Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania

Hillary M Topazian; Kara A Moser; Billy Ngasala; Peter O Oluoch; Catherine S Forconi; Lwidiko E Mhamilawa; Ozkan Aydemir; Oksana Kharabora; Molly Deutsch-Feldman; Andrew F Read; Madeline Denton; Antonio Lorenzo; Nicole Mideo; Bernhards Ogutu; Ann M Moormann; Andreas Mårtensson; Boaz Odwar; Jeffrey A Bailey; Hoseah Akala; John Michael Ong'echa; Jonathan J Juliano

doi:10.3389/fepid.2022.852237

Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania

Front Epidemiol. 2022 Jun 6:2:852237. doi: 10.3389/fepid.2022.852237. eCollection 2022.

Authors

Hillary M Topazian¹, Kara A Moser², Billy Ngasala³, Peter O Oluoch^{4

5}, Catherine S Forconi⁴, Lwidiko E Mhamilawa^{3

6}, Ozkan Aydemir⁷, Oksana Kharabora², Molly Deutsch-Feldman⁸, Andrew F Read⁹, Madeline Denton², Antonio Lorenzo¹⁰, Nicole Mideo¹⁰, Bernhards Ogutu⁵, Ann M Moormann⁴, Andreas Mårtensson⁶, Boaz Odwar⁵, Jeffrey A Bailey⁷, Hoseah Akala⁵, John Michael Ong'echa⁵, Jonathan J Juliano^{2

8

11

12}

Affiliations

¹ Department of Infectious Disease Epidemiology, Imperial College, London, United Kingdom.
² Institute for Global Health and Infectious Diseases, University of North Carolina, Chapel Hill, NC, United States.
³ Department of Parasitology and Medical Entomology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
⁴ Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, United States.
⁵ Center for Global Health Research, Kenyan Medical Research Institute, Kisumu, Kenya.
⁶ Department of Women's and Children's Health, International Maternal and Child Health, Uppsala University, Uppsala, Sweden.
⁷ Department of Pathology and Laboratory Medicine, Brown University, Providence, RI, United States.
⁸ Department of Epidemiology, Gillings School of Global Public Health, Chapel Hill, NC, United States.
⁹ Department of Entomology, Penn State University, University Park, PA, United States.
¹⁰ Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada.
¹¹ Division of Infectious Diseases, School of Medicine, University of North Carolina, Chapel Hill, NC, United States.
¹² Curriculum in Genetics and Molecular Biology, School of Medicine, University of North Carolina, Chapel Hill, NC, United States.

Abstract

Background: Plasmodium falciparum resistance to artemisinin-based combination therapies (ACTs) is a threat to malaria elimination. ACT-resistance in Asia raises concerns for emergence of resistance in Africa. While most data show high efficacy of ACT regimens in Africa, there have been reports describing declining efficacy, as measured by both clinical failure and prolonged parasite clearance times.

Methods: Three hundred children aged 2-10 years with uncomplicated P. falciparum infection were enrolled in Kenya and Tanzania after receiving treatment with artemether-lumefantrine. Blood samples were taken at 0, 24, 48, and 72 h, and weekly thereafter until 28 days post-treatment. Parasite and host genetics were assessed, as well as clinical, behavioral, and environmental characteristics, and host anti-malarial serologic response.

Results: While there was a broad range of clearance rates at both sites, 85% and 96% of Kenyan and Tanzanian samples, respectively, were qPCR-positive but microscopy-negative at 72 h post-treatment. A greater complexity of infection (COI) was negatively associated with qPCR-detectable parasitemia at 72 h (OR: 0.70, 95% CI: 0.53-0.94), and a greater baseline parasitemia was marginally associated with qPCR-detectable parasitemia (1,000 parasites/uL change, OR: 1.02, 95% CI: 1.01-1.03). Demographic, serological, and host genotyping characteristics showed no association with qPCR-detectable parasitemia at 72 h. Parasite haplotype-specific clearance slopes were grouped around the mean with no association detected between specific haplotypes and slower clearance rates.

Conclusions: Identifying risk factors for slow clearing P. falciparum infections, such as COI, are essential for ongoing surveillance of ACT treatment failure in Kenya, Tanzania, and more broadly in sub-Saharan Africa.

Keywords: Kenya; P. falciparum; Plasmodium; Tanzania; artemisinin; artemisinin combination therapy; parasite clearance.

Copyright © 2022 Topazian, Moser, Ngasala, Oluoch, Forconi, Mhamilawa, Aydemir, Kharabora, Deutsch-Feldman, Read, Denton, Lorenzo, Mideo, Ogutu, Moormann, Mårtensson, Odwar, Bailey, Akala, Ong'echa and Juliano.