Outsmarting Parasites in the DRC

August 30, 2018

Drs. Steve Meshnick, Antoinette Tshefu and Benjamin Atua, the head of the National Malaria Control Program stand in front of the Congo River in 2010.

In 2002, a group of newly recruited infectious diseases faculty in the UNC Department of Epidemiology, submitted a grant proposal to the National Institute of Child Health and Human Development’s Global Network for Women and Children’s Health Research. It was to be the first time working in the Democratic Republic of the Congo (DRC) for both Steve Meshnick, M.D., Ph.D., and Annelies van Rie, M.D., Ph.D., but not for Robin Ryder, Ph.D., and Frieda Behets, Ph.D. The grant was awarded and UNC’s collaboration with the Kinshasa School of Public Health began.

Ryder and Behets were old Congo hands, having worked there in the 1980s. Both left in the early 1990s when the DRC erupted into a long and deadly civil war. When the war ended, Ryder and Behets rekindled old collaborative relationships, especially with Kash Kashamuka, M.S.P.H., and Antoinette Tshefu, M.D., Ph.D., of the Kinshasa School of Public Health. When Ryder retired, Carl Bose, M.D., of the UNC Department of Pediatrics took over the leadership of the Global Network project. The Global Network project remains active today, mainly focused on clinical trials in the remote northwest province of Equateur. The group has done numerous interesting and important studies, including one to assess whether adding ground-up caterpillars (as a source of protein) to infant food promotes infant development.

Mapping Tropical Diseases
In 2010, Meshnick and Michael Emch, Ph.D., of the UNC Department of Geography, received a grant from the newly established Gillings Innovation Labs (GIL). Meshnick and Emch used the grant to pioneer a new approach to infectious disease surveillance. Previously, most information on tropical diseases was obtained from a handful of sites, usually chosen by chance or simply because they were accessible. Thus, the prevalence numbers were often quite biased.

But this time, the DRC had just finished a large nation-wide, population-representative survey called the Demographic and Health Survey (DHS). The survey, conducted in 2007, yielded 9,000 dried blood spots. These were analyzed to generate the first maps of tropical diseases (African sleeping sickness and malaria) in the DRC since 1951. The Gillings Innovation Labs funding was followed by several new National Institutes of Health (NIH) grants leveraging 26,000 samples from the second Demographic and Health Survey completed in 2013. The group of UNC researchers has coalesced into the Infectious Disease, Epidemiology and Ecology Lab (IDEEL); the DRC remains its most active research site. Jon Juliano, M.D., M.S.P.H., and Jonathan Parr, M.D., M.P.H., have joined Meshnick and Emch in leadership roles in this endeavor.

A Stealthy Foe
The UNC IDEEL investigators have made important contributions to the understanding of malaria in the DRC and in Africa in general. They showed how data from the Demographic and Health Survey could be used to guide interventions, choices of antimalarials, and even choices of insecticide-treated bed nets. Most importantly, they discovered that the gene that coded for the histidine rich protein (HRP) in the most common malaria, P. falciparum, was being deleted and this deletion was spreading. The spread of this gene mutation is important because detection of the HRP is used for diagnosis in commonly used rapid, point-of-care tests. The malaria parasite was essentially developing “stealth technology” and becoming undetectable.

Also, the team discovered that a second malaria parasite, P. vivax, was actually quite common in the DRC – it had previously been thought to be absent. The team is also conducting a combined epidemiological and entomological longitudinal cohort study in the Kinshasa province where they plan to evaluate new types of bed nets and diagnostics.

The malaria work served as a jumping off point for prevalence studies of other infectious diseases, including hepatitis B, hepatitis C and flaviviruses such as dengue, Zika and yellow fever. Even though there is a vaccine for hepatitis B, the group found a very high prevalence (3.2 percent) of children in the DRC with hepatitis B. The flavivirus work was done in collaboration with the Aravinda de Silva, Ph.D., M.P.H., of the UNC Department of Microbiology & Immunology. The DRC hepatitis group now includes Parr along with Peyton Wilson, M.D., a pediatric infectious diseases fellow at UNC; Ravi Jhaveri, M.D., of UNC’s Division of Pediatric Infectious Diseases; and Rohit Ramaswammy, Ph.D., of UNC’s Department of Maternal and Child Health. The group is now piloting an intervention to prevent vertical transmission of hepatitis B with support, again, from the Gillings Innovation Labs.

By Steve Meshnick, M.D., Ph.D.,  Professor of Epidemiology, Microbiology and Immunology at UNC and a researcher in the Democratic Republic of the Congo.