Currently, it is not well understood how young people in Low and Middle-Income Countries (LMICs) access health services such as primary care and mental health services, which are easier to access in other parts of the world. Since adolescents are a significant, unique population in these countries, there is evidence to suggest that health services need distinct features and considerations to be adolescent-friendly and responsive. However, there is no universal, comprehensive definition of adolescent-friendly health services. To fill this gap in the body of knowledge, we are conducting a systematic review to collate, synthesize and identify the barriers and facilitators of adolescent-responsive health services. We worked closely with a research librarian to perform a robust search through a range of databases (CAB Direct, CINAHL, Cochrane, Embase, Global health Medicus, PsychINFO, and PubMed) which resulted in 4751 unique abstracts. During the title and abstract screening, two members of the team reviewed each article. Currently, 171 articles have been selected for full-text screening to confirm they are appropriate for inclusion and for analysis. Next, we will create a narrative synthesis of the features of service, keywords, factors, and outcomes identified. The research will provide a clear, comprehensive definition of adolescent-responsive health care and services in LMICs. This information will be particularly useful to international organizations, like the UN, healthcare providers, and policymakers as it will inform new programs, initiatives, or guidelines to improve the quality of adolescent health services in LMICs.

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted pathogen that is estimated to infect around 23 million people per year. Despite high global prevalence, there are not any approved vaccines that are therapeutic or preventative. Most vaccines that we use today rely on injecting antigens intramuscularly in order to elicit an adaptive immune response. However, given that most pathogens gain entry to the host across barrier surfaces, a focus on eliciting mucosal immunity may enhance protection; vaccine-induced local immunity at the site of first pathogen exposure may have the best chance at preventing the spread of infection beyond the pathogen portal of entry. We hypothesized that a mucosal immunization would prime memory T cells to reside in vaginal tissues and provide better protection against vaginal HSV-2 exposure than other routes of immunization. Our initial data suggests that intranasal immunization is effective in protecting mice from vaginal HSV-2 infection. Ongoing work focuses on characterizing the role of vaccine-elicited mucosal CD8+ T cells in preventing infection to provide insight into the mechanisms of protection induced by mucosal immunization for HSV-2. These findings contribute to the efforts to generate an effective vaccine to prevent HSV-2 infection and disease.

Global climate change is here and it is already affecting exposure to heat across Washington state. Heat exposure can exacerbate climate-sensitive health threats by increasing risks for groups who are more susceptible--particularly in non-acclimatized areas. The World Health Organization has predicted that diabetes will be the 7th leading cause of death by 2030. It is critical to define the interactions between heat and diabetes to prevent excess risk; having diabetes leads to reduced thermoregulation (body's ability to regulate heat) which affects other organs critical for sustaining life. My research focuses on the intersection of health impacts of heat on people with diabetes and how these relationships change with increasing temperatures. It also considers how mitigation and adaptation can protect the 1 in 8 people in Washington who have diabetes as part of the overall goal of managing the health risks of climate change. I consider the relationship between heat and diabetes by performing a literature review of peer-reviewed, original research in different academic journals. Then, outcomes are compared and synthesized to determine if there is a causal relationship where temperature affects the odds of diabetes morbidity and mortality. My research found that those who have diabetes have higher odds of negative health outcomes and death as temperatures increase. Through a variety of mitigation and adaptation strategies, we can reduce the odds of and prevent excess morbidity and mortality. Taking this research into account, Washington can be more conscious in its public health interventions during periods of increased heat to prevent excess diabetes-related morbidity and mortality. More research is needed on the effectiveness of specific interventions for Washington on reducing the odds of morbidity and mortality for people with diabetes.

Human Herpesvirus-8 (HHV-8) causes Kaposi’s sarcoma (KS)-- a cancer of cells that line lymph or blood vessels. Individuals whose T cells have been compromised by HIV are particularly at risk for KS. The disease remains endemic in many parts of sub-Saharan Africa, making KS a leading cause of cancer death in Uganda. While HHV-8 has been known to cause KS since 1994, and T-cells that can recognize HHV-8 are likely to be critical for control of KS, there is little known about the specific parts of the virus recognized by T-cells. Our goal is to ultimately determine the antigenic targets of HHV-8-specific T-cells. Because recovery of live T-cells from biopsies is challenging, we are re-creating “artificial T-cells” with candidate T-cell receptor (TCR) sequences obtained from KS lesion biopsies from Uganda. These candidate TCRs will be queried for reactivity to HHV-8. To do this, we are generating a set of every known HHV-8 protein by moving cloned DNA expressing these proteins into a specific plasmid that is useful for these T-cell studies. To create artificial T-cells, we are cloning candidate TCRs into lentiviral vectors which allow us to force the TCRs to be expressed in these cells and fluoresce green if the cells recognize a viral protein through their TCRs. These artificial T-cells are then screened against every HHV-8 protein to find which protein they recognize. Currently, flow cytometry results demonstrate adequate expression of candidate TCRs by artificial T-cells, and the HHV-8 protein set is >90% complete. Ultimately, we hope to determine HHV-8 proteins that are recognized by HHV-8-specific T-cells in order to better understand which parts of the virus are targeted by these T-cells and to design T cell or vaccine therapies to treat persons with KS.

Tuberculosis (TB) is one of the leading causes of death from infectious disease worldwide. Macrophages are the primary replicative niche and provide critical host defense against Mycobacterium tuberculosis (Mtb), the causative organism. A TOLLIP deficiency is associated with an increased risk of TB in human studies and mouse models. TOLLIP is a ubiquitin-binding protein that interacts with toll-like receptors (TLR) involved in modulating inflammatory signaling. TOLLIP has four critical domains: a ubiquitin-binding CUE domain, a membrane binding C2 domain, an autophagosome interacting motif (AIM), and a Tom1-binding domain that participates in endosomal sorting. However, the domains required for TOLLIP’s immune regulatory function during Mtb infection in macrophages are uncertain. To understand the role of selected domains on TOLLIP’s function, we are developing lentiviral vectors to insert TOLLIP with selected protein domains deleted, along with green fluorescent protein (GFP) to tag transduced cells. We measured viral load and transduction efficiency in HEK cells by analyzing GFP fluorescence through microscopy and flow cytometry. We are currently transducing TOLLIP fragments, whole TOLLIP, and control genes into macrophages lacking the TOLLIP gene. TOLLIP (-/-) bone-marrow derived macrophages (BMDM) were infected with lentivirus after 3 days and stimulated with LPS (10ng/ml) after 5 days. Viral supernatants were collected to evaluate TOLLIP gene expression through fluorescent microscopy. The approaches developed in this project will provide the foundation for understanding the critical structural elements of the TOLLIP protein and their role in preventing TB disease.

Globally, about 10% of people living with HIV (PLHIV) also have concurrent Hepatitis B virus (HBV) infection. Without routine screening for HBV, the choice of antiretroviral therapy can be more difficult to manage, as not all medications treat both infections. The objective of this research was to identify risk factors that put PLHIV at higher risk of HBV infection. We conducted a prospective clinic-based study from 2013 – 2017 in Durban, South Africa. Participants were enrolled into the study if they tested positive for HIV, and all PLHIV were tested for HBV after enrollment. Follow up assessments were conducted at 3, 6, and 12 months after enrollment. Patients completed questionaries pertaining to sociodemographic status, medical history, clinical symptoms and mental health at each visit. I compared prevalence of HBV between age groups using a T-test. Univariate and multivariate logistic regression models were conducted on co-variates of the data set using the ‘dplyr’ and ‘stats’ packages in R. I measured adjusted odds ratios (aORs) for each covariate to compare risk factors for those with HBV and HIV compared to PLHIV. A total of 3105 PLHIV were enrolled, with a mean age of 33 years and 43% (n=1331) male. Of those, 196 (6%) individuals tested positive for HBV, with a mean age of 33 years and 62% (n=121) male. Participants aged >25, who were born before South Africa implemented routine infant vaccination for HBV in 1995, were more likely to have HBV (p=0.043). HBV diagnosis was associated with drinking alcohol over the past year (aOR = 1.17), lack of condom use (aOR = 1.10), and income >10,000 ZAR/month (aOR = 1.63). Implementing routine HBV testing for adults born before 1995 can help prevent the further increase of HBV infection rates. These study findings also provide additional support for enhanced HBV screening among PLHIV.

Towards Universal Newborn and Early Childhood Hearing Screening in Kenya (TUNE) is a project designed to introduce low-cost phone applications, akin to a standard tool, to screen for middle ear fluid in children. The device, which can be used by non-specialists, has the potential to provide low- and middle-income countries the opportunity to address problems in ear and hearing health that could otherwise impair childhood development. Kenya does not have a universal newborn and early childhood audiology screening program due to a lack of trained screeners and the high cost of assessment tools. The TUNE team met twice weekly via Zoom since colleagues lived in both Seattle and Nairobi, Kenya. My early responsibilities included documentation of stakeholder input. In September 2021, we sponsored a healthcare worker training program in Nairobi. In support of this work, I generated the training videos, created a website, and developed slide decks. These tools were used to provided healthcare workers with a background on hearing health and the importance of early identification of hearing loss, general information about the phone application, and trained them to use the device with a detailed instructional video. Healthcare workers were then given time to practice using the application. Finally, they were asked to complete a survey about the application. Most respondents reacted positively to the tool, with 100% of participants reporting they “would be comfortable using the device ‘as is’ in their work.” Most indicated that they would recommend using the application but noted that there were updates that could make the application more user friendly. We used the resulting qualitative data to inform future iterations of the application, a stakeholder workshop and policy recommendations. Ultimately this technology may help ensure that children’s growth, development, and educational needs are met in low- and middle-income countries.