Mawson Anthony R, Makunde Williams H, Penman Alan D, Hernandez Morales Veronica de Los Angeles, Kalinga Akili K, Francis Filbert, Rubinchik Semyon, Kibweja Addow
Department of Epidemiology and Biostatistics, School of Public Health, Jackson State University, Jackson, MS, USA.
Tanga Research Centre, National Institute for Medical Research, Tanzania, Tanga, Tanzania.
Infect Dis (Auckl). 2017 Sep 20;10:1178633617731741. doi: 10.1177/1178633617731741. eCollection 2017.
Based on the observation that the parasite selectively absorbs vitamin A from the host, and the known toxicity of vitamin A in higher concentration, it was hypothesized that dying microfilariae (mf) release their stores of vitamin A (retinoids) into the host circulation in toxic concentrations, inducing the signs and symptoms of onchocerciasis. We conducted a pilot study to test the hypothesis in Songea communities in Southern Tanzania, where mass drug administration with ivermectin had not been implemented by the time of the survey. The specific aim was to evaluate the correlation between the diagnosis of onchocerciasis and increased levels of retinoic acid at infection sites. The analysis was performed by determining copy numbers of a genome of present in skin snip samples of persons with onchocerciacis, and correlating these numbers with expression levels of retinoic acid receptor-α (RAR-α), which is inducible by retinoic acid. Total DNA and RNA were extracted from each of 25 mf-positive and 25 mf-negative skin samples and evaluated using quantitative polymerase chain reaction with appropriate negative controls. Analysis of the samples, adjusted with glyceraldehyde 3-phosphate dehydrogenase gene levels, revealed that most samples with detectable RAR-α transcripts had higher levels of RAR-α expression than the assay control. However, the quality and number of samples were insufficient for statistical analysis. Fold data on the expression levels of both DNA and RAR RNA suggested a possible trend toward higher relative RAR-α expression in samples with higher levels of DNA ( = 0.25, = .079). Evidence of a contribution of vitamin A to the pathology of onchocerciasis thus remains elusive. Future studies on the role of retinoids in onchocerciasis will require larger groups of participants as well as careful monitoring of the cold chain and tissue storage procedures in view of the sensitivity of vitamin A to heat and light.
基于寄生虫会选择性地从宿主中吸收维生素A这一观察结果，以及高浓度维生素A已知的毒性，有人提出假说，即垂死的微丝蚴会将其储存的维生素A（类视黄醇）以有毒浓度释放到宿主循环系统中，从而引发盘尾丝虫病的体征和症状。我们在坦桑尼亚南部的松盖阿社区开展了一项试点研究，以验证这一假说，在调查时该社区尚未实施伊维菌素群体给药。具体目的是评估盘尾丝虫病的诊断与感染部位视黄酸水平升高之间的相关性。分析方法是确定盘尾丝虫病患者皮肤切片样本中存在的一种基因组的拷贝数，并将这些数字与视黄酸受体-α（RAR-α）的表达水平相关联，RAR-α可由视黄酸诱导产生。从25份微丝蚴阳性和25份微丝蚴阴性皮肤样本中分别提取总DNA和RNA，并使用定量聚合酶链反应及适当的阴性对照进行评估。用甘油醛-3-磷酸脱氢酶基因水平进行校正后对样本进行分析，结果显示，大多数可检测到RAR-α转录本的样本，其RAR-α表达水平高于检测对照。然而，样本的质量和数量不足以进行统计分析。DNA和RAR RNA表达水平的倍数数据表明，在DNA水平较高的样本中，相对RAR-α表达可能有升高的趋势（P = 0.25，r = 0.079）。因此，维生素A对盘尾丝虫病病理学的作用证据仍然难以捉摸。鉴于维生素A对热和光敏感，未来关于类视黄醇在盘尾丝虫病中作用的研究将需要更大规模的参与者群体，以及对冷链和组织储存程序的仔细监测。
