Effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on immune responses to vaccines among rural Ugandan adolescents: randomised controlled trial protocol B for the 'POPulation differences in VACcine responses' (POPVAC) programme.
Effect of intermittent preventive treatment for malaria with dihydroartemisinin-piperaquine on immune responses to vaccines among rural Ugandan adolescents: randomised controlled trial protocol B for the 'POPulation differences in VACcine responses' (POPVAC) programme.
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DOI：
10.1136/bmjopen-2020-040427
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发表时间：
2021-02-16
期刊：
影响因子：
2.9
通讯作者：
POPVAC trial team
中科院分区：
文献类型：
--
作者：
Natukunda A;Nkurunungi G;Zirimenya L;Nassuuna J;Oduru G;Amongin R;Kabuubi PN;Mutebe A;Onen C;Amongi S;Nakazibwe E;Akello F;Kiwanuka S;Kiwudhu F;Sewankambo M;Nsubuga D;Kizindo R;Staedke SG;Cose S;Webb E;Elliott AM;POPVAC trial team
低收入国家与高收入国家相比，以及农村与城市相比，疫苗效力较低和疫苗特异性免疫应答受损的驱动因素尚未完全阐明。反复接触寄生虫感染和通过寄生虫感染进行免疫调节可能很重要。我们专注于恶性疟原虫疟疾，旨在确定疟疾感染对疫苗反应是否有可逆性影响。我们设计了一项随机、双盲、安慰剂对照、平行组试验，比较间歇性预防性疟疾治疗与安慰剂，以确定对乌干达金贾地区疟疾流行农村地区学龄青少年（9至17岁）疫苗应答结果的影响。研究的疫苗包括“零”日接种的卡介苗;第4周接种的黄热病、口服伤寒和人乳头瘤病毒疫苗;第28周接种的破伤风/白喉加强疫苗。间歇性预防性疟疾治疗组的受试者将在首次免疫接种前接受按体重给药的双氢青蒿素/哌喹（DP），间隔1个月，此后每月接受一次治疗。我们预计招收640名青少年。主要结果是BCG免疫后8周的BCG特异性干扰素-γ ELISpot应答，以及对于其他疫苗，免疫后4周对关键疫苗抗原的抗体应答。在二次分析中，我们将确定每月DP治疗（与安慰剂相比）对保护性免疫相关性、疫苗应答减弱、初免与加强免疫是否存在差异效应以及疟疾感染流行率的影响。我们还将在参与者的子集中进行探索性免疫学测定，以进一步验证干预对疫苗应答的影响。已获得乌干达和英国相关伦理委员会的伦理批准。研究结果将与乌干达卫生部、相关区议会、社区领袖和研究参与者分享。将通过会议记录和出版物进一步传播。当前对照试验标识符：ISRCTN 62041885。
Drivers of lower vaccine efficacy and impaired vaccine-specific immune responses in low-income versus high-income countries, and in rural compared with urban settings, are not fully elucidated. Repeated exposure to and immunomodulation by parasite infections may be important. We focus on Plasmodium falciparum malaria, aiming to determine whether there are reversible effects of malaria infection on vaccine responses. We have designed a randomised, double-blind, placebo-controlled, parallel group trial of intermittent preventive malaria treatment versus placebo, to determine effects on vaccine response outcomes among school-going adolescents (9 to 17 years) from malaria-endemic rural areas of Jinja district (Uganda). Vaccines to be studied comprise BCG vaccine on day ‘zero’; yellow fever, oral typhoid and human papilloma virus vaccines at week 4; and tetanus/diphtheria booster vaccine at week 28. Participants in the intermittent preventive malaria treatment arm will receive dihydroartemisinin/piperaquine (DP) dosed by weight, 1 month apart, prior to the first immunisation, followed by monthly treatment thereafter. We expect to enrol 640 adolescents. Primary outcomes are BCG-specific interferon-γ ELISpot responses 8 weeks after BCG immunisation and for other vaccines, antibody responses to key vaccine antigens at 4 weeks after immunisation. In secondary analyses, we will determine effects of monthly DP treatment (versus placebo) on correlates of protective immunity, on vaccine response waning, on whether there are differential effects on priming versus boosting immunisations, and on malaria infection prevalence. We will also conduct exploratory immunology assays among subsets of participants to further characterise effects of the intervention on vaccine responses. Ethics approval has been obtained from relevant Ugandan and UK ethics committees. Results will be shared with Uganda Ministry of Health, relevant district councils, community leaders and study participants. Further dissemination will be done through conference proceedings and publications. Current Controlled Trials identifier: ISRCTN62041885.
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影响因子：
3.2
作者：
Corstjens PL;Nyakundi RK;de Dood CJ;Kariuki TM;Ochola EA;Karanja DM;Mwinzi PN;van Dam GJ
通讯作者：
van Dam GJ
影响因子：
168.9
作者：
Black, GF;Weir, RE;Dockrell, HM
通讯作者：
Dockrell, HM
影响因子：
3.1
作者：
Brandt, L;Cunha, JF;Andersen, P
通讯作者：
Andersen, P
重复剂量的二氢二甲素 - 二喹用于预防和治疗疟疾的安全性，耐受性和功效：系统评价和荟萃分析。
DOI：
10.1016/s1473-3099(16)30378-4
发表时间：
2017-02
期刊：
The Lancet. Infectious diseases
影响因子：
--
作者：
Gutman J;Kovacs S;Dorsey G;Stergachis A;Ter Kuile FO
通讯作者：
Ter Kuile FO
影响因子：
5.5
作者：
Brown, Joelle;Baisley, Kathy;Watson-Jones, Deborah
通讯作者：
Watson-Jones, Deborah