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1994 - 2009年肯尼亚西部高流行区疟疾传播强度历史变化监测的血清学标志物

Serological markers for monitoring historical changes in malaria transmission intensity in a highly endemic region of Western Kenya, 1994-2009.

作者信息

Wong Jacklyn, Hamel Mary J, Drakeley Chris J, Kariuki Simon, Shi Ya Ping, Lal Altaf A, Nahlen Bernard L, Bloland Peter B, Lindblade Kim A, Were Vincent, Otieno Kephas, Otieno Peter, Odero Chris, Slutsker Laurence, Vulule John M, Gimnig John E

机构信息

Division of Parasitic Diseases and Malaria, Centers for Disease Control and Prevention, Atlanta, GA, USA.

出版信息

Malar J. 2014 Nov 22;13:451. doi: 10.1186/1475-2875-13-451.

Abstract

BACKGROUND

Monitoring local malaria transmission intensity is essential for planning evidence-based control strategies and evaluating their impact over time. Anti-malarial antibodies provide information on cumulative exposure and have proven useful, in areas where transmission has dropped to low sustained levels, for retrospectively reconstructing the timing and magnitude of transmission reduction. It is unclear whether serological markers are also informative in high transmission settings, where interventions may reduce transmission, but to a level where considerable exposure continues.

METHODS

This study was conducted through ongoing KEMRI and CDC collaboration. Asembo, in Western Kenya, is an area where intense malaria transmission was drastically reduced during a 1997-1999 community-randomized, controlled insecticide-treated net (ITN) trial. Two approaches were taken to reconstruct malaria transmission history during the period from 1994 to 2009. First, point measurements were calculated for seroprevalence, mean antibody titre, and seroconversion rate (SCR) against three Plasmodium falciparum antigens (AMA-1, MSP-119, and CSP) at five time points for comparison against traditional malaria indices (parasite prevalence and entomological inoculation rate). Second, within individual post-ITN years, age-stratified seroprevalence data were analysed retrospectively for an abrupt drop in SCR by fitting alternative reversible catalytic conversion models that allowed for change in SCR.

RESULTS

Generally, point measurements of seroprevalence, antibody titres and SCR produced consistent patterns indicating that a gradual but substantial drop in malaria transmission (46-70%) occurred from 1994 to 2007, followed by a marginal increase beginning in 2008 or 2009. In particular, proportionate changes in seroprevalence and SCR point estimates (relative to 1994 baseline values) for AMA-1 and CSP, but not MSP-119, correlated closely with trends in parasite prevalence throughout the entire 15-year study period. However, retrospective analyses using datasets from 2007, 2008 and 2009 failed to detect any abrupt drop in transmission coinciding with the timing of the 1997-1999 ITN trial.

CONCLUSIONS

In this highly endemic area, serological markers were useful for generating accurate point estimates of malaria transmission intensity, but not for retrospective analysis of historical changes. Further investigation, including exploration of different malaria antigens and/or alternative models of population seroconversion, may yield serological tools that are more informative in high transmission settings.

摘要

背景

监测当地疟疾传播强度对于制定基于证据的控制策略以及评估其长期影响至关重要。抗疟抗体可提供累积暴露信息,并且已证明在传播已降至低持续水平的地区,对于回顾性重建传播减少的时间和幅度很有用。尚不清楚血清学标志物在高传播环境中是否也具有信息价值,在这种环境中,干预措施可能会降低传播,但降至仍有大量暴露的水平。

方法

本研究是通过肯尼亚医学研究协会(KEMRI)和美国疾病控制与预防中心(CDC)正在进行的合作开展的。肯尼亚西部的阿森博是一个在1997 - 1999年社区随机对照杀虫剂处理蚊帐(ITN)试验期间疟疾传播强度大幅降低的地区。采用两种方法重建1994年至2009年期间的疟疾传播历史。首先,计算了在五个时间点针对三种恶性疟原虫抗原(AMA - 1、MSP - 119和CSP)的血清阳性率、平均抗体滴度和血清转化率(SCR)的点测量值,以便与传统疟疾指标(寄生虫患病率和昆虫学接种率)进行比较。其次,在ITN试验后的各年份内,通过拟合允许SCR变化的替代可逆催化转换模型,对按年龄分层的血清阳性率数据进行回顾性分析,以检测SCR的突然下降。

结果

总体而言,血清阳性率、抗体滴度和SCR的点测量值呈现出一致的模式,表明从1994年到2007年疟疾传播逐渐但大幅下降(46 - 70%),随后在2008年或2009年开始略有上升。特别是,在整个15年研究期间,AMA - 1和CSP(而非MSP - 119)的血清阳性率和SCR点估计值的比例变化(相对于1994年基线值)与寄生虫患病率趋势密切相关。然而,使用2007年、2008年和2009年数据集进行的回顾性分析未能检测到与1997 - 1999年ITN试验时间相符的传播突然下降情况。

结论

在这个高度流行的地区,血清学标志物有助于生成疟疾传播强度的准确点估计值,但对于历史变化的回顾性分析并无帮助。进一步的研究,包括探索不同的疟疾抗原和/或人群血清转化的替代模型,可能会产生在高传播环境中更具信息价值的血清学工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fe8/4258276/a2389cda02d9/12936_2014_3619_Fig1_HTML.jpg

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