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。人们对使用 婴儿和幼儿的化学预防策略，通常是间歇性预防治疗（IPT） 磺胺乙胺嘧啶（SP）。然而，IPT的最佳药物或给药策略尚未确定。 鉴定同时，对感染艾滋病毒的儿童的标准政策现在包括化学预防， 甲氧苄啶-磺胺甲恶唑（TS），它提供了高度的保护，防止疟疾。给定 对抗叶酸药物（TS和SP）、新药（如基于青蒿素的 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，确定疟疾的最佳化学预防策略是一个紧迫的优先事项 在非洲儿童中，以及评估不同方案的潜在缺点，如毒性增加或 停止化学预防后疟疾风险增加（反弹）。我们将比较 三种化学预防策略的有效性和安全性，而没有化学预防，这是目前 在乌干达的婴儿和儿童中，具体目标是：1）比较 4-12个月大的婴儿和儿童中疟疾的发病率， 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4-12个月大的婴儿和儿童中， 每日TS、每月SP或每月DP; 3）比较1年内儿童疟疾发病率 在无化学预防的干预后，每日TS、每月SP或每月DP。这项研究将是一个 800名未感染HIV的婴儿被随机分配到相同数量的婴儿中， 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 36个月。将在24个月龄时停止化学预防，以便额外随访1年 干预后。主要研究终点将是症状性疟疾的发病率。二次 终点将包括并发疟疾、疟疾和呼吸道感染的发病率; 无症状寄生虫血症、贫血和配子体血症的患病率; 研究药物。

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.