Health Grand Challenge
The Health Grand Challenge, established in 2007 as part of the University’s Grand Challenges Program and administered by CHW, is an integrated research and teaching program that seeks solutions to the pressing problems of global health and infectious disease. Explore our active projects below.
Ebola Outbreak Case Studies
PIs: Jennifer Widner, Princeton University; Rebecca Weintraub, Harvard University
This project aims to distill lessons about managing infection disease epidemics through research on the global response to the 2014-15 West African Ebola Outbreak. It is vital that the global health community and national health systems process and learn from the recent West Africa Ebola Outbreak so that we can continue to develop new and better responses to similar problems. The objective of this case study research project is to develop a series of 7-8 case studies about different aspects of the global response to the ebola outbreak across Guinea, Sierra Leone, Liberia, and neighboring countries. There is no way to address the whole response to the Ebola Outbreak in a single case study, while preserving the level of operational detail essential to careful reflection and learning. The interview-based case studies will focus on functional variation across countries and offer comparative insights.
Enhanced Production of Influenza Vaccine by Inhibition of Multiple Viral Restriction Factors
PI: Thomas Shenk, Princeton University
A set of human proteins have been identified that act to block the growth of viruses. They are termed viral restriction factors. We discovered several of the known viral restriction factors, including the family of sirtuin proteins. It is possible to delete or “knock down” expression of viral restriction factors to improve the growth of viruses.
We plan to identify an optimal set of viral restriction factors that, when inactivated (deleted or knocked down), markedly improve the growth of influenza virus in cultured cells. Improved yields of the virus has the potential to revolutionize the influenza vaccine industry, markedly reducing the cost of goods and making the vaccine available to a much larger portion of the world’s population.
Health as an Ecosystem Service Around Tanzanian Lakes and National Parks
PI: Andrew Dobson, Princeton University
Although sub-Saharan Africa’s national parks provide significant foreign currency to the government, the revenues they generate are rarely invested in the surrounding community health systems. Rural natives living in the parks’ vicinity have minimal access to basic health care, and many by default rely on traditional healers for treatment for zoonotic and vector-borne diseases.
This project investigates the dynamics and control of zoonotic and vector-borne disease in East Africa and the ‘ecosystem service’ that biodiversity plays in buffering and reducing disease outbreaks. How much do local people benefit from the presence of national parks? Specifically, do the parks serve as sources of ‘trickle down’ revenue from tourism to the local community, or as sources of ‘trickle down’ infections that impact their health and that of their livestock? Alternatively, does the park present a significant opportunity cost through loss of land for forage and crops? Or does it in turn protect local people and domestic livestock from disease outbreaks through the presence of host species that are preferred by vectors, or by other biological mechanisms that buffer disease outbreaks and improve water quality and volume? The research will address the health and economic costs and benefits of conserving biodiversity in the national parks and wildlife reserves.
Informational Structure of Infectious Diseases
PIs: Ramanan Laxminarayan and Simon Levin, Princeton University
Infectious diseases are carried by individuals, but survive in populations. The transmission of infectious disease is influenced possibly as much by information and human behavior as by the biology of the infection and the ecological landscape. In some sense, information and human behavior are part of the larger ecological landscape in which diseases operate but are relatively less understood than other features such as the population age structure, spatial detail or vector ecology (in the case of vector-borne diseases).
Research in economics and epidemiology has demonstrated that individual behavior is not static and changes with the risk of infection and effectiveness and cost of prevention and treatment. For example, the availability of inexpensive, effective treatment for malaria could reduce bednet purchase and use if individuals perceive a lower cost to being infected. These individual perceptions of risk are formed using a number of factors, including public information (such as on disease risk and prevalence), private information (on one’s own circumstances and behavior) and actions undertaken by others. The effect of herd immunity has been incorporated into disease models; but herd behavior and information cascades, which form the basis for how individuals acquire information, are also important. Taken together, the structure of public (both government and rest of society) and private information plays a key role in disease ecology and the dynamics of transmission.
Informational structure, just like spatial structure, could fundamentally change our understanding of disease progression, predictions of disease models, and effectiveness of public health interventions. Information is among the most powerful tools available to government authorities in time of disease outbreaks, and it is unclear how this tool ought to be used either by itself or in conjunction with other policies such as quarantining or mass vaccination. Also information from public authorities may have to preempt rumors and other sources of information that could exacerbate a disease outbreak.
Political Islam and the politics of health care in the Arab world
PIs: Amaney Jamal, Princeton Univerisry; Tarek Masoud, Harvard University; Elizabeth Nugent, Princeton University
This research grant will contribute to a large, multi-country study of political Islam and its impact on health outcomes in the Arab world. The project seeks to define and quantify the Islamic share of the market for medical services, to identify where and to what social groups such services are offered, to test systematically how the provision of Islamic medical services translates (or fails to translate) into political support for parties espousing identifiably Islamic agendas. This project will also trace the impact of Islamist governance on health outcomes—particularly for women. Do they for example, strive to make basic health services more accessible to women and children? Do they limit funding for family planning or for infectious diseases linked to sexual activity?
The project will involve multiple methodologies: GIS mapping of Islamic clinics; interviews with Islamic healthcare providers; statistical analyses of the correlations between Islamic vote shares and the “Islamic” share of the medical market; experimental and mass surveys of citizens’ political attitudes, voting behavior, and patterns of health care usage; and close analyses of health care legislation introduced by Islamist parliamentarians. The grant will be used to undertake a study in Tunisia in the summer of 2013, with a view toward making a larger proposal to a major research agency, such as the National Science Foundation and National Institutes of Health, to undertake further, cross-national research. The project promises not only to shed light on how Islamists view health care, but also the relationship between the provision of health care and winning elections, and how political Islam affects human development outcomes in the countries in which it has risen to power.
Pollution, Early-Life Health, and Child Development in Developing Countries
PI: Tom Vogl, Princeton University
This proposal seeks to launch a research agenda that examines environmental influences on early-life health and child development in developing countries. Funding from an HGC small seed grant will enable the completion of the agenda’s first study, on the health consequences of air pollution from the harvesting of sugarcane, an important global energy source. Three new studies will examine the effects of agricultural air pollution, urban water pollution, and slum conditions on child health and development. Much of the proposed research focuses on Brazil, so a key component of the proposal is its funding of undergraduate summer field research abroad. On campus, undergraduate and graduate students will have opportunities to collaborate on the proposed research, and findings will be incorporated into a range of interdisciplinary teaching activities. Beyond this educational use, the findings of the proposed research will have important implications for policymakers in developing countries seeking to balance population health with energy sustainability, agricultural livelihood, and rapid urbanization.
Predictive Models of Meningitis Risk in the African Meningitis Belt
PIs: Nicole E. Basta, Princeton Universiry; Paul Ginoux, NOAA; Elena Shevliakova, Princeton University
The complex ecological factors driving the distinct seasonality of meningococcal disease epidemics in the African meningitis belt are poorly understood. Evidence suggests that dust, low absolute humidity, rainfall, wind direction and velocity, land cover, and surface temperature may contribute, and a plausible biological mechanism by which these factors could increase risk of meningococcal disease among asymptomatic carriers has been proposed. We aim to develop, test, and validate an epidemiologic meningococcal disease risk model for Mali and Niger using climatic factors drawn from several high-resolution climate models including a recently published model of global dust circulation.
Our goal is to develop tools to better understand the role of environmental factors in predicting meningitis outbreaks in Africa. Developing these tools will set the stage for more extensive research aimed at modeling epidemiologic risk across the entire meningitis belt and identifying high-priority areas that would most benefit from vaccination, thus addressing a significant public health challenge.
Should we mass-deworm the world? A clinical trial to test whether anthelmintic treatment increases risk of virus- and bacteria-induced diarrhea
PI: Andrea Graham, Princeton University
Mass, school-based ‘deworming’ programs are becoming routine in developing countries, to eliminate parasitic helminths from the intestinal tracts of children. However, experimental evidence suggests that anthelmintics may increase host susceptibility to other infections (bacteria, viruses, or protozoa). This is because helminth removal opens up ecological and immunological niches for pathogens to invade. Thus, deworming – although aimed at improving the health and cognition of helminth-infected children – may instead have detrimental effects, including increased incidence of viral and bacterial diseases.
Unfortunately, mass deworming campaigns fail to monitor for undesirable consequences of treatment, ignoring the prevalence and health impact of co-occurring infections. We have unique preliminary evidence from Vietnam suggesting that helminths may indeed protect children against other enteric infections. We now propose to conduct a placebo-controlled clinical trial in Vietnamese schoolchildren to examine the effects of anthelmintic treatment on risks of diarrheal disease due to opportunistic bacteria and viruses.
Towards eradication of human malaria: molecular characterization of plasmodial dormancy
PI: Alexander Ploss, Princeton University
Malaria is a life-threatening parasitic disease for which approximately half of the world's population is at risk. About 300-500 million cases of malaria are estimated to occur each year, causing nearly one million deaths. Although progress has been made in preventing and treating malaria, more effective, tolerable, and affordable therapies and vaccines are needed. The malaria parasites, which are transmitted through the bites of infected mosquitoes, causing the most harm to humans are Plasmodium falciparum (Pf) and Plasmodium vivax (Pv). They exhibit a unique and mechanistically undefined human tropism, and animal models that recapitulate these parasitic life cycles are scarce. Pv establishes frequently persistent forms in the liver called hypnozoites and in any attempt to eradicate malaria it will be necessary to know how, when and where to attack these forms. Due to the lack of experimental systems hypnozoites are almost completely undefined and mechanisms of their formation and/or reactivation are unknown. Here, we propose to utilize humanized mice, which harbor a human liver to analyze Pv infection in their native environment. We will transcriptionally profile Pv liver stages and their host cells using deep sequencing approaches. Molecular signatures of malarial dormancy will be critical for identifying putative therapeutic intervention points.
Uncovering the molecular mechanisms of viral pathogenicity and life-viral vector attenuation
PI: Alexander Ploss, Princeton University
Arthropod-borne Flaviviruses, such as dengue virus (DENV), West Nile virus (WNV) and yellow fever virus (YFV), are a cause of major health and economic concerns, cumulatively infecting hundreds of millions of people worldwide. These viruses can cause a broad range of diseases in human, frequently leading to a lethal outcome. Although no vaccine or treatments currently exist to prevent or treat many Flavivirus’ infections, the YF 17D attenuated strain is the sole exception and is one of the most efficient vaccines ever developed. However, the molecular mechanisms responsible for its strong induction of immune responses are not known. Here, we propose to take advantage for the first time of a humanized immune system mice model that recapitulates the YF lethal course of infection observed in humans. Uncovering novel virus-host immune signatures that define YF pathogenesis in vivo can provide valuable information for the rational design of innovative vaccine strategies against some of the more challenging human pathogens.
Understanding the Impact of Meningococcal B Vaccination among Princeton University Students
PI: Nicole E. Basta, Princeton University
Outbreaks of bacterial meningitis are a significant public threat whenever they occur because of the severity of the disease and the high case fatality. Since the spring of 2013, an outbreak of bacterial meningitis caused by Neisseria meningitidis serogroup B has led to seven cases among Princeton University students, one case among a visitor, and the death of a Drexel University student. This prolonged outbreak has posed a significant public health threat and prompted the introduction of a recently developed, novel meningococcal B vaccine known as Bexsero, through the US Food and Drug Administration’s Investigational New Drug application process since the vaccine is not yet licensed in the US.
Plans to vaccinate incoming students in Fall 2014 presents a unique opportunity to assess the impact of the vaccine on immune response to the outbreak strain and to menB strains more broadly both before and after vaccination. Following our successful study of the impact of Bexsero among Princeton students after the 2013-2014 vaccination campaigns, we will investigate the immunogenicity of Bexsero by conducting an epidemiological study of immune markers of protection against invasive disease both before and after the Bexsero vaccination campaign in a cohort of incoming students. Our aim is to better understand the immune response to meningococcal B vaccination during an outbreak, to evaluate the immunogenicity of the vaccine among college students recently vaccinated with quadrivalent ACWY meningococcal vaccine, and to collect data that could provide evidence-based recommendations to guide future disease control and prevention policies.
Vaccine preventable diseases in Madagascar: Estimating burden, and optimizing targeting for control efforts
PI: Jessica Metcalf, Princeton University
The exceptionally high case fatality rate associated with measles in children, coupled with the existence of a safe, effective, and inexpensive vaccine has led to measles control being referred to as a “best buy” in public health. Rubella, while mild in children, can cause birth of a child with an array of congenital issues if contracted by mothers during the first trimester of pregnancy. Again, a safe, effective vaccine is available. Rabies has the highest case fatality rate of any human disease, and infection is completely preventable if individuals receive post-exposure prophylaxis. However, limited access to care characterises many low-income settings, and rabies continues to cause many deaths. Measles elimination is targeted in all WHO regions by 2020, rabies by 2030; and introduction of rubella containing vaccine is being assessed across Africa. Little is known about the dynamics of measles in Madagascar, and rubella data are almost completely lacking. A survey of the serological status across age for measles and rubella that reflected rural and urban communities would identify targets for vaccination campaigns necessary for successful elimination, as well as evaluation of the burden of Congenital Rubella Syndrome, which, in turn, informs the desirability of introduction of rubella-containing vaccine. For rabies, both the true burden in humans, but also dynamics in dog populations are very poorly characterized, despite over a century of control efforts. Combining existing sources of data from treatment centers with contact-tracing of dynamics in dogs will generate new estimates and inference, providing guidance into the scope and scale of dog vaccination targeting required for elimination.
Wild baboons as a model to understand immune function and disease risk during pregnancy and lactation
PIs: Jeanne Altmann, Princeton University; Elizabeth Archie, University of Notre Dame
Scientific understanding of women’s disease risk and immune function during pregnancy and lactation is surprisingly limited. This is partly because pregnant and lactating women are challenging study subjects; hence human studies are often constrained to small sample sizes, sub-optimal controls, and/or biased metadata. Our project will address these challenges by working in the well-studied Amboseli baboon population, which offers decades of dense, longitudinal sampling on behavior and physiology. We propose two aims to reveal how female reproductive status influences three major indices of immune function and disease risk: wound healing, the incidence of illness, and parasite burdens. Our preliminary results suggest that wound healing is delayed during lactation. The resulting data sets will be among the largest in the world on this topic, for either humans or animals, and the proposed project will place us in a competitive position to receive future funding on perinatal health.
Selected Health Grand Challenge projects receive funding support through CHW's Program on U.S. Health Policy:
Epidemiology of Antibiotic Use in U.S. Hospitals
Impact of Meningcoccocal B Vaccination during the 2013 Princeton University Outbreak
Modeling the Impact of Pre-Exposure Prophylaxis and Targeted Hepatitis C Case-finding and Treatment on the HIV and HCV epidemics in Newark, NJ
The Grand Challenges Program is a collaboration involving the Princeton Environmental Institute,
the School of Engineering and Applied Science, and the Woodrow Wilson School of Public and International Affairs.
The Health Grand Challenge is funded by the Woodrow Wilson School’s Center for Health and Wellbeing and by the Princeton Environmental Institute.
The Center for Health and Wellbeing administers the Health Grand Challenge.