Kayode Tolulope, Niyukuri David, Holzschuh Aurel, Da Silva Gustavo, Huwe Tiffany, Lerch Anita, Nyandwi Joseph, Koepfli Cristian
Eck Institute for Global Health and Department of Biological Sciences, University of Notre Dame, Indiana, United States of America.
Environmental Change Initiative, University of Notre Dame, Indiana, United States of America.
medRxiv. 2025 Jun 23:2025.06.22.25330092. doi: 10.1101/2025.06.22.25330092.
Antimalarial resistance, including failure of artemisinin combination therapy, is increasing in Africa. Molecular surveillance of markers of drug resistance is essential to monitoring drug resistance. isolates from Cibitoke Province, Burundi were sequenced for ten markers of resistance (including potential background markers conferring 13mediated artemisinin partial resistance) by Illumina or Nanopore sequencing. and copy number variations were typed by digital PCR. Among 157 isolates, no validated mutations linked to artemisinin partial resistance (ART-R) were detected. However, a novel mutation, A675T, was identified. A mutation in the same position (A675V) had been found and validated in neighboring Rwanda previously. Background mutations were frequent, including D193Y (45.9%) and V127M (11.5%). Sulfadoxine-pyrimethamine (SP) resistance was widespread, with quintuple haplotypes detected in 82.3% and sextuple haplotypes in 12.3% of mono-infections. The IET triple mutant haplotype (94.9%) and N-F-D mutant haplotype (57.9%) indicate sustained CQ resistance and efficacy of artemether-lumefantrine (AL). No duplications but rare amplifications (1.8%) were identified. These findings indicate substantial SP resistance, posing a threat to the efficacy of IPTp and SMC strategies in Burundi. The findings also show potential ART-R and partner drug resistance in Burundi, highlighting the need for strengthened surveillance and coordinated regional efforts to mitigate resistance and sustain malaria control.
包括青蒿素联合疗法失效在内的抗疟耐药性在非洲呈上升趋势。耐药性标志物的分子监测对于监测耐药性至关重要。通过Illumina或纳米孔测序对布隆迪锡比托克省的分离株进行了10种耐药性标志物（包括赋予青蒿素部分耐药性的潜在背景标志物）的测序。通过数字PCR对拷贝数变异进行分型。在157株分离株中，未检测到与青蒿素部分耐药性（ART-R）相关的经过验证的突变。然而，鉴定出一种新的突变，A675T。此前在邻国卢旺达发现并验证了同一位置的突变（A675V）。背景突变很常见，包括D193Y（45.9%）和V127M（11.5%）。磺胺多辛-乙胺嘧啶（SP）耐药性普遍存在，在单感染中，82.3%检测到五倍体单倍型，12.3%检测到六倍体单倍型。IET三重突变单倍型（94.9%）和N-F-D突变单倍型（57.9%）表明持续存在氯喹耐药性以及蒿甲醚-本芴醇（AL）的疗效。未发现拷贝数增加，但鉴定出罕见的扩增（1.8%）。这些发现表明存在大量SP耐药性，对布隆迪的孕期间歇性预防治疗（IPTp）和季节性疟疾化学预防（SMC）策略的疗效构成威胁。这些发现还显示了布隆迪潜在的青蒿素部分耐药性和联合用药耐药性，突出了加强监测以及开展区域协调努力以减轻耐药性并维持疟疾控制的必要性。
