Severini Carlo, Menegon Michela, Sannella Anna Rosa, Paglia Maria Grazia, Narciso Pasquale, Matteelli Alberto, Gulletta Maurizio, Caramello Pietro, Canta Francesca, Xayavong Maniphet V, Moura Iaci N S, Pieniazek Norman J, Taramelli Donatella, Majori Giancarlo
Department of Infectious, Parasitic and Immunomediated Diseases, Vector-Borne Diseases and International Health Section, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy.
Infect Genet Evol. 2006 Jul;6(4):262-8. doi: 10.1016/j.meegid.2005.07.002. Epub 2005 Sep 8.
The development in Plasmodium falciparum of the resistance to chloroquine (CQ) constitutes a public health priority, due to its direct influence in childhood mortality. The molecular basis for CQ resistance (CQR) is still unclear but, recently, a new relevant gene, named pfcrt, with several point mutations was identified in P. falciparum. Two mutations, K76T and A220S, have been considered crucial for CQR in further studies, making the pfcrt a good candidate as determinant for CQR in P. falciparum. To contribute to this topic, we have undertaken a molecular screening on 164 P. falciparum isolates from Africa: 120 isolates were Italian imported malaria cases, 27 and 17 isolates were from a school-children survey from Congo and Tanzania, respectively. In vitro tests (pLDH and WHO-Mark III tests) for CQ sensitivity have been also carried out on 28 plasmodial isolates and results compared to those obtained by molecular analysis in the same isolates. The SVIET pfcrt haplotype has been identified in the samples from Congo, and this is the first time that this haplotype is detected in Africa. Our results give further evidence to the reliability of the 76T (and the linked 74I-75E) pfcrt point mutation as molecular marker for CQR.
恶性疟原虫对氯喹（CQ）产生耐药性这一情况已成为公共卫生领域的一个优先事项，因为它对儿童死亡率有直接影响。CQ耐药性（CQR）的分子基础仍不清楚，但最近在恶性疟原虫中发现了一个新的相关基因，名为pfcrt，该基因有多个点突变。在进一步研究中，K76T和A220S这两个突变被认为对CQR至关重要，这使得pfcrt成为恶性疟原虫中CQR决定因素的一个很好的候选基因。为了对这一课题有所贡献，我们对来自非洲的164株恶性疟原虫分离株进行了分子筛查：120株分离株为意大利输入性疟疾病例，27株和17株分离株分别来自刚果和坦桑尼亚的在校儿童调查。还对28株疟原虫分离株进行了CQ敏感性的体外试验（pLDH和WHO-Mark III试验），并将结果与在相同分离株中通过分子分析获得的结果进行了比较。在刚果的样本中鉴定出了SVIET pfcrt单倍型，这是该单倍型首次在非洲被检测到。我们的结果进一步证明了76T（以及与之连锁的74I-75E）pfcrt点突变作为CQR分子标记的可靠性。
