rate of AD/ADRD and associated risk factors among adults age ≥55 years in urban and rural Zambia, a LMIC in sub- Saharan Africa. Based on our pilot work, we hypothesize that the prevalence rate of AD/ADRD among adults age ≥55 years will be approximately 9.5% and prevalence of associated risk factors will differ between urban and rural participants. These hypotheses will be tested through a population-based study of adults age ≥55 years in the urban Lusaka and rural Mazabuka Districts of Zambia. AD/ADRD prevalence will be assessed using formal neuropsychological testing, participant, and informant report according to DSM-V criteria. Additional validated questionnaires, a physical examination, and laboratory investigations will assess AD/ADRD risk factors. This project will also build and expand the neuropsychiatric expertise and workforce necessary to conduct prospective AD/ADRD research by providing training and AD/ADRD research experience for a Zambian neuropsychologist, neuropsychologists-in-training, and a cohort of community health workers. The proposed research is highly innovative because it examines AD/ADRD prevalence in a population with limited existing data and expected growth in rates of AD/ADRD and associated risk factors. Knowledge gained from this work will determine (1) the prevalence of AD/ADRD and (2) the prevalence of modifiable risk factors which have the greatest impact on AD/ADRD prevalence in this rapidly aging population. This project will have a significant impact by expanding the capacity for AD/ADRD studies in Zambia and will lay the groundwork for the conduct of future longitudinal studies and trials assessing low-cost interventions to reduce AD/ADRD prevalence and improve patient care.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

In Vietnam, adolescent and young men vulnerable to HIV through sexual behaviors are among those most affected by the infection, with an HIV prevalence that quadrupled from 3% in 2011 to 13% in 2020. More than 20% of Vietnamese young men living with HIV had moderate-to-severe depression and anxiety symptoms. These youths experienced extensive stigma related to their HIV status and sexual behaviors. There is a dearth of youth-friendly mental health services in Vietnam where there is less than one psychiatrist per 100,000 people. Project YES+ is an intervention integrating two evidence-based interventions, Project YES! and Self-Help+ to improve mental health, stigma, and HIV outcomes among youth living with HIV in Zambia (5R01TW012411). Youth Engaging for Success (Project YES!) is an HIV clinic-based peer mentoring CDC-designated intervention that successfully decreased HIV self-stigma and increased viral suppression. Self-Help+ is a group-based lay-delivered program endorsed by WHO that effectively prevents the onset of mental disorders and reduces mental health symptoms in different cultures. We propose to adapt Project YES+ for adolescent and young men living with HIV in Vietnam to create To Hieu (I Understand) and to pilot test the adapted intervention. The specific aims are to (1) Adapt Project YES+ to create To Hieu to improve mental health and reduce internalized HIV stigma for adolescent and young men living with HIV in Vietnam and (2) Examine acceptability and feasibility of To Hieu among adolescent and young men living with HIV through a pilot randomized controlled trial. In Aim 1, the adaption will follow the 8-step ADAPT-ITT framework.38 We will conduct in-depth interviews with adolescent and young men living with HIV (N=20) to explore preferences for the core components and formats of To Hieu. We will hold a human-centered design workshop to engage adolescent and young men living with HIV in co-design activities to refine To Hieu. In Aim 2, we will recruit 80 adolescent and young men living with HIV with depression or anxiety symptoms at two HIV clinics in Hanoi, Vietnam and randomize them 1:1 into two arms. The intervention arm will receive To Hieu in 4 months, while the control arm will receive standard of care at the clinics. The RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework will guide the measurement of the outcomes. We will calculate participation rates of participants (Reach) at baseline. We will assess acceptability through the Client Satisfaction Questionnaire and feasibility through intervention attendance (Adoption) at 4 months. Depression, anxiety symptoms, internalized HIV and sexual stigma, ART adherence and viral suppression of participants will be evaluated at baseline, 4 months and compared between groups (preliminary Effectiveness). We will conduct exit interviews with participants, youth peer mentors and HIV providers (N=30) to explore acceptability, feasibility (Implementation) and sustainability (Maintenance) of To Hieu. This research will build local capacity and develop networks for collaborative research on mental health and stigma among adolescent and young men living with HIV between Vietnam and the US.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

ABSTRACT: Suboptimal gestational weight gain (GWG) is a modifiable risk factor for adverse pregnancy outcomes, postpartum weight retention and obesity, and subsequently, the long-term development of non-communicable diseases (NCD) among women and children. In South Africa, 45% of women exceed the Institute of Medicine’s (IOM) recommended weight gain in pregnancy, and 38% gain too little weight, putting them at risk for poor perinatal and postpartum NCD outcomes. Women in low- and middle-income countries (LMICs) with a high burden of HIV and NCDs, such as South Africa, are at particularly high risk of suboptimal weight gain due to poor diet quality, limited physical activity, high levels of psychosocial stressors, and, for women with HIV (WHIV), possible antiretroviral-associated weight gain. By supporting healthy GWG, there is strong potential to reduce postpartum NCD risk and improve perinatal outcomes for women with and without HIV. However, few GWG interventions are available for delivery in LMICs, and none have been adapted to address excessive and inadequate GWG or enhanced to meet the unique needs of women with and without HIV. To address this gap, our team previously developed an innovative, theoretically driven group prenatal care (GPNC) intervention and adapted it to reduce GWG and NCD (GPNC-NCD) risk in resource-constrained settings. GPNC-NCD is an evidence-based intervention, based on social cognitive theory, that builds health literacy, self-efficacy, social support, and satisfaction with care, leading to improved perinatal, GWG, NCD, and perinatal outcomes. The goal of this proposal is to adapt the GPNC-NCD intervention for use in South Africa to support healthy GWG (not too much or too little), enhance it to address the needs of WHIV and without HIV, and evaluate the feasibility, acceptability, and preliminary efficacy of the intervention to improve GWG, NCD, perinatal, and HIV care and prevention outcomes in a pilot randomized trial. Our specific aims are: 1) to adapt the GPNC-NCD intervention for use in South Africa to support healthy GWG and enhance it to address HIV status as a driver of GWG, and 2) to determine the feasibility, acceptability, and preliminary efficacy of the adapted and enhanced GPNC intervention. In a pilot trial, 80 women will be individually randomized by HIV status at ≤14 weeks gestation to GPNC (n=20 WHIV, n=20 HIV-) versus usual care (n=20 WHIV, n=20 HIV-). We hypothesize that adapted GPNC will be feasible, acceptable and show preliminary efficacy to improve GWG, NCD (blood pressure, breastfeeding, diet, physical activity), HIV care/prevention (ART adherence, viral suppression, or PreP uptake), and perinatal (birthweight, large-for-gestational age, cesarean delivery) outcomes. This proposal addresses the goals of PAR-23-191 by leveraging the evidence-based GPNC intervention to support healthy GWG, addresses HIV-NCD disparities, and builds capacity for HIV/NCD research in LMICs. If successful, our adapted GPNC intervention has strong potential to serve as a model for how to integrate NCD and HIV care and prevention support into routine prenatal care in LMICs to improve perinatal, HIV, and NCD outcomes.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

ABSTRACT: Suboptimal gestational weight gain (GWG) is a modifiable risk factor for adverse pregnancy outcomes, postpartum weight retention and obesity, and subsequently, the long-term development of non-communicable diseases (NCD) among women and children. In South Africa, 45% of women exceed the Institute of Medicine’s (IOM) recommended weight gain in pregnancy, and 38% gain too little weight, putting them at risk for poor perinatal and postpartum NCD outcomes. Women in low- and middle-income countries (LMICs) with a high burden of HIV and NCDs, such as South Africa, are at particularly high risk of suboptimal weight gain due to poor diet quality, limited physical activity, high levels of psychosocial stressors, and, for women with HIV (WHIV), possible antiretroviral-associated weight gain. By supporting healthy GWG, there is strong potential to reduce postpartum NCD risk and improve perinatal outcomes for women with and without HIV. However, few GWG interventions are available for delivery in LMICs, and none have been adapted to address excessive and inadequate GWG or enhanced to meet the unique needs of women with and without HIV. To address this gap, our team previously developed an innovative, theoretically driven group prenatal care (GPNC) intervention and adapted it to reduce GWG and NCD (GPNC-NCD) risk in resource-constrained settings. GPNC-NCD is an evidence-based intervention, based on social cognitive theory, that builds health literacy, self-efficacy, social support, and satisfaction with care, leading to improved perinatal, GWG, NCD, and perinatal outcomes. The goal of this proposal is to adapt the GPNC-NCD intervention for use in South Africa to support healthy GWG (not too much or too little), enhance it to address the needs of WHIV and without HIV, and evaluate the feasibility, acceptability, and preliminary efficacy of the intervention to improve GWG, NCD, perinatal, and HIV care and prevention outcomes in a pilot randomized trial. Our specific aims are: 1) to adapt the GPNC-NCD intervention for use in South Africa to support healthy GWG and enhance it to address HIV status as a driver of GWG, and 2) to determine the feasibility, acceptability, and preliminary efficacy of the adapted and enhanced GPNC intervention. In a pilot trial, 80 women will be individually randomized by HIV status at ≤14 weeks gestation to GPNC (n=20 WHIV, n=20 HIV-) versus usual care (n=20 WHIV, n=20 HIV-). We hypothesize that adapted GPNC will be feasible, acceptable and show preliminary efficacy to improve GWG, NCD (blood pressure, breastfeeding, diet, physical activity), HIV care/prevention (ART adherence, viral suppression, or PreP uptake), and perinatal (birthweight, large-for-gestational age, cesarean delivery) outcomes. This proposal addresses the goals of PAR-23-191 by leveraging the evidence-based GPNC intervention to support healthy GWG, addresses HIV-NCD disparities, and builds capacity for HIV/NCD research in LMICs. If successful, our adapted GPNC intervention has strong potential to serve as a model for how to integrate NCD and HIV care and prevention support into routine prenatal care in LMICs to improve perinatal, HIV, and NCD outcomes.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Weight gain following initiation of integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is a major emerging public health threat, significantly increasing risks for dyslipidemia, systemic inflammation, hypertension, diabetes, and cardiovascular disease among people with HIV (PWH) in both the United States (U.S.) and globally. Addressing this challenge is a priority for U.S. health, as identifying why some individuals experience "excessive" weight gain (well beyond “return to health” weight gain) will enable earlier, targeted interventions in at-risk U.S. populations. This research environment cannot be replicated in the U.S. due to extreme clinical heterogeneity: the U.S. Food and Drug Administration (FDA) has approved 26+ individual ARV medications across 7 mechanistic classes, leading to diverse prescribing patterns in which only ~52% of patients follow recommended initial regimens. Furthermore, the median U.S. ART treatment duration is 9.8 years, creating a complex history of prior drug exposures that act as significant confounders in metabolic studies. In contrast, Nigeria uniquely offers a high volume of new HIV diagnoses and a near-uniform use of TLD (tenofovir/lamivudine/dolutegravir). This uniformity provides a unique "natural laboratory" that yields faster, more direct answers about metabolomic and lipidomic signatures by eliminating the noise introduced by varied drug histories. Consequently, these findings can be scaled and adapted globally, directly benefiting the U.S. by informing next-generation diagnostic tools, treatment strategies, and prevention modalities. We hypothesize that substantial early weight gain on TLD is driven by distinct alterations in metabolic and lipid pathways. To test this, we will: 1) Determine the effect of substantial early weight gain on TLD on insulin resistance, blood pressure, dyslipidemia, and inflammation. We will enroll previously ART-naïve patients who initiated TLD regimens (n=200 total) in northern Nigeria and gained <3% body weight (n=100) versus >10% body weight (n=100) over their first 12–24 months of therapy. 2) Determine the metabolic and lipid pathways associated with weight gain during the first 12 months of TLD exposure using metabolomic and lipidomic profiling. We will enroll 60 ART-naïve patients initiating TLD and collect longitudinal sociodemographic, behavioral, clinical, metabolomic, and lipidomic data, along with abdominal CT imaging, to characterize visceral adiposity, hepatic density, and alterations in carbohydrate and lipid metabolism among participants with differing weight trajectories.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Sickle cell disease (SCD) affects approximately 100,000 Americans, making it the most common inherited blood disorder in the United States. Over 1.2 million people are living with HIV in the U.S. Both chronic illnesses are endemic in overlapping geographic areas and reported in thousands of U.S. patients. A systematic review found conflicting conclusions on the effect of HIV on SCD and revealed numerous knowledge gaps, including the clinical profile of SCD patients living with HIV (PLWHIV), and the impact of HIV infection and HIV treatment on SCD outcomes. The clinical management of the comorbidity is currently uncertain in the U.S. because of lack of evidence. The previous studies were unable to include SCD severity due to the phenotype variability within SCD genotypes that may have different associations with severity of SCD and HIV status. Although the study results will be applicable to the medical care of Americans with HIV and SCD, the study will be conducted in Cameroon because the higher HIV prevalence allows the enrollment of more HIV+ patients with SCD. In addition, four of the five SCD genotypes are found in Central Africa allowing the study of this important covariate. Findings from Cameroon are generalizable in the U.S. because the diagnosis, the pathophysiology, and the ART regimens are similar. Based upon the genotypic, clinical, and biological particularities of SCD the project will address the gap in knowledge on the effects of HIV infection on SCD in two Specific Aims: Aim 1: We shall establish a clinical registry that includes all SCD patients to measure HIV prevalence, demographic and clinical characteristics in Cameroon. This will be a cross-sectional and descriptive study involving all SCD patients registered and followed-up in in the country. The investigators will screen all the 866 patients for HIV to confirm their status and to potentially identify new HIV positive patients. This research phase will describe the baseline clinical profile of SCD, determine the frequency of HIV infection in SCD patients and compare socio-demographic and clinical factors between HIV+ and HIV- SCD patients. Aim 2: Using a sample from the same patient population, we shall conduct a cross-sectional study on a matched random sampling of 48 HIV-positive SCD patients, and 96 HIV-negative SCD patients. Additionally, we shall randomly select 48 consenting HIV positive non-SCD patients among the HIV patients currently followed-up at the YUTH HIV care center as a second control group for the study. We shall measure prospectively the levels of biological markers of thrombosis, hemolysis, inflammation and organ failure and compare them according to HIV status. We shall assess if the SCD genotype will be an effect modifier of the relation between HIV status and SCD biological markers. The medical registry and data collected during this exploratory study will serve as the preliminary data for a future R01 application. The study will provide important data to improve specific ways US care through future interventional studies on immune system modulation, targeted infection prophylaxis, iron management, tailored ART regimens and gene therapy optimization in American SCD patients living with HIV.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Around the world, HIV concentrates in carceral settings. In Mozambique, the 12% nationwide HIV prevalence is about doubled in its prisons. If research finds pioneering programs for new areas of HIV care, such as managing non-communicable diseases (NCD), are effective in high prevalence prisons, they rapidly inform US carceral healthcare, where HIV prevalence is 1.1%. Recruiting and delivering interventions are faster when prevalence is high. Addressing HIV poses challenges to carceral systems globally due to low resources and overcrowding. Currently, the Mozambican prison system holds 2.5 times its capacity. Nonetheless, nearly all people in their prisons living with HIV know their status and take antiretrovirals. Of those treated, ~75% are suppressed. HIV care everywhere is now expanding focus to managing not just co-infections (like TB) but also HIV-associated NCDs, to prevent premature mortality. Findings from new prison programs can be scaled up for other low- and middle-income countries (LMIC) facing limited healthcare infrastructure and an HIV burden 10-20x that is found in US facilities. Years of collaboration between Emory, Servico Nacional Penitenciario or SERNAP, and the non-governmental organization Health through Walls has resulted in two TB/HIV screening studies managed by a tablet-based data management system. We will transition to the Virtu Cares Electronic Health Record (EHR). We are inviting the National Health Service, Instituto Nacional de Saude (INS), along with consultants in cardiovascular disease and health economics to join our collaboration and build up research infrastructure. Members of SERNAP's Health Service prioritized 5 NCDs: smoking, other substance use disorders (SUD), depression, hypertension (HTN), and malnutrition. We will integrate screening for these conditions into mass screenings for TB in 2026-7 and compare NCD prevalence in those with and without HIV. Over the following year, we will invite colleagues from a local university and INS to roll-out interventions to address these issues and then measure improvement. The team will compare residents living with/without HIV, while pursuing the following aims: (1) Refine the EHR, add screening for SERNAP's 5 priority NCD to HIV/TB screening, compare those with/without HIV; (2) Work with Mozambican academic/public health leaders to refine/deliver interventions to prison residents; measure readiness to change, then address in a status-neutral manner multiple NCDs: SUD via 12-step groups; smoking cessation via cognitive behavioral therapy; HTN via smoking cessation, diet, and medical management; and malnutrition, via a nutrition program; track results longitudinally; (3) Conduct follow-up, facility-wide screenings, using the EHR to measure improved NCD management; administer evaluations among staff and patients about the EHR and interventions and implementation fidelity/acceptability. We will then use the RE-AIM implementation framework to evaluate both the EHR and the status-neutral delivery of NCD interventions. We anticipate that integrating NCD/HIV management will improve prison healthcare in both LMIC and the US.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Women comprise about 50% of the 36.7 million people living with HIV worldwide and in many sub-Saharan African countries including Nigeria, ~2 out of 3 HIV infected adults are women. Even more worrisome is the observation that overwhelming number of new infections in Nigeria occur among young women of childbearing age, and as such, one-third of all global cases of mother-to-child transmission of HIV occurs in the country. Not only is the burden of HIV higher in women, the impact of its scourge is far more reaching. HIV is the leading cause of morbidity and mortality among women of reproductive age in Nigeria. HIV complicates every aspect of health across a woman’s lifespan, including reproductive health where it impacts partner sero-sorting and sexual habits, fertility desires and contraceptive choices, pregnancy and delivery, menopause and aging. Tackling the myriads of health challenges confronting women living with HIV is a necessary step to achieving the WHO global strategy for women’s, children’s and adolescent health. It will require nurturing a critical mass of local health scientists and equipping them with the skills to conduct valid research that addresses the local health needs of women living with HIV. To address these needs, we established the Emory-Nigeria HIV Research Training Program (EN-RTP). The EN-RTP leverages the research education infrastructure at Emory University and the partnering Nigerian institutions (Nigerian Institute of Medical Research (NIMR); University of Lagos (UNILAG); and AIDS Prevention Initiative Nigeria (APIN)) to provide state-of-the-art in-country research training with focus on methodologies, rigorous mentorship, and grant management capacity building. The EN-RTP training is focused on three main domains of HIV/women’s health research: a) HIV prevention and reproductive health; b) Challenges in HIV therapeutics unique to women living with HIV (WLWH); and c) Complications of chronic HIV infection relevant to WLWH. Preceptors are selected based on their expertise in these areas and their international research education and mentoring experience. We can report that the EN- RTP is now an established program with a cohesive administrative structure and program plan that includes both didactic and mentored research components implemented by a multidisciplinary team of in-country faculty and US-based investigators who have a wide range of mentoring experiences. The short- and medium-term accomplishments include high scholar productivity (over $3M in grant funding, including 3 NIH K 43 awards and more than 150 peer-reviewed publications by trainees), fostering robust scientific networking opportunities, developing emerging in-country scientific leaders, and nurturing the next generation of HIV research mentors. The EN-RTP has demonstrated a potential to be truly transformative in promoting mentored research training and the growth of the HIV biomedical research workforce. Committed to the primary goal of capacity building in HIV research, we look forward with enthusiasm the next cycle – particularly the opportunity to pilot new initiatives and best practices arising from our evaluation processes to enhance program outcomes.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Healthy Choices is a four-session behavior change communication intervention that was developmentally tailored for emerging adults to address self-management of health behaviors and HIV with evidence of positive effect on stigma and depression, built on Motivational Enhancement Therapy, integrating Motivational Interviewing with brief cognitive-behavioral strategies. Healthy Choices can be delivered in community settings by trained community health workers. When delivered with fidelity and in adequate dose, Healthy Choices results in reductions in alcohol use, HIV stigma, viral loads, and depression over follow-up compared to standard care. In the Dominican Republic, stigmas harm young people with HIV (YPWH). The Dominican Republic is a low- to middle- income country in the Latin America and Caribbean region, is 1 of 5 countries that accounts for over 95% of Caribbean HIV infections and has a culture that perpetuates stigmatizing attitudes and behaviors toward YPWH. To our knowledge, there are no Spanish-language interventions that concurrently address mental health, viral suppression, and stigma, tailored for young adults who are in a developmental period marked by exploration and a need for autonomy in health decision making. Considering the need for stigma reduction among YPWH to improve rates of viral suppression, reduce poor mental health, and encourage healthy coping by reducing problem alcohol use, we propose to adapt Healthy Choices for Spanish with local contexts plus co-create implementation strategies with community advising for future scale up. We will pilot test the adapted intervention and proposed intervention strategies, using a community-led implementation approach for feasibility, acceptability, and to assess for a signal of potential effectiveness on continuum of care outcomes including antiretroviral adherence and viral load. Considering the importance of context and the community-orientation of this study, we will apply the Exploration, Preparation, Implementation, Sustainment (EPIS) implementation science model, focusing on the Exploration and Preparation phases. We will engage community-based organizations (CBO) and a clinic in the Dominican Republic that work extensively with YPWH. Our investigator team has a long history of successful collaboration with impact on public health policy in the Latin American and Caribbean region. We propose three aims: (1) Elucidate barriers and implementation strategies for the Healthy Choices intervention; (2) Adapt and culturally translate the intervention for local contexts, and (3) Pilot test Healthy Choices with implementation strategies for feasibility and acceptability. If successful, we will have preliminary data for a full-scale hybrid type 1 effectiveness implementation randomized controlled trial of the intervention for underserved Spanish-speaking YPWH in the Dominican Republic with potential relevance to Spanish-speaking groups in the United States.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Abstract Despite advancements in HIV prevention and treatment and the expansion of services, HIV prevalence among men who have sex with men (MSM) in Vietnam has risen dramatically, from 6.6% in 2015 to 12.5% in 2023. Persistent stigmatization of MSM as "social evils," exacerbated by government campaigns associating MSM with the spread of HIV during the early period of HIV epidemic in Vietnam and reinforced by collectivist cultural norms against homosexuality, has exacerbated intersectional stigmas among MSM in Vietnam. This has led to discrimination, fear of disclosure, and avoidance of healthcare services, severely limiting MSM's access to HIV prevention and care services. To address these challenges, this study will culturally adapt a patient-provider stigma-reduction intervention-Finding Respect and Ending Stigma around HIV (FRESH) intervention- into DONGHANH ( meaning “companionship, understanding, and mutual support" in Vietnamese), for implementation among Vietnamese MSM (the patients) and healthcare providers (HCP- the providers). FRESH is a workshop-based intervention that has been successfully used to reduce stigma among healthcare workers and marginalized populations, including MSM, globally. Toward the end of the DONGHANH intervention, participants are expected to work together to develop stigma reduction strategies that they can take back to their respective communities, thus increasing the impact of the intervention. The intervention will also involve the creation of an e-module (a website), allowing participants to determine its delivery and engage in ongoing learning at their convenience. The study will be conducted in three phases: Phase I: using the ADAPT-ITT framework, we will adapt FRESH intervention based on findings from in-depth interviews and focus group discussions to create the culturally tailored DONGHANH intervention. Phase II: We will use a randomized wait-list control trial design to pilot test DONGHANH intervention among 180 participants (MSM=120; HCP=60). Ninety participants (MSM=60, HCPs=30) will participate in the intervention, while the remaining 90 participants (MSM=60, HCPs=30) will be assigned to the 3-month wait-list control. We will assess the intervention’s feasibility, acceptability, and fidelity as well as assess the preliminary efficacy of the intervention on reducing experiences of intersectional stigma and discrimination, increasing HIV testing, PrEP uptake and PrEP/ART adherence. Phase III: We will evaluate assess facilitators and barriers to implementation through interviews with MSM, HCP and project intervention staff, using the Consolidated Framework for Implementation Research to identify contextual factors of the intervention for future scale-up. If the DONGHANH intervention is successful, it can provide a scalable model for reducing intersectional stigmas and improve HIV prevention and care among MSM in Vietnam and other low-and middle- income countries.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Peru's HIV epidemic is concentrated in MSM, where high rates of stigma and discriminaton toward them have undermined treatment outcomes. Despite high diagnostic and linkage rates, MSM have low levels of ART initiation and viral suppression related to low retention in care. For MSM with HIV, multi-dimensional stigma related to sexual orientation, substance use disorders, sex work, multiple sexual partners, etc. undermine treatment efforts through numerous clinical interactions that have the potential to reinforce stigma and delay ART initiation. This grant proposes a transformative approach to reduce HIV-related stigma through a Behavioral Design Intervention (BDI) that utilizes same-day ART (SD-ART) protocols to streamline the treatment initiation process. Unlike other stigma-reduction interventions, BDIs operate at the organizational level, rather than at the clinician or patient level. Our strategy builds upon robust evidence that rapid-start ART (RS-ART) significantly increases ART initiation, retention and viral suppression, thus improving individual and public health. To address the entrenched stigma and operational barriers that persist in treatment initiation, this research will deploy innovative methodologies and technologies. We will first develop a tailored SD-ART protocol utilizing asynchronous online focus groups and flowcharting techniques to map the current ART initiation process and design a streamlined SD-ART protocol. This protocol will use choice architecture to streamline the ART initiation process by minimizing clinical interactions that can reinforce stigma. Using nominal group techniques (NGT), a mixed methods strategy, we will assess multi-level barriers and facilitators to SD-ART from the perspectives of patients (MSM), clinicians, and administrators. From this process, scripts for framing and nudging will be created to inform refinements to the SD-ART protocol to ensure it addresses the specific needs of MSM and thereby enhancing its effectiveness and acceptability. The SD-ART protocol tailored to MSM using behavioral design will be pilot-tested with 125 newly diagnosed MSM. This phase will include longitudinal dyadic analyses to measure changes in stigma, physician trust, social support, and psychological well-being. These insights will not only assess the protocol's impact but also guide further improvements, paving the way for a future implementation trial. Our approach is distinctively designed to reduce the stigma experienced by MSM in clinical settings. By restructuring the decision-making process to prioritize clinical indicators over subjective assessments, our intervention aims to foster a more supportive and non-discriminatory healthcare environment. We hypothesize that this will decrease both perceived and enacted stigma, thereby improving patient-level health outcomes while reducing negative stereotypes by clinicians as MSM succeed in their treatment. By integrating behavioral design into the ART initiation trajectory, this project represents a novel approach to addressing the complex challenges of HIV treatment in high-stigma contexts, offering significant potential for replication and scalability elsewhere.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

This IRSDA K-award will provide me with mentored research and career development training to build expertise in translating global health findings to benefit U.S. populations and underserved healthcare systems. I will learn to validate neurocognitive impairment (NI) screening tools and analyze inflammatory biomarkers that predict NI in meningitis patients with or without HIV in rural, northern Uganda, an area of high meningitis burden within Africa’s meningitis belt. Meningitis affects over 2.5 million people globally each year, and causes significant disability, with 20-32% of survivors experiencing long-term morbidity and 14-38% developing prolonged NI, yet data on NI burden in meningitis patients remain scarce. Despite evidence that inflammation in central nervous system infections is associated with NI, limited information is available about the biomarkers involved in NI development. This study seeks to fill the gaps in our understanding of the burden and pathogenesis of NI by identifying which brain injury biomarkers are expressed in patients with NI and can be used to predict NI development among meningitis patients with and without HIV. This study will be embedded within my primary mentor’s existing Meningitis Diagnosis and Treatment Program (MEN-DTP) at Lira Regional Referral Hospital in northern Uganda, which focuses on understanding mortality due to various meningitis etiologies in an area with high meningitis and HIV burden. Aim 1 is to validate neurocognitive assessment tools to determine the burden of NI among meningitis patients living with and without HIV, including follow-up for two years to assess long- and short-term NI burden. Aim 2 is to identify clinical parameters and immune/inflammatory biomarkers predictive of NI. Serum and CSF samples will be collected from meningitis patients who do or do not develop NI to identify biomarkers specifically associated with NI. Investigating immunologic and brain injury biomarkers will provide insights into inflammatory pathways activated by meningitis that lead to NI in those with or without HIV. Our neurocognitive assessments will help determine the true burden of NI and enable timely diagnoses and interventions. Our findings from this high-burden setting will inform neurocognitive assessment and early intervention strategies to improve care for meningitis patients that could be implemented in underserved U.S. populations and globally.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

The incidence of Alzheimer’s disease (AD) in the USA is expected to increase from 7.2 million to 13.8 million by 2060, highlighting the urgent need to discover new treatments. Madagascar is known for its unique plant biota and hosts about 12,000 plant species, of which 80% are endemic. Malagasy flora has provided clinically used bioactive compounds such as the anticancer drug vincristine. Madagascar is now among the top priority conservation sites in the world since the forest is deteriorating due to urban expansion, pollution, bushfires, and poverty. The overall goals of this proposal are (1) to assist in conserving the unique plants of Madagascar by developing a model program for bioprospection and conservation, (2) to identify plants from Madagascar that contain phytochemicals that can be used against Alzheimer’s disease (AD), and (3) to promote scientific training and capacity development in the island. This project will focus on three main objectives involving medicinal plant inventory and conservation, exploration/discovery, and training and capacity building. Plants have been used in traditional medicines for central nervous system (CNS)-related conditions and many are known to produce antioxidant compounds. We aim to perform an ethnobotanical survey and develop conservation approaches for plants that are being used in traditional medicine for brain-related diseases including dementia and contain neuroprotective constituents from among the rich biodiversity of flora in Madagascar. Oxidative stress can impair the functions and activities of the CNS and has been shown to contribute to the onset and progression of many neurodegenerative conditions including AD. Our previous studies have shown that that activation of NRF2, which is an antioxidant regulatory transcription factor, elicits neuroprotection both in vitro and in vivo, can attenuate decreases in dendritic arborization and synaptic density, reduces oxidative stress, and improves mitochondrial function in hippocampal neurons isolated from AD mice as well as in the brains of AD mice treated with NRF2 activators. These data suggest that identification of NRF2-activating compounds could be a useful approach to discovering novel AD therapeutic compounds. Based on the structures of previously isolated bioactive compounds and their plant families of origin, we hypothesize that plant species with a high level of endemicity from the Malagasy flora will produce many previously unknown NRF2-activating compounds. The project will assist aging populations developing AD diseases by not only identifying and standardizing plants that have already been used in traditional medicine but also discovering new chemical scaffolds for discovering AD drugs.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Candidate: Charles “Nate” Nessle, DO is a US pediatric hematologist oncologist based in Kenya with a clinical research focus on improving fever management in children with cancer. He will gain expertise in implementation science and wearable sensors with the goal to implement wearable sensors into routine clinical practice to advance care delivery, reduce disease burden, and improve the journey for children with cancer in resource-constrained settings in the US negatively impacted by healthcare worker shortages. Career Development Plan: Dr. Nessle received clinical research training through NIH NCI T32 and NIH FIC fellowships. He will gain expertise in: 1) application of pragmatic implementation science 2) principles of choice preference methodologies 3) adaptive use of wearable sensors in low-resourced settings 4) leadership, team science, grantsmanship. He assembled a team of mentors with expertise in oncology, implementation science, and wearable sensors. Through a combination of high-yield didactics, practical experience, and mentorship, Dr. Nessle will be well-positioned to lead implementation initiatives using novel technologies, like wearable sensors, to improve pediatric cancer outcomes in resource-constrained settings in the US. Research Plan: Severe healthcare worker shortages in the US contribute to poor patient outcomes. Fevers and infections are the top preventable causes of treatment related mortality in children with cancer in resource-constrained settings, associated with poor nurse-to-patient ratios (1 nurse to 30 patients) and management delays. Prompt fever management improves patient outcomes, yet this can be challenging and multifactorial in resource-constrained settings; Kenya currently reflects the future US healthcare worker shortages. Shifting the task of fever detection from overburdened nurses to wearable sensors is an innovative solution to increase uptake of effective fever management. Yet to our knowledge, no published studies have evaluated task-sharing and wearable sensors in children with cancer. Dr. Nessle will rigorously evaluate the implementation process of wearable sensors for hospitalized children with cancer in Kenya, which foreshadows healthcare worker shortages in the US; without this understanding, wearable sensor clinical trials in resource-constrained settings in the US will fall short of their potential. First, we will evaluate the implementation barriers and facilitators to pre-implementation outcomes of adoption, appropriateness, and cost through a quantitative survey and stakeholder interviews in internal and external settings to identify a group of mitigating strategies (Aim 1). Then, a choice experiment and a human centered design workshop will evaluate key wearable sensor attributes from the perspectives of children, caregivers and healthcare providers (Aim 2) to inform the selection of a wearable sensor for the pilot study (Aim 3). The group of strategies from Aim 1 will minimize the impact of barriers to support the single-arm wearable sensor pilot study in 30 hospitalized children with acute leukemia, where we will measure feasibility, acceptability, and usability over a 30-day trial period (Aim 3).

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

ABSTRACT In many low- and middle-income countries, including Thailand, morbidity and mortality rates from cardiometabolic diseases (CMD) have been rising notably over the past few decades, affecting younger individuals who are at working age. However, CMD research in these countries are rather weak. In response to PAR-22-104, the University of California, Los Angeles (UCLA) proposes to provide research training and capacity building at Mahidol University (MU) in Thailand, focusing on Life-cOurse oCcupational, environmentAl, and Lifestyle contribution to CardioMetabolic Diseases (LOCAL-CMD). The partnership is built upon the two universities’ prior and ongoing research and training collaborations and will leverage the existing research and mentoring infrastructures at UCLA, including the UCLA Fielding School of Public Health (FSPH), David Geffen School of Medicine (DGSOM), School of Nursing (SON), UCLA Center for Occupational and Environmental Health (COEH), National Institute for Occupational Safety and Health (NIOSH) Southern California Education and Research Center (SCERC), and University of California Global Health Institute (UCGHI) GloCal Health Fellowship Program. The proposed LOCAL-CMD project will support (i) a 5-year PhD program for one trainee, (ii) a 6-month program for eight PhD students, and (iii) a 9-month program for eight junior faculty, followed by one-year intensive in-country training and support when they return to their home institutes. Specifically, three training components are offered, including (1) research (develop research agenda and apply for independent research funding), (2) mentoring (improve skills and curriculum to teach and mentor the next generation of public health professionals), and (3) leadership (nurture leadership skills and ascend into leadership positions in an Education and Research Center for LOCAL-CMD (ERC-LOCAL-CMD) as an output of this program). Each trainee will develop individualized training objectives based on their academic qualification, research interest, relevant manuscripts, conference presentations, career advancement or research proposals, participation in cross-border projects, mentorship in CMD research, and leadership roles. The training activities will include workshops, seminars, courses, and collaborations at UCLA, as well as in- country training at UM in Thailand and exercise of leadership skills within ERC-LOCAL-CMD. A highly comprehensive mentorship system, featuring a primary mentor, in-country mentor, transnational mentor, and peer mentor, will ensure that trainees receive holistic guidance in subject expertise, understanding of local culture and resources, and forging global collaborations. This program will cultivate ERC-LOCAL-CMD with a cadre of multidisciplinary faculty and researchers in Thailand, positioning them to lead the subsequent cycle of Fogarty training program application as leaders in CMD research and training in Southeast Asia.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Project Summary Candidate: Roxanna Garcia, MD, MS, MPH is a neurosurgeon and fellowship trained neuro-critical intensivist serving as Assistant Professor of Neurological Surgery at Northwestern University. Dr Garcia’s long-term career goal is to be an independent physician-scientist who uses expertise in implementation research to improve adoption of evidence-based practice in neurosurgical disease, with a focus on traumatic brain injury (TBI) globally. Background: TBI is a public health crisis that disproportionately affects low- and-middle income countries (LMICs), where the risk of mortality is 3 to 4-fold greater than compared to high-income countries. The incidence of TBI represents the leading cause of neurologic disease globally, with approximately 69 million incident cases every year. Moderate TBI (Glasgow Coma Scale[GCS] scores 9-12) and severe TBI (GCS scores 3-8, msTBI) can produce lifelong disability, and is estimated to contribute to over 30% of deaths caused by trauma. Timing to surgery is an important factor, especially among patients with structural lesions. A four- hour timeframe from event to surgical decompression can improve survival. Health system factors delaying timing to intervention have not evaluated, especially in LMICs. Training Plan: In order to achieve research independence, Dr Garcia will need to strengthen skills in (1) applying implementation science methodologies, (2) learning mixed methods to develop (3) expertise in clinical trials research design. Dr Garcia will be mentored by an outstanding multinational team including primary mentor Dr Andrew Naidech (Northwestern University), and Dr Patricia Garcia (Universidad Peruano Cayetano Heredia). Her co-mentors Dr Lisa Hirschhorn (Northwestern University) and Dr Fizan Abdullah (Northwestern University). This team represents experts in health systems and services research, as well implementation science and global health and surgical research. Research Plan: With guidance from her mentor team, Dr Garcia will apply the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework to understand to open cranial surgical intervention for msTBI in the acute emergency setting among health providers in Lima, Peru at high volume trauma centers. The study will continue to build upon an existing prior NIH related post-doctoral research fellowship experience. Dr Garcia will (1) explore the current clinical practices, and define the barriers, and facilitators influencing timing to open cranial surgery for patients suffering from msTBI. She will then apply (2) mechanistic mapping through a co-creation process to create codesign strategies for addressing critical barriers and leveraging facilitators among key stakeholders; and (3) conduct a feasibility implementation pilot to improve timing of open cranial surgery for msTBI. The study will utilize mixed-methods including semi- structured interviews, surveys and focus groups to inform an implementation research logic model and plan, and inform an R01 proposal focused on implementation and sustainment.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Over 43 million people died globally from non-communicable diseases (NCDs) in 2021. Mali has one of the highest NCD burdens where it contributes to 59,135 deaths and 16,399 DALYs per 100,000 lost contributing to 25% of the total disease burden annually. We propose a training program to develop Mali’s capacity to recognize, measure, and to respond to the health and economic consequences of major risk factors for NCDs. This program will be based on close collaboration between two institutions – the George Washington University Milken Institute School of Public Health (GWSPH), USA and University of Sciences, Techniques and Technology of Bamako (USTTB), Mali to respond to two critical gaps – lack of trained human resources and lack of data. The overall goal of the George Washington University-University of Sciences, Techniques and Technology of Bamako Enhancing Research Capacity on Non-Communicable Disease Risk Factors in Mali (NCDRisk- Mali) program is to strengthen capacity on the conduct of research on NCDs, related risk factors and their health, social and economic consequences across the lifespan in Mali. Our model will use US expertise to strengthen a Malian institution, promote a sustainable research enterprise focused on major risk factors for NCDs and enable dissemination of research to influence policy in Mali through the following specific aims. Specific Aim 1: To develop a nucleus of researchers focused on NCD risk factors at USTTB. We will offer (1) enhancement of pedagogical capacity of key USTTB faculty on NCD risk factor curricula and mentoring in Mali; (2) establishment of NCD risk factors specialization within the existing USTTB MPH program including co-development of new courses on NCD risk factors and implementation research; and (3) development of a long-term training program for pre-doctoral (Master of Public Health) trainees and post-doctoral trainees (with demonstrated professional accomplishments per completion of doctoral training) in Mali. Specific Aim 2: To enhance research on NCD risk factors directly relevant to the health priorities of Mali. Our trainees will conduct research around three domains: (1) understanding the prevalence, characteristics and determinants of these NCD risk factors; (2) evaluation of age and sex differences - how risk factors for NCDs differ between and among different sexes and age groups; and (3) expansion of implementation research to support identification of locally relevant, effective policies and interventions for these NCD risk factors. The generated evidence will inform national decisions around NCD risk factors (unhealthy diet, physical inactivity, hypertension, overweight & obesity) that contribute the most to NCD burden (e.g. diabetes, stroke) in Mali. Specific Aim 3: To influence research, implementation, and policy on NCDs, their risk factors and consequences in Mali through short-term training activities. We will (1) implement training workshops at USTTB each year; (2) develop and offer a Certificate Program on NCD risk factors and implementation research and (3) promote the translation of research evidence through annual NCDRisk-Mali Symposium.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Alcohol use is a major contributor to injury burden worldwide and remains an important public health challenge in the United States (US), particularly in underserved regions with limited access to trauma and behavioral health services. Cameroon, like other Sub-Saharan African countries, is disproportionately affected by alcohol- related injuries (ARIs), with higher injury burden and alcohol consumption than neighboring countries. Similar barriers to integrating alcohol use disorder (AUD) interventions into trauma care also persist in low-resource trauma settings in the US, where workforce shortages and constrained trauma systems limit delivery of evidence-based AUD care. As involvement in an ARI significantly increases the risk of subsequent ARIs, failure to address AUD in injured patients currently represents a missed opportunity for both AUD treatment and injury prevention. The Screening, Brief Intervention, and Referral to Treatment (SBIRT) model is an evidence-based intervention used in emergency departments (EDs) in high-income countries, including the US, to identify and address AUD. However, implementation of SBIRT remains inconsistent in US resource- limited trauma settings due to staffing, workflow, and infrastructure barriers. Cameroon provides a unique opportunity to evaluate scalable SBIRT implementation strategies in a severely resource-constrained trauma system where AUD services are limited but where strong trauma research infrastructure and pilot data already exist. The long-term goal of this project is to reduce the burden of ARIs by leveraging research infrastructure in Cameroon to develop scalable evidence-based models for integrating AUD interventions into trauma systems. The overall objective is to evaluate the feasibility and effectiveness of a Cameroon-adapted SBIRT intervention in the ED setting. We hypothesize that the adapted SBIRT intervention will significantly reduce hazardous alcohol use among trauma patients. To achieve this objective, the study will pursue three aims: 1) train ED healthcare providers on a Cameroon-adapted SBIRT program; 2) evaluate feasibility, acceptability, and fidelity of SBIRT implementation in the Cameroonian ED context; and 3) evaluate effectiveness of SBIRT implementation in reducing hazardous drinking behaviors and PEth biomarker levels. This study will leverage implementation science methods to evaluate real-world implementation and scalability of SBIRT in a resource- constrained trauma system. Findings from this work may inform scalable implementation approaches for underserved trauma settings in the US, including rural hospitals and trauma deserts with limited access to integrated AUD care, while also supporting broader implementation across low-resource settings globally.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Malaria presents a significant health challenge in sub-Saharan Africa (SSA). It is a threat to US citizens in relation to health security, safe travel, missionary work and military operations. The relevance of malaria control and elimination in SSA to US economic opportunity and role in geopolitics cannot be underestimated. In SSA, a large fraction of the population across all ages harbors the malaria parasite Plasmodium falciparum without clinical manifestation, providing a vast infection reservoir for mosquito transmission. This asymptomatic reservoir is sustained by enormous antigenic diversity of the parasite. Our proposal addresses the hypothesis that progress toward falciparum malaria elimination should focus on reducing the number of antigenically diverse strains. Here we test this hypothesis in Ghana, a stable country in West Africa with a National Strategic Plan for malaria elimination including regions of economic and strategic importance to the US. Malaria Reservoir Study-II (MRS-II) takes advantage of enhanced intervention efforts in northern Ghana as major perturbations reducing the transmission reservoir, to address the sharp transition postulated by previous theory in both parasite diversity and infection prevalence with changes in transmission intensity. We test the importance of strain diversity to resilience of the transmission system, with a framework that combines longitudinal surveys of unprecedented depth with novel metrics for molecular surveillance of variant antigen diversity and computational models encompassing generalized and variant antigen immunity. Our three major inter-related aims are: (1) Field work for surveillance of enhanced interventions in two sites of northern Ghana differing in recent malaria control; (2) Characterization of the resilience of high-transmission systems to the major perturbation of targeted mass drug administration to children aged 3 months to 12 years in terms of changes in strain diversity; (3) Computational modeling to evaluate and predict dynamical responses to enhanced intervention in the context of the fundamental positive feedback between strain diversity and transmission intensity. The project will provide real world experience for US trainees in disease surveillance and control as well as training in quantitative tools for biomedicine. Quantitative characterization based on molecular surveillance, together with mathematical models that consider strain diversity and structure, will inform public health policy on the impact of control efforts in high-transmission regions. Current efforts are designed to reduce disease burden in children with no surveillance of the impact on the reservoir of asymptomatic infections in the community. MRS-II fills this significant gap in regions of northern Ghana with relevance to high-transmission areas of the Sahel in West Africa. More generally, our study aims to shift the paradigm in malaria epidemiology to make the parasite rather than the infected host the unit of measurement for evaluation of control and a target for elimination.

FIC - John E. Fogarty International Center for Advanced Study in the Health Sciences

Sean McClellan, MD, MAS, is a family physician and cancer survivorship care provider at the University of Illinois Chicago (UIC). He will acquire mentored training to become an independent clinician-investigator leading implementation research in the U.S. and globally to improve care for cancer survivors. This award will accelerate research on integrating primary care into survivorship care, which has been identified by the National Cancer Institute (NCI) as a critical priority for survivors in the U.S. The project will build on and extend NCI-funded research in the U.S. by leveraging distinct national conditions in Mexico, where limited existing survivorship infrastructure creates an opportunity to evaluate the potential impact of a primary care approach more fully by designing new models that involve primary care physicians from the start rather than adapting them to established, oncology-led systems. Through this work, we will develop practical strategies to implement and scale up primary care-led survivorship care that can be adapted to the U.S. Conditions in Mexico will also support the development of efficient care models that can inform high-value care in the U.S.; implementation strategies translatable to low-resource U.S. settings; and culturally tailored resources adaptable to Hispanic or Latino communities in the U.S. Through this project, Dr. McClellan will acquire experience in reciprocal innovation, the mutually beneficial, bilateral exchange of innovation between countries to address shared health challenges and improve the health of Americans. SIGNIFICANCE: Reflecting the shared needs of breast cancer survivors globally, U.S. and international expert organizations such as the National Comprehensive Cancer Network and the Breast Health Global Initiative (BHGI) have developed closely aligned guidelines recommending evidence-based interventions (EBIs) for survivorship care. To expand the reach of survivorship EBIs, integrating primary care into survivorship care is critical, as primary care physicians are uniquely positioned to address survivors’ diverse needs and improve access. APPROACH: This award will develop an implementation strategy package for BHGI survivorship guidelines in Mexico City. We will use the Implementation Mapping process to select and tailor implementation strategies. We will partner with a public healthcare system to: 1) examine stakeholder perspectives on the implementation of BHGI survivorship guidelines (survivors, caregivers, PCPs, specialists, institutional leaders); 2) develop CAMINOS, an implementation strategy package for BHGI survivorship guidelines that integrates PCPs into survivorship care; and 3) conduct a feasibility study of CAMINOS at two clinics (total n = 30) to inform a future large-scale implementation/effectiveness hybrid trial. TRAINING: Dr. McClellan will build expertise in 1) the impact of social risk factors on cancer control interventions; 2) implementation science methods used to develop implementation strategy packages; and 3) clinical trial design and evaluation. His mentors are Dr. Marian Fitzgibbon of UIC and Dr. Carmen García-Peña of the Mexican National Institute of Geriatrics.