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Dirofilaria repens immitis patogeneza si clinic 2

Dirofilaria repens immitis patogeneza si clinic 2



Simpozion Medical CYF Medical Diagnosticul Dirofilariozei

Simpozion Medical CYF Medical Diagnosticul Dirofilariozei
cyfmedical@gmail.com , pentru diagnostic metode de diagnostic si teste sunati la 0723318308.



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    Dirofilaria repens immitis patogeneza si clinic 2 Dirofilaria repens immitis patogeneza si clinic 2 Presentation Transcript

    • Dirofilaria infections in animals and humans Pathogenesis and clinical presentation: Dirofilaria immitis versus Dirofilaria repens  Claudio Genchi, Med Vet, PhD, EVPC Dipl Dept of Veterinary Science and Public Health, Università degli Studi of Milano Bucharest, June 14th, 2012
    • In spite of his denomination [heartworm disease] is a respiratory [pulmonary] disease In dogs, the heart is usually involved in the late stage of the disease
    • Host response to HW infection Cat: susceptible but resisting host; usually not microfilaraemic unpredictable Dog: usually microfilaraemic reservoir predictable disease
    • • Chronic disease • Sometime acute phases in the late stage of the infection • Clinical picture very typical • Acute symptoms • Sometime chronic disease • No typical symptoms
    • No lesions/symptoms for years Inflammatory pulmonary disease Arterial pulmonary disease (pulmonary hypertension, “cor pulmonale”) right heart congestive failure DOG Pathogenesis
    • Pulmonar disease Vascular disease Parenchymal disease Cor polmonale
    • Vascular disease • proliferative endarteritis • thrombosis
    • 1995 Wolbachia pipiens is a Gram-negative bacterium belonging to rickettesiales
    • Tetracycline in drinking water (0.3%) prevents infection by B. pahangi and L. sigmodontis, but not by A. vitae, in gerbils 1971: Wolbachia and the antifilarial properties of tetracycline. An untold story Prompted by a serious outbreak of staphylococcal dermatitis affecting the filarial infected and non-infected Mongolian jirds, in 1971 J.W. McCall observed that tetracycline used in treating the condition had a prophylactic affect against Brugia pahangi and Litomosoides sigmodontis but not against Acanthocheilonema viteae. The results were presented at the 48th Annual Meeting of the American Society of Parasitologists (25-29 June 1973), but none of this data was published until 10 years later. The following studies showed that B. pahangi and L. sigmondis arer Wolbachia infected while A. vieae is an uninfected species.
    • What we learned in the ‘90s 4. Wolbachia is present in most filarial nematodes, with a few exceptions in non pathogenic species such as Acantocheilonema vitae Wolbachia pipientis an “old/new” story
    • Onchocerca volvulus Onchocerca ochengi Onchocerca gutturosa Onchocerca gibsoni Thelazia lacrimalis Dirofilaria repens Dirofilaria immitis Wuchereria bancrofti Brugia pahangi Brugia malayi Litomosoides sigmodontis Acanthocheilonema viteae 93 100 95 65 100 61 100 58 68 100 100 100 100 73 64 100 100 There is a consistency of filaria/Wolbachia phylogenies Filaria phylogeny Wolbachia phylogeny Modified from Casiraghi et al. 2001, Parasitology
    • Electron micrograph of an embryo of D. immitis containing two wolbachiae Immunohistochemical staining of W. pipientis in D. immitis using Ab against WSP Wolbachia is a widespread intracellular symbiont of filarial nematodes and arthropods
    • Wolbachia pipientis: what we know today Wolbachia is necessary for the host nematode 100% prevalence in infected species (lateral chords male and females/reproductive tract females/larvae) whole branches of filarial trees consist of infected species consistency of host/Wolbachia phylogenies vertical transmission
    • Wolbachia pipientis: what we know today Tetracycline treatment of filarial-infected hosts inhibits: embryogenesis development of L3-adult microfilarial production long term survival of adults
    • Antibiotic treatments are effective both on Wolbachia and on filarial nematodes development and embryogenesis, causing prophylactic effects and infertility of adult females (Genchi et al., 1998; Casiraghi et al. 2002)
    • Effects of antibiotic treatment on D. immitis embryogenesis From Sacchi et al. 2003, Parassitologia control treated treated
    •  Inflammation  Cytokine pattern and polarization of the immune response  Adverse reaction to chemotherapy  Desensitization of innate immunity  Defence against host response (e.g. through catalase activity)  the release of bacteria has been shown to be associated with the up-regulation of pro-inflammatory cytokines, neutrophil recruitment and an increase in aspecific immunoglobulins There is an overall consistency of data indicating that Wolbachia plays an important role in the pathogenesis of filarial disease throughout
    •  Adverse reactions to filaricidal therapy (ivermectin, DEC) are associated with Wolbachia and/or its DNA in the bloodstream and peak levels of Wolbachia correlate with levels of pro-inflammatory cytokines. Furthermore, a major surface protein of Wolbachia (WSP) from D. immitis has been shown to provoke chemiokinesis and IL-8 production in canine neutrophils in vitro. There is an overall consistency of data indicating that Wolbachia plays an important role in the pathogenesis of filarial disease throughout
    • The last two points (desensitization of innate immunity and defence against host response) open the question of the biological role of Wolbachia in filarial nematodes: Wolbachia “manipulates” the immune response, thus allowing the long-term survival of the filariae in immuno-competent hosts.
    • then … Dirofilaria/Wolbachia symbiosis is friendly for the parasite but is quite a foe for the host
    • Proliferative endarteritis: lesions are progressively worsening during the infection and when worms are dying D. immitis in an asymptomatic dog: the endothelium has no evident damages Proliferative endarteritis in a dog death for thromboembolism
    • Thrombosis The thrombosis is a consequence of the platelet activation on the sub-epithelial tissues caused by pro- and inflammatory products released by the worms (Wolbachia endosymbionts) after spontaneous or pharmacological death
    • Spontaneous thromboembolism
    • Parenchymal disease • Alveolar damage • Eosinophilic pneumonia [very severe in cats]
    • … as a consequence the heart disease • increase of pulmonal resistance • cor polmonale • right heart congestive failure LV RV To note, the right ventricle, as a consequence of its anatomical structure (pocket cling to left ventricle), is adaptable to volume overloading but not to pressure overloading
    • Reduction of vascular stream (obstruction of small arteries and capillaries) + loss of wall elasticity (severe arteritis) Pulmonar hypertension Increase of the post-charge
    • Post-charge overloading Cor pulmonale (recruitment of collateral vessels) right heart congestive failure
    • Microfilarial pathology Mfs can embolise in several organs, as the kidney causing glomerulonephritis complicate by the deposition of Ag/Ab complexes.
    • Acute on chronic Chronic respiratory disease caval syndrome thromboembolism pneumothorax Clinical Presentation
    • Clinical Presentation no symptoms for years unless exaggerated worm burden and/or strenuous exercise coughing lipothymias abdominal effusion
    • Apparently good health [fat], but ascites [abdominal effusion] Clinical Presentation
    • right heart congestive failure ascites weight loss disorexia atrial fibrillation (> 15 kg bw)
    • Pneumothorax
    • Caval Syndrome • Due to sudden rising of pulmonary pressure (thromboembolism) and/or cardiac output failure • Heartworm displacement from pulmonary arteries to the right cardiac chambers.
    • Caval Syndrome
    • Caval Syndrome • Most frequently in small size dogs (< 11 kg) 3 main symptoms : • Dyspnoea • Cardiac murmur (thrill) • Haemoglobinuria (haematuria)
    • Caval syndrome Mechanical damage of RBC for blood high pressure and vortex
    • Caval syndrome
    • Cat Where canine HW infection exists, feline HW infection exists too! HW prevalence in cats is 8-10% of prevalence in dogs. In cats, HW infection is basically pulmonary. Clinically, the infection can be asymptomatic, chronic or acute. The most frequent signs are respiratory or digestive. Frequent respiratory signs are dyspnoea, and tachypnoea and less frequently, sneezing. Vomiting not associated with eating is frequent but other symptoms such as diarrhoea are occasionally described. Some affected cats also present prostrated, anorectic, showing weight loss.
    • Dyspnoea Coughing Vomiting Hemoptysis Lipothymias Coughing Vomiting Weight loss Diarrhoea
    • In those very rare cases where worms are located in the right heart, a systolic cardiac murmur due to tricuspid valve insufficiency and galloping cardiac rhythm are common findings at auscultation. Neurological signs such as ataxia, syncope, blindness, or vestibular alterations, can be seen depending on the ectopic localization of the migrating worms. In acute cases, cats can die so quickly that owners are usually not able to report any clinical signs before sudden death. Cat
    • Four year-old, female cat. Sudden death, the owner told that the cat was normal until the previous evening and he found the cat dead early in the morning without any previous clinical sign. At necropsy, one female adult worm and signs of thrombembolism Sudden death and hemoptysis
    • Clinical signs are usually more evident when young parasites arrive in the pulmonary arteries (4 to 6 months after infection) and later when adult worms die. Congestive heart failure, common in dogs, is not frequently in cats. Some infected cats recover spontaneously. However, even in cases of chronic infection, there is always the risk of reversion to the acute phase when adult parasites die. It is associated with an intense pulmonary inflammatory reaction in response to thromboembolism that is responsible for pulmonary infarction and hemorrhage. Circulatory collapse and respiratory failure usually follow. Clinical signs at this stage can include dyspnea, cyanosis, hypothermia, ataxia, hemoptysis and syncope. Cat
    • 34 9 79% 21% self cured death 3 6 11 23 7% 14% 26% 53% sudden death died after 8-4 months asymptomatic, self cured after 21-48 months symptomatic, self cured 18-49 months 43 cats HW Ag and ECHO positive
    • Cat Feline HW disease is now recognized as a significant pulmonary syndrome defined as Heartworm Associated Respiratory Disease (HARD). The syndrome has been observed in aborted infections too. Clinical signs associated with HARD are anorexia, lethargy, weight loss, coughing, rapid heart rate, vomiting, diarrhoea, blindness, convulsions, collapse and sudden death.
    • Cat: HARD Both experimental and in filed studies have shown that the HARD occurs even in cats with no adult parasites. Thus, unlike in dogs, HW disease in cats should not be linked only with adult worms and parenchymal disease but should be associated with the arrival and the early death of immature worms soon after they reach the pulmonary arteries. HW-Ab positive cats, but free of adult HWs, have the same type of pulmonary lesions, suggesting that even transient infection with HW leaves cats with long-lasting pulmonary pathology.
    • Prophilaxys Chemically abbreviated HW infection infection PulmonalyarteriolesAlveoli
    • When the worms reach the pulmonary arteries, acute inflammatory responses at the vascular and parenchymal level follow characterized by the activation of pulmonary intravascular macrophages (PIM, abundant in cats but not in dogs). The activation of PIMs is a unique and likely the most important feature of HW infection in cats and is responsible for the exacerbated pulmonary reaction. At this stage, pulmonary radiographic findings include an interstitial inflammatory pattern related to the increased production of cytokines by macrophages. Cat: HARD
    • Studying the pathogenesis of acute death syndrome in HW infected cats, it has been shown that the most severe lung reactions occurred in hypersensithyzed cats [IgE response] exposed to dead worms or antigens from adult parasites. The acute death syndrome is a consequence of an acute, IgE mediated systemic anaphylactic reaction. Cat
    • Although Dirofilaria immitis causes a very severe disease in dogs and cats, there is increasing concern about D. repens infection  Owners require healthy pets  D. repens can causes distress in infected animals  In sensitized hosts the disease can be severe/ very severe
    • Dirofilaria repens  Most infections asymptomatic or accidentally diagnosed during surgery  Subcutaneous, cold, not painful and nodules movable on the underlying tissues containing the adult parasite or mf Courteously Z. Svobodova, Fac. Med Vet, Brno, Czeck Republic Dirofilaria repens infection: subcutaneous dirofilariosis
    • Worms are visulized by ECO as double linear parallel hyperechoic structures similar but thinner than D. immitis adult’s echoes Dirofilaria repens worms can be visualized by echography in cutaneous nodules and removed by a mini-invasive procedure Venco et al Int J Appl Vet Med 9:217-223 2011
    • D. repens scrotal nodule
    • Seldom, in severe infection, the clinical findings [localized alopecia due to scratching and rubbing] and generalized dermatitis seems to be mediated by Wolbachia endosymbionts Courtesy T Živičnjak et al, 2006