Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum.

Potential impact of host immunity on malaria treatment outcome in Tanzanian children infected with Plasmodium falciparum.
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坦桑尼亚儿童感染恶性疟原虫的宿主免疫对疟疾治疗结果的潜在影响。

DOI:
10.1186/1475-2875-6-153
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发表时间:
2007-11-16
期刊:
影响因子:
3
通讯作者:
Alifrangis, Michael
Alifrangis, Michael
中科院分区:
医学3区
文献类型:
--
作者:
Enevold, Anders;Nkya, Watoky M. M. M.;Theisen, Michael;Vestergaard, Lasse S.;Jensen, Anja T. R.;Staalsoe, Trine;Theander, Thor G.;Bygbjerg, Ib C.;Alifrangis, Michael

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在疟疾流行地区,儿童在化疗后可能从疟疾中康复,尽管他们携带有具有基因抗药性的恶性疟原虫。这种现象表明,药物治疗和获得性免疫之间存在协同作用。在坦桑尼亚的一个中等强度的恶性疟原虫传播地区,在磺胺嘧啶-乙胺嘧啶(SP)或阿莫地喹(AQ)的药物试验期间,对这一假设进行了检验。100名患有单纯性疟疾的儿童接受SP或AQ治疗,并随访28天。使用PCR和序列特异性寡核苷酸探针和酶联免疫吸附试验(SSOP-ELISA)确定了与SP和AQ抗性以及人类镰状细胞性状和α-地中海贫血相关的寄生虫基因突变,并评估了对一组恶性疟原虫抗原的IgG抗体应答,并与治疗结果相关。在接受SP或AQ的儿童中,分别观察到68%和38%的寄生虫或临床治疗失败(TF)。与TF儿童相比,在具有足够临床和寄生虫学应答(ACPR)的患者中,对于两种治疗方案,抗富含谷氨酸蛋白(GLURP)特异性IgG抗体的患病率和水平显著较高(P < 0.001),而与SP和AQ抗性相关的寄生虫单倍型患病率较低(分别为P = 0.02和P = 0.07)。有趣的是,抗GLURP-IgG抗体与治疗结果的相关性比抗寄生虫单倍型更强,而对其他11种疟疾抗原的IgG应答与ACPR无显著相关性。这些结果表明,在这种情况下,GLURP特异性IgG抗体有助于清除耐药感染,并支持获得性免疫增强药物治疗的临床疗效的假设。结果应在更大规模、更大样本量和透射强度变化的情况下进行确认。
In malaria endemic areas children may recover from malaria after chemotherapy in spite of harbouring genotypically drug-resistant Plasmodium falciparum. This phenomenon suggests that there is a synergy between drug treatment and acquired immunity. This hypothesis was examined in an area of moderately intense transmission of P. falciparum in Tanzania during a drug trail with sulphadoxine-pyrimethamine (SP) or amodiaquine (AQ). One hundred children with uncomplicated malaria were treated with either SP or AQ and followed for 28 days. Mutations in parasite genes related to SP and AQ-resistance as well as human sickle cell trait and alpha-thalassaemia were determined using PCR and sequence-specific oligonucleotide probes and enzyme-linked immunosorbent assay (SSOP-ELISA), and IgG antibody responses to a panel of P. falciparum antigens were assessed and related to treatment outcome. Parasitological or clinical treatment failure (TF) was observed in 68% and 38% of children receiving SP or AQ, respectively. In those with adequate clinical and parasitological response (ACPR) compared to children with TF, and for both treatment regimens, prevalence and levels of anti-Glutamate-rich Protein (GLURP)-specific IgG antibodies were significantly higher (P < 0.001), while prevalence of parasite haplotypes associated with SP and AQ resistance was lower (P = 0.02 and P = 0.07, respectively). Interestingly, anti-GLURP-IgG antibodies were more strongly associated with treatment outcome than parasite resistant haplotypes, while the IgG responses to none of the other 11 malaria antigens were not significantly associated with ACPR. These findings suggest that GLURP-specific IgG antibodies in this setting contribute to clearance of drug-resistant infections and support the hypothesis that acquired immunity enhances the clinical efficacy of drug therapy. The results should be confirmed in larger scale with greater sample size and with variation in transmission intensity.
DOI: 10.1186/1475-2875-4-61
发表时间: 2005-12-15
期刊: Malaria journal
影响因子: 3
作者:
Enevold A;Vestergaard LS;Lusingu J;Drakeley CJ;Lemnge MM;Theander TG;Bygbjerg IC;Alifrangis M
通讯作者: Alifrangis M
DOI: 10.4269/ajtmh.2003.69.558
发表时间: 2003-11-01
影响因子: 3.3
作者:
Djimdé, AA;Doumbo, OK;Plowe, CV
通讯作者: Plowe, CV
DOI: 10.1016/s0035-9203(01)90250-0
发表时间: 2001-05-01
影响因子: 2.2
作者:
Omar, SA;Adagu, IS;Warhurst, DC
通讯作者: Warhurst, DC