Laboratory of Malaria Vaccinology and Immunology, NIH/NIAID, 12735 Twinbrook Pkwy, Rockville, MD 20852, USA.
J Infect Dis. 2013 Jul;208(1):139-48. doi: 10.1093/infdis/jit132. Epub 2013 Mar 28.
Millions of individuals being treated for human immunodeficiency virus (HIV) live in malaria-endemic areas, but the effects of these treatments on malaria transmission are unknown. While drugs like HIV protease inhibitors (PIs) and trimethoprim-sulfamethoxazole (TMP-SMX) have known activity against parasites during liver or asexual blood stages, their effects on transmission stages require further study.
The HIV PIs lopinavir and saquinavir, the nonnucleoside reverse-transcriptase inhibitor nevirapine, and the antibiotic TMP-SMX were assessed for activity against Plasmodium falciparum transmission stages. The alamarBlue assay was used to determine the effects of drugs on gametocyte viability, and exflagellation was assessed to determine the effects of drugs on gametocyte maturation. The effects of drug on transmission were assessed by calculating the mosquito oocyst count as a marker for infectivity, using standard membrane feeding assays.
Lopinavir and saquinavir have gametocytocidal and transmission blocking activities at or approaching clinically relevant treatment levels, while nevirapine does not. TMP-SMX is not gametocytocidal, but at prophylactic levels it blocks transmission.
Specific HIV treatments have gametocyte killing and transmission-blocking effects. Clinical studies are warranted to evaluate these findings and their potential impact on eradication efforts.
数以百万计的人类免疫缺陷病毒 (HIV) 感染者生活在疟疾流行地区,但这些治疗方法对疟疾传播的影响尚不清楚。虽然像 HIV 蛋白酶抑制剂 (PIs) 和复方磺胺甲噁唑 (TMP-SMX) 这样的药物在肝脏或无性血液阶段对寄生虫具有已知的活性,但它们对传播阶段的影响需要进一步研究。
评估了 HIV PIs 洛匹那韦和沙奎那韦、非核苷类逆转录酶抑制剂奈韦拉平以及抗生素 TMP-SMX 对疟原虫传播阶段的活性。alamarBlue 测定法用于确定药物对配子体活力的影响,通过评估出芽来确定药物对配子体成熟的影响。通过计算蚊子卵囊数作为感染性标志物,使用标准膜喂养测定法来评估药物对传播的影响。
洛匹那韦和沙奎那韦在接近或达到临床相关治疗水平时具有配子体杀伤和传播阻断作用,而奈韦拉平则没有。TMP-SMX 不具有配子体杀伤作用,但在预防性水平下可阻断传播。
特定的 HIV 治疗方法具有配子体杀伤和传播阻断作用。需要进行临床研究来评估这些发现及其对根除工作的潜在影响。