AUTHOR=Topazian Hillary M. , Moser Kara A. , Ngasala Billy , Oluoch Peter O. , Forconi Catherine S. , Mhamilawa Lwidiko E. , Aydemir Ozkan , Kharabora Oksana , Deutsch-Feldman Molly , Read Andrew F. , Denton Madeline , Lorenzo Antonio , Mideo Nicole , Ogutu Bernhards , Moormann Ann M. , Mårtensson Andreas , Odwar Boaz , Bailey Jeffrey A. , Akala Hoseah , Ong'echa John Michael , Juliano Jonathan J. TITLE=Low Complexity of Infection Is Associated With Molecular Persistence of Plasmodium falciparum in Kenya and Tanzania JOURNAL=Frontiers in Epidemiology VOLUME=2 YEAR=2022 URL=https://www.frontiersin.org/journals/epidemiology/articles/10.3389/fepid.2022.852237 DOI=10.3389/fepid.2022.852237 ISSN=2674-1199 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.