Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.
Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study.
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DOI：
10.1016/s0140-6736(20)32227-3
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发表时间：
2020-12-05
期刊：
影响因子：
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通讯作者：
ACCESS-SMC Partnership
中科院分区：
文献类型：
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作者：
ACCESS-SMC Partnership
季节性疟疾化学预防（SMC）的目的是在疟疾高发季节预防儿童疟疾。萨赫勒地区实现催化性扩大SMC项目寻求在2015年和2016年在七个国家消除扩大SMC的障碍。我们对该项目进行了评估，包括覆盖范围，干预措施的有效性，安全性，可行性，耐药性和成本效益。在这项观察性研究中，我们收集了在布基纳法索、乍得、冈比亚、几内亚、马里、尼日尔和尼日利亚每年（2015年和2016年）对5岁以下儿童进行4个月SMC给药期间的给药、有效性、安全性、对耐药性的影响、给药成本、对疟疾发病率和死亡率的影响以及成本效益的数据。SMC由社区卫生工作者每月进行一次，他们挨家挨户上门访问。通过统计表和家庭集群抽样覆盖率调查监测药物管理。药物警戒基于有针对性的自发报告，并加强了监测系统。从社区调查中评估了SMC引入前和引入后2年一般人群中磺胺嘧啶-乙胺嘧啶和阿莫地喹抗性的分子标记。每月SMC治疗的有效性进行了测量的病例对照研究，比较确认疟疾患者和社区匹配的社区控制有资格接受SMC之间的SMC接收。根据布基纳法索和冈比亚国家卫生管理信息系统报告的确诊门诊病例、住院和与疟疾有关的死亡，以及选定门诊设施的数据（所有国家），评估了对发病率和死亡率的影响。根据财务成本、卫生保健工作人员时间成本和志愿者机会成本估算了SMC的提供者成本，并计算了成本效益比，即每个国家SMC的总成本除以预测避免的病例数。 2015年，对3650455名儿童的目标人群进行了12467933次每月SMC治疗，2016年对7551491名目标人群进行了25117480次治疗。 2015年，在符合条件的儿童中，每月平均覆盖率为76.4%（95%CI 74.0 - 78.8），54.5%的儿童（95%CI 50.4 - 58.7）接受了所有四种治疗。2016年实现了类似的覆盖率（74.8%[72.2 - 77.3]每月治疗，53.0%[48.5 - 57.4]治疗四次）。在2015-16年的779份个体病例安全性报告中，报告了36例严重药物不良反应（1例儿童皮疹，2例发热，31例胃肠道疾病，1例锥体外系综合征和1例昆克水肿）。未报告重度皮肤反应（Stevens-Johnson或Lyell综合征）病例。在病例对照研究（2185例确诊疟疾病例和4370例对照）中，SMC治疗28天的保护有效性为88.2%（95%CI 78.7 - 93.4）。在布基纳法索和冈比亚，实施SMC与高传播期住院疟疾死亡人数减少相关，布基纳法索为42.4%（95%CI 5.9至64.7），冈比亚为56.6%（28.9至73.5）。在2015-16年期间，七个国家在高传播期门诊确诊疟疾病例的估计减少幅度从尼日利亚的25.5%（95%CI 6.1至40.9）到冈比亚的55.2%（42.0至65.3）不等。抗性分子标记出现频率较低。在10-30岁无SMC的个体中，与阿莫地喹耐药相关的联合突变（pfcrt CVIET单倍型和pfmdr 1突变[86 Tyr和184 Tyr]）的患病率为0.7%（95% CI 0.4 - 1.2），2018年为0.4%（0.1 - 0.8）（患病率0.5 [95% CI 0.2 - 1.2]），以及与磺胺嘧啶-乙胺嘧啶抗性相关的五重突变（pfdhfr和pfdhps突变的三重突变[437 Gly和540 Glu]）在2016年的患病率为0.2%（0.1 - 0.5），在2018年为1.0%（0.6 - 1.6）（患病率为4.8 [1.7 - 13.7]）。每月进行4次SMC治疗的加权平均经济成本为每名儿童3.63美元。大规模的SMC在预防疟疾发病率和死亡率方面是有效的。严重不良反应很少报告。覆盖面各不相同，有些地区通过挨家挨户的宣传一直达到很高的水平。对磺胺嘧啶-乙胺嘧啶和阿莫地喹的耐药性标记仍然不常见，但对磺胺嘧啶-乙胺嘧啶的耐药性有一些选择，需要仔细监测这种情况。这些调查结果应有助于确保在西非和中非高水平的SMC覆盖率的努力。UNITAID。
Seasonal malaria chemoprevention (SMC) aims to prevent malaria in children during the high malaria transmission season. The Achieving Catalytic Expansion of SMC in the Sahel (ACCESS-SMC) project sought to remove barriers to the scale-up of SMC in seven countries in 2015 and 2016. We evaluated the project, including coverage, effectiveness of the intervention, safety, feasibility, drug resistance, and cost-effectiveness. For this observational study, we collected data on the delivery, effectiveness, safety, influence on drug resistance, costs of delivery, impact on malaria incidence and mortality, and cost-effectiveness of SMC, during its administration for 4 months each year (2015 and 2016) to children younger than 5 years, in Burkina Faso, Chad, The Gambia, Guinea, Mali, Niger, and Nigeria. SMC was administered monthly by community health workers who visited door-to-door. Drug administration was monitored via tally sheets and via household cluster-sample coverage surveys. Pharmacovigilance was based on targeted spontaneous reporting and monitoring systems were strengthened. Molecular markers of resistance to sulfadoxine–pyrimethamine and amodiaquine in the general population before and 2 years after SMC introduction was assessed from community surveys. Effectiveness of monthly SMC treatments was measured in case-control studies that compared receipt of SMC between patients with confirmed malaria and neighbourhood-matched community controls eligible to receive SMC. Impact on incidence and mortality was assessed from confirmed outpatient cases, hospital admissions, and deaths associated with malaria, as reported in national health management information systems in Burkina Faso and The Gambia, and from data from selected outpatient facilities (all countries). Provider costs of SMC were estimated from financial costs, costs of health-care staff time, and volunteer opportunity costs, and cost-effectiveness ratios were calculated as the total cost of SMC in each country divided by the predicted number of cases averted. 12 467 933 monthly SMC treatments were administered in 2015 to a target population of 3 650 455 children, and 25 117 480 were administered in 2016 to a target population of 7 551 491. In 2015, among eligible children, mean coverage per month was 76·4% (95% CI 74·0–78·8), and 54·5% children (95% CI 50·4–58·7) received all four treatments. Similar coverage was achieved in 2016 (74·8% [72·2–77·3] treated per month and 53·0% [48·5–57·4] treated four times). In 779 individual case safety reports over 2015–16, 36 serious adverse drug reactions were reported (one child with rash, two with fever, 31 with gastrointestinal disorders, one with extrapyramidal syndrome, and one with Quincke's oedema). No cases of severe skin reactions (Stevens-Johnson or Lyell syndrome) were reported. SMC treatment was associated with a protective effectiveness of 88·2% (95% CI 78·7–93·4) over 28 days in case-control studies (2185 cases of confirmed malaria and 4370 controls). In Burkina Faso and The Gambia, implementation of SMC was associated with reductions in the number of malaria deaths in hospital during the high transmission period, of 42·4% (95% CI 5·9 to 64·7) in Burkina Faso and 56·6% (28·9 to 73·5) in The Gambia. Over 2015–16, the estimated reduction in confirmed malaria cases at outpatient clinics during the high transmission period in the seven countries ranged from 25·5% (95% CI 6·1 to 40·9) in Nigeria to 55·2% (42·0 to 65·3) in The Gambia. Molecular markers of resistance occurred at low frequencies. In individuals aged 10–30 years without SMC, the combined mutations associated with resistance to amodiaquine (pfcrt CVIET haplotype and pfmdr1 mutations [86Tyr and 184Tyr]) had a prevalence of 0·7% (95% CI 0·4–1·2) in 2016 and 0·4% (0·1–0·8) in 2018 (prevalence ratio 0·5 [95% CI 0·2–1·2]), and the quintuple mutation associated with resistance to sulfadoxine–pyrimethamine (triple mutation in pfdhfr and pfdhps mutations [437Gly and 540Glu]) had a prevalence of 0·2% (0·1–0·5) in 2016 and 1·0% (0·6–1·6) in 2018 (prevalence ratio 4·8 [1·7–13·7]). The weighted average economic cost of administering four monthly SMC treatments was US$3·63 per child. SMC at scale was effective in preventing morbidity and mortality from malaria. Serious adverse reactions were rarely reported. Coverage varied, with some areas consistently achieving high levels via door-to-door campaigns. Markers of resistance to sulfadoxine–pyrimethamine and amodiaquine remained uncommon, but with some selection for resistance to sulfadoxine–pyrimethamine, and the situation needs to be carefully monitored. These findings should support efforts to ensure high levels of SMC coverage in west and central Africa. Unitaid.