Phillips Anna E, Gazzinelli-Guimaraes Pedro H, Aurelio Herminio O, Ferro Josefo, Nala Rassul, Clements Michelle, King Charles H, Fenwick Alan, Fleming Fiona M, Dhanani Neerav
Schistosomiasis Control Initiative, Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom.
Faculdade of Health Sciences, Universidade Católica de Moçambique (UCM) Beira, Moçambique.
PLoS Negl Trop Dis. 2017 Dec 8;11(12):e0006061. doi: 10.1371/journal.pntd.0006061. eCollection 2017 Dec.
In Mozambique, schistosomiasis is highly endemic across the whole country. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) coordinates a five-year study that has been implemented in various African countries, including Mozambique. The overall goal of SCORE was to better understand how to best apply preventive chemotherapy with praziquantel (PZQ) for schistosomiasis control by evaluating the impact of alternative treatment approaches.
This was a cluster-randomised trial that compared the impact of different treatment strategies in study areas with prevalence among school children of ≥21% S. haematobium infection by urine dipstick. Each village was randomly allocated to one of six possible combinations of community-wide treatment (CWT), school-based treatment (SBT), and/or drug holidays over a period of four years, followed by final data collection in the fifth year. The most intense intervention arm involved four years of CWT, while the least intensive arm involved two years of SBT followed by two consecutive years of PZQ holiday. Each study arm included 25 villages randomly assigned to one of the six treatment arms. The primary outcome of interest was change in prevalence and intensity of S. haematobium among 100 children aged 9-to-12-years that were sampled each year in every village. In addition to children aged 9-to-12 years, 100 children aged 5-8 years in their first-year of school and 50 adults (aged 20-55 years) were tested in the first and final fifth year of the study. Prevalence and intensity of S. haematobium infection was evaluated by two filtrations, each of 10mL, from a single urine specimen.
In total, data was collected from 81,167 individuals across 149 villages in ten districts of Cabo Delgado province, Northern Mozambique. Overall PZQ treatment resulted in a significant reduction in the prevalence of S. haematobium infection from Year 1 to Year 5, where the average prevalence went from 60.5% to 38.8%, across all age groups and treatment arms. The proportion of those heavily infected also reduced from 17.6% to 11.9% over five years. There was a significantly higher likelihood of males being infected than females at baseline, but no significant difference between the sexes in their response to treatment. The only significant response based on a study arm was seen in both the 9-to-12-year-old and first-year cross sections, where two consecutive treatment holidays resulted in a significantly higher final prevalence of S. haematobium than no treatment holidays. When the arms were grouped together, four rounds of treatment (regardless of whether it was CWT or SBT), however, did result in a significantly greater reduction in S. haematobium prevalence than two rounds of treatment (i.e. with two intermittent or consecutive holiday years) over a five-year period.
Although PC was successful in reducing the burden of active infection, even among those heavily infected, annual CWT did not have a significantly greater impact on disease prevalence or intensity than less intense treatment arms. This may be due to extremely high starting prevalence and intensity in the study area, with frequent exposure to reinfection, or related to challenges in achieving high treatment coverage More frequent treatment had a greater impact on prevalence and intensity of infection when arms were grouped by number of treatments, however, cost efficiency was greater in arms only receiving two treatments. Finally, a significant reduction in prevalence of S. haematobium was seen in adults even in the SBT arms implying the rate of transmission in the community had been decreased, even where only school children have been treated, which has significant logistical and cost-saving implications for a national control programme in justifying CWT.
在莫桑比克,血吸虫病在全国范围内高度流行。血吸虫病运筹学与评价联合会(SCORE)协调了一项在包括莫桑比克在内的多个非洲国家开展的为期五年的研究。SCORE的总体目标是通过评估替代治疗方法的影响,更好地了解如何最好地应用吡喹酮(PZQ)进行预防性化疗以控制血吸虫病。
这是一项整群随机试验,比较了不同治疗策略对血吸虫病感染率≥21%(通过尿试纸检测)的学龄儿童所在研究区域的影响。在四年时间里,每个村庄被随机分配到社区范围治疗(CWT)、学校为基础的治疗(SBT)和/或药物假期的六种可能组合之一,然后在第五年进行最终数据收集。干预强度最大的组包括四年的CWT,而干预强度最小的组包括两年的SBT,随后连续两年为PZQ假期。每个研究组包括25个随机分配到六种治疗组之一的村庄。感兴趣的主要结果是每个村庄每年抽样的100名9至12岁儿童中血吸虫病的感染率和感染强度的变化。除了9至12岁的儿童外,在研究的第一年和最后一年的第五年,还对100名一年级的5至8岁儿童和50名成年人(20至55岁)进行了检测。通过对单个尿液标本进行两次各10mL的过滤来评估血吸虫病感染的感染率和感染强度。
总共从莫桑比克北部德尔加杜角省十个区的149个村庄的81167个人收集了数据。总体PZQ治疗导致从第1年到第5年血吸虫病感染率显著降低,在所有年龄组和治疗组中,平均感染率从60.5%降至38.8%。重度感染人群的比例在五年内也从17.6%降至11.9%。在基线时,男性感染的可能性显著高于女性,但在对治疗的反应方面两性之间没有显著差异。基于研究组的唯一显著反应出现在9至12岁组和一年级组中,其中连续两个治疗假期导致血吸虫病的最终感染率显著高于无治疗假期的情况。当将这些组合并在一起时,然而,在五年期间,四轮治疗(无论是否为CWT或SBT)确实比两轮治疗(即有两个间歇或连续的假期年)导致血吸虫病感染率显著更大幅度的降低。
尽管预防性化疗成功减轻了活动性感染的负担,即使在重度感染人群中也是如此,但与干预强度较小的治疗组相比,年度CWT对疾病感染率或感染强度的影响并没有显著更大。这可能是由于研究区域开始时的感染率和感染强度极高,且频繁接触再感染,或者与实现高治疗覆盖率方面的挑战有关。然而,当按治疗次数对组进行分组时,更频繁的治疗对感染率和感染强度有更大影响,仅接受两次治疗的组成本效益更高。最后,即使在SBT组中,成年人的血吸虫病感染率也显著降低,这意味着即使仅对学龄儿童进行了治疗,社区中的传播率也已降低,这对于国家控制计划在证明CWT的合理性方面具有重大的后勤和成本节约意义。