For the 2018 Global Health Disparities Research Fellowship, you may apply to no more than two (2) of the research projects described below. Please read the descriptions carefully and ensure that you have the qualifications required to complete the project. If you have any questions, please contact the MHIRT program. Please DO NOT contact the professors directly.
BRAZIL — Bacterial Infections (1 slot)
Lee Riley & Claudete Cardoso, Sergio Arruda, Beatriz Moreira
Background: The Riley laboratory has been involved in collaborative projects in Brazil since 1990. The collaboration has focused on infectious diseases of importance to urban centers, specifically on infectious diseases of urban slums. Brazil has undergone more than 350% increase in its urban population since 1960. This has engendered completely new types of health problems with magnitude not seen in most developing or developed countries. Urbanization and the explosive increase in shantytown populations have created a new set of health problems: chronic infectious (TB, AIDS, post-infectious cardiovascular and renal diseases) and non-infectious diseases (hypertension, diabetes, asthma, and unintentional and unintentional injuries). A single placement with the Riley lab will be available in Brazil, but the particular project and site will be negotiated once a student joins the lab. The options are outlined below.
Possible Project 1: Biomarkers for TB diagnosis and monitoring response to treatment (Oswaldo Cruz Foundation, Salvador; collaborator-Cardoso): Exploiting the knowledge gained from basic TB pathogenesis research conducted at UC Berkeley, we are evaluating immunological responses in patients with latent infection, to determine responses predictive of those who may progress to active disease. In particular, we are exploring host response to M. tuberculosis lipids as biomarkers for infection and response to treatment for TB. This is done in collaboration with researchers at Oswaldo Cruz Foundation in Salvador, Brazil. This project will require some experiences working in a laboratory, especially with immunology procedures.
Possible Project 2:Biomarkers for pediatric TB diagnosis (Federal University of Fluminense, Rio de Janeiro; Collaborator–Arruda): Pediatric TB diagnosis is complicated by the fact that small children cannot expectorate sputum. Hence, samples containing M. tuberculosis cannot be readily obtained. We have identified several candidate biomarkers that may be detected in blood by simple ELISA. Samples from children with and without TB will be obtained to validate the biomarker assay. This project will require experiences in working in a laboratory and familiarity with immunology procedures.
Possible Project 3: Drug-resistant Gram-negative bacterial infections (Federal University of Rio de Janeiro; Collaborator–Moreira): Hospital infections are a major emerging problem in Rio de Janeiro as well as in other major cities of Brazil. For the last 15 years, we have been conducting molecular epidemiologic studies with the Federal University of Rio de Janeiro, to understand risk factors for transmission and characterize pathogens implicated in infections in a large university hospital in Rio. This project will require some experiences in microbiology research.
BRAZIL II— Zika Epidemic (1 slot)
Lee Riley & Claudete Cardoso
Background: The Riley laboratory has been involved in collaborative projects in Brazil since 1990. The collaboration has focused on infectious diseases of importance to urban centers, specifically on infectious diseases of urban slums. In 2015, Brazil became the first country in Latin America to experience the explosive epidemic of Zika virus infections. Subsequently, Zika virus infection in fetus has been shown to cause a severe congenital neurologic disease microcephaly. Microcephaly cases are currently occurring in Brazil in epidemic proportions.
Project Description: The Riley Lab in collaboration with a Brazilian pediatric infectious disease researcher Dr. Claudete Cardoso of Federal Fluminense University has begun a prospective study of newborns whose mothers were exposed to Zika virus during pregnancy. This is part of a pediatric cohort study that includes biomarker assessment for the diagnosis of pediatric TB. Over the next 2 years, we will create a cohort of newborns with normocephaly whose mothers were exposed to the Zika virus during pregnancy. This cohort will be prospectively followed for cognitive and developmental abnormalities.
International Site:The Federal University of Fluminense is one of the largest universities in Brazil, and has been experiencing a huge growth in the number of undergraduate and post-graduate courses, as well as in research and extension activities. The academic arena, the university offers to its students scientific initiation, innovation, monitoring and internship.
Required Qualifications: This project will require working knowledge of Portuguese or Spanish, and experiences performing ELISA and PCR.
CHINA I – HIV Transcription Activation and Latency Reversal (2 slots)
Title: Functional characterization of novel Tat partners key for activation of HIV-1 transcription and exit from latency.
Background: We are interested in elucidating the mechanisms and identifying host cellular co-factors that control HIV-1 transcription and latency. It was 15 years ago when the human transcription elongation factor P-TEFb was first identified as a host cofactor for activation of HIV-1 transcription by the viral encoded Tat protein. Recruited by Tat to the viral LTR, P-TEFb stimulates RNA polymerase II elongation, a process essential for viral replication. Since 1997, this landmark discovery has provided the basic framework for our understanding of Tat function during the HIV life cycle, and P-TEFb remains the only widely accepted functional Tat partner till this day. However, published data suggest that Tat-transactivation involves more than the interaction between Tat and P-TEFb. A major effort of ours is thus aimed at identifying additional cellular factors that may associate with Tat-P-TEFb to further enhance Tat-transactivation.
Project Description: Recently, our laboratory has successfully identified the first new Tat partners in more than a decade. These partner proteins together with P-TEFb exist in a preformed complex called the Super Elongation Complex. The MHIRT research apprentice will use a combination of molecular and biochemical techniques to characterize this complex and determine the mechanism by which it cooperates with Tat to stimulate HIV-1 transcription and exist from latency. A portion of this project will be conducted in our collaborator’s lab, led by Dr. Yuhua Xue at Xiamen University in China.
International Site: The partner for this project is Dr. Yuhua Xue in the School of Pharmaceutical Sciences at Xiamen University, China. Xiamen University has standard training and educational programs in place for international students at both the undergraduate and graduate levels. The visiting student will first be paired with a senior graduate student or a postdoc in the lab in order to become familiar with the daily operations in the lab.
Required Qualifications: Advanced undergraduates or graduate students in MCB will have the appropriate background to complete this project.
CHINA II– Data Science for Advancing an Environmental Understanding of Infectious Disease Dynamics(2 slots)
Justin Remais (UC Berkeley) & Changhong Yang (China Centers for Disease Control and Prevention)
Title: Methods for optimizing the surveillance of infectious diseases in rapidly changing low- and middle-income environments
Background: This project — part of a recently funded NIH R01 — aims to develop statistical and computational approaches for better designing surveillance systems for high-priority global infectious diseases. Graduate or undergraduate students contributing to this project will advance methods to characterize dynamics of key infections in China in the presence of epidemiological and environmental changes, and subject to diverse surveillance system designs.
Project Description: Members of our team will be embedded in the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention, where they will query and analyze high dimensional surveillance data streams on the dynamics of TB, malaria, dengue, schistosomiasis, Japanese encephalitis and leptospirosis. Graduate or undergraduate students contributing to this project will investigate the informational value of diverse surveillance architectures for monitoring these infections in China, and will acquire and analyze ‘Big’ surveillance data drawn from China’s massive NIDR system in order to do so. Other activities include the development of tools for the characterization and infectious disease surveillance networks using both epidemiological analysis and simulation science. Undergraduate, Master’s thesis and doctoral-level research opportunities are available within the group.
International Site: These studies are being carried out in collaboration with the Institute for Public Health Informatics at the China Centers for Disease Control and Prevention in Chengdu, Sichuan Province, PRC. The interns will be supervised by Dr. Changhong Yang, the director of the institute, as well as by Professor Remais and his scientific staff.
Required Qualifications: Undergraduate or graduate training in quantitative science is desirable, such as mathematics, modeling and simulation, computer science, environmental science, dynamical systems, engineering, population biology, or infectious disease epidemiology, although successful group members in the Remais Lab also have had backgrounds in physics, biology, anthropology and medicine. Technical skillsets, such as statistical analysis, geospatial analysis/GIS, time-series, differential equations, programming in any language (we are known to use R, Python, Matlab, Ruby, Perl, C, etc.), environmental modeling, theoretical ecology, or remote sensing, would be additionally desirable; effective written and verbal communication are essential.
INDIA I — Public Health Research Institute of India (PHRII) (2 slots)
Title: Molecular and Field Epidemiology Studies with Woman and Child Cohorts in Mysore, India
International Site Information: Public Health Research Institute of India (PHRII) is a Charitable Trust focused on public health research and evidence based care for women and children in India. Located in Mysore, the second largest city in Karnataka, PHRII has established collaborations with University of California, Berkeley; JSS University, National Rural Health Mission (NRHM); Karnataka State AIDS Control Society, and the Positive Women’s network. The organization has a full service diagnostic laboratory, a reproductive health clinic in central Mysore City, and mobile clinics serving rural areas of Mysore District.
Currently, some of the ongoing projects at PHRII include:
- Mental health issues in pregnant and postnatal women;
- Prevention of vertical transmission of HIV;
- Under 5-child mortality among disadvantaged populations in remote tribal and rural areas;
- Cognitive and mental development of infant and relationship to maternal mental health;
- Primary and secondary prevention of cervical cancer;
- Development of diagnostics for cancer screening and gestational diabetes;
- Understanding risk behaviors among emerging adults;
PHRII’s research collaboration with UCB Riley Laboratories has focused on the pathogenesis of infectious and chronic diseases; molecular epidemiology on tuberculosis and drug-resistant gram-negative bacterial infections; field epidemiology and slum health.
Project Description: Candidates may select from a variety of ongoing projects in the areas described above including field based and/or laboratory work at PHRII in Mysore, India. Specific project selection will occur following the selection process and upon mutual agreement of the PIs and candidate. Interested applicants may seek additional information about available projects via Dr. Madhivanan who can be reached via the MHIRT office.
Required Qualifications: Preference will be given to candidates who have analytical skills, molecular microbiology or field experience and have worked in international settings before.
Title: Enhancing HIV treatment adherence in Bangalore: The Chetana Study
Project Description: The study brings together researchers from the University of California, San Francisco and St. John’s National Academy of Health Sciences in Bangalore, India. The overall goal of this study is to evaluate the impact of a promising Antiretroviral Therapy (ART) adherence-enhancing intervention grounded in Social Cognitive Theory (SCT) that addresses the needs of people living with HIV (PLHIV). This intervention targets not only medication adherence, but also other culturally-relevant topics designed to enhance physical and mental health among PLHIV, including yoga/meditation, nutrition, legal services, and assistance accessing local resources. We are testing this promising intervention in a Randomized Controlled Trial (RCT) among 500 sub-optimally adherent patients, comparing it to a time-matched active control condition, consisting of the non-adherence specific components of the intervention.
Specific we propose to:
1. To evaluate the impact of the Chetana intervention on antiretroviral medication adherence and treatment outcome, as measured by self-report, viral load, Wisepill wireless monitoring, and medical chart review. We hypothesize that participants in the intervention arm will show a significant reduction in missed pills as well as a reduced number of treatment interruptions and improved viral suppression, compared to participants in the time-matched active control group.
2. To evaluate the impact of the Chetana intervention on reported adherence barriers. We hypothesize that participants in the intervention arm will report a significant reduction in number of adherence barriers, compared to participants in the time-matched active control group.
3. To examine wireless adherence monitoring as a predictor of treatment outcome. We hypothesize that this ongoing, objective real-time measure of adherence will better predict subsequent viral load than our self-reported Optimal Adherence measure that combines past month adherence and treatment interruptions.
The study may yield valuable information on improving adherence among sub-optimally adherent PLHIV in South India. Participation may help individuals develop strategies to improve adherence and minimize treatment interruptions. Because suboptimal adherence can lead to virologic failure and the development of drug resistance, developing and evaluating adherence- enhancing interventions are critical components of maximizing the durability of affordable HIV treatment options and the prevention of HIV drug resistance. This is especially true in Resource Limited Settings (RLS), where second line therapy may be unavailable or unaffordable.
Research site: St. John’s National Academy of Health Sciences (SJNAHS), Bangalore.
Title: Reducing AIDS stigma among health professionals in South India (The DriSti Study)
Project Description: This study brings together researchers from the University of California, San Francisco; Research Triangle Institute in Washington DC; St. John’s National Academy of Health Sciences in Bangalore, India; and the All India Institute of Medical Sciences in New Delhi, India to evaluate the efficacy of a promising intervention designed to reduce HIV stigma among Indian health professionals. The intervention builds on results of our previous research, identifying prevalence and drivers of stigma and discrimination in Indian healthcare settings among PLHIV, health care providers and uninfected patients.
Specifically, the study will:
1. Adapt our pilot-tested 3-session stigma reduction intervention for partial tablet-based delivery to increase its long-term sustainability in health care settings. The two tablet-administered sessions of the intervention use interactive touch screen methodology and video vignettes tailored to situations likely to be encountered by Indian nurses and ward attendants. The third session focuses on skills-building in a group format and is co-facilitated by a PLHIV.
2. Evaluate the efficacy of the intervention in 24 hospitals in North and South India on:
a) behavioral manifestations of HIV stigma, including endorsement of coercive policies, behavioral intentions to discriminate, and non/stigmatizing provider-patient interactions.
b) the factors underlying stigma proposed by our conceptual model and targeted in the intervention modules, including fears and misconceptions regarding casual transmission (instrumental stigma), and negative attitudes toward marginalized, vulnerable groups (symbolic stigma).
Across the globe, HIV stigma inflicts hardship and suffering on people with HIV and has been found to reduce the likelihood of seeking HIV counseling and testing and PMTCT. Stigma also deters infected individuals from disclosing their status, seeking timely medical treatment for HIV-related problems, reduces ART adherence, and leads to delays in clinic appointments and prescription refills, which can lead to virologic failure and the development and transmission of drug resistance.
Medical professionals unfortunately constitute a significant source of stigma for PLHIV. The study will yield valuable information on the efficacy of the intervention strategies in reducing stigma and improving patient-interaction skills among ward staff and nursing students. We expect this knowledge will inform the development and implementation of future AIDS stigma reduction programs efforts in India and similar settings.
Research site: St. John’s National Academy of Health Sciences (SJNAHS), Bangalore.
INDIA IV – Validating a Low-cost Treatment Adherence Monitoring Device
Title: Tel-Me-Box: Validating and testing a novel, low cost, real-time monitoring device with hair level analysis among adherence-challenged patients
Project Description: “Tel-Me-Box” is a small, low-cost, adherence monitoring device, developed by our team that transmits a wireless signal to a server when opened. Since it cannot assess actual drug ingestion, validation against a biological measure of adherence is crucial. The overarching hypothesis of this application is that adherence data captured by Tel-Me-Box will demonstrate strong relationships with an objective biomarker of adherence (i.e. hair concentrations of ARVs) and predict virologic suppression in treated HIV-infected individuals. We additionally hypothesize that tailored real-time adherence feedback via this device will improve adherence rates to HIV therapy for adherence-challenged patients in a pilot randomized clinical trial. This five-year study is being conducted in collaboration with our colleagues at St. John’s National Academy of Health Sciences in Bangalore and the Karnataka State government.
Specific objectives include:
Aim 1 will refine Tel-Me-Box by adding tailored reminder features. We will also demonstrate feasibility of hair analysis in RLS by training local staff to conduct the relevant hair assays.
Aim 2 will validate the Tel-Me-Box adherence measure, using ARV hair concentrations and HIV viral load, and examine the predictive utility of Tel-Me-Box monitoring and hair drug levels on virologic suppression in HIV-infected patients.
Aim 3, will conduct a pilot RCT to examine acceptability and feasibility and estimate the effect size of automated tailored real-time adherence reminders on hair ARV concentrations, device-monitored adherence, and viral load suppression in adherence-challenged patients.
Novel, validated methods to monitor adherence to HIV treatment in real time are urgently needed given the well-known limitations of self-reported adherence, pill counts, and medication electronic monitoring system caps. In order to be scalable and sustainable in LMICs, such devices need to be low-cost and designed in a way that does not increase the risk of accidental HIV disclosure and subsequent stigma. Devices which both monitor adherence in real time and provide tailored reminders to patients for medication-taking have the potential to greatly improve adherence to HIV treatment as well as to treatment for other chronic diseases.
Research site: St. John’s National Academy of Health Sciences (SJNAHS), Bangalore.
INDIA V – Improving Health and Nutrition of Women with AIDS All India Institute of Medical Sciences (AIIMS), New Delhi
Title: ASHA Improving Health and Nutrition of Indian Women with AIDS and Their Children
Project Description: The overall goal of this study is to enhance the physical and mental health of rural Indian women living with AIDS and their children. We will achieve these goals through the use of trained village women as Accredited Social Health Activists (ASHA) to enhance the health of women and children through improved ART adherence, CD4 levels, and physical and mental health. This Indo-US collaboration between University of California, Los Angeles, University of California, San Francisco and All India Institutes of Medical Sciences (AIIMS) builds on our previous work with rural women living with AIDS and our successful ASHA program.
Specific objectives include:
• Using a 2×2 factorial design, we plan to assess the effects of nutrition training and/or food supplements on primary outcomes for rural women living with AIDS in improving body composition and immune status (CD4 levels) as assessed at 6-, 12- and 18-month follow-up.
• Examining the effects of the program arms and their interaction on adherence to ART, psychological health, nutritional adequacy, and lipid profile over time.
Rural women living with AIDS experience profound challenges in accessing and following treatment for AIDS, while caring for children and maintaining a positive mental health outcome; yet, there has been very little research conducted regarding their nutritional needs and that of their growing children, some of whom may also have HIV/AIDS. This study is innovative as it addresses the role of ASHA care and support and a focus on nutrition in improving the physical and emotional health of a very high risk population – rural women in India who are on ART and their vulnerable families; strengthen family health; and obtain data for a multi-site implementation study. By understanding the adequacy and role of nutrition and strengthened family health outcome, we hope to develop readily accessible and feasible scale-up assessment and delivery modalities to use in rural public health clinics. This program, if found efficacious, could easily be scaled up and sustained by local governmental and non-governmental organizations in rural and urban settings across India and elsewhere.
Research site: All India Institute of Medical Sciences (AIIMS), New Delhi
NICARAGUA – Zika in Nicaragua (2 slots)
Title: Zika Virus Infection in Nicaragua
Background: In 2015/16, Zika virus (ZIKV) of the Flavivirus genus caused explosive epidemics that began in Brazil and spread throughout the Americas. Zika rapidly became a global concern, as it has been linked to severe congenital birth defects, including microcephaly and mis¬carriage, prompting the WHO to declare the ZIKV pandemic a Public Health Emergency of International Concern in February of 2016. As of June 30, 2016, 50 countries are reporting active mosquito-borne ZIKV transmission. Over 2,500 cases have been reported in the US and its territories, with 14 confirmed cases of sexual transmission. Some of the affected countries have reported increased numbers of congenital birth defects and Guillain-Barré syndrome (GBS) cases. Acute ZIKV infection is associated with inapparent or mild symptoms, ranging from myalgia, arthralgia, low-grade fever, conjunctivitis, maculopapular rash, and headache, to prostration. While the link between ZIKV infection among pregnant women and congenital defects such as microcephaly has been deemed likely, it has not been confirmed in long-term prospective cohort studies. Further, little is known about the clinical presentation of Zika among pregnant women or long-term sequelae in children, nor about pathogenic mechanisms or anti-ZIKV immune responses. No effective ZIKV antivirals or vaccines currently exist. Nicaragua reported its first Zika case in January of 2016. Since then, Dr. Eva Harris and long-term collaborators at the Ministry of Health and Sustainable Sciences Institute in Managua, Nicaragua, have been conducting a series of investigations of Zika infection and disease in a pediatric cohort study, a pediatric hospital-based study, a household transmission study, and starting in Fall of 2016 in pregnant women and their infants. Numerous virological, molecular biological, and immunological studies are ongoing.
Project Description: We aim to describe the Zika epidemic in Nicaragua by collecting information about likely risk factors and analyzing blood samples of individuals with Zika-like symptoms through a retrospective serological study. The samples analyzed are captured as annual sample collection as part of an ongoing community-based pediatric cohort study. The project includes determining previous ZIKV infection via enzyme linked immunosorbent assay (ELISA), as well as correlating these results with associated risk factors using the survey administered to each participant. Regarding the Zika household transmission study and the Zika in Infants and Pregnancy (ZIP) study, samples need to be processed via molecular biological and serological techniques to diagnose ZIKV infection and analyze the immune response.
International Site: Our foreign research site is embedded within the Ministry of Health of Nicaragua and administered in collaboration with the Sustainable Sciences Institute (SSI). Placement is available at the National Virology Laboratory of the National Center for Diagnosis and Reference (CNDR) of the Ministry of Health. The site is well-established, with over 60 study employees, and serves several large prospective studies of dengue, chikungunya, influenza and Zika. Numerous MHIRT, MPH, and PhD students have been hosted by SSI and the National Virology Laboratory in Managua. Dr. Harris has been collaborating productively with the Nicaraguan CNDR/Ministry of Health for over 28 years.
Required qualifications: Motivated undergraduate or graduate students with Spanish language proficiency. Previous laboratory experience, particularly molecular biology, required. STATA/SAS experience preferred, but not required.
Title: From asymptomatic parasitemia to cerebral malaria – investigating causes for a wide spectrum of malaria infection outcomes
Background: Our group has performed clinical, epidemiologic and translational research on malaria infection in Blantyre, Malawi for the past 30 years. The collaboration is between Michigan State University (MSU), Queen Elizabeth Central Hospital and the University of Malawi College of Medicine, with collaborative efforts based at several other US and UK based institutes. Our focus has historically been on severe disease with a long standing observational study on children with cerebral malaria being the ‘backbone’ of our research efforts. Recent efforts have moved away from the hospitalized patient and into the community where we are investigating the role of asymptomatic malaria infection and its role in maintaining a disease transmission reservoir.
Project Description: Topics of investigation may range from clinical to epidemiologic to basic science aspects of malaria infection and its consequences. We are specifically interested in the host and/or parasite factors that lead to varied clinical outcomes after Plasmodium infection. Techniques could range from immunologic to entomologic to molecular and genetic.
International Site: The project will be based in Blantyre, Malawi at the University of Malawi College of Medicine campus. Infrastructure in Blantyre includes a Pediatric Research ward for inpatient care, a Molecular and Genomics Core laboratory, a fully functional insectary, and several well-characterized rural sites within a 60km radius.
Required Qualifications: Students currently studying biology or public health are preferred.
UGANDA – Translational Research in Malaria (1 slot)
Title: Investigating parasite and host factors associated with clinical malaria outcomes.
Background: Our group performs clinical and translational research on malaria and other infectious diseases in Africa, at UCSF and at Dominican University of California. The team at UCSF also includes Grant Dorsey and Bryan Greenhouse (Division of Infectious Diseases, Dept. of Medicine) along with many collaborators at Makerere University. This ongoing collaboration is formally known as the Makerere University-UCSF Uganda Malaria Research Program.
Project Description: Topics may include clinical, epidemiology, or molecular aspects of malaria research. In particular, we are interested in predictors of and mechanisms of drug resistance, antimalarial immune responses, and parasite-host markers of severe malaria. Other studies in Uganda involve surveillance of malaria at rural locations across the country.
International Site: This study is based in Kampala, Uganda, at the Molecular Research Laboratory (Molab) located in the New Mulago Hospital Complex. This is a long running partnership between researchers at UCSF and Makerere University in Kampala, Uganda. Additional studies take place in Tororo, Uganda. Please see http://www.muucsf.org for more information.
Required Qualifications: Students currently studying biology or public health are preferred.