Severe Malaria in African Children--A Clinical Network

疟疾仍然是撒哈拉以南非洲的一大祸害，每年导致100-200万儿童死亡。随着杀死疟疾寄生虫的药物的出现，我们对疾病发病机制的理解已经取得了重大进展，奎宁是目前的首选药物-但严重疟疾的死亡率并没有改变。患有脑型疟疾、疟疾相关酸中毒和/或严重贫血的儿童中有15%-40%将死亡，其中一半死亡发生在到达医院后12小时内。五个在非洲儿童中有丰富严重疟疾经验的临床中心联合起来，组成了一个临床试验网络(SMAC)。我们自己试图证明有希望的干预措施对疟疾死亡率的任何影响，我们对此感到沮丧，我们决定，降低非洲儿童与严重疟疾相关的死亡率这一根本目标，最好是通过开展基于死亡率的多中心研究来实现。这种方法是必要的，因为没有替代标记物的结果死亡在任何一个地点都是罕见的。我们建议评估液体复苏对合并酸中毒的疟疾儿童的治疗，并将己酮可复(PTX)作为脑型疟疾儿童的辅助治疗。这两项研究都需要在更大规模的临床试验之前进行试点研究(1年)。我们的网络也处于有利地位，可以评估可能阐明致病过程或揭示潜在新靶点的“疾病关联”。因为它易于评估，而且存在可信的生物学和寄生虫学影响，我们想要确定白斑内DiQment在儿童恶性疟原虫感染中的预测价值。这项研究将是正在进行的网络活动的一部分，利用预期收集并存档在数据库中的标准化信息描述每个地点的疟疾经验。统计和行政“核心”将为网络的工作提供便利。数据将在每个地点输入，并传输到一个中央设施(在五个地点之一)进行分析。将举行SMAC年度会议，会议之间的间隔将被地点之间的频繁访问所打断，这样年轻的调查人员就可以标准化他们的观察并体验其他环境。这种对严重的儿科疟疾进行多中心试验的能力以前从未存在过。一大群人的统计能力可以发现，与特定干预相关的死亡率甚至有微小的下降。鉴于疟疾造成的巨大伤亡，这可能意味着整个撒哈拉以南非洲的死亡率大幅下降。

Malaria remains a major scourge in sub-Saharan Africa, killing 1-2 million children each year. Major advances in our understanding of disease pathogenesis have occurred, along with the emergence of drugs which kill the malaria parasite twice as rapidly quinine, the current drug of choice--- but the mortality rate for severe malaria has not changed. Between 15-40% of children with cerebral malaria, malaria-associated acidosis and/or severe anemia will die, and half of those deaths occur within 12 hours of arriving at a hospital. Five clinical centers with much experience of severe malaria in African children have joined together to form a clinical trials network (SMAC). Individually frustrated by our own attempts to demonstrate any impact of promising interventions on malaria mortality, we have decided that our fundamental goal, to lower the death rate associated with severe malaria in African children, would be best realized by conducting mortality-based multi-center studies. This approach is necessary because there are no surrogate markers for outcome deaths in any one site are rare We are proposing to evaluate fluid resuscitation in children with malaria complicated by acidosis, and pentoxifvrnne (PTX) as adjunct therapy in children with cerebral malaria. Both of these require pilot studies (1 year) prior to the larger clinical trials. Our network is also well-positioned to evaluate "disease associations" which may illuminate pathogenetic processes or reveal potential new targets. Because it is simple to assess and because there are plausible biological and parasitological implications, we would like to determine the predictive value of intraleukocvtic DiQment in children with P. falciparum infections. This study will be part of an ongoing network activity, describing the malaria experience in each site using standardized information collected prospectively and archived in a database. The statistical and administrative "cores" will facilitate the efforts of the network. Data will be entered at each site and transmitted to a central facility (at one of the five sites) for analysis. There will be an annual SMAC meeting, and the intervals between meetings will be punctuated by frequent visits between sites so that young investigators can standardize their observations and experience other settings. This capacity to conduct multi-center trials in severe pediatric malaria has not existed before. The statistical power of a large group can unearth even a small decrease in mortality associated with a particular intervention. Given the enormous toll of malaria, this could re resent a significant decline in the death rate across sub-Saharan Africa.