Drzewnioková Petra, Brian Irene, Mancin Marzia, Fortin Andrea, Gourlaouen Morgane, Angot Angélique, Niang Mamadou, Dah Isaac, Berete Kouramoudou, Diakite Adama, Lo Fatou Tall, Meseko Clement, Go-Maro Emilie, D'Amico Valeria, Valastro Viviana, Soumare Baba, De Benedictis Paola, Monne Isabella, Panzarin Valentina
Istituto Zooprofilattico Sperimentale delle Venezie, Legnaro, Padua, Italy.
Department of Public Health, University of Pavia, Pavia, Italy.
J Clin Microbiol. 2025 Aug 13;63(8):e0008025. doi: 10.1128/jcm.00080-25. Epub 2025 Jul 1.
Molecular methods are widely accepted as gold-standard techniques for the laboratory diagnosis of most human and animal pathogens. However, most molecular protocols rely on reagents that need to be transported and stored at a freezing temperature, a requirement that might affect their reliability in areas where the cold chain cannot be guaranteed. Over the years, several lyophilized molecular products have been marketed to circumvent this issue. We therefore evaluated the feasibility of replacing liquid reagents with freeze-dried formulations for the molecular diagnosis of avian influenza (AIV) and rabies (RABV) viruses, two priority zoonotic pathogens widely spread in Sub-Saharan Africa. Among six different commercial freeze-dried kits, we selected one reagent due to its easy-to-use features, single-reaction format, and preliminary performance assessment. Through a more in-depth evaluation, we determined its analytical and diagnostic performance and formulation stability and obtained results comparable to those of standard liquid master mixes. However, for the detection of divergent lyssaviruses, the lyophilized reagent's sensitivity was affected by suboptimal complementarity between the oligonucleotides and target sequences. Finally, a multi-site evaluation in four veterinary diagnostic laboratories located in Sub-Saharan Africa demonstrated the successful deployment of AIV and RABV assays utilizing the freeze-dried reagent, which can interchangeably replace liquid qRT-PCR/RT-PCR kits. Altogether, our results indicate that the investigated lyophilized master mix represents a valid alternative to liquid reagents for the molecular diagnosis of avian influenza and rabies and has the potential for broader applications to other relevant infectious diseases upon proper validation.IMPORTANCEMolecular diagnostic protocols rely on reagents that need to be transported and stored at freezing temperatures. Meeting this requirement can be challenging in areas where the maintenance of the cold chain is not guaranteed, such as in Sub-Saharan Africa. Our study aimed to assess the feasibility of using lyophilized reagents as a replacement for liquid reagents in the molecular diagnosis of two widespread zoonotic pathogens in Sub-Saharan Africa, namely, avian influenza and rabies. To accomplish this, we selected a commercially available lyophilized reagent based on its format and performance characteristics. We conducted a laboratory validation to assess the use of the lyophilized reagent throughout the entire diagnostic process. We also conducted a reproducibility test involving African laboratories as potential end-users. Our findings confirm that the lyophilized reagent can replace traditional liquid reagents to diagnose rabies and avian influenza and suggest its possible use for a wider range of infectious diseases after undergoing appropriate validation.
分子方法被广泛认为是大多数人类和动物病原体实验室诊断的金标准技术。然而,大多数分子检测方案依赖于需要在冷冻温度下运输和储存的试剂,在无法保证冷链的地区,这一要求可能会影响其可靠性。多年来,已有几种冻干分子产品上市以解决这一问题。因此,我们评估了用冻干制剂替代液体试剂用于禽流感(AIV)和狂犬病(RABV)病毒分子诊断的可行性,这两种人畜共患病原体是在撒哈拉以南非洲广泛传播的重点病原体。在六种不同的商用冻干试剂盒中,我们选择了一种试剂,因其使用方便、单反应形式和初步性能评估。通过更深入的评估,我们确定了其分析和诊断性能以及制剂稳定性,获得了与标准液体预混液相当的结果。然而,对于检测不同的狂犬病病毒,冻干试剂的灵敏度受到寡核苷酸与靶序列之间互补性欠佳的影响。最后,在位于撒哈拉以南非洲的四个兽医诊断实验室进行的多地点评估表明,利用冻干试剂成功开展了禽流感和狂犬病检测,该试剂可互换替代液体qRT-PCR/RT-PCR试剂盒。总之,我们的结果表明,所研究的冻干预混液是禽流感和狂犬病分子诊断中液体试剂的有效替代品,经过适当验证后有可能更广泛地应用于其他相关传染病。
重要性
分子诊断方案依赖于需要在冷冻温度下运输和储存的试剂。在无法保证冷链的地区,如撒哈拉以南非洲,满足这一要求可能具有挑战性。我们的研究旨在评估在撒哈拉以南非洲两种广泛传播的人畜共患病原体,即禽流感和狂犬病的分子诊断中,使用冻干试剂替代液体试剂的可行性。为实现这一目标,我们根据其形式和性能特征选择了一种市售冻干试剂。我们进行了实验室验证,以评估冻干试剂在整个诊断过程中的使用情况。我们还进行了一项可重复性测试,将非洲实验室作为潜在的最终用户。我们的研究结果证实,冻干试剂可以替代传统液体试剂来诊断狂犬病和禽流感,并表明经过适当验证后,其可能用于更广泛的传染病诊断。