Close Proximity to Mining Is Associated with Increased Prevalence of the Drug Resistance–Associated Mutation dhps540E in Eastern Democratic Republic of the Congo

Cedar L. Mitchell Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;

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Mark M. Janko Duke Global Health Institute, Duke University, Durham, North Carolina;

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Robert Verity Medical Research Council Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom;

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Melchior M. Kashamuka Kinshasa School of Public Health, Kinshasa University, Kinshasa, Democratic Republic of the Congo;

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Jeffrey A. Bailey Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, Rhode Island;

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Antoinette K. Tshefu Kinshasa School of Public Health, Kinshasa University, Kinshasa, Democratic Republic of the Congo;

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Jonathan B. Parr Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina

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Jonathan J. Juliano Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina;
Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, North Carolina

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Increasing sulfadoxine-pyrimethamine (SP) resistance in the Democratic Republic of the Congo (DRC) has threatened its use for prevention of malaria in one of the most malarious countries in the world. Using geographic information on mining operations in the DRC and genetic data on SP drug resistance markers from the 2013–2014 Demographic and Health Surveys, we evaluated associations between close residence to mining and the presence of mutations conferring resistance to sulfadoxine. Close residential proximity to mining was associated with increased prevalence odds ratio (POR) of the dhps540E mutation (POR: 2.11, 95% uncertainty interval: 1.15–3.96) with adjustments for confounding variables and space. Our findings indicate that exposure to mining is associated with increased presence of an antimalarial drug resistance haplotype that threatens effective use of SP for vulnerable populations. Areas actively engaged in mining could be considered for interventions to reduce the spread of emerging drug resistance in the DRC.

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Author Notes

Financial support: This study was made possible by National Institutes of Health (grant numbers K24AI134990, R21AI121465, R01AI139520, T32AI070114, and R01AI151056). M. M. Janko was supported by NASA (80NSSC22K1046). R. Verity acknowledges funding from the Medical Research Council (MRC) Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK MRC and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement, and is also part of the EDCTP2 program supported by the European Union.

Disclosure: Ethical approval was obtained from the University of North Carolina Institutional Review Board and the Kinshasa School of Public Health.

Conflicts of interest: J. B. Parr reports research support from Gilead Sciences, nonfinancial support from Abbott Laboratories, and consulting for Zymeron Corporation, all outside the scope of this work.

Authors’ contributions: C. L. Mitchell and J. J. Juliano wrote the original manuscript draft, and M. M. Janko and J. B. Parr contributed substantially to revisions. C. L. Mitchell, M. M. Janko, and J. J. Juliano conceptualized and designed the study. C. L. Mitchell analyzed the data and performed analytic experiments, M. M. Janko and J. J. Juliano provided analytical guidance, and R. Verity, M. M. Kashamuka, J. A. Bailey, A. K. Tshefu, and J. B. Parr facilitated access to the data and contributed analysis materials. All authors read and approved the final manuscript.

Data availability: Data from the 2013 DRC, DHS, and PCR results are publicly available through the DHS program (dhsprogram.com/data). Raw sequencing data from Verity et al. was previously deposited in the Sequence Read Archive (accession numbers: PRJNA454490, PRJNA545345, and PRJNA545347).

Authors’ addresses: Cedar L. Mitchell, Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, E-mail: cedarmit@live.unc.edu. Mark M. Janko, Duke Global Health Institute, Duke University, Durham, NC, E-mail: mark.janko.collab@gmail.com. Robert Verity, Medical Research Council Centre for Global Infectious Disease Analysis, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom, E-mail: r.verity@imperial.ac.uk. Melchior M. Kashamuka and Antoinette K. Tshefu, Kinshasa School of Public Health, Kinshasa University, Kinshasa, Democratic Republic of Congo, E-mails: mkashamuka@yahoo.com and antotshe@yahoo.com. Jeffrey A. Bailey, Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI, E-mail: jeffrey_bailey@brown.edu. Jonathan B. Parr, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: jonathan_parr@med.unc.edu. Jonathan J. Juliano, Division of Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC, E-mail: jonathan_juliano@med.unc.edu.

Address correspondence to Jonathan J. Juliano, Department of Epidemiology, Gillings School of Global Public Health, 130 Mason Farm Rd., CB#7030, University of North Carolina, Chapel Hill, NC 27599. E-mail: jonathan_juliano@med.unc.edu
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