Background

Sulfadoxine-pyrimethamine (SP) is used as intermittent preventive therapy in pregnancy (IPTp) for malaria in sub-Saharan Africa. The resistance marker dhps A581G has been associated with reduced IPTp-SP efficacy and enhanced morbidity in SP-recipients.

Methods

We measured SP-resistance allele frequencies in Malawian women participating in a trial (www.isrctn.com/ISRCTN69800930) comparing IPTp with SP against intermittent screening by rapid diagnostic tests (ISTp). We genotyped PCR-detected parasites using deep sequencing of SP-resistance alleles.

Results

Among 125 placental infections, A581G-bearing parasites were associated with reduced birthweight (mean difference[MD]:252g, 95% CI:46,457, p=0.017). Relative to ISTp, IPTp-SP was associated with higher birthweights in women with wildtype parasites (MD:116g, 95% CI:-40,272; p=0.142) and lower birthweights in women with A581G-bearing parasites (MD:192g, 95% CI:-264,648; p=0.385) (p_interaction=0.033). Similar associations were noted on gestational age (p_interaction=0.075). Amongst only IPTp-SP recipients, relative to women who last received SP >4 weeks before delivery, recent SP receipt was associated with lower birthweight in women with wildtype parasites (MD:118g, 95% CI:-376,139; p=0.361) and higher birthweight in women with A581G-bearing parasites (MD:783g, 95% CI:-20,1586; p=0.054) (p_interaction=0.005).

Conclusions

The effectiveness on birthweight of IPTp-SP is compromised by A581G-bearing parasites, but there was no evidence that the adverse effects of these parasites are exacerbated by antenatal SP.

中文翻译：

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马拉维产前磺胺嘧啶-乙胺嘧啶，抗药性恶性疟原虫寄生虫与分娩结果之间的相互作用。

背景

磺胺多辛-乙胺嘧啶（SP）被用作撒哈拉以南非洲疟疾的孕妇间歇性预防治疗（IPTp）。耐药标记dhps A581G与IP受体的IPTp-SP功效降低和发病率增加相关。

方法

我们在参加试验的马拉维妇女中测量了SP抵抗等位基因频率（www.isrctn.com/ISRCTN69800930），将IPTp和SP与通过快速诊断测试（ISTp）进行的间歇性筛查进行了比较。我们使用SP耐药等位基因的深度测序对PCR检测到的寄生虫进行基因分型。

结果

在125例胎盘感染中，携带A581G的寄生虫与出生体重降低有关（平均差异[MD]：252g，95％CI：46,457，p = 0.017）。相对于ISTp，IPTp-SP与野生型寄生虫妇女的出生体重较高（MD：116g，95％CI：-40,272； p = 0.142）和携带A581G寄生虫的妇女出生体重较低（MD：192g，95％）相关。 CI：-264,648； p ＝ 0.385）（p_相互作用＝ 0.033）。在胎龄上也发现了类似的关联（p_相互作用= 0.075）。在仅有IPTp-SP的接受者中，相对于上次在分娩前4周以上接受SP的妇女而言，最近接受SP所致的野生型寄生虫妇女的体重较轻（MD：118g，95％CI：-376,139； p = 0.361），并且患有A581G寄生虫的妇女的出生体重较高（MD：783g，95％CI：-20,1586; p = 0.054）（p_相互作用= 0.005）。

结论

携带A581G的寄生虫损害了IPTp-SP对出生体重的有效性，但没有证据表明这些寄生虫的不良影响会因产前SP而加剧。