Clinical and parasitological studies on immunity to Plasmodium falciparum malaria in children.
Clinical and parasitological studies on immunity to Plasmodium falciparum malaria in children.
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儿童恶性疟原虫疟疾免疫的临床和寄生虫学研究。
DOI：
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发表时间：
1996
期刊：
影响因子：
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通讯作者：
B. Hogh
中科院分区：
文献类型：
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作者：
B. Hogh
疟疾仍然是许多热带国家的主要健康问题之一。恶性疟原虫是非洲最常见的疟疾寄生虫，它比任何其他类型的疟疾寄生虫引起更严重和进行性的疾病。生活在撒哈拉以南非洲的儿童正在承受这种疾病和死亡率的主要负担。无论使用什么参数来衡量疟疾的死亡率或发病率，真正的问题都可能被低估。发病率和死亡率的模式取决于传播强度;疟疾传播强度越大，出现症状的疟疾年龄范围就越早和越窄。无症状携带者状态很常见，在高度流行地区，60-80%的儿童在任何给定时间都患有恶性疟原虫寄生虫病。因此，仅仅根据血液中寄生虫的存在来定义病例，在衡量发病率方面是没有意义的。认识到疟疾没有具体的临床诊断参数，但发烧很常见，而且发病率在某种程度上取决于寄生虫密度，我们使用逻辑回归模型描述了与体温和寄生虫密度有关的疟疾患病概率。获得性临床和寄生虫学免疫在反复暴露于感染后数年内逐渐发展。保护首先是针对死亡或严重的临床疾病，然后是针对较温和的临床攻击，但对感染的保护永远不会完全。临床和寄生虫学免疫发展伴随着，表现为相关的寄生虫密度测量体温。然而，控制疾病和寄生虫密度的能力比预防寄生虫感染的能力发展得更早。负责获得性免疫的个体免疫机制仍然不确定，但经典的多价丙种球蛋白从免疫供体到非免疫个体的转移实验表明，抗体起着重要作用。疟疾疫苗的潜在靶点包括子孢子和裂殖子表面的抗原。恶性疟原虫的几种蛋白质抗原已在分子水平上进行了表征，并且大多数表征的抗原具有被来自疟疾流行区的个体的免疫血清识别的共同特征。通过将自然获得的免疫应答与确定的恶性疟原虫抗原相关联，可以鉴定保护性疫苗开发的潜在有用靶标，我们研究了来自子孢子阶段（CS-蛋白）和血液阶段（Pf 155/RESA、GLURP和MSP 1）的抗原，以及恶性疟原虫诱导的红细胞上的新抗原（带3新抗原）。在各个年龄组中分析了对这些确定的恶性疟原虫抗原的免疫应答与临床和寄生虫学保护之间的关系。抗原特异性免疫反应的贡献进行了评价，并确定了在确定的年龄组中的寄生虫密度或临床疟疾发作的概率与对单个抗原的抗体反应的正相关性。然而，这种相关性并没有跨越所有年龄组，因此对确定的抗原的总体应答并不被认为是可靠的保护指标。这些发现可能有助于了解寄生虫血症和恶性疟原虫抗原的免疫和临床宿主反应。对无性阶段感染和人体免疫反应影响的研究导致了对恶性疟原虫血液阶段寄生虫的特异性和非特异性反应的研究以及对配子体血症的观察。我们证明乙胺嘧啶/磺胺嘧啶和氯喹不能诱导配子体发生，但预先形成的配子体在
Malaria remains one of the major health problems in many tropical countries. Plasmodium falciparum is the most common malaria parasite in Africa, and it causes much more severe and progressive illness than any of the other types of malaria parasite. Children living in sub-Saharan Africa are bearing the major burden of the disease and the mortality. Whatever parameter is used to measure the mortality or the morbidity from malaria, the true problem is likely to be underestimated. The pattern of morbidity and mortality depends on the transmission intensity; the more intensity of malaria transmission is increased, the earlier and more confined the age range of symptomatic malaria. The asymptomatic carrier status is common, and 60-80% of the children in highly endemic areas have P. falciparum parasitaemia at any given time. Consequently a case definition based on the mere presence of parasites in the blood is non-informative in terms of measuring morbidity. Recognizing that there are no specific diagnostic clinical parameters for malaria, but that fever is very common, and that morbidity is to some extent dependent on the parasite density, we described using a logistic regression model the probability of being sick from malaria in relation to body temperature and parasite density. Acquired clinical and parasitological immunity develop progressively over several years after repeated exposure to infection. Protection is acquired first against death or severe clinical disease, then against milder clinical attacks, but protection against infection is never complete. Clinical and parasitological immunity develop concomitantly, as demonstrated by relating the parasite densities to measured body temperature. However, the ability to control the disease and parasite density develops earlier than the ability to prevent the parasite infection. The individual immune mechanisms that are responsible for the acquired immunity remain uncertain, but classical transfer experiments with polyvalent gamma globulin from immune donors to non-immune individuals showed that antibodies play an important role. Potential targets for malarial vaccines include antigens on the surface of the sporozoites and the merozoites. Several protein antigens from P. falciparum have been characterized at the molecular level, and most of the characterized antigens have the common characteristic that they are recognized by immune sera from individuals living in malaria endemic areas. Working on the approach that potentially useful targets for protective vaccine development can be identified by correlating the naturally acquired immune responses with defined P. falciparum antigens, we examined antigens from both the sporozoite stage (CS-protein) and the blood stages (Pf155/RESA, GLURP, and MSP1), as well as P. falciparum induced neoantigens on the red blood cell (band-3 neoantigens). The relationship between the immune response to these defined P. falciparum antigens and clinical and parasitological protection was analysed in the individual age groups. The contribution of the antigen-specific immune response was evaluated, and a positive correlation of parasite density or probability of an episode of clinical malaria with antibody response to the individual antigens was identified in defined age groups. This correlation, however, did not span all age groups, and thus overall responses to defined antigens are not considered to be reliable indicators of protection. The findings may contribute to the understanding of immunological and clinical host responses to parasitaemia and to defined P. falciparum antigens. The studies on the impact of asexual stage infection and the human immune response led to studies on specific and non-specific responses to P. falciparum blood-stage parasites and observations on gametocytaemia. We demonstrated that pyrimethamine/sulfadoxine and chloroquine did not induce gametocytogenesis as suggested previously, but preformed gametocytes persisted after