| 一般情况 | |
|---|---|
| 品种：威尔士柯基犬 |
| 年龄：15个月 | |
| 性别：雌 | |
| 是否绝育：是 | |
| 诊断：管圆线虫病 | |
01 主诉及病史
因中度再生障碍性贫血和呼吸困难就诊。
在过去3个月中逐渐出现运动不耐受、气喘、体重减轻和嗜睡等症状。无咳嗽。疫苗接种情况良好，从未出过挪威。
02 检查
体况评分3/9，肌肉轻度萎缩，粘膜苍白，心动过速，呼吸急促，混合呼吸模式轻度增强。
中度到明显的再生障碍性贫血（PCV 19% [35-55]），碱性凝集反应阴性，血涂片未发现球形细胞或鬼影细胞。除了C反应蛋白中度升高（45 mg/L [0-15]）外，血生化无异常。尿液分析无异常。
活化部分凝血活酶时间（aPTT）和凝血酶原时间（PT）延长（aPTT 158.0秒 [72.0-102]；PT 18.0秒 [11.0-17.0]）。血栓弹力图显示中位角较低（37.7 mm [42.9-67.9]），由于技术故障，未获得LY30和LY60结果。
胸片显示弥漫至斑块状、相对对称的肺间质形态，伴有多灶或周围肺泡成分和轻度支气管形态。尾部外周肺动脉中度扩张。
腹部超声显示脾脏呈弥漫性异质回声。其他检查无异常。进行了脾脏细针穿刺，无并发症。细胞学检查符合髓外造血和反应性增生。
经胸超声心动图显示，与左心室相比，右心室轻度扩张（下图）。
室间隔平坦（下图）。右心房轻度扩张。与主动脉相比，主肺动脉扩张，右肺动脉分支扩张。肺动脉速度曲线显示速度正常，但加速时间短于减速时间。
彩色血流多普勒未显示肺动脉瓣关闭不全。通过右胸骨旁切面和左心尖切面的彩色血流多普勒检查可以看到三尖瓣反流，但由于无法获得清晰的反流轮廓，因此无法通过频谱多普勒测量反流速度。总之，超声心动图检查结果符合重度肺动脉高压。
对血清进行的犬心丝虫抗原检测呈阴性。用Baermann法对单份粪便样本（25 g）进行检查，发现了许多幼虫，长度约为320微米，尾端呈锥形，有褶皱和背棘（下图）。根据形态特征，这些幼虫被确定为管圆线虫A. vasorum的第一阶段幼虫（L1）。对血清样本进行确证检验，结果呈强阳性。
↑ (A)光镜下观察到的A. vasorum一级幼虫（L1）。(B）放大图可见其独特的扭结尾部。
从5-10只幼虫身上分离DNA，并针对ITS-2基因进行了PCR检测。阳性PCR产物（218碱基对）纯化后进行了双链Sanger测序。结果发现与来自奥地利的A. vasorum的序列相似度最高（98.28%）。
03 治疗
输注充盈红细胞、使用FIO2 40%的氧气笼、使用芬苯达唑（51 mg/kg q24h PO）两周疗程、吡虫啉/莫昔克丁（250 mg/62.5 mg [爱沃克]）局部外用、西地那非（0.45 mg/kg q12h PO）一周疗程。2周和4周后再次使用吡虫啉/莫昔克丁治疗。
04 预后
24小时后，呼吸急促、厌食和嗜睡症状明显改善。
36小时后出院。
出院1周后，主人称运动不耐受的情况有所改善。复查发现贫血症状已缓解（PCV 36%），超声心动图评估显示心脏形态有所改善，但右心室仍有轻度偏心性肥厚，室间隔没有变平，肺动脉也没有扩张。西地那非治疗终止。
出院1个月后，超声心动图检查（下图）显示右心室主观上正常，右心室和右心房面积在正常区间内。右肺动脉直径小于治疗前，扩张指数正常。没有三尖瓣反流迹象。肺动脉与主动脉比率正常，肺加速与射血时间比率正常。
05 讨论
脉管圆线虫（Angiostrongylus vasorum，A. vasorum），又称法国心丝虫，是一种偏口线虫，几种食肉动物，尤其犬，是它的最终宿主[1]。犬感染这种寄生虫后通常会出现呼吸道症状、止血功能障碍或神经症状[2-5]。
A. vasorum在欧洲的传播被描述为“爆炸性”传播[1]，并提出了与这种传播有关的因素（如气候变化、犬活动增加、腹足纲动物入侵、狐狸城市化）[1]。
挪威是欧洲少数几个没有确诊家犬感染A. vasorum病例的国家之一。在斯堪的纳维亚半岛，犬和食肉动物中的A. vasorum流行病学情况在不同国家呈现出不同的模式。
丹麦报告的感染率很高，而且最近还在蔓延，特别是在某些地区，这证实了除赤狐外，其他野生食肉动物（浣熊、水貂和臭鼬）也可能成为家畜心肺线虫的贮藏地。与之前的研究相比，丹麦大多数地区的赤狐体内A. vasorum的流行率都有所上升，新西兰北部等地区的流行率从1993年的48.7%上升到2002年的90%[6, 7]。
在瑞典，A. vasorum的存在已得到证实，但报告的狗和狐狸中的流行率相对较低。在瑞典的一次全国性血清流行病学调查中，0.10%的狗抗原和抗体均呈阳性，而阳性狗粪便样本和尸检A. vasorum阳性狐狸的年流行率分别为0.3-0.9%和0.0-1.4%不等[7]。
与挪威一样，芬兰的A. vasorum地理分布情况不详，但在2019年有3只狗感染了A. vasorum的报告[8]。没有犬感染报告的国家大多位于欧洲东部边缘，如白俄罗斯、拉脱维亚、立陶宛和乌克兰[1]；这可能反映出缺乏检测，而不是没有寄生虫。
在挪威，2016年首次报告了两只狐狸感染A. vasorum的病例，两只狐狸地理位置相距甚远（约460公里）。这是一项监测计划的一部分，该计划通过Baermann分析法检测了234只狐狸的粪便样本，并通过PCR和测序验证了阳性样本[9]。
后来的监测报告称，2018年67份狐狸血液样本中有4份检测到了A. vasorum抗原[10]，2019年300份狐狸血清样本中有8份检测到了A. vasorum抗原[11]。
虽然有零星报告称挪威犬感染了A. vasorum，但这些报告都与前往流行地区的犬有关。然而2017年和2018年期间对挪威进口犬寄生虫的年度调查发现，在2017年进口的72只接受检测的犬中[12]或在2018年进口的41只犬中[13]，均未发现A. vasorum感染病例。
肺动脉高压（Pulmonary hypertension，PH）常见于管圆线虫病犬[4, 14-17]，但缺乏评估心肺变化缓解情况的纵向研究。本病例报告描述了首例未离开挪威的犬感染A. vasorum的病例，重点介绍了临床表现和诊断检查。
本病例的临床症状也可部分归因于PH的存在。在自然感染A. vasorum的狗中，有临床症状明显的PH[4]，但在实验接种的狗中，2/6的狗出现轻度PH[15]。造成这种差异的原因可能是寄生虫免疫反应的个体差异、血栓形成的个体易感性和/或血管反应性以及肺内动静脉吻合口的潜在募集[38, 39]。
之前报道的管圆线虫病和PH的肺部结果与本病例胸片相似[39-41]。不过，本病例胸片上的一个显著发现是尾部肺动脉增大。这一发现更常见于犬心丝虫病[41]，但也可能见于管圆线虫病[41,42]。
因此，混合型肺部病变伴有外周肺泡成分，同时伴有血管变化，应提醒临床医生将管圆线虫病作为犬心丝虫感染的一个重要鉴别诊断，在没有管圆线虫病流行的国家也是如此。
文献来源：Robbestad J, Jiménez-Meléndez A, Robertson LJ, Vatne LI, Hauback MN, Nerhagen S. First case of autochthonous Angiostrongylus vasorum infection in a Norwegian dog. Acta Vet Scand. 2024 Sep 2;66(1):41.
参考文献
1. Morgan ER, Modry D, Paredes-Esquivel C, Foronda P, Traversa D. Angiostrongylosis in Animals and Humans in Europe. Pathogens. 2021;25:1236.
2. Schelling GC, Greene CE, Prestwood AK, Tsang CV. Coagulation abnormalities associated with acute Angiostrongylusvasorum in dogs. Am J Vet Res. 1986;47:2669–73.
3. Gredahl H, Willesen JL, Jensen HE, Nielsen OL, Kristensen AT, Koch J, et al. Acute neurological signs as the predominant clinical manifestation in four dogs with Angiostrongylusvasorum infections in Denmark. Acta Vet Scand. 2011;53:43.
4. Borgeat K, Sudunagunta S, Kaye B, Stern J, Fuentes LV, Connoly DJ. Retrospective evaluation of moderate-to-severe pulmonary hypertension in dogs naturally infected with Angiostrongylusvasorum. J Small Anim Pract. 2015;56:196–202.
5. Koch J, Willesen JL. Canine pulmonary angiostrongylosis: an update. Vet J. 2009;179:348–9.
6. Lemming L, Jørgensen AC, Nielsen Buxbom L, Nielsen ST, Mejer H, Chriél M, et al. Cardiopulmonary nematodes of wild carnivores from Denmark: do they serve as reservoir hosts for infections in domestic animals? Int J Parasitol Wildl. 2020;15(13):90–7.
7. Grandi G, Lind EO, Schaper R, Ågren E, Schnyder M. Canine angiostrongylosis in Sweden: a nationwide seroepidemiological survey by enzyme-linked immunosorbent assays and a summary of five-year diagnostic activity (2011–2015). Acta Vet Scand. 2017;59:85.
8. Tiškina V, Lindqvist EL, Blomqvist AC, Orav M, Stensvold RC, Jokelainen P. Autochthonous Angiostrongylusvasorum in Finland. Vet Rec Open. 2019. 10.1136/vetreco-2018-000314.
9. Enemark HL, Hansen H, Madslien K, Jonsson ME, Henriksen K, Mohammad SN, et al. The surveillance programme for Angiostrongylus vasorum in red foxes (Vulpes vulpes) in Norway 2016. 2018.
10. Hamnes IS, Enemark HL, Henriksen K, Madslien ELK, Er C. The surveillance programme for Angiostrongylus vasorum in red foxes (Vulpes vulpes) in Norway 2018. 2019.
11. Hamnes IS, Enemark HL, Henriksen K, Madslien ELK, Er C. The surveillance programme for Angiostrongylus vasorum in red foxes (Vulpes vulpes) in Norway 2019. 2020.
12. Jørgensen HJ, Hamnes IS, Nordstoga AB, Klevar S. The surveillance programme for imported dogs in Norway in 2017. 2018.
13. Nordstoga AB, Hamnes IS, Klevar S, Jørgensen HJ. The surveillance programme for imported dogs in Norway in 2018. 2019.
14. Audrey PN, Chetboul V, Tessier-Vetzel D, Sampedrano CC, Aletti E, Pouchelon J-L. Severe pulmonary arterial hypertension due to Angiostrongylosusvasorum in a dog. Can Vet J. 2006;47:792–5.
15. Matos JM, Schnyder M, Bektas R, Mariano M, Kutter A, Jenni S, et al. Recruitment of arteriovenous pulmonary shunts may attenuate the development of pulmonary hypertension in dogs experimentally infected with Angiostrongylusvasorum. J Vet Cardiol. 2012;14:313–22.
16. Adams DS, Marolf AJ, Valdés-Martínez A, Randall EK, Bachand AM. Associations between thoracic radiographic changes and severity of pulmonary arterial hypertension diagnosed in 60 dogs via Doppler echocardiography: a retrospective study. Vet Radiol Ultrasound. 2017;58:454–62.
17. Estèves I, Tessier D, Dandrieuz J, Polack B, Carlos C, Boulanger V, et al. Reversible pulmonary hypertension presenting simultaneously with an atrial septal defect and angiostrongylosis in a dog. J Small Anim Pract. 2004;45:206–9.
18. Wiinberg B, Kristensen AT. Thromboelastography in veterinary medicine. Semin Thromb Hemost. 2010;36:747–56.
19. Thomas WP, Gaber CE, Jacobs GJ, Kaplan PM, Lombard CW, Moise NS, et al. Recommendations for standards in transthoracic two-dimensional echocardiography in the dog and cat. echocardiography committee of the specialty of cardiology, American college of veterinary internal medicine. J Vet Intern Med. 1993;7:247–52.
20. Vezzosi T, Domenech O, Costa G, Marchesotte F, Venco L, Zini E, et al. Echocardiographic evaluation of the right ventricular dimension and systolic function in dogs with pulmonary hypertension. J Vet Intern Med. 2018;32:1541–8.
21. Vezzosi T, Domenech O, Iacona M, Marcesotti F, Zini E, Venco L, et al. Echocardiographic evaluation of the right atrial area index in dogs with pulmonary hypertension. J Vet Intern Med. 2018;32:42–7.
22. Feldhütter EK, Domenech O, Vezzosi T, Tognetti R, Eberhard J, Friederich J, et al. Right ventricular size and function evaluated by various echocardiographic indices in dogs with pulmonary hypertension. J Vet Intern Med. 2022;36:1882–91.
23. Visser LC, Im MK, Johnson LR, Stern JA. Diagnostic value of right pulmonary artery distensibility index in dogs with pulmonary hypertension: comparison with doppler echocardiographic estimates of pulmonary arterial pressure. J Vet Intern Med. 2016;30:543–52.
24. Schober K, Baade H. Doppler echocardiographic prediction of pulmonary hypertension in West Highland White Terriers with chronic pulmonary disease. J Vet Intern Med. 2006;20:912–20.
25. Reinero C, Visser LC, Kellihan HB, Masseau I, Rozanski E, Clercx C, et al. ACVIM consensus statement guidelines for the diagnosis, classification, treatment, and monitoring of pulmonary hypertension in dogs. J Vet Intern Med. 2020;34:549–73.
26. Al-Sabi MN, Deplazes P, Webster P, Willesen JL, Davidson RK, Kapel CMO. PCR detection of Angiostrongylusvasorum in faecal samples of dogs and foxes. Parasitol Res. 2010;107:135–40.
27. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser. 1999;41:95–8.
28. Penagos-Tabares F, Groß KM, Hirzmann J, Hoos C, Lange MK, Taubert A, et al. Occurrence of canine and feline lungworms in Arion vulgaris in a park of Vienna: first report of autochthonous Angiostrongylusvasorum, Aelurostrongylusabstrusus and Troglostrongylusbrevior in Austria. Parasitol Res. 2020;119:327–31.
29. Cury MC, Lima WS, Guimarães MP, Carvalho MG. Hematological and coagulation profiles in dogs experimentally infected with Angiostrongylusvasorum. Vet Parasitol. 2002;104:139–49.
30. Adamantos S, Waters S, Boag A. Coagulation status in dogs with naturally occurring Angiostrongylus vasorum infection. J Small Animal Pract. 2015;56:487–90.
31. Sigrist NE, Tritten L, Kümmerle-Fraune C, Hofer-Inteeworn N, Schefer RJ, Schnyder M, et al. Coagulation status in dogs naturally infected with Angiostrongylusvasorum. Pathogens. 2021;10:1077.
32. Sigrist NE, Kümmerle-Fraune C, Hofer-Inteeworn N, Schefer RJ, Schnyder M, Kutter APN. Hyperfibrinolysis and Hypofibrinogenemia diagnosed with rotational thromboelastometry in dogs naturally infected with Angiostrongylusvasorum. J Vet Intern Med. 2017;31:1091–9.
33. Ramsey IK, Littlewood JD, Dunn JK, Herrtage ME. Role of chronic disseminated intravascular coagulation in a case of canine angiostrongylosis. Vet Rec. 1996;138:360–3.
34. Cole L, Barfiled D, Chan DL, Cortellini S. Use of a modified thromboelastography assay for the detection of hyperfibrinolysis in a dog infected with Angiostrongylusvasorum. Vet Rec. 2018. 10.1136/vetreccr-2017-000554.
35. Kranjc A, Schnyder M, Dennler M, Fahrion A, Makara M, Ossent P, et al. Pulmonary artery thrombosis in experimental Angiostrongylus vasorum infection does not result in pulmonary hypertension and echocardiographic right ventricular changes. J Vet Intern Med. 2010;24:855–62.
36. Cesare AD, Traversa D, Manzocchi S, Meloni S, Grillotti E, Auriemma E, et al. Elusive Angiostrongylus vasorum infections. Parasit Vectors. 2015;8:438.
37. Gallagher B, Brennan SF, Zarelli M, Mooney CT. Geographical, clinical, clinicopathological and radiographic features of canine angiostrongylosis in Irish dogs: a retrospective study. Ir Vet J. 2012;65:5.
38. Khan M, Bordes SJ, Murray IV, Sharma S. Physiology, pulmonary vasoconstriction. Treasure Island (FL): StatPearls Publishing; 2023.
39. Novo Matos J, Malbon A, Dennler M, Glaus T. Intrapulmonary arteriovenous anastomoses in dogs with severe Angiostrongylusvasorum infection: clinical, radiographic, and echocardiographic evaluation. J Vet Cardiol. 2016;18:110–24.
40. Boag AK, Lamb CR, Chapman PS, Boswood A. Radiographic findings in 16 dogs infected with Angiostrongylusvasorum. Vet Record. 2004;154:426–30.
41. Coia ME, Hammond G, Chan D, Drees R, Walker D, Murtagh K, et al. Retrospective evaluation of thoracic computed tomography findings in dogs naturally infected by Angiostrongylusvasorum. Vet Radiol Ultrasound. 2017;58:524–34.
42. Glaus T, Schnyder M, Dennler M, Tschuor F, Wenger M, Sieber-Ruckstuhl N. Natural infection with Angiostrongylusvasorum: characterisation of 3 dogs with pulmonary hypertension. Schweiz Arch Tierheilkd. 2010;152:331–8.