Project Summary

Infectious diseases are still the leading cause of disability and death in developing countries, including the Democratic Republic of Congo (DRC). Until recently, only educated guesses about the distributions and burdens of important diseases like malaria, trypanosomiasis, and HIV had been made at the national or and subnational levels. By leveraging leftover dried blood spots and the wealth of data from the 2007 Demographic and Health Survey in DRC, and using methods from molecular and spatial epidemiology, the SHRG and other collaborators based at UNC and in the DRC have begun to fill this knowledge gap by building models to understand both the spatial distribution of these diseases and estimate factors associated with their incidence. The results of this work have informed us about a variety of issues related to malaria control, including an early understanding of the spatial structure of drug-resistant malaria in the DRC.

Now, we are moving forward with our research in the DRC using the 2013/14 DHS. In particular, we are working on the following:

Gametocytemia. The gametocyte is the malaria lifecycle stage that is infectious to mosquitoes, and therefore we are working to understand if and how the prevalence of gametocytemia differs from parasitemia, and what the consequences of this are for the spatial distribution of malaria in DRC. Methodologically, we’re measuring P. falciparum gametocytemia from malaria-infected dried blood spots using quantitative reverse-transcriptase, real time PCR (rtPCR).  Multilevel models and survival analyses are being used to identify individual- and community-level cofactors that predict an individual’s probability of gametocytemia.  Bayesian geostatistical methods will be applied for inference and to effectively measure uncertainty in estimates.

Landscape Genetics. How malaria moves from place to place continues to be a major concern for public health. In this work, we are leveraging two DHSs to understand how different mutations of the malaria parasite diffuse geographically. We are doing this work by integrating methods from spatial statistics and population genetics in a rapidly evolving field known as Landscape Genetics. Parasite microsatellites will be measured and used to determine the genetic relatedness (Rst and Gst) and the estimated number of migrants (Nm) between P. falciparum populations in different DHS clusters, while spatial statistical models will be built to try and understand not just the pattern, but the process governing diffusion. We are particularly interested in drug-resistant malaria and the factors that promote or prevent its diffusion.

Importantly, this project has expanded, and continues to expand, the mission of the DHS Program to include gathering prevalence data on endemic and emerging infectious diseases using high-throughput molecular diagnostics. Furthermore, the results of our work are shared with the DRC Ministry of Health to help guide control programs.

Project Team Members

Michael Emch

Mark Janko

Cory Keeler

Varun Goel

Larry Han

Griffin Bell

Publications

Mwandagalirwa MK, Levitz L, Thwai KL, Parr JB, Goel V, Janko M, Tshefu A, Emch M, Meshnick SR, Carrel, M (2017, in press) Individual and household characteristics of persons with Plasmodium falciparum malaria in sites with varying endemicities in Kinshasa Province, Democratic Republic of the Congo. Malaria Journal.

Stebbins R, Emch M, Meshnick SR (2017, in press) The Effectiveness of Community Bed Net Use on Malaria Parasitemia Among Children Under 5 in Liberia. American Journal of Tropical Medicine and Hygiene.

Parr JB, Lodge E, Holzmayer V, Pepin J, Frost EH, Fried MW, McGivern DR, Lemon SM, Keeler C, Emch E, Mwandagalirwa K, Tshefu A (2017) Dried blood spots allow for efficient, largescale surveys of hepatitis C viremia. Clinical Infectious Diseases. Clinical Infectious Diseases, cix771, doi.org/10.1093/cid/cix771.

Parr JB, Verity R, Doctor SM, Janko M, Carey-Ewend K, Turman BJ, Keeler C, Hannah C. Slater, Whitesell AN, Mwandagalirwa K, Ghani AC, Likwela JL, Tshefu AK, Emch M, Juliano JJ, Meshnick SR (2017) Pfhrp2-deleted Plasmodium falciparum 1 parasites in the Democratic Republic of Congo: A national cross-sectional survey. Journal of Infectious Diseases. 216 (1): 36-44.

Doctor SM, Liu Y, Anderson OG, Whitesell AN, Mwandagalirwa MK, Muwonga J, Keeler C, Emch M, Likwela JL, Tshefu A, Meshnick SR. (2016) Low prevalence of Plasmodium malariae and Plasmodium ovale mono-infections among children in the Democratic Republic of the Congo: a population-based, cross-sectional study. Malaria Journal. 15:350. PMID 27392905.

Parr J, Belson C, Patel J, Hoffman I, Kamthunzi P, Martinson F, Tegha G, Thengolose I, Drakeley C, Meshnick S, Escamilla V, Emch M, Juliano J. (2016) Estimation of Plasmodium falciparum Transmission Intensity in Lilongwe, Malawi, by Microscopy, Rapid Diagnostic Testing, and Nucleic Acid Detection. American Journal of Tropical Medicine and Hygiene. 3;95(2):373-7.

Carrel M, Janko M, Mwandagalirwa MK, Morgan C, Fwamba F, Muwomba J, Tshefu AK, Meshnick S, Emch M (2016) Changing spatial patterns and increasing rurality of HIV prevalence in the Democratic Republic of the Congo between 2007 and 2013. Health & Place. 39: 79-85.

Doctor S, Liu Y, Whitesell A, Thwai K, Taylor S, Janko M, Emch M, Kashamuka M, Muwonga J, Tshefu A, Meshnick S. (2016) Malaria Surveillance in the Democratic Republic of the Congo: Comparisons of Microscopy, PCR, and Rapid Diagnostic Test. Diagnostic Microbiology and Infectious Disease. 85(1):16-8. PMID 26915637.

Carrel M, Patel JC, Taylor S, Janko M, Kashamuka M, Tshefu A, Escalante A, McCollum A, Alam MT, Udhayakumar V, Meshnick S, Emch M (2015) The geography of malaria genetics in the Democratic Republic of Congo: a complex and fragmented landscape. Social Science & Medicine. 133: 233-241.

Janko, M and Emch, M. (2016) “The Geography of Malaria Control in the Democratic Republic of Congo.” Eds. Harrington, DW, McLafferty, S, and Elliott, SJ.  Population Health Intervention Research: Geographical Perspectives. Ashgate Publishing Ltd, Surrey, England.

Carrel M; Patel JC; Taylor S; Janko, M; Kashamuka M; Tshefu A; Escalante A; McCollum A; Alam MT; Udhayakumar V; Meshnick S; Emch M. (2015) The geography of malaria genetics in the Democratic Republic of Congo: a complex and fragmented landscape. Social Science & Medicine. 133: 233-241.

Antonia AL; Taylor SM; Janko M; Emch M; Tshefu AK; Meshnick SR. (2014, in press) A Cross-sectional Survey of Plasmodium falciparum pfcrt Mutant Haplotypes in the Democratic Republic of Congo. American Journal of Tropical Medicine and Hygiene.

Patel JC; Taylor SM; Juliao JJ; Parobek CM; Janko M; Gonzalez LD;  Tshefu AK; Emch M; Udhayakumar V; Lindblade K; Meshnick SR (2014, in press) Genetic evidence for the importation of falciparum malaria by Guatemalan soldiers returning from the Democratic Republic of the Congo. Emerging Infectious Diseases.

Messina, JP; Mwandagalirwa, K; Taylor, SM; Emch, M; Meshnick, SR. (2013) Assessing the Spatial, Social, and Disease-related Determinants of Anemia in Congolese Women. Health & Place.24: 54-64.

Carrel, M. and Emch, M. (2013) Genetics: A New Landscape for Medical Geography. Annals of the Association of American Geographers. 103(6): 1452-1467.

Taylor, SM; Antonia AL; Parobek CM; Juliano JJ; Janko M; Emch M; Alam MT; Udhayakumar V; Tshefu A; Meshnick SR (2013) Plasmodium falciparum Sulfadoxine Resistance is Geographically and Genetically Partitioned within the DR Congo. Scientific Reports. 3: 1165.

Messina, JP; Taylor, SM; Hand, CC; Juliano, JJ; Muwonga, J; Tshefu, AK; Atua, B; Alam, MT; Udhayakumar, V; Emch, M; Meshnick, SR (2011) Measurement of malaria in the Democratic Republic of the Congo by molecular analyses of leftover dried blood spots from the 2007 Demographic Health Survey. The Lancet. Published abstract.

Messina, JP; Taylor, SM; Meshnick, SR; Linke, A; Tshefu, AK; Atua, B; Mwandagalirwa, K; Emch, M (2011) Population, behavioral and environmental drivers of malaria prevalence in the Democratic Republic of Congo. Malaria Journal. 10:161. link to article

Mumba, D; Bohorquez, E; Messina, J; Kande, V; Taylor, SM; Tshefu, A; Muwonga, J;  Mwandagalirwa, MK; Emch, M; Tidwell, R; Büscher, P; Meshnick, SR. (2011) Prevalence of human african trypanosomiasis in the Democratic Republic of the Congo. PLoS Neglected Tropical Diseases. 5(8): e1246. link to article

Taylor, SM.; Messina, JP.; Hand, CC.; Juliano, JJ.; Muwonga, J; Tshefu, AK; Atua, B; Emch, M; Meshnick, SR. (2011) Molecular malaria epidemiology: mapping and burden estimates for the Democratic Republic of the Congo, 2007. PLoS One. 6(1): 1-9. link to article

Taylor, SM; van Eijk, A; Hand, CC; Mwandagalirwa, MK; Messina, J; Tshefu, A; Atua, B; Emch, M; Muwonga, J; Meshnick, SR; ter Kuile, F. (2011) Quantification of the burden and consequences of pregnancy-associated Malaria in the Democratic Republic of the Congo. Journal of Infectious Diseases. 204(11): 1762-1771. link to article

Messina, JP, Emch, M, Muwonga, J, Mwandagalirwa, K, Edidi, SB, Mama, N, Okenge, A; Meshnick, SR. (2010) Spatial and socio-demographic patterns of HIV prevalence in the Democratic Republic of Congo. Social Science and Medicine. 71(8): 1428-1435. link to article

Funding

  1. Emch, M. (P.I.) and Meshnick, S. (CoI). Research Experience for Undergraduates: Spatio-Temporal Patterns of Drug Resistant Malaria in the Democratic Republic of Congo. National Science Foundation, REU, $7000, 2014-2017.
  2. Meshnick, S. (P.I.) and Emch, M (CoI). Epidemiological and Spatial Models of Malaria Transmission. National Institute of Allergies and Infectious Disease, National Institutes of Health, RO1, $ 2,243,272(direct), 2014-19.
  3. Emch, M. (P.I.) and Meshnick, S. (CoI). Spatio-Temporal Patterns of Drug Resistant Malaria in the Democratic Republic of Congo. National Science Foundation, BSC-1339949, $344,869, 2014-2018.
  4. Meshnick, S. (P.I) and Emch, M. (CoI) Genetic epidemiology of malaria in the Democratic Republic of the Congo. National Institute of Allergies and Infectious Disease, National Institutes of Health, 1R56AI097609, $488,403 (direct), 2012-2013.
  5. Meshnick, S. (PI); Emch, M.E. (CoPI); and Miller, M. (CoPI) Center for Accurate Data on Endemic and Emerging Infectious Diseases in Developing Countries, Gillings Innovation Labs, UNC School of Public Health, $504,452, 2008-10.