Trichuris trichiura

Trichuris trichiura
  • 文章类型: Journal Article
    土壤传播的蠕虫(STH)感染,通常用苯并咪唑治疗,通过β-微管蛋白同种型1基因中第167、198或200位的单核苷酸多态性(SNP)与抗性相关。这项研究的目的是建立一种新颖的基因分型测定法,其特征在于其快速性和特异性。设计该测定以检测Trichuris的部分β-微管蛋白基因内SNP的存在。这是通过使用两个等位基因特异性正向引物的竞争性结合在密码子167、198和200处的双等位基因区分来实现的。该测定的特异性和可靠性随后使用从圈养的灵长类动物分离的鞭虫样品进行确认。此外,进行了一项分子研究,以证实β-微管蛋白基因作为分子标记的实用性。当应用于现场样品时,该测定法显示出高灵敏度和特异性。然而,在来自分析种群的任何成虫或卵中都未检测到β-微管蛋白基因内的SNP。所有标本一致显示SS基因型。对β-微管蛋白基因的检查进一步验证了T.trichiura进化枝和猪Trichuris进化枝之间已建立的密切关系。这重申了其作为系统发育分析标记的实用性。
    Soil-transmitted helminth (STH) infections, commonly treated with benzimidazoles, are linked to resistance through single nucleotide polymorphisms (SNPs) at position 167, 198, or 200 in the β-tubulin isotype 1 gene. The aim of this study was to establish a novel genotyping assay characterized by its rapidity and specificity. This assay was designed to detect the presence of SNPs within the partial β-tubulin gene of Trichuris trichiura. This was achieved through the biallelic discrimination at codons 167, 198, and 200 by employing the competitive binding of two allele-specific forward primers. The specificity and reliability of this assay were subsequently confirmed using Trichuris samples isolated from captive primates. Furthermore, a molecular study was conducted to substantiate the utility of the β-tubulin gene as a molecular marker. The assays showed high sensitivity and specificity when applied to field samples. Nevertheless, none of the SNPs within the β-tubulin gene were detected in any of the adult worms or eggs from the analyzed populations. All specimens consistently displayed an SS genotype. The examination of the β-tubulin gene further validated the established close relationships between the T. trichiura clade and Trichuris suis clade. This reaffirms its utility as a marker for phylogenetic analysis.
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  • 文章类型: Journal Article
    肯尼亚实施了一项全国学校驱虫计划,这导致土壤传播的蠕虫(STHs)的患病率大幅下降,尽管仍然存在一些感染。为了有效地设计导致Trichuristrichiura显着减少的STH控制程序,尽管正在进行治疗计划,但仍需要了解持续感染的驱动因素.
    这项研究于2019年7月至9月在肯尼亚南海岸进行,采用两阶段抽样设计。首先,在已知Trichiura流行地区的部分学校中随机选择的2265名学童中进行了一项基于学校的横断面调查。在这之后,我们进行了一项巢式病例对照研究,其中所有TrichiuraT.(142)阳性儿童与148名阴性对照根据年龄和村庄进行匹配.然后对病例和对照的所有家庭成员进行了家庭调查。此外,在治疗后第21天,我们对116名被发现感染TrichiuraT.的儿童进行了随访,以评估阿苯达唑的疗效.通过多水平逻辑回归研究了T.trichiura存在的预测因素,考虑到感染的聚类。
    总的来说,34.4%的儿童感染了至少一种STH;T.trichiura是最常见的(28.3%),89.1%的Trichiura患者有光照强度感染。在男性儿童中,T.trichiura的患病率显着升高,并且与较年轻的年龄和家庭中感染T.trichiura的人数呈正相关。毛虫的寄生虫治愈率和减卵率分别为35%和51%,分别。确定的其他STH是钩虫(9.6%)和A虫(5.7%)。
    T.在阿苯达唑对寄生虫的治疗效果研究领域,trichilura仍然是一个重大的公共卫生挑战,低于世界卫生组织建议的阈值。由于在当前区域观察到T.trichiura的局灶性传播,应根据当地条件和针对较低执行单位的控制努力,以实现传输的最佳结果。
    UNASSIGNED: Kenya has implemented a national school-based deworming program, which has led to substantial decline in the prevalence of soil-transmitted helminths (STHs), although some pockets of infections remain. To effectively design an STH control program that leads to significant reductions of Trichuris trichiura, there is a need to understand the drivers of persistent infection despite ongoing treatment programs.
    UNASSIGNED: This study was conducted between July and September 2019 at the south coast of Kenya, using a two-stage sampling design. First, a school-based cross-sectional survey was conducted in 2265 randomly selected school children from selected schools in areas known to be endemic for T. trichiura. After this, we conducted a nested case-control study wherein all children positive for T. trichiura (142) were matched to 148 negative controls based on age and village. A household survey was then conducted with all household members of cases and controls. In addition, a subsample of 116 children found to be infected with T. trichiura were followed up to assess the efficacy of albendazole at day 21 post-treatment. The predictors of presence of T. trichiura were investigated through multilevel logistic regression, considering clustering of infection.
    UNASSIGNED: Overall, 34.4% of the children were infected with at least one STH species; T. trichiura was the most common (28.3%), 89.1% of those with T. trichiura had light-intensity infections. The prevalence of T. trichiura was significantly higher in male children and was positively associated with younger age and number of people infected with T. trichiura in a household. The parasitological cure rate and egg reduction rate of T. trichiura were 35% and 51%, respectively. Other STHs identified were hookworm (9.6%) and Ascaris lumbricoides (5.7%).
    UNASSIGNED: T. trichiura remains a significant public health challenge in the study area with albendazole treatment efficacy against the parasite, remaining lower than the World Health Organization-recommended thresholds. Because of the observed focal transmission of T. trichiura in the current area, control efforts tailored to local conditions and targeting lower implementation units should be used to achieve optimal results on transmission.
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  • 文章类型: Journal Article
    蠕虫病仍然是流行地区的公共卫生问题。已经提出了各种药物来提高对抗蠕虫的功效。该研究旨在评估三种不同驱虫药组合治疗Trichuris感染的安全性和有效性。我们进行了一项随机评估盲临床试验,涉及2-17岁的T.trichiura儿童。参与者被随机分配到三个治疗组之一。在第一天和第三天,所有参与者服用阿苯达唑400毫克,第二天,阿苯达唑(A臂),甲苯咪唑500毫克(B臂),或吡喃酮125毫克/千克(臂C)。我们使用治疗后3周和6周的治愈率(CR)和减蛋率(ERR)评估治疗效果。治疗后3周,研究A组的ERR和CR最高[ERR=94%,与B组和C组相比,95%置信区间(CI):92-95;CR=71%;95%CI:58-81]。仅在B臂与A臂相比,ERR的降低是显著的(P值<0.001);在B和C臂中,ERR的降低是显著的(P值<0.001)。当比较A和B组(P值=1.00)和C组(P值=0.27)时,CR没有观察到统计学差异。在6周,在三个组中观察到ERR的减少,仅对C臂有意义,81%(95%CI:78-83)。在处理后3和6周之间观察到卵数的显著增加。所有治疗均安全,有轻度不良事件。阿苯达唑400mg/天(A组)对毛虫病的疗效最高。尽管如此,该治疗方案能够治愈一半的治疗个体,这突出了对控制T.trichiura传播的担忧.临床试验在ClinicalTrials.gov(NCT04326868)注册。
    Helminthiasis remains a public health issue in endemic areas. Various drugs have been proposed to improve efficacy against helminths. The study aimed to assess the safety and efficacy of three different anthelmintic combinations to treat Trichuris trichiura infections. We conducted a randomized assessors-blind clinical trial involving children aged 2-17 years with T. trichiura. Participants were randomly assigned to one of three treatment arms. On the first and third days, all participants got albendazole 400 mg, and on the second day, albendazole (arm A), mebendazole 500 mg (arm B), or pyrantel 125 mg/kg (arm C). We assessed treatment efficacy using the cure rate (CR) and egg reduction rate (ERR) at 3 and 6 weeks post-treatment. At 3 weeks post-treatment, ERR and CR were highest in study arm A [ERR = 94%, 95% confidence interval (CI): 92-95; CR = 71%; 95% CI: 58-81] compared to the B and C arms. Decrease in ERR was significant only for arm B versus arm A (P-value <0.001); decrease in ERR was significant for arms B and C (P-value <0.001). No statistical difference was observed in CR when comparing arms A and B (P-value =1.00) and C (P-value =0.27). At 6 weeks, a decrease in ERR was observed in three arms, significant only for arm C, 81% (95% CI: 78-83). A significant increase in egg counts was observed between 3 and 6 weeks post-treatment. All treatments were safe with mild adverse events. Albendazole 400 mg/day (arm A) showed the highest efficacy against trichuriasis. Nonetheless, this treatment regimen was able to cure half of the treated individuals highlighting concerns about controlling the transmission of T. trichiura.CLINICAL TRIALRegistered at ClinicalTrials.gov (NCT04326868).
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  • 文章类型: Case Reports
    毛虫病是一种被忽视的热带病,由毛虫引起,通过摄入受污染土壤中的胚胎卵传播,水,或食物。在非流行地区,Ttrichiura感染是非常罕见和零星的,通常在来自菲律宾等流行国家的移民中被诊断出来。鞭虫以人血为食,也会侵蚀结肠粘膜,从而引起炎症反应。以温和的形式,毛虫病可以是无症状的,通常是结肠镜检查的偶然诊断。大量感染的患者通常表现为腹痛,恶心,呕吐,重弹,慢性腹泻,缺铁性贫血,或发育迟缓。在结肠镜检查期间,可以用活检钳去除胸椎蠕虫;然而,大多数患者需要一个疗程的阿苯达唑,甲苯咪唑,或者伊维菌素.我们描述了Ttrichiura的独特病例,作为筛查结肠镜检查期间的偶然发现。使用活检钳检索鞭虫,并对患者进行阿苯达唑治疗。在结肠镜检查的时候,患者没有表现出与蠕虫感染相关的任何特定症状。
    Trichuriasis is a neglected tropical disease caused by Trichuris trichiura that spreads through the ingestion of embryonated eggs in contaminated soil, water, or food. In nonendemic areas, T trichiura infestation is very rare and sporadic and is often diagnosed in immigrants from endemic countries such as the Philippines. Whipworms feed on human blood and also erode the colonic mucosa, thereby evoking an inflammatory response. In milder forms, trichuriasis can be asymptomatic and often an incidental diagnosis on screening colonoscopy. Heavily infested patients usually present with abdominal pain, nausea, vomiting, tenesmus, chronic diarrhea, iron deficiency anemia, or stunted growth. T trichiura worms can be removed with biopsy forceps during a colonoscopy; however, most patients require a course of albendazole, mebendazole, or ivermectin. We describe a unique case of T trichiura as an incidental finding during a screening colonoscopy. The whipworms were retrieved using biopsy forceps and the patient was treated with albendazole. At the time of the colonoscopy, the patient did not exhibit any specific symptoms related to the worm infestation.
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  • 文章类型: Journal Article
    背景:土壤传播的蠕虫(STH)感染是流行地区的公共卫生问题。为了有效控制,该疾病的流行病学需要监测。这份报告评估了患病率,发病率,治疗后感染(PTI)率,以及加蓬两个农村地区STH感染的危险因素。
    方法:在这项纵向和前瞻性研究中,纳入了来自Lambaréné附近的6~30岁参与者,以及使用简单随机分组方法选择的家庭,并对参与者进行了为期6个月和9个月的连续两个随访.在每个后续阶段(FUP)的开始和结束时获得粪便样品。Kato-Katz技术用于检测STH卵,而Harada-Mori技术和共同培养用于在最多四个小时的收集时间内检测粪便中的幼虫。在研究的三个主要时间点确定患病率,在两个研究阶段评估发病率,PTI定义为治疗后9个月检测到的感染。
    结果:共纳入262名参与者。在6个月和9个月FUP的基线时,STH感染的总体患病率为42%(95CI:34-50)和44%(95CI:37-51)。分别。在每个评估时间点,Trichiura都是最普遍的物种。在6个月和9个月的随访中,STH的累积发生率为18%(95CI:12-27)和35%(95CI:27-43),分别,而发病率为41(95CI:28-55)和56(95CI:46-67)每100人年,分别。TrichiuraT.的9个月随访时的PTI率,钩虫,和蛔虫为58%(95CI:41-74),31%(95CI:11-59)和18%(95CI:5-40),分别。STH感染强度一般较轻。
    结论:在Lambaréné附近,STH感染的患病率中等,T.trichiura是最普遍的物种。我们的结果揭示了该疾病在人群中的快速传播,主要是在干预之后,特别是对于毛虫病,因此,呼吁在该领域全面实施世界卫生组织的建议。试验注册clinicaltrials.gov标识符NCT02769013。2016年4月21日注册,https://clinicaltrials.gov/study/NCT02769013。
    BACKGROUND: Soil-transmitted helminth (STH) infections are a public health concern in endemic areas. For efficient control, the epidemiology of the disease needs to be monitored. This report assesses the prevalence, incidence, post-treatment infection (PTI) rate, and risk factors for STH infections in two rural areas of Gabon.
    METHODS: In this longitudinal and prospective study, participants aged six to 30 years from the vicinity of Lambaréné and selected households using a simple randomization process were included and followed in two consecutive periods of six and nine months. Stool samples were obtained at the beginning and the end of each follow-up phase (FUP). The Kato-Katz technique was used for the detection of STH eggs, while the Harada-Mori technique and coproculture were used for the detection of larvae in stool processed within a maximum of four hours of collection. Prevalence was determined at the three main time points of the study, incidence was assessed during the two study phases, and PTI was defined as an infection detected nine months post-treatment.
    RESULTS: A total of 262 participants were included. The overall prevalence of STH infections was 42% (95%CI: 34-50) and 44% (95%CI: 37-51) at baseline for the six and nine month FUPs, respectively. Trichuris trichiura was the most prevalent species at each time point of assessment. The cumulative incidence of STH at the 6- and 9-month follow-ups was 18% (95%CI: 12-27) and 35% (95%CI: 27-43), respectively, while the incidence rates were 41 (95%CI: 28-55) and 56 (95%CI: 46-67) per 100 person-years, respectively. The PTI rates at the 9-month follow-up for T. trichiura, hookworm, and Ascaris lumbricoides were 58% (95%CI: 41-74), 31% (95%CI: 11-59) and 18% (95%CI: 5-40), respectively. The STH infection intensity was generally light.
    CONCLUSIONS: The prevalence level of STH infection is moderate in the vicinity of Lambaréné, with T. trichiura being the most prevalent species. Our results reveal a rapid spread of the disease in the population mainly following intervention, particularly for trichuriasis, and therefore call for the full implementation of the World Health Organization\'s recommendations in the area. Trial registration clinicaltrials.gov Identifier NCT02769013. Registered 21 April 2016, https://clinicaltrials.gov/study/NCT02769013.
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  • 文章类型: Journal Article
    从车内的安全来看,KnowsleySafari为游客提供了与圈养的橄榄狒狒的近距离接触。因为离开的车辆可能被狒狒凳污染,为解决公共卫生问题,进行了全面的协同检查。狒狒凳子是从车辆上获得的,和睡眠区,包括狒狒-车辆互动的视频分析。故意选择的4天采样期,可以对2662辆汽车进行比较检查,共检查了669个狒狒凳子(371个来自车辆,298个来自睡眠区)。根据我们的试点研究,一线诊断方法是:QUIK-CHEK快速诊断测试(RDT)(贾第鞭毛虫和隐孢子虫),Kato-Katz共镜(Trichuris)和木炭培养(Strongyloides)。约有13.9%的车辆被狒狒粪便污染。贾第鞭毛虫病的患病率为37.4%,而隐孢子虫病的患病率<0.01%,然而,通过质量控制共检没有粪便囊肿,同时低于预期的贾第虫特异性DNA水平,判定RDT结果具有误导性,严重高估了患病率。旋毛虫病患病率为48.0%,线虫病患病率为13.7%,英国Strongloidesfuelleborni的第一份报告。我们建议定期对殖民地进行驱虫药的全面管理,探索浇灌配方,此后,较小规模的指标调查就足够了。
    From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate.
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  • 文章类型: Journal Article
    仰光学童的粪便中发现了标准和大尺寸的Trichuristrichiura卵,2017-2019年缅甸流行病学调查和阿苯达唑大规模驱虫。标准大小的卵被鉴定为T.trichiura的卵,但是有必要排除属于毛虫的大型卵的可能性,一只狗鞭虫。我们进行了形态学和分子研究,以确定两种类型的毛虫卵的种类。从Kato-Katz粪便涂片(n=20)中分离出两种大小的单个卵,并使用23G注射针进行机械破坏。提取了核DNA,并在15个标准大小的卵和15个大大小的卵中对18SrRNA区域进行测序。标准大小鸡蛋的平均大小(T.trichiura)为55.2×26.1μm(范围:51.7-57.6×21.3-28.0μm;n=97),而大型卵的大小为69.3×32.0μm(范围:65.1-76.4×30.1-34.5μm;n=20),略小于已知的T.vulpis大小。关于标准大小的鸡蛋,18SrRNA核苷酸序列与存放在GenBank中的T.trichiura具有100%的同源性,与T.vulpis具有88.6-90.5%的同源性。关于大型鸡蛋,核苷酸序列与GenBank中的T.trichiura具有99.8-100%的同源性,与T.vulpis具有89.6-90.7%的同源性。Trichurisspp的标准和大型卵。在2017-2019年期间在缅甸发现的学童在形态和分子上被证实属于T.trichiura。卵从较小尺寸转变为较大尺寸可能是由于阿苯达唑的驱虫治疗。
    Standard- and large-sized eggs of Trichuris trichiura were found in the feces of schoolchildren in Yangon, Myanmar during epidemiological surveys and mass deworming with albendazole in 2017-2019. The standard-sized eggs were identified as those of T. trichiura, but it was necessary to exclude the possibility of the large-sized eggs belonging to Trichuris vulpis, a dog whipworm. We conducted morphological and molecular studies to determine the species of the 2 types of Trichuris eggs. Individual eggs of both sizes were isolated from Kato-Katz fecal smears (n=20) and mechanically destroyed using a 23G injection needle. Nuclear DNA was extracted, and the 18S rRNA region was sequenced in 15 standard-sized eggs and 15 large-sized eggs. The average size of standard-sized eggs (T. trichiura) was 55.2×26.1 μm (range: 51.7-57.6×21.3-28.0 μm; n=97), whereas the size of large-sized eggs was 69.3×32.0 μm (range: 65.1-76.4×30.1-34.5 μm; n=20), slightly smaller than the known size of T. vulpis. Regarding standard-sized eggs, the 18S rRNA nucleotide sequences exhibited 100% homology with T. trichiura deposited in GenBank and 88.6-90.5% homology with T. vulpis. Regarding large-sized eggs, the nucleotide sequences showed 99.8-100% homology with T. trichiura in GenBank and 89.6-90.7% homology with T. vulpis. Both standard- and large-sized eggs of Trichuris spp. found in Myanmar schoolchildren during 2017-2019 were morphologically and molecularly confirmed to belong to T. trichiura. The conversion of eggs from smaller to large sizes might be due to anthelmintic treatments with albendazole.
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  • 文章类型: Case Reports
    Trichuristrichiura通过粪便-口腔传播仅寄生于人类。在非流行地区,由于来自流行国家的移民人数不断增加,内窥镜识别的频率一直在增加.为了防止感染,重要的是要注意卫生条件,如土壤和水源。
    Trichuris trichiura parasitizes only humans through fecal-oral transmission. In non-endemic areas, the frequency of endoscopic identification has been increasing due to the increasing number of immigrants from endemic countries. To prevent infection, it is important to pay attention to sanitary conditions such as soil and water sources.
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  • 文章类型: Journal Article
    世界卫生组织(WHO)报告说,在撒哈拉以南非洲,全世界有超过15亿人感染了土壤传播的蠕虫(STH)。美利坚合众国,中国,和东亚。重度感染和多寄生虫与较高的发病率相关,并且患者对其他疾病的脆弱性增加。因此,准确的诊断,然后进行大规模治疗以控制发病率是必要的。STH诊断通常涉及对粪便样品中STH卵和幼虫的存在进行显微镜观察。此外,分子方法越来越多地用于监测和监测,因为它们显示出更高的灵敏度。它们区分钩虫种类的能力是优于Kato-Katz技术的优势。这篇综述讨论了用于STH检测的显微镜和各种分子工具的优点和局限性。
    World Health Organization (WHO) reported that over 1.5 billion people are infected by soil-transmitted helminths (STH) worldwide in sub-Saharan Africa, the United States of America, China, and East Asia. Heavy infections and polyparasitism are associated with higher morbidity rates, and the patients are exposed to increased vulnerability to other diseases. Therefore, accurate diagnosis followed by mass treatment for morbidity control is necessary.STH diagnosis commonly involves the microscopic observation of the presence of the STH eggs and larvae in the faecal samples. Furthermore, molecular approaches are increasingly utilised in monitoring and surveillance as they show higher sensitivity. Their capability to differentiate hookworm species is an advantage over the Kato-Katz technique. This review discusses the advantages and limitations of microscopy and various molecular tools used for STH detection.
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  • 文章类型: Systematic Review
    该荟萃分析旨在评估在DNA提取过程中添加打珠(BB)步骤以有效地从粪便样品中分离TrichurisTrichilaDNA以进行基于定量聚合酶链反应(qPCR)的诊断的效果。在分析中包括了基于qPCR的分子研究,比较了在从粪便样品提取DNA过程中包含打珠步骤和没有该步骤的提取。包括在社区环境中使用真实患者样本的研究。PubMed数据库和Google搜索引擎于2019年12月进行了搜索。使用诊断准确性研究质量评估-2清单评估偏倚和适用性的风险。将个体研究的赔率比(OR)组合以估计随机效应模型OR。从两篇已发表的原始文章中收集了总共六个独立的子研究。由于所进行研究的性质,将两项主要研究分为六个子研究是必不可少的。当在DNA提取期间使用BB时,总共192个样品中的128个(在所有研究中)是Trichiura的阳性,而当排除BB时是108/192。合并OR为1.66(95%置信区间:1.059~2.602)。虽然只有两篇文章被纳入研究,分析了六个独家的个体子研究。研究人群中蠕虫背景患病率的固有差异可能会影响qPCR的敏感性。发现在DNA提取过程中包含BB步骤显着提高了测试的灵敏度。这项研究没有在任何数据库中注册。
    This meta-analysis was designed to assess the effect of the addition of a bead-beating (BB) step during DNA extraction to effectively isolate Trichuris trichiura DNA from stool samples for quantitative polymerase chain reaction (qPCR)-based diagnosis. qPCR-based molecular studies comparing the inclusion of a bead-beating step during the DNA extraction from stool samples with extraction without the step were included in the analysis. Studies using real patient samples in community settings were included. The PubMed database and Google search engine were searched in December 2019. Risk of bias and applicability were assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 checklist. Odds ratios (ORs) for individual studies were combined to estimate the random effects model OR. A total of six independent sub-studies were gathered from two published original articles. The division of the two major studies into six sub-studies was indispensable due to the nature of the study carried out. 128 of the total 192 samples (in all studies) were positive for T. trichiura when BB was used during DNA extraction compared to 108/192 when BB was excluded. The combined OR was 1.66 (95% confidence interval: 1.059 to 2.602). Though only two articles were included in the study, six exclusive individual sub-studies were analyzed. Inherent differences in the background prevalence of helminths in the study population could impact the sensitivity of qPCR. It was found that the inclusion of the BB step during DNA extraction significantly increased the sensitivity of the test. This study was not registered in any database.
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