Mas Alicia, Martínez-Rodrigo Abel, Orden José Antonio, Molina Ricardo, Jiménez Maribel, Jiménez María Ángeles, Carrión Javier, Domínguez-Bernal Gustavo
INMIVET, Departamento de Sanidad Animal, Facultad de Veterinaria, Universidad Complutense de Madrid, Madrid, Spain.
Laboratorio de Entomología Médica, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Spain.
Transbound Emerg Dis. 2021 Mar;68(2):704-714. doi: 10.1111/tbed.13733. Epub 2020 Aug 1.
Recent anthropic activity related to the construction of the Bosquesur Green Park in a large urban setting in Madrid (Spain) has resulted in the largest reported community outbreak of human leishmaniosis in Europe. Previous phylogenetic and molecular-typing studies of parasite isolates have implicated the Leishmania infantum ITS-Lombardi genotype in this outbreak. In an unusual scenario, visceral leishmaniosis (VL) is affecting a significant number of individuals, suggesting that an increase in parasite virulence has occurred. In this work, using an in vivo BALB/c model of VL, we aimed to investigate the properties of emergent virulence of the L. infantum POL2FL7 and BOS1FL1 isolates obtained from Phlebotomus perniciosus collected in the outbreak area and compare them with those of the well-characterized strain BCN150 MON-1 isolated from a dog. The P. perniciosus specimens were collected during an entomological survey conducted in the transmission season of 2012. We observed a range of virulence phenotypes from moderately to highly aggressive after 5 weeks of infection. IV challenge of mice with outbreak isolates from sand flies induced higher splenic and liver parasite burdens, higher serological titres of specific anti-Leishmania antibodies and impaired capacities to control infection, as revealed by the arginine metabolism and low ratios of Th1/Th2 cytokine profiles analysed, compared with the corresponding measures evaluated in mice infected with the BCN150 strain. The BOS1FL1 isolate showed the highest degree of virulence among the isolates, superior to that of POL2FL7, as evidenced by the analysed biomarkers and the histopathological severity of liver lesions. These results provide insight into how L. infantum isolates from sand flies collected in the outbreak area have been able to affect not only immunosuppressed patients but also middle-aged people with normal immunocompetence in the largest human VL outbreak in Europe.
近期，在西班牙马德里一个大型城市环境中建设博斯克苏尔绿色公园的人类活动，导致了欧洲报告的最大规模人类利什曼病社区疫情。此前对寄生虫分离株的系统发育和分子分型研究表明，此次疫情涉及婴儿利什曼原虫ITS-隆巴迪基因型。在一个不同寻常的情况下，内脏利什曼病（VL）正在影响大量个体，这表明寄生虫毒力有所增加。在这项研究中，我们使用VL的体内BALB/c模型，旨在研究从疫情爆发地区采集的嗜人按蚊中获得的婴儿利什曼原虫POL2FL7和BOS1FL1分离株的新出现毒力特性，并将它们与从一只狗身上分离出的特征明确的BCN150 MON-1菌株的特性进行比较。嗜人按蚊标本是在2012年传播季节进行的昆虫学调查期间采集的。感染5周后，我们观察到一系列从中度到高度侵袭性的毒力表型。与感染BCN150菌株的小鼠所评估的相应指标相比，用来自白蛉的疫情分离株对小鼠进行静脉内攻击，导致脾脏和肝脏寄生虫负荷更高、特异性抗利什曼原虫抗体的血清学滴度更高，以及通过精氨酸代谢和分析的Th1/Th2细胞因子谱低比率所揭示的控制感染能力受损。BOS1FL1分离株在分离株中显示出最高程度的毒力，优于POL2FL7，分析的生物标志物和肝脏病变的组织病理学严重程度证明了这一点。这些结果有助于深入了解在欧洲最大规模的人类VL疫情中，从疫情爆发地区采集的白蛉中的婴儿利什曼原虫分离株如何不仅能够影响免疫抑制患者，还能影响免疫功能正常的中年人。
