Daramola O O, Alonso P L, O'Dempsey T J, Twumasi P, McArdle T F, Greenwood B M
Medical Research Council Laboratories, Fajara, Banjul, The Gambia.
Trans R Soc Trop Med Hyg. 1991 May-Jun;85(3):345-8. doi: 10.1016/0035-9203(91)90285-7.
In The Gambia co-trimoxazole is used widely to treat children with an acute respiratory infection (ARI). Because malaria may sometimes be mistaken for ARI, some children with malaria are treated with co-trimoxazole. Therefore, we investigated the sensitivity of Gambian isolates of Plasmodium falciparum to this drug. Six days after the start of treatment with co-trimoxazole 3.3% of blood films of 65 asymptomatic subjects were positive, and 7.7% were positive after 21 d. One of 10 patients with ARI and malaria treated with co-trimoxazole had a positive blood film 3 d after the start of treatment but was negative thereafter. All 10 patients recovered satisfactorily. Thirty 'wild' isolates of P. falciparum were tested in vitro against co-trimoxazole at a ration of 5 parts sulphamethoxazole (SMZ) to 1 part trimethoprim (TMP). The mean EC50s, using a 36 h assay, were 1.2 x 10(-7) and 2.5 x 10(-8) M for SMZ and TMP respectively. When a [3H]hypoxanthine incorporation assay was employed, values of 5.7 x 10(-7) M for SMZ and 1.2 x 10(-7) M for TMP were obtained. These values are well below the peak plasma concentration. Our findings suggest that co-trimoxazole is effective against falciparum malaria in The Gambia. However, if it were to be used widely, the parasite would be likely to develop resistance to this and other dihydrofolate reductase inhibitor antimalarials.
在冈比亚,复方新诺明被广泛用于治疗患有急性呼吸道感染(ARI)的儿童。由于疟疾有时可能被误诊为ARI,一些患有疟疾的儿童也用复方新诺明进行治疗。因此,我们研究了冈比亚恶性疟原虫分离株对该药物的敏感性。在开始用复方新诺明治疗6天后,65名无症状受试者的血片中3.3%呈阳性,21天后7.7%呈阳性。10名患有ARI和疟疾且用复方新诺明治疗的患者中,有1例在开始治疗3天后血片呈阳性,但此后转阴。所有10名患者均康复良好。对30株“野生”恶性疟原虫分离株进行了体外试验,以5份磺胺甲恶唑(SMZ)对1份甲氧苄啶(TMP)的比例测试其对复方新诺明的敏感性。使用36小时检测法,SMZ和TMP的平均半数有效浓度(EC50)分别为1.2×10⁻⁷和2.5×10⁻⁸M。当采用[³H]次黄嘌呤掺入检测法时,SMZ和TMP的值分别为5.7×10⁻⁷M和1.2×10⁻⁷M。这些值远低于血浆峰值浓度。我们的研究结果表明,复方新诺明对冈比亚的恶性疟有效。然而,如果广泛使用,疟原虫可能会对该药物及其他二氢叶酸还原酶抑制剂抗疟药产生耐药性。