Competition between different strains of malaria

A recent study in Burkina Faso showed that genetic diversity in strains of malaria resulted in different degrees of disease severity and showed evidence of competition between strains.

Of the five species of malaria parasites known to infect humans,Plasmodium falciparumis the most virulent, but this virulence is variable. One factor determining the great variability in clinical symptoms associated with falciparum malaria is, which of the many strains of the parasite is infecting the patient.

Many of the genes encoding proteins produced byP. falciparumoccur in a variety of forms, or alleles, and different strains of the parasite express different forms of these proteins. One such family of proteins, called merozoite surface proteins, have been linked to differences in clinical outcomes of disease, such as mild or severe anaemia or cerebral malaria.

Merozoite surface proteins

Merozoite surface proteins(MSP)是通过疟原虫的梅罗洛伊特阶段入侵红细胞所必需的蛋白质家族。顾名思义,它们位于merozoite的表面上。寄生虫的不同菌株表达不同形式的MSP。

MSP1 is the most abundant of these proteins. It is alarge GPI-anchored protein在红细胞侵袭之前经历了碎片,似乎参与了寄生虫的初始结合to the cell.

The role of MSP1 in red blood cell invasion. Source: https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(15)00376-5

The second most abundant MSP is MSP2, a smaller molecule whose function is unknown.

由于疟疾中流行地区的人们通常被多个被感染的蚊子咬伤,因此他们可以同时被多种寄生虫感染。研究,例如一个in Gabon, have suggested that increasing severity of malaria is linked with increasing variety in the forms of MSP1 that parasites within the patient are expressing.

患者存在的疟疾菌株

最近在布基纳法索进行的一项研究focussed on patients infected with strains expressing different forms of MSP1 and MSP2. The researchers looked at symptoms associated with the different strains and investigated whether strains competed within the host and whether mixed infections caused more, or less, disease severity.

Blood was taken from patients taking part in a separate drug evaluation trial and assessed microscopically for the presence of malaria parasites and haemoglobin levels measured. Dried blood samples were used to detect the presence of alleles forMSP1MSP2基因家族。根据三个参数确定疾病的严重程度:高体温,贫血和寄生虫密度。

The study took place in two sites over 2 years and during this time, 1010 patients in the study were diagnosed positive for malaria. ThreeMSP1-allelic families andMSP2-在血液样本中检测到家庭,并且有许多患者有一个以上的等位基因家庭循环。一百五十五名患者全部三个MSP1等位基因家庭在场。这些基因家族的患病率在两个地点相似,表明它们之间的人口流动。

Strains and virulence factors

The presence of oneMSP1等位基因家族MAD20与最高的寄生虫密度有关,尽管这不是最常见的家庭。我想知道这种特殊形式的蛋白质结构是否增强了与红细胞结合的结合。

令人惊讶的是,当存在多种菌株的寄生虫混合感染时,与单株感染相比,寄生虫的数量并没有增加MSP1-MAD20实际上在混合感染中减少。作者认为,寄生虫菌株之间存在竞争,而MAD20的增长被这场竞争所掩盖,尽管他们对他们的竞争方式没有任何建议。

In contrast, no difference in strain density was found when single or mixed infections with the twoMSP2比较等位基因家庭。

Patient temperature increased with parasite density (parasitaemia) but temperature was not affected by the presence of different parasite strains, either as single or mixed infections.

Haemoglobin levels (a measure of anaemia) were also unaffected by which strain ofMSP1was present, but oneMSP2等位基因家庭,FC27在单一感染和混合感染中均显示出最低的血红蛋白水平,因此更具致病性。

Strains and severe malaria

寄生虫密度,发烧和贫血都是严重疟疾感染的特征。这项研究确实表明,疟原虫的菌株患者感染了一定程度的感染临床结果,特别是在存在的情况下MSP2-FC27 allele.

The authors point out that no patients with cerebral malaria were present in their study, so an association between these particular MSP strains and patients with extremely severe malaria could not be ruled out.

In endemic populations, development of immunity to malaria is dependent upon the exposure to a variety of strains of malaria that will occur with age. This is the likely explanation for the researchers’ finding that parasite density decreased with patient age. However, this was not the case for infections with all threeMSP1同时菌株。这些三重感染是在年轻患者中发现的事实,可能还没有暴露于所有菌株。

It would be useful to determine whether early detection of parasites associated with virulence factors did indeed act as an indicator of the clinical progression of the infection and thereby inform patient management.

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