Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade.
Increased risk of low birth weight in women with placental malaria associated with P. falciparum VAR2CSA clade.
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DOI：
10.1038/s41598-017-04737-y
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发表时间：
2017-08-11
影响因子：
4.6
通讯作者：
Meshnick SR
中科院分区：
文献类型：
--
作者：
Patel JC;Hathaway NJ;Parobek CM;Thwai KL;Madanitsa M;Khairallah C;Kalilani-Phiri L;Mwapasa V;Massougbodji A;Fievet N;Bailey JA;Ter Kuile FO;Deloron P;Engel SM;Taylor SM;Juliano JJ;Tuikue Ndam N;Meshnick SR
妊娠相关疟疾(PAM)由于恶性疟原虫在胎盘中积聚，导致不良妊娠和分娩结局。胎盘堆积是由恶性疟原虫蛋白VAR2CSA介导的，VAR2CSA是PAM特异性疫苗的主要靶点。其抗原多样性的程度和对临床结果的影响仍然知之甚少。通过对马拉维和贝宁妇女的胎盘疟疾样本进行扩增子深度测序，我们评估了VAR2CSA的ID1-DBL2x区域的序列多样性，该区域包含假定的疫苗靶标，并估计了特定分支与不良出生结果的关联。总体而言，var2csa的多样性很高，单倍型分为五个分支，其中最大的两个分支定义为与3D7或FCR3寄生虫株的同源性。在两个队列中，与仅感染FCR3样变异体的妇女相比，仅感染3D7样变异体的妇女生下的婴儿出生体重较低(差异：−267.99 g；95%可信区间[CI]：−466.43 g，−69.55 g)，低出生体重(<；2500 g)的几率较高(优势比[OR]5.41；95%CI：0.99，29.52)和小于胎龄(OR：3.65；95%CI：1.01，13.38)。在两个不同的疟疾流行非洲环境中，携带类似3D7的VAR2CSA变异的寄生虫与较差的出生结局有关，这支持了感染特定寄生虫株的不同影响。这种巨大的多样性加上这种多样性的不同临床效果表明，基于VAR2CSA的有效疫苗可能需要多价活性。
Pregnancy associated malaria (PAM) causes adverse pregnancy and birth outcomes owing to Plasmodium falciparum accumulation in the placenta. Placental accumulation is mediated by P. falciparum protein VAR2CSA, a leading PAM-specific vaccine target. The extent of its antigen diversity and impact on clinical outcomes remain poorly understood. Through amplicon deep-sequencing placental malaria samples from women in Malawi and Benin, we assessed sequence diversity of VAR2CSA’s ID1-DBL2x region, containing putative vaccine targets and estimated associations of specific clades with adverse birth outcomes. Overall, var2csa diversity was high and haplotypes subdivided into five clades, the largest two defined by homology to parasites strains, 3D7 or FCR3. Across both cohorts, compared to women infected with only FCR3-like variants, women infected with only 3D7-like variants delivered infants with lower birthweight (difference: −267.99 g; 95% Confidence Interval [CI]: −466.43 g,−69.55 g) and higher odds of low birthweight (<2500 g) (Odds Ratio [OR] 5.41; 95% CI:0.99,29.52) and small-for-gestational-age (OR: 3.65; 95% CI: 1.01,13.38). In two distinct malaria-endemic African settings, parasites harboring 3D7-like variants of VAR2CSA were associated with worse birth outcomes, supporting differential effects of infection with specific parasite strains. The immense diversity coupled with differential clinical effects of this diversity suggest that an effective VAR2CSA-based vaccine may require multivalent activity.
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影响因子：
3.7
作者：
Brolin KJ;Persson KE;Wahlgren M;Rogerson SJ;Chen Q
通讯作者：
Chen Q
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