ISGlobal, Hospital Clínic-Universitat de Barcelona, Barcelona, Spain.
Centro de Investigação em Saúde de Manhiça, Maputo, Mozambique.
PLoS Med. 2020 Aug 14;17(8):e1003227. doi: 10.1371/journal.pmed.1003227. eCollection 2020 Aug.
Malaria eradication remains the long-term vision of the World Health Organization (WHO). However, whether malaria elimination is feasible in areas of stable transmission in sub-Saharan Africa with currently available tools remains a subject of debate. This study aimed to evaluate a multiphased malaria elimination project to interrupt Plasmodium falciparum malaria transmission in a rural district of southern Mozambique.
A before-after study was conducted between 2015 and 2018 in the district of Magude, with 48,448 residents living in 10,965 households. Building on an enhanced surveillance system, two rounds of mass drug administrations (MDAs) per year over two years (phase I, August 2015-2017), followed by one year of reactive focal mass drug administrations (rfMDAs) (phase II, September 2017-June 2018) were deployed with annual indoor residual spraying (IRS), programmatically distributed long-lasting insecticidal nets (LLINs), and standard case management. The four MDA rounds covered 58%-72% of the population, and annual IRS reported coverage was >70%. Yearly parasite surveys and routine surveillance data were used to monitor the primary outcomes of the study-malaria prevalence and incidence-at baseline and annually since the onset of the project. Parasite prevalence by rapid diagnostic test (RDT) declined from 9.1% (95% confidence interval [CI] 7.0-11.8) in May 2015 to 2.6% (95% CI 2.0-3.4), representing a 71.3% (95% CI 71.1-71.4, p < 0.001) reduction after phase I, and to 1.4% (95% CI 0.9-2.2) after phase II. This represented an 84.7% (95% CI 81.4-87.4, p < 0.001) overall reduction in all-age prevalence. Case incidence fell from 195 to 75 cases per 1,000 during phase I (61.5% reduction) and to 67 per 1,000 during phase II (65.6% overall reduction). Interrupted time series (ITS) analysis was used to estimate the level and trend change in malaria cases associated with the set of project interventions and the number of cases averted. Phase I interventions were associated with a significant immediate reduction in cases of 69.1% (95% CI 57.5-77.6, p < 0.001). Phase II interventions were not associated with a level or trend change. An estimated 76.7% of expected cases were averted throughout the project (38,369 cases averted of 50,005 expected). One malaria-associated inpatient death was observed during the study period. There were 277 mild adverse events (AEs) recorded through the passive pharmacovigilance system during the four MDA rounds. One serious adverse event (SAE) that resulted in death was potentially related to the drug. The study was limited by the incomplete coverage of interventions, the quality of the routine and cross-sectional data collected, and the restricted accuracy of ITS analysis with a short pre-intervention period.
In this study, we observed that the interventions deployed during the Magude project fell short of interrupting P. falciparum transmission with the coverages achieved. While new tools and strategies may be required to eventually achieve malaria elimination in stable transmission areas of sub-Saharan Africa, this project showed that innovative mixes of interventions can achieve large reductions in disease burden, a necessary step in the pathway towards elimination.
ClinicalTrials.gov NCT02914145.
消除疟疾仍然是世界卫生组织(WHO)的长期愿景。然而,在撒哈拉以南非洲稳定传播地区,利用现有的工具来实现疟疾消除是否可行,这仍然是一个争论的话题。本研究旨在评估一个多阶段的疟疾消除项目,以中断莫桑比克南部一个农村地区的恶性疟原虫疟疾传播。
在 2015 年至 2018 年期间,在马古德区进行了一项前后对照研究,该地区有 48448 名居民居住在 10965 户家庭中。在强化监测系统的基础上,在两年内进行了两轮每年一次的大规模药物治疗(MDA)(第一阶段,2015 年 8 月至 2017 年),随后进行了一年的反应性局部大规模药物治疗(rfMDA)(第二阶段,2017 年 9 月至 2018 年 6 月),每年进行室内滞留喷洒(IRS)、计划分发长效驱虫蚊帐(LLIN)和标准病例管理。四轮 MDA 覆盖了 58%-72%的人口,每年 IRS 的报告覆盖率>70%。年度寄生虫调查和常规监测数据用于监测研究的主要结果-疟疾患病率和发病率-在基线和项目开始后的每年。通过快速诊断测试(RDT)的寄生虫患病率从 2015 年 5 月的 9.1%(95%置信区间[CI] 7.0-11.8)下降到 2.6%(95%CI 2.0-3.4),代表第一阶段后 71.3%(95%CI 71.1-71.4,p<0.001)的减少,第二阶段后降至 1.4%(95%CI 0.9-2.2)。这代表所有年龄组患病率总体下降 84.7%(95%CI 81.4-87.4,p<0.001)。病例发病率从第一阶段的 195 例/1000 人降至 75 例/1000 人(61.5%减少),第二阶段降至 67 例/1000 人(总体减少 65.6%)。中断时间序列(ITS)分析用于估计与项目干预措施相关的疟疾病例数量及其变化水平和趋势,以及避免的病例数量。第一阶段的干预措施与病例的显著立即减少有关,减少了 69.1%(95%CI 57.5-77.6,p<0.001)。第二阶段的干预措施与水平或趋势变化无关。整个项目期间预计有 76.7%的病例被避免(避免 50005 例预期病例中的 38369 例)。研究期间观察到一例与疟疾相关的住院死亡病例。在四轮 MDA 期间,通过被动药物警戒系统记录了 277 例轻度不良事件(AE)。一例导致死亡的严重不良事件(SAE)可能与药物有关。该研究受到干预措施不完全覆盖、收集的常规和横断面数据质量以及 ITS 分析的短期干预前期间限制准确性的限制。
在这项研究中,我们观察到马古德项目中部署的干预措施未能达到预期的覆盖率,从而中断恶性疟原虫的传播。虽然在撒哈拉以南非洲稳定传播地区最终实现疟疾消除可能需要新的工具和策略,但该项目表明,创新的干预措施组合可以大大降低疾病负担,这是消除疟疾的必经之路。
ClinicalTrials.gov NCT02914145。