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Grant to assess how HIV affects the occurrence and progression or oral diseases among Kenyan children with HIV/AIDS

Oral diseases are among the most prevalent non-communicable diseases (NCDs) worldwide. Salivary antimicrobial peptides (AMPs) are proteins regulated by our immune system that disrupt the membrane integrity of bacteria. There is very limited data on AMPs in young children living with HIV. In Kenya, where about 5% of the population is HIV positive, there are an estimated 105,000 infected children and adolescents aged 0-14. A newly awarded National Institute of Health (NIH) grant entitled “Dynamics of HIV-infection, Oral Innate Immunity and The Development of Oral Diseases in Children” aims to assess the extent to which HIV infection influences the occurrence and progression of oral diseases among HIV/AIDS Kenyan children and to create research capacity in global oral health by expanding current lab infrastructure to allow local analysis of salivary AMPs in the context of HIV. This University of Washington (UW) and University of Nairobi (UoN) award is led by Drs. Ana Lucia Seminario and Whasun Chung at UW, and Arthur Kemoli at UoN.

Ana Lucia Seminario and Caitlin Fehlinger at Jaramogi Oginga Odinga Teaching and Referral Hospital.”
Ana Lucia Seminario and Caitlin Fehlinger at Jaramogi Oginga Odinga Teaching and Referral Hospital.”

This longitudinal study will be conducted in a cohort of children who receive care at Jaramogi Oginga Odinga Teaching & Referral Hospital (and other affiliated HIV clinics in the Kisumu area), the largest local teaching and referral hospital in western Kenya. Over 12 months, we will recruit and follow a cohort of approximately 300 children (3-4 years old) stratified by presence of HIV. We will assess participants for anti-retroviral therapy (ART) adherence, length and regimen; dental plaque; CD4; HIV-1 RNA; and additional medications. Our aims are to: 1) Describe the impact of HIV infection on the secretion of salivary antimicrobial peptides at baseline and over a 12-month follow-up period. 2) Determine the associations between salivary AMPs and oral diseases in the context of HIV. 3) Enhance existing HIV research capacity. We will expand current human and infrastructure resources to include oral health research. While currently the study of salivary AMPs is conducted out of Kenya, we will build upon existing lab assets allowing locals to conduct these analyses, thus starting a line of research that increases Kenyan research opportunities.

Moureen Aluoch and Arthur Kemoli working on protocols for the DeRouen Center’s new NIH R21 grant.
Moureen Aluoch and Arthur Kemoli working on protocols for the DeRouen Center’s new NIH R21 grant.

In February 2023, researchers traveled to Kisumu, Kenya to kick-off the grant and begin enrollment.

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Polymorphisms and oral diseases in Thailand

The taste buds in our tongues contain receptor cells that detect food particles dissolved in saliva.  G-protein coupled receptors on the surface of those receptor cells have been identified that respond to sweet, savory, or bitter tasting chemicals.  Twenty-five different G-protein coupled bitter taste receptors have been identified in humans.  When these bitter receptors are activated on the tongue, we sense a bitter taste that promotes rejection of the food we are eating.  It turns out that bitter taste receptors are not just in the taste buds of the tongue, however.  Bitter taste receptors are also found in the epithelium of the nasal cavity, trachea, gut, urethra and other tissues.  The bitter taste receptors in tissues outside the taste buds do not play a role in taste perception.  Instead, these receptors detect chemicals released by pathogens.  Activation of the bitter receptors in these other tissues trigger host-defense and immune responses that help protect against disease.

BMC LogoAt the University of Washington, we identified one type of bitter taste receptor (T2R38) in gingival epithelial cells of the gums.  There are three important single nucleotide polymorphisms (genetic differences) in the TAS2R38 bitter taste receptor gene, which codes for the T2R38 receptor.  These polymorphisms result in two common genetic haplotypes, which are labeled PAV (Proline, Alanine, Valine) and AVI (Alanine, Valine, Isoleucine) based on the amino acid substitutions that result at positions 49, 262, and 296 of the receptor.  People inherit two haplotypes, one from their father and the other from their mother, resulting in a genetic diplotype.  People who have PAV/PAV or PAV/AVI genetic diplotypes perceive thiourea-containing compounds as bitter tasting, whereas those with the AVI/AVI genotype find these compounds to be almost taste-less.  In our work at University of Washington, we found that gingival epithelial cells with PAV/PAV and AVI/AVI diplotypes responded differently to the bacteria involved in dental caries and periodontal disease.  Gingival epithelial cells with PAV/PAV genotype responded more to S. mutans (a pathogen involved in caries), whereas gingival epithelial cells with the AVI/AVI genotype responded more to P. gingivalis (a pathogen involved in periodontal disease).

Previous studies have shown a protective effect against caries for those with the PAV haplotype of TAS2R38.  The previous laboratory work at University of Washington led us to believe that the AVI haplotype might be protective against periodontal disease.  We conducted a cross-sectional study at Khon Kaen University in Thailand to learn more about genetic differences in the T2R38 bitter taste receptor among Thai people.  We also examined the association of genetic differences with measures of caries (decayed-missing-filled teeth) and periodontal disease (defined as one site with probing depth greater than 5 mm).  In the study, we genotyped 250 patients seeking care at Khon Kaen University Dental Hospital.  Of those patients, 46% were PAV/PAV genotype, 42% were PAV/AVI, and 12% were AVI/AVI.  These distributions are similar to that seen in other studies of Asian populations.  As we expected based on the prior laboratory work at University of Washington, those patients with an AVI haplotype had less periodontal disease than those with the PAV/PAV genotype.  However, trends for differences in decayed-missing-filled teeth did not reach statistical significance in our study.  This study provides evidence of the importance of the T2R38 bitter taste receptor in maintaining oral health.

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The DeRouen Center for Global Oral Health R56 trip to Lima, Peru

On March 31st, 2022, I flew on a redeye flight to Lima, Peru. This was my first time going to South America and I was very excited to be going to a new continent! My Spanish language skills were and still are severely lacking, so I made sure to download google translate onto my phone. It was a life saver while I was there! On April 1st, I arrived in the capital of Peru in the evening. As the driver took me through the capital, I was incredibly struck by the busyness of the city. The driver told me that it would take about an hour to get to the hotel from the airport because of all the traffic. Lima is a very big city having nearly 10 million inhabitants! As we started to get closer to Barranco, the borough of Lima we I was staying, we drove past the Pacific Ocean. Even after sunset the ocean was breathtaking and so many people were still catching the last bit of sunshine and surfing on the waves! I love the ocean and enjoyed being so close to it while in Lima!
UW DeRouen Team and part of the Yale Team
UW DeRouen Team and part of the Yale Team
Pachacamac
Pachacamac
Plaza De Armas De Lima
Plaza De Armas De Lima

Over the 15 days I was there, the DeRouen team was hard at work holding working meetings at the two partner sites, Centro de Investigaciones Tecnológicas Biomédicas y Medioambientales (CITBM) and Asociación Civil Impacta Salud Y Educación (IMPACTA). We also met with our colleagues and partners on this project from Yale University and ate at a great restaurant called La Rosa Náutica. We enjoyed Pisco Sours and ceviche dishes. We also worked with some amazing field workers from CITBM and IMPACTA and learned about the amazing work that is being done in Peru with HIV. This team was instrumental in setting up the surveys to be distributed to study participants. Both CITBM and IMPACTA know their communities well and made our jobs very easy. We are lucky to have worked with them on this R56 preliminary project and look forward to seeing what comes from the results!

Between meetings and working, I was able to get away to see the beautiful places and history of Lima. I visited the Catacombs at the Catedral de Lima and went to Pachacamac to look at ancient civilizations that are dated before the Inca’s. The history was incredible, and the ocean was a site to see from the ruins. It certainly took me back in time! It was great to not only learn from the Peruvian communities but also about the vast history in Lima and in Peru. I look forward to returning in the future!

CITBM team with UW DeRouen Team
CITBM team with UW DeRouen Team
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NIH D71 Grant Stakeholder Analysis Results

The DeRouen Center has been working on an NIH D71 Planning Grant in Kenya. In February, 2022, a group of researchers including Ana Lucia Seminario, Arthur Kemoli, Immaculate Opondo, Matthew Saxton, and Sara Stanley traveled to four sites in Kenya to meet with stakeholders in oral health and HIV research. During these in-person and zoom meetings we asked stakeholders a series of questions surrounding oral health and HIV, research, and institutional capacity.

These interviews were analyzed by a team in the University of Washington’s Information School, led by Dr. Matthew Saxton. The team of 9 reviewers each analyzed 1 transcript while free-coding the text. Transcripts were chosen randomly from among the 17 interviews. Reviewers were instructed to capture and utilize the terms or phrases generated by the informants themselves.

Prior to beginning the free coding, reviewers took part in a training workshop that used sample responses from multiple transcripts. Coding was conducted at the question response level, but each response could have more than one code. The free coding phase of the analysis resulted in 457 unique codes, with many duplicates across transcripts.

The team then performed an iterative grouping analysis where each code was typed on a virtual “post-it” note in a collaborative online whiteboard environment (MIRO). Typically, the researchers would conduct this type of exercise in a face-to-face setting, but the need for isolation during pandemic conditions made it challenging to gather physically in a safe manner.  Based on this analysis, a series of word clouds were generated that looks at the most relevant issues within each category including motivation, obstacles, research, and support:

Research
Research Word Cloud
Support
Support Word Cloud
Motivation Word Cloud
Motivation Word Cloud
Obstacles
Obstacles Word Cloud

The research team led by Dr. Ana Lucia Seminario will be submitting an NIH D43 grant which will provide training pathways to increase oral health and HIV research in Kenya.

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DeRouen Center Team Travels to Kenya for D71 Grant

Kenya Map
The DeRouen Center D71 grant team visited four locations within Kenya – Kisumu, Eldoret, Mombasa, and Nairobi

In February 2022, the University of Washington (UW) Timothy A. DeRouen Center team travelled to Kenya as part of our National Institute of Health’s D71 Grant entitled “TABASAMU: A multidisciplinary collaboration on building up research capacity in oral health and HIV/AIDS.” The purpose of this interdisciplinary planning grant is to develop a training program with the ultimate goal of creating sustainable institutional capacity in research and training for oral health and HIV/AIDS.

Team members from UW (Dr. Ana Lucia Seminario, Dr. Matthew Saxton, and Sara Stanley), University of Nairobi (Dr. Arthur Kemoli), and Maseno University (Dr. Immaculate Opondo) visited with University, Hospital, County, and Federal representatives in four cities in Kenya – Kisumu, Eldoret, Mombasa, and Nairobi. We were grateful to be able to visit multiple areas of the country in order to help with cultural competency, meeting with various stakeholders, and get to know more about the strengths and challenges in different areas. We were able to gain a robust representation of future mentors and trainees from the whole country.

Obama Children's Clinic
DeRouen Center D71 grant team at Obama Children’s Clinic in Eldoret, Kenya
JOOTRH HIV Clinic
DeRouen Center D71 grant team at Jaramogi Oginga Odinga Teaching & Referral Hospital in Kisumu, Kenya
D71 Grant team
DeRouen Center D71 grant team with colleagues from Cost General Hospital Teaching & Referral Hospital in Mombasa, Kenya

During the two-week trip, the team conducted 11 virtual and 15 in-person stakeholder interviews and conducted 33 informational meetings in preparation for writing and submitting an NIH D43 Training Grant in Summer, 2023. Our team was well-received, and we were also able to visit with our Global Innovation Fund grant students, and with the AMPATH group in Eldoret. This trip was a successful beginning to expanding oral health and HIV research capacity in Kenya, and we are excited about the next steps towards the NIH D43 5-year training grant to expand research capacity.

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Children and adolescents living with HIV have poorer oral health-related quality of life

JDR Clinical & Transitional Research journal
JDR Clinical & Transitional Research journal

Children and adolescents living with HIV (CALHIV) have a higher risk of oral tissue diseases than those without HIV. Increasing awareness regarding the need to integrate oral health within medical care among pediatric HIV populations is crucial. Our study published in JDR Clinical & Translational Research entitled Oral diseases and oral health-related quality of life among Kenyan children and adolescents with HIV examines the associations between oral diseases and oral health-related quality of life (OHRQoL) in Kenyan CALHIV.

This cross-sectional study conducted in Nairobi, Kenya, administered oral examinations and oral health surveys (via the parent or guardian of the child/adolescent) to 71 children and adolescents ranging in age from 10 to <21 years. The survey measured oral symptoms, functional limitations, and emotional and social well-being. The overall mean OHRQoL score was 12.6. Results indicated that children/adolescents with ulcers had the worst overall OHRQoL scores (mean of 21.8). Children/adolescents with other oral diseases such as dry mouth and untreated caries had overall higher OHRQoL scores than those without disease.

Access to oral health care for CALHIV could be significantly improved by integrating it within the ongoing comprehensive medical care received in HIV treatment programs throughout Kenya.

Because dental care is included in the National Health Insurance, integration of oral care into HIV care could be efficient, cost-effective, and highly acceptable. Incorporating oral health protocols into children’s HIV care programs has the potential to increase surveillance of HIV disease trajectory, monitor the effectiveness of HIV anti-retroviral therapy, and improve the quality of life for children and adolescents living with HIV.

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The challenges of oral health in the United States

Pad with dental photos and dataA 2021 report by the U.S. National Institutes of Dental and Craniofacial Research (NIDCR) at the Department of Health and Human Services entitled “Oral Health in America: Advances and Challenges” examines the current state of oral health in the United States, and the progress that has been made over the past twenty years. The report touches on all aspects of oral health including the effect of oral health on the overall well-being, community, and the economy; oral health across the lifespan; oral health workforce, education, and practice; oral health and pain, substance abuse, and mental illness; and emerging sciences and technologies.

While there have been a few improvements in areas such the medical community acknowledging that oral health is important for overall health, and access to care has improved for children from low-income families in part due to increased collaboration between oral health professionals and pediatricians, there are still troubling trends in oral disease prevalence in the U.S. For example, 47% of U.S. adults 30 years of age or older have periodontal disease, and nine out of ten adults 20 to 64 years of age have had dental caries. Dental caries in permanent teeth still rank among the most common childhood diseases.

In order to improve oral health for Americans there are several areas of reform that would make a large impact, such as increasing access to dental care and tackling high costs associated with oral health. Over the past twenty years, per-person oral care costs have increased 30%, with $55 billion paid in out-of-pocket expenses. Communities that are the disproportionally impacted by oral health diseases have the least access to health services. To improve oral health across the spectrum, policies are needed to integrate medical, behavioral, and oral health. Adding preventive services to all aspects of the community including schools, assisted-living facilities, primary care clinics, community care clinics, and dental clinics would improve access.

The 2000 NIDCR report recognized that oral health is crucial to overall health. It’s critical that oral health be included in all aspects of health care, discovery, and policy in order to fully integrate and improve oral health for all Americans.

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Refugee displacement and public health systems

Map of UkraineThe war currently raging in Ukraine has created one of the largest refugee crises in modern history, according to the latest data from the Pew Research Center. After a month of the war, nearly 4 million Ukrainian’s have fled to other countries. So far, it’s the sixth-largest refugee exodus in the past sixty years. This number doesn’t include the amount of internally displaced Ukrainians who are still within the countries borders. All told, approximately ten million Ukrainians have been either internally or externally displaced, which amounts to nearly a fourth of the country’s population.

This massive geographical displacement of refugees will significantly impact public health systems of the welcoming countries. The current United States administration announced in March that they will be accepting up to 100,000 people fleeing the war in Ukraine, with priority to those who already have family in the US. US policy for arriving refugees mandates a medical assessment within 30 days after arrival. In the state of Washington, while medical assessments does not formally mandate oral health evaluation, all clinics allowed by the government to conduct such assessments include some aspect of oral health and therefore assisting with establishing a dental home as soon as possible. Inter-professional collaboration within the public health system is an opportunity to increase awareness and access to dental care among refugee populations.

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NIH awards the UW DeRouen Center an R56 grant

NIH/NIDCR logo
NIDCR is funding the R56 grant in Peru

Grant to study the impact of alcohol-use disorder on progression of dental disease in MSM with HIV

Despite successful antiretroviral therapy (ART), dental caries and periodontal disease remain more prevalent in persons with HIV (PWHIV) than those without HIV. Pain, xerostomia, lower quality of life, and impaired masticatory functions lead to reduced nutritional intake, which can increase HIV progression and amplify systemic co-morbidities. In Lima, Peru, HIV prevalence is 100-fold higher in men who have sex with men (MSM) relative to the general population (22.3% vs 0.2%), a proportion comparable to generalized epidemics in Sub-Saharan countries. Prior data confirms high levels (55%) of alcohol use disorder (AUD) which is defined as hazardous, harmful and dependent drinking, a co-morbid NCD, among MSM in Peru.

Men’s health is often neglected in global health research according in the January/February 2022 Global Health Matters newsletter through Global Fogarty International Center. There have been significant improvements in global health over the past few decades with many of those advancements focus on maternal and child health. The collaborative research between the UW School of Dentistry and the DeRouen Center for Global Health (PI Dr. Ana Lucia Seminario, and Drs. Philippe Hujoel, Brian Leroux, Noel Weiss, and Caroline Shiboski – University of California San Fancisco), Yale University (Co-PI Dr. Fredrick Altice), Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales (CITBM) (Dr. Jorge Sanchez), and Asociación Civil Impacta Salud y Educación (IMPACTA) (Dr. Javier Valencia) will address the oral health implications of MSM living with HIV.

In April, the DeRouen research team will visit the CITBM and IMPACTA clinics in Lima Peru to discuss and begin to implement the first phase of the study. The Peruvian research teams will administer a survey to their MSM patients and assess past and current alcohol consumption behavioral risk, use of dental care services as well as knowledge, attitudes, and behaviors towards oral health. The Peruvian team, UW team, and Yale team have begun the preliminary work for the launch of the of study in April 2022. These processes and procedures being developed will be used as part of the planning of a future R01 submission that aims to assess the impact of HIV and AUD on dental disease in Peruvian MSM.

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Children from under-resourced communities are at high risk for oral disease

BDJ Journal logo
Our new article, “Dental caries and anthropometrics of children living in an informal floating Amazonian community: a cross-sectional pilot study” is published in the Brazilian Dental Journal

Oral diseases are among the most prevalent non-communicable diseases worldwide, disproportionally affecting vulnerable populations. Oral diseases manifest as pain, impairment, and loss of function, and can affect individuals throughout their lifetime. Our study published in Brazilian Dental Journal entitled “Dental caries and anthropometrics of children living in an informal floating Amazonian community: a cross-sectional pilot study” examines the associations between poor oral health and growth in children in the community of Claverito, on the outskirts of Iquitos, Peru.

InterACTION Labs is a transdisciplinary research program where researchers collaborate with the Claverito community on health research and interventions to improve conditions in the slum community. In 2017 the University of Washington (UW) Population Health Initiative, the Centro de Investigaciones Technologicas, Biomedicas y Medio Ambientales (CITBM), and 100,000 Strong in the Americas awarded InterACTION Labs a pilot study to understand and address health disparities in Claverito.

For this project, the focus was on the relationship between poor oral health and growth in children ages 1 to 18 years old. To quantify oral health status, we looked at traditional decayed, missing, filled teeth (dmft/DMFT) scores as well as an innovative metric of the Significant Caries Index (SiC). To quantify growth, we calculated age-sex-specific scores for height and weight: height-for-age (HAZ), weight-for-age (WAZ), and body mass index for age (ZBMI). Results found that there was a statistically significant negative association between SiC and HAZ scores. Based on our results, there is evidence to suggest a relationship between dental disease and poor growth in children.

Floating communities living in poverty are found globally, and dental caries (tooth decay) is the most common chronic disease affecting children. This research contributes to the growing body of literature demonstrating the relationship between dental disease and anthropometric deprivation in underserved communities – knowledge which is critical to promoting an integrated response to the World Health Organization’s Sustainable Development Goals.

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