Vector-borne diseases result from an infection transmitted to humans by blood-feeding insects, such as mosquitoes, ticks, and fleas. Zika was declared an international public health emergency by the World Health Organization in February 2016. Although sexual transmission is possible, people are primarily infected by mosquitoes. The virus has been linked to microcephaly in infants and Guillain-Barre syndrome, a disorder that causes the immune system to attack the body’s nerves.
Although eradicated from the U.S. in 1951, malaria is a major global killer, and one of the top three killers of children worldwide. Malaria is caused by several species of parasites that are transmitted by mosquito bites. According to the latest estimates by the WHO, there were about 220 million cases of malaria in 2010, the vast majority in Africa. Most malaria deaths are in children who have not yet built up immunity to the disease.
At UNC, faculty researchers and trainees working to help lessen the burden of Zika, malaria and other vector-borne illnesses worldwide, with research into the the biology, prevention and treatment of these diseases. In 2015, IDEEL@UNC (Infectious Disease, Epidemiology and Ecology Lab at University of North Carolina) was formed by a group of principal investigators who share a vision for improving the health of the world’s poorest populations by improving their understanding of the infectious diseases that impact them most.
IGHID researchers are investigating Zika at sites around the world. UNC faculty, including Natalie Bowman, MD, MPH, are collaborating with investigators at Universidad Nacional de la Amazonía Peruana in Peru to study the effect of prior and acute Zika virus infection on male fertility. This is a multi-site study that also includes subjects from León, Nicaragua (UNAN-León). The study will assess changes in sperm count, morphology, and viability as well as advanced studies of sperm health to see if Zika causes durable derangements in human male reproductive function.
Also at UNAN-León, Sylvia Becker-Dreps, MD, MPH, and Elizabeth Stringer, MD, MSc, are conducting additional studies to better understand, and eventually reduce the burden of Zika:
- Surveillance for Zika infection in populations of pregnant women using remnant blood (left-over blood that has been collected for routine prenatal care.)
- Evaluation of neurodevelopment of infants exposed to Zika during pregnancy.
- Study on Zika shedding and its implications for sexual transmission by testing for Zika in different body fluids (blood, saliva, urine, semen, vaginal secretions, breast milk) to understand where Zika is found and could potentially transmit infections.
- Collaboration with RTI International in Durham, N.C., to understand neurological sequelae of Zika infection.
Driven in large part by their study of returned travelers with risk of arbovirus infection, Aravinda de Silva, PhD, and Matthew Collins, MD, PhD, are collaborating more broadly to define key determinants of the human adaptive immune response to Zika virus. A deeper understanding of how the immune system interacts with Zika as a primary flavivirus infection, as well as in the context of prior infection by related flaviviruses such as dengue, will elucidate mechanisms of pathogenesis and protection that advance important research priorities.
Malaria vaccine trial
In partnership with the PATH Malaria Vaccine Initiative and GlaxoSmithKline, UNC is conducting phase III clinical trials of a malaria vaccine in Malawi. So far the vaccine, RTS,S, has been shown to reduce the number of malaria cases in young children by almost 50 percent and to reduce malaria in infants by 27 percent. Contact: Irving Hoffman
Malaria and Pregnancy
At UNC, studies are underway using molecular tools to understand how malaria causes poor birth outcomes. Research in Malawi has revealed that malaria infections during pregnancy can lead to the delivery of low-birth-weight infants. Researchers are working to develop new ways to protect pregnant women and their children from the effects of the disease. Contact: Steve Meshnick
Plasmodium vivax is the most widespread human malaria parasite outside of Africa, but it has largely been neglected in comparison to its sister species, Plasmodium falciparum, because it does not usually cause death. It does uniquely causes relapsing disease. IGHID is working with partners in India and Cambodia to understand the genetic determinants of P. vivax relapse by identifying and characterizing relapses using next generation sequencing methods. Contact: Jessica Lin
Drug Resistant Malaria
One of the greatest challenges to the control of malaria is the emergence of drug resistance. In collaboration with the NIH and partners around the globe, research at UNC into the genetics and genomics of drug resistance are lending insight into how drug resistance emerges and spreads in parasite populations. Contact: Jonathan Juliano
Diversity of Malaria Vaccine Antigens
Many of the possible targets for malaria vaccines are highly diverse. This complicates the design of vaccines. Research at UNC has been characterizing the genetic diversity of leading vaccine candidate antigens and trying to understand how this diversity impacts vaccine efficacy. Contact: Jonathan Juliano
Tick Microbiome Studies
Ticks carry many pathogenic bacteria, but they also carry many that are not pathogenic. The relationship between pathogens and non-pathogens are being studied, both in lone star and blacklegged ticks. Contact: Steve Meshnick
High throughput genotyping methods are being used to map malaria in the Democratic Republic of the Congo (DRC). Drivers of malaria transmission, including public health interventions and ecological factors such as deforestation, are being studied. Contacts: Steve Meshnick and Mike Emch.
Ticks in North Carolina
Tick-borne diseases are a significant concern for millions of people who live and work in tick-infested environments. If not treated early, these diseases can lead to severe illness or even death. In 2011, IGHID faculty affiliates partnered with the NCSU Department of Entomology, the NC Department of Health and Greensboro-based company Insectshield to test the efficacy of tick-repellent uniforms for State Park, Fish and Wildlife and Forestry rangers in western North Carolina. Contact: Steve Meshnick
In Malawi, through the Safeguard the Family Project, IGHID provides a comprehensive, integrated health care delivery system throughout the Central West Region of Malawi, serving 134 health facilities and 3.8 million people. Through this program, patients are screened, tested and treated for malaria and bednets are distributed to prevent infection.
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Collins MH, McGowan E, Jadi R, et al. Lack of Durable Cross-Neutralizing Antibodies Against Zika Virus from Dengue Virus Infection. Emerg. Infect. Dis. 2017; 23:773–781.
Collins MH, Metz SW. Progress and Works in Progress: Update on Flavivirus Vaccine Development. Clin. Ther. 2017; 39:1519–1536.
Givens MB, Lin JT, Lon C, Gosi P, Char MC, et al. Development of a capillary electrophoresis-based heteroduplex tracking assay to measure in-host genetic diversity of initial and recurrent Plasmodium vivax infections in Cambodia (Journal of Clinical Microbiology, 2013).
Bowman NM, Congdon S, Mvalo T, Patel JC, Escamilla V, et al. Comparative population structure of Plasmodium falciparum circumsporozoite protein NANP repeat lengths in Lilongwe, Malawi (Scientific Reports, 2013).
Andrianaranjaka V, Lin JT, Golden C, Juliano JJ, Randrianarivelojosia M. Activation of minority-variant Plasmodium vivax hypnozoites following artesunate + amodiaquine treatment in a 23-year old man with relapsing malaria in Antananarivo, Madagascar (Malaria journal, 2013).
RTS,S Clinical Trials Partnership (incl. Martinson F and Hoffman I) et al. A phase 3 trial of RTS,S/AS01 malaria vaccine in African infants (New England Journal of Medicine, 2012).
Bailey JA, Mvalo T, Aragam N, Weiser M, Congdon S, et al. Use of massively parallel pyrosequencing to evaluate the diversity of and selection on Plasmodium falciparum csp T-cell epitopes in Lilongwe, Malawi (Journal of Infectious Diseases, 2012).
Taylor SM, Parobek CM, Aragam N, Ngasala BE, Mårtensson A, Meshnick SR, Juliano JJ. Pooled Deep Sequencing of Plasmodium falciparum Isolates: An Efficient and Scalable Tool to Quantify Prevailing Malaria Drug-Resistance Genotypes (Journal of Infectious Diseases, 2013).
Turner AN, Tabbah S, Mwapasa V, Rogerson SJ, Meshnick SR, et al. Severity of Maternal HIV-1 Disease Is Associated With Adverse Birth Outcomes in Malawian Women: A Cohort Study (Journal of Acquired Immune Deficiency Syndrome, 2013).
Lin JT, Patel JC, Kharabora O, Sattabongkot J, Muth S, et al. Plasmodium vivax isolates from Cambodia and Thailand show high genetic complexity and distinct patterns of P. vivax multidrug resistance gene 1 (pvmdr1) polymorphisms (American Journal of Tropical Medicine and Hygiene, 2013).
McClure EM, Goldenberg RL, Dent AE, Meshnick SR. A systematic review of the impact of malaria prevention in pregnancy on low birth weight and maternal anemia (International Journal of Gynaecology and Obstetrics, 2013).
Bohórquez EB, Juliano JJ, Kim HS, Meshnick SR. Mefloquine exposure induces cell cycle delay and reveals stage-specific expression of the pfmdr1 gene (Antimicrobal Agents and Chemotherapy, 2013).
Lin JT, Mbewe B, Taylor SM, Luntamo M, Meshnick SR, Ashorn P. Increased prevalence of dhfr and dhps mutants at delivery in Malawian pregnant women receiving intermittent preventive treatment for malaria (Tropical Medicine and International Health, 2013).
Bohórquez EB, Chua M, Meshnick SR. Quinine localizes to a non-acidic compartment within the food vacuole of the malaria parasite Plasmodium falciparum (Malaria journal, 2012).
Lin JT, Juliano JJ, Kharabora O, Sem R, Lin FC, et al. Individual Plasmodium vivax msp1 variants within polyclonal P. vivax infections display different propensities for relapse (Journal of Clinical Microbiology, 2012).
Agnandji ST, Lell B, Soulanoudjingar SS Fernandes JF, Abossolo BP, et al. First results of phase 3 trial of RTS,S/AS01 malaria vaccine in African children (New England Journal of Medicine, 2011).