计算巨大的时间和工具:诊断和量化肠道血吸虫病的负担。

In the control of parasitic diseases, the correct diagnostic tool at the right time will accurately assess the burden of disease, monitor the impact of the disease control intervention and save valuable resources. Knowing where and when to use which diagnostic tools is paramount to the control of parasitic diseases of public health and veterinary importance. A recent study compares two different diagnostic tools in use for schistosomiasis, presenting findings that have important implications for public health policy in the context of schistosomiasis control and elimination efforts.

The ideal goal of a parasite is for it to move within and between hosts undetected and undisturbed, so it is hardly surprising that the development of ‘gold standards’ for locating, isolating and quantifying them is an on-going process and what keeps many parasitologists fascinated by these peculiar creatures.

Parasitic protozoa, nematoda, trematoda and cestoda of public health and in many cases veterinary importance, are endoparasitic (i.e. living within the definitive hosts internal organs and tissues). This lifecycle choice is not only more damaging for the host, but also means that the root causative agent of illness, the mature parasite within the host, is not easily accessible without some kind of intrusive method. Therefore most measures to determine presence of the parasite within the host often rely on using biological markers in host blood, serum and excreta.

Scanning Electron Image of a Schistosome worm pair. Image credit: Trustees of the Natural History Museum

血吸虫

血吸虫是一组Trematoda类的寄生血液泛滥,并且在人类中广泛引起两种不同的疾病:泌尿生殖和肠道细菌病,分别在泌尿生殖区域和肠道周围的静脉内生活和交配的成年蠕虫和交配。这种被忽视的热带疾病感染了估计的190 million people a year主要是撒哈拉以南非洲,以及通过使用praziquantel的大规模大规模药物管理(MDA)进行预防化疗的大规模药物管理(MDA),以治疗和减少流行人群的发病率。

诊断血吸虫感染

Ideal diagnostics for schistosomiasis need to consistently provide the correct diagnoses to know whether treatment is necessary, but they also need to quantify the burden of disease a host is enduring. This quantification allows the examiner to determine the extent of on-going transmission and re-infection in a study area receiving regular treatment, as well as determine the impact and effectiveness of ongoing treatment interventions. With a constant risk of parasites becoming resistant to many anti-parasitic drugs, it is also pertinent to quantify parasite abundance so that drug efficacy can be accurately assessed, i.e. to establish whether there had been a significant, if not complete, reduction in parasite load following a targeted treatment.

A recent research article published inJoaquin Prada及其同事的寄生虫和媒介encompasses some of these issues by comparing two widely used diagnostic tests for intestinal schistosomiasis (caused bySchistosoma mansoni)in Uganda. The authors do so by comparing the difference between the two traditional diagnostics, aKato-Katz thick smear以及一个新的且日益流行的循环阴极抗原测试(CCA),用于螺旋体检测。

  • Kato Katz厚涂片技术involves using light microscopy to manually count the number of schistosome eggs from a specific amount of stool sample. Although, this technique is highly specific, it most importantly lacks in sensitivity, which can result in false negatives from positive individuals. These false negatives are often due to low or不同的血吸虫鸡蛋输出,,,,meaning that the estimation of disease burden through egg counts can also be skewed.
  • 循环阴极抗原测试(CCA)detectsS. mansoni肠道抗原在活性血液喂养过程中被蠕虫反流,因此存在于宿主尿液中。测试很敏感(although not 100%),,,,and is regarded as a “point-of-care” diagnostic enabling quick, non-invasive sampling and requires no sophisticated equipment to view results. As these schistosome antigens disappear from the urine within24-48 hours of the host being treated and fully clearing the infection,,,,it enables differentiation between active parasites and refugia (i.e. juvenile parasites remaining in the body post-treatment that may not produce eggs, these require over a week to reach maturity).
CCA test. Image credit: Amadou Garba

When a gold standard isn’t the gold standard?

关于肠道血吸虫病的公共卫生政策决策是基于卡托 - 卡茨计算的患病率,但是CCA is increasingly being used in mapping the diseaseand could be used in forming policy if the relationship between Kato-Katz and CCA across pre- and post-treatment settings is better understood. Prada和他的同事们因此,根据三个时间点,根据Kato-Katz(乌干达)儿童(乌干达)儿童判断的患病率和强度的关系模型:在治疗后一个月和六个月之前。

尽管加藤 - 卡茨被认为是“黄金标准”S. mansoni诊断,事实上CCA,是模仿the best predictor of schistosomiasis prevalence, and in particular after treatment had occurred, likely due to higher CCA sensitivity at lower post treatment infection intensities. Model outputs also dispelled the previous uncertainty on interpretation of “trace” readings (i.e. test providing a weak positive), as these researchers concluded that these were most likely associated with truly infected individuals. In these high endemnicity settings, truly uninfected individuals with trace results make up only a small minority (15%), giving a brilliant guideline for control programme managers having to deal with these “trace” results.

何时,何处和哪个测试?

这些工人provide evidence that future surveys should follow a multiple diagnostic approach depending on the epidemiological setting of the targeted area. As highly endemicS. mansoni区域通常与高传输区域相关,因此具有高感染强度的个体,Kato-Katz能够识别这些重型感染。但是,在实施MDA(如这里研究的Mayuge地区)时,受过治疗个体的感染强度大幅下降需要使用更敏感的诊断,例如CCA来评估真正的患病率。

正是这样的研究应该直接纳入未来的政策,因为在合适的时间选择正确的诊断工具将节省资源,最重要的是准确地评估血吸虫病的负担以及疾病控制干预措施的影响moving towards elimination

接受praziquantel和阿苯达唑治疗的学童。图片版权:Steffi Knopp

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