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西非和中非大规模季节性疟疾化学预防可有效降低发病率和死亡率
作者:小柯机器人 发布时间:2020/12/6 22:52:55

英国伦敦卫生和热带医学院Paul Milligan团队观察了西非和中非大规模季节性疟疾化学预防的效果。2020年12月5日,该研究发表在《柳叶刀》杂志上。

季节性疟疾化学预防(SMC)旨在在疟疾高发季节预防儿童疟疾。ACCESS-SMC项目旨在消除2015-2016年在七个国家扩大SMC规模的障碍。研究组评估了该项目的覆盖范围,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,研究组在布基纳法索、乍得、冈比亚、几内亚、马里、尼日尔和尼日利亚每年向5岁以下儿童提供每月4次的SMC给药。2015年对3650455名儿童目标人群进行了12467933次SMC治疗,2016年对7551491名儿童进行了25117480次。

2015年,在符合条件的儿童中,每月平均覆盖率为76.4%,有54.5%的儿童接受了全部四次治疗;2016年实现了类似的覆盖率,分别为74.8%和53.0%。在2015-2016年度的779例病例安全报告中,共发生36例严重药物不良反应,其中1例皮疹,2例发烧,31例胃肠道疾病,1例锥体外系综合征和1例昆克氏水肿。尚无严重皮肤反应的病例报道。

在病例对照研究(2185例确诊疟疾病例和4370例对照者)中,SMC治疗在28天内的保护效果为88.2%。在布基纳法索和冈比亚,SMC的实施与高发季节医院疟疾死亡人数的减少有关,其中布基纳法索减少了42.4%,冈比亚减少了56.6%。

2015-2016年,在七个国家的高发季节,门诊确诊的疟疾病例估计减少率从尼日利亚的25.5%至冈比亚的55.2%不等。耐药分子标记的发生频率较低。在10-30岁无SMC的个体中,2016年与阿莫地喹耐药相关的组合突变的发生率为0.7%,2018年为0.4%;2016年与磺胺多辛-乙胺嘧啶耐药相关的五倍体突变的发生率为0.2%,2018年为1.0%。每月进行4次SMC治疗的加权平均经济成本为每名儿童仅3.63美元。

研究结果表明,大规模SMC可有效预防疟疾的发病率和死亡率。很少有严重的不良反应报道。

附:英文原文

Title: Effectiveness of seasonal malaria chemoprevention at scale in west and central Africa: an observational study

Author: Ebenezer Baba, Prudence Hamade, Harriet Kivumbi, Maddy Marasciulo, Kolawole Maxwell, Diego Moroso, Arantxa Roca-Feltrer, Adama Sanogo, Joanna Stenstrom Johansson, James Tibenderana, Rahila Abdoulaye, Patrice Coulibaly, Eric Hubbard, Huja Jah, Eugene Kaman Lama, Lantorina Razafindralambo, Suzanne Van Hulle, George Jagoe, André-Marie Tchouatieu, David Collins, Colin Gilmartin, Gladys Tetteh, Yacine Djibo, Fara Ndiaye, Momodou Kalleh, Balla Kandeh, Bala Audu, Godwin Ntadom, Alice Kiba, Yacouba Savodogo, Kodbesse Boulotigam, Djiddi Ali Sougoudi, Timothee Guilavogui, Moussa Keita, Diakalidia Kone, Hadiza Jackou, Ibrahim Ouba, Emile Ouedraogo, Halimatou Alassana Messan, Fatou Jah, Markieu Janneh Kaira, Mariama Sire Sano, Mamadou Chérif Traore, Nadine Ngarnaye, Aishatu Yinusa Cassandra Elagbaje, Christine Halleux, Corinne Merle, Noha Iessa, Shanthi Pal, Houda Sefiani, Rachida Souleymani, Ibrahim Laminou, Daugla Doumagoum, Hamit Kesseley, Matt Coldiron, Rebecca Grais, Musa Kana, Jean Bosco Ouedraogo, Issaka Zongo, Tony Eloike, Sonny Johnbull Ogboi, Jane Achan, Kalifa Bojang, Serign Ceesay, Alassane Dicko, Abdoulaye Djimde, Issaka Sagara, Abdoulaye Diallo, Jean Louis NdDiaye, Kovana Marcel Loua, Khalid Beshir, Matt Cairns, Yolanda Fernandez, Sham Lal, Raoul Mansukhani, Julian Muwanguzi, Susana Scott, Paul Snell, Colin Sutherland, Rhosyn Tuta, Paul Milligan

Issue&Volume: 2020/12/05

Abstract:

Background

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.

Methods

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.

Findings

12467933 monthly SMC treatments were administered in 2015 to a target population of 3650455 children, and 25117480 were administered in 2016 to a target population of 7551491. 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.

Interpretation

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.

DOI: 10.1016/S0140-6736(20)32227-3

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32227-3/fulltext

期刊信息

LANCET:《柳叶刀》,创刊于1823年。隶属于爱思唯尔出版社,最新IF:59.102
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