Chemopreventive therapy for malaria in HIV uninfected children

疟疾仍然是非洲儿童最常见的严重疾病。人们对它的使用兴趣与日俱增 婴幼儿化学预防策略，一般为间歇性预防治疗(IPT) 磺胺多辛-乙胺嘧啶(SP)。然而，IPT的最佳药物或剂量策略尚未得到 已确认身份。同时，针对感染艾滋病毒儿童的标准政策现在包括化学预防 甲氧苄氨嘧啶-磺胺甲恶唑(TS)，提供对疟疾的高度保护。vt.给出 对抗叶酸药物(TS和SP)的抗药性增加，较新的药物，如青蒿素类药物 双氢青蒿素-哌喹(DP)联合治疗可提供更好的预防效果。 考虑到这一背景，确定最佳的疟疾化学预防战略是当务之急。 以及评估不同方案的潜在缺点，如增加毒性或 停止化学预防后疟疾风险增加(反弹)。我们将比较 无化学预防的三种化学预防策略的有效性和安全性，这是目前的 乌干达婴儿和儿童的护理标准。具体目标将是：1)比较 登记在4-12个月大的婴儿和儿童中的疟疾发病率 无化学预防、每日TS、每月SP或每月DP；2)比较不良事件的发生率 在登记的4-12个月大的婴儿和儿童中，随机没有接受任何化学预防， 每天的TS、每月的SP或每月的DP；3)比较1年内儿童的疟疾发病率 在没有化学预防的干预后，每天的TS、每月的SP或每月的DP。这项研究将是一项 800名未感染艾滋病毒的婴儿随机分成相同数量的开放标签随机试验 介入臂。参与者将接受所有常规和急性医疗护理，直到他们达到年龄 已经36个月了。化学预防将在24个月龄时停止，以允许额外一年的随访 干预后。研究的主要终点将是有症状的疟疾的发病率。次要的 终点将包括复杂疟疾、腹泻疾病和呼吸道感染的发病率； 无症状寄生虫血症、贫血和配子细胞症的患病率； 研究毒品。

Malaria remains the most common serious illness of children in Africa. There is increasing interest in the use of chemopreventive strategies for infants and young children, generally intermittent preventive therapy (IPT) with sulfadoxine-pyrimethamine (SP). However, the optimal drugs or dosing strategies for IPT have not been identified. Concurrently, standard policy for HIV-infected children now includes chemoprophylaxis with trimethoprim-sulfamethoxazole (TS), which offers a high degree of protection against malaria. Given increasing levels of resistance to the antifolate drugs (TS and SP), newer drugs, such as the arteminsininbased combination therapy dihydroartemisinin-piperaquine (DP), may offer better preventive efficacy. Considering this background, it is an urgent priority to identify optimal chemopreventive strategies for malaria in African children, as well as assess potential drawbacks of different regimens, such as increased toxicity or an increased risk of malaria after discontinuation of chemoprevention (rebound). We will compare the efficacy and safety of three chemopreventive strategies with no chemoprevention, which is the current standard of care, among infants and children in Uganda. The specific aims will be: 1) to compare the incidence of malaria among infants and children enrolled at 4-12 months of age and randomized to receive no chemoprevention, daily TS, monthly SP, or monthly DP; 2) to compare the incidence of adverse events among infants and children enrolled at 4-12 months of age and randomized to receive no chemoprevention, daily TS, monthly SP, or monthly DP; and 3) to compare the incidence of malaria among children for 1 year following intervention with no chemoprevention, daily TS, monthly SP, or monthly DP. This study will be a randomized, open-label, trial of 800 HIV-uninfected infants randomized to equal numbers of each intervention arm. Participants will be followed for all routine and acute medical care until they reach the age of 36 months. Chemoprevention will be stopped at 24 months of age to allow for 1 additional year of followup post-intervention. The primary study endpoint will be the incidence of symptomatic malaria. Secondary endpoints will include incidence of complicated malaria, diarrheal illnesses and respiratory tract infections; prevalence of asymptomatic parasitemia, anemia, and gametocytemia; and incidence of adverse events to study drugs.