Malaria and other Vector-Borne Diseases

close up of moquito feeding on a human

Malaria is transmitted by mosquitoes

Vector-borne diseases result from an infection transmitted to humans by blood-feeding insects, such as mosquitoes, ticks, and fleas. In 2013, the U.S. CDC reported that incidence of tick-borne lyme disease is as much as ten times higher than previously thought (many as 300,000 cases per year). Tick-borne rickettsial diseases, such as Rocky Mountain spotted fever, ehrlichiosis, and anaplasmosis, are also a significant public health problem in the US.

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 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.

Research

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

A malaria clinic in Thailand, near the bordder with Cambodia, where Jessica Lin is conducting research.

A malaria clinic in northern Cambodia, where Jessica Lin is conducting research.

Relapsing Malaria

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

Mapping Malaria

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

Training

UMJT Fogarty Global Health Fellows Program

Service Initiatives

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.

Who’s Involved

Carla Cerami

Irving Hoffman

Jonathan Juliano

Jessica Lin

Cherry Liu

Steve Meshnick

Recent publications

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).

Meshnick S. Perspective: artemisinin-resistant malaria and the wolf (American Journal of Tropical Medicine and Hygenie, 2012).

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).

Vaughn MF, Meshnick SR. Pilot study assessing the effectiveness of long-lasting permethrin-impregnated clothing for the prevention of tick bites (Vector Borne Zoonotic Diseases, 2011).

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).