Petersen E, Hogh B, Hanson A P, Bjorkman A, Flacks H
Liberian Institute for Biomedical Research, Charlesville, Margibi County.
Ann Trop Med Parasitol. 1990 Dec;84(6):563-71. doi: 10.1080/00034983.1990.11812511.
In vivo susceptibility of Plasmodium falciparum to chlorproguanil and in vitro susceptibility to pyrimethamine, cycloguanil and chlorcycloguanil were studied in 38 children from two Liberian villages. Children in one village (Lagbala) had received monthly chemosuppression with chlorproguanil from 1976-1985, and children in the other village (JDF) had received fortnightly chlorproguanil from 1981-1985. The highest and lowest IC100 for pyrimethamine differed by a factor of 10(5), but they differed only by a factor of 10(3) for chlorcycloguanil. The mean IC100 for chlorcycloguanil was significantly lower (P less than 0.0001) than the mean IC100 for pyrimethamine and cycloguanil, and the IC100 for the samples most resistant to chlorcycloguanil (10(-8) M) was still well below peak blood concentrations after chlorproguanil administration. Resistance could be defined as IC100 greater than or equal to 10(-6) M for pyrimethamine and IC100 greater than or equal to 10(-8) M for chlorcycloguanil. The isolates most resistant or most sensitive to pyrimethamine were also the most resistant or most sensitive to chlorcycloguanil, indicating partial cross-resistance between the two drugs. The in vivo response to chlorproguanil 1.5 mg kg-1 in Lagbala was equal to the response in 1983. Chlorproguanil 1.5 mg kg-1 resulted in lower parasite rates on day 3 and 7, but did not prevent 60% of the children requiring treatment with chloroquine during the four weeks' follow-up after chlorproguanil administration.
在利比里亚两个村庄的38名儿童中，研究了恶性疟原虫对氯胍的体内敏感性以及对乙胺嘧啶、环氯胍和氯环胍的体外敏感性。一个村庄（拉格巴拉）的儿童在1976年至1985年期间每月接受氯胍化学预防，另一个村庄（JDF）的儿童在1981年至1985年期间每两周接受氯胍预防。乙胺嘧啶的最高和最低IC100相差10⁵倍，但氯环胍仅相差10³倍。氯环胍的平均IC100显著低于（P<0.0001）乙胺嘧啶和环氯胍的平均IC100，并且对氯环胍耐药性最强的样本（10⁻⁸M）的IC100仍远低于氯胍给药后的血药峰值浓度。对于乙胺嘧啶，耐药性可定义为IC100≥10⁻⁶M，对于氯环胍，耐药性可定义为IC100≥10⁻⁸M。对乙胺嘧啶耐药性最强或最敏感的分离株对氯环胍也是耐药性最强或最敏感的，表明这两种药物之间存在部分交叉耐药性。拉格巴拉的儿童对1.5mg/kg氯胍的体内反应与1983年的反应相同。1.5mg/kg氯胍在第3天和第7天导致较低的寄生虫率，但在氯胍给药后的四周随访期间，并未阻止60%的儿童需要使用氯喹进行治疗。
