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ARTICLES
A P R N ATRIAL P R S S O E A S CA E WT PAET AAYT L SOITD IH EHRLICHIA CANIS I F C I N IN A DOG. N E TO A CLINICAL CASE R P R EOT
WanerT^'andOhadD. G.
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'Rehovot Veterinary Clinic, 9 Meginay Hagalil Street, Rehovot 76200 Israel. Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, P.O.Box 12, Rehovot 76100, Israel * Corresponding author: Dr. Trevor Waner, Rehovot Veterinary Clinic, 9 Meginay Hagalil Street, Rehovot 76200 Israel. Telephone: +972-8-9452834, E-mail: wanertnt@shani.net
A SR C BTAT
To date no clinical cardiac related changes have b e documented or associated with canine monocytic ehrlichi en (CME) caused by Ehrlichia canis. Evidence of increased activity of cardiac isoenzymes creatinine kinase and lactate dehydrogenase has been documented in dogs in the acute stage of the disease. In a recent study of serum cardiac Trop I concentration in dogs with naturally acquired ehrlichiosis, acute infection with E. canis has been established to be a factor for myocardial injury. In a n m e of h m n cases of ehrlichiosis cardiac involvement has been reported. Th u br u a communication presents for the first time a clinical case of CME associated with apparent electrocardiographic chang interpreted to be atrial parasystole. The electrocardiographic changes resolved following treatment for CME.
apparent association between potentialy abnormal ECG Canine monocytic ehrlichiosis (CME) is a c m o worldwidefindings, CME infection (presence of E. canis antibody an o mn tick borne disease caused by Ehrlichia canis. The principal typical hematological findings) followed by therapy with vector of the rickettsia is the brown dog-tick Rhipicephalus Doxycycline and subsequent resolution of hematological sanguineus. After an incubation period of 8-20 days, signs of changes, clinical signs and ECG findings. clinical disease appear characterized by fever, anorexia, weight AE EOT loss, depression, lymphadenomegaly a d splenomegaly. C S R P R n Dogs may present bleeding tendencies, mainly petechiae andA 10-year-old spayed female Maltese poodle-cross presen y po s ecchymoses of the skin and m c u m m r n s (1). After with s m t m of coughing. Her vaccination record was up u o s e ba e date. 1 to 4 weeks with no medical treatment (or after inadequate A full physical examination with a complete blood c treatment) dogs may recover the acute disease and may enter(CBC) and blood chemistry examination were carried o the subclinical phase of CME (2). Dogs in this stage may remainAuscultation of the lungs revealed fine crackles and a stro persistent carriers of the rickettsia for m nh and years. S m cough reflex which was readily elicited by tracheal palpati ots oe um dogs may subsequently develop the chronic pancytopenic formNormal heart sounds were auscultated and no audible m r of the disease (3). Thrombocytopenia is the most c m o was present. The clinical chemistry results were not indicativ o mn and consistent hematologic finding in all phases of CME. of any specific disease and a tentative diagnosis of low-grad Mild leukopenia and mild anemia (usually non-regenerativebronchitis was made. A mild thrombocytopenia was noted normocytic normochromic) may occur in the acute stage of(175 x 10platelets/uL blood) (Table 1). The dog was treated CME. The disease is a multi-systemic with clinical s m t m with Ceforal (Cephalexin, Teva, Israel) (30 mg/kg PO ql2). y po s reflected mainly due to changes in the hematopoietic system. month later after the owner reported no improvement treatm wi Besides the fever and hematological changes seen as a result th enrofloxacin (Baytril, Bayer, Germany) (10 mg/kg q was of infection with E. canis, changes in liver enzymes indicative initiated. of liver involvement are commonly observed (4). There is a dearth of clinical reports of the effects of CME on specific Four months after the initial examination, on account of organs, although ocular pathology is commonly reported (5-7). nuing cough, thoracic radiography was carried out, alon conti Until now, elctrocardiographic manifestations of heart disease with a repeat CBC. Two lateral (right and left) radiograph in dogs with CME have not been described. (Figure 1A & IB) did not reveal any obvious pathologica In this case presentation we describe for the first time an changes and there was no cardiomegaly of any kind (Vertebr
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Heart Sum was 9.2v and 10.lv, respectively, while referenceA follow-up CBC preformed 3 w e s later showed that t ek range in dogs is 9.7 ± 0.5v) (8) and pulmonary parenchyma hematological parameters remained in the normal range (Ta appeared radiographically normal. No dorsoventral or ventro- 1). dorsal radiographs were obtained. A tentative diagnosis was Echocardiography was carried out 8.5 m nh following initia ots m d ofpossible pulmonary fibrosis associated with aging. The ae presentation, revealing only trivial mitral, tricuspid, and aor CBC showed a mild decline in total leukocytes and a further drop in platelet n m es (117 x 10 platelets/uL blood). The valve insufficiencies, with no resultant hemodynamic effec u br m a corpuscular volume (MCV) was slightly decreased and such as measurable abnormalities in atrial or ventricular en the m a corpuscular hemoglobin concentration was slightly internal diameter, ventricular force of contraction, or wal en increased (Table 1). No treatment was instigated at that time. thickness. None of these findings was considered, in retrosp as related to the previously documented electrocardiographic hematological or other findings. Three m nh later (7 m nh following initial presentation) ots ots the owner reported signs of exercise intolerance a d n weakness. It was decided to carry out a repeat CBC and an D C S I N I U SO S electrocardiographic (ECG) examination. The ECG w s In the case presented in this report an apparent associatio a examined for lead II (Figure 2): Heart rate and rhythm were been found between potentialy abnormal ECG finding has normal (sinus rhythm with an R-to-R interval of 605±10 CME infection (presence of E. canis antibody and typica miliseconds, which translates to a heart rate of 99±2 bpm).hematological findings), and resolution of hematological Measurable amplitudes and intervals were all within reference changes, clinical signs and ECG findings following Doxycyclin range, as follows: P = 0 miliseconds, Q S 5 miliseconds, R10 R =0 therapy. The stage of infection with E. canis in this case Q = 8 miliseconds, R=0.7 millivolts). The only suspected T10 have been atfirstsubclinical, suggested by the persistent abnormal finding w s a extra, low-amplitude, positive reduced platelet counts, the increased m a platelet volu a n en deflection preceding the P-wave that occurred frequently andand E. canis antibody titer (2). For no apparent reason this m consistently over several consecutive cardiac cycles, although regressed to the mild pancytopenic form. The reduction have it's morphology and time interval relative to the following Pin erythrocyte, leukocyte and platelet counts were mild w wave was not constant. The differential diagnosis list includedparameters falling below the normal range. The rapid clini an artifactual recording, atrial parasystole, or atrial dissociation.response to treatment with the antibiotic Doxycycline an Of these differential diagnoses atrial parasystole s e e to bee quick return of the hematological parameters to with e m d th the most relevant choice. The ECG appeared to s o evidencehe normal range is added evidence for active CME infectio hw t of two independent atrial rhythms, one of which triggered (10). a QRS complex while the other did not. Each of these two rhythms appeared to have its own "internal" P-to-P interval,This case appeared to be a case of progression of CME from and they did not interfere with each other. subclinical form to the chronic state. The factors responsib for the transition from subclinical to chronic ehrlichiosis a At the time when the extra P-like wave was recorded the unknown and in this case no specific initiating cause could hematological parameters showed mild anemia, leukopenia entified. Possibly if this dog had not been treated promptly id and thrombocytopenia (Table 1). On the basis of these resultswould have declined into the chronic severe pancytopenic s a tentative diagnosis of canine monocytic ehrlichiosis was with a poor prognosis. Besides the consistent thrombocytope made. An indirect immunofluoresence antibody (IFA) test seen, no other hematological parameters gave a suggestion revealed a titer of IgG E. canis antibodies of 1:1280, which the ongoing disease (2). is considered indicative to exposure to E. canis (9). Treatment was exact etiology of the cough and exercise intolerance The c m e c d with Doxycycline (Doxylin, Dexxon, Israel) at 10 not established. A subjective impression of age-related o m ne was mg/kg PO SID for three weeks. After 10 days of treatment thepulmonaryfibrosisw s m d on radiology. No further a ae owner reported that although the cough had still not resolved agnostic procedures were carried out at the request of di the dog was perkier and had returned to her normal self. At owners. The cough remains static to this day without an this stage the hematological parameters had all returned tofurther deterioration. within normal limits and the platelet count was now 356 x 10 platelets/uL blood, an increase of 104% from the count Although the ECGfindingsare compatible with either pac performed before c m e c m n of treatment (Table 1). o m ne e t making or conduction aberrancies the exact nature of organ or structural changes is not known. Of the three different The ECG was repeated (Figure 3) and demonstrated normal diagnoses, artifactual recording, atrial parasystole, or atr emd sinus rhythm at a heart rate of ~120/minute, with normaldissociation, atrial parasystole s e e to be the most applica intervals and amplitudes which were essentialy identical to choice. The origin of this independent pacemaker appear to those recorded previously, except for the absence of an extra be atrial as there was no inscription of a repolarization event, which would have been expected to follow ventric P-like wave. depolarization. There appears to be two independent atr
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pacemaker sites remote from each other, one at the SA node infiltrate the myocardium and produce pro-inflammatory that "fired" normally and the other elsewhere in one of the cytokines or induce their production by other cells (22, 23 atria. Whether similar myocardial pathophysiology occurs in canine The possibility that this finding was artifact m s also be patients with CME remains to be investigated. ut considered (11). Although this is a possibility, its likelihood is considered low: the association of the additional P-wave In conclusion, this report presents a case of chronic CM during the pinnacle of the disease and its disappearance after associated with suspected electrocardiographic changes. To treatment with resolution of the clinical signs may add s m the best knowledge of the authors this is the first clinical repo oe credibility to ECG recordings, both at the time of the disease of a possible relationship between infection with E. canis and at recovery. The diagnosis of atrial dissociation has also abnormal electrocardiographicfindingsin a dog. Further research is warranted to clarify the association between CME been rejected due to its being very rare and typical of advanced heart disease (unlike the presently reported patient) and due toand its potential cardiac effects. the fact that, as opposed to the trace in the presently reported patient, its P-like wave is typically smaller than the one Legends to figures resulting from sinus rhythm. (11, 12)
Figure 1A
To the authors' knowledge no association between CME Thoracic radiograph in right lateral recumbency in a 10 yea ots and electrocardiographic changes has yet been m d in old female spayed dog with CME, 4 m nh following initia ae dogs. Evidence of possible cardiologic effects of CME presentation with a chronic cough. may be based on post m re and histological findings, as ot m well as on biochemical studies. Epicardial and endocardial Figure IB Thoracic radiograph in left lateral recumbency of the s m do ae hemorrhages have been observed in 84% of dogs dying from CME (13). Histologically, hemorrhage was seen to extend as in Figure 1A. between myocardial fibers but did not appear to originate from myocardial blood vessels. In addition, the blood vessels inFigure 2 ECG the myocardial fat were often surrounded with both plasma lead II rhythm strip (10 mm/mV, 50 mm/sec) recorde ae cells and reticuloendothelial cells. Small foci of mononuclear during the chronic phase of CME from the s m dog as ots cells were observed in close proximity to small vessels in thFigure 1, 7 m nh following initial presentation. Note the e myocardium and only one dog had a focus of non-suppurative suspected extra P-wave. myocarditis (13). Further evidence of CME-related cardiac injury was seen in a study carried out on dogs artificiallyFigure 3 infected with E. canis. This study showed an increase in the lead II (10 mm/mV, 50 mm/sec) recorded from the s m ECG a activities of the serum cardiac isoenzymes creatinine kinasedog as in Figure 1,10 days after treatment with Doxycycline and lactate dehydrogenase during the acute phase of the and recovery from s m t m and clinical signs. Note the y po s disease (14). In a recent study of serum cardiac Troponin Idisappearance of the extra P-wave. concentration in dogs with ehrlichiosis, acute infection with E. canis was found to be a risk factor for myocardial injury in naturally infected Brazilian dogs. The authors were however not able to evaluate the contribution of the severity of anemia and systemic inflammatory response syndrome which might have also contributed to the pathophysiology of myocardial d m g in these dogs (15). a ae H m n monocytic ehrlichiosis (HME) is caused by the u a monocytotrophic ehrlichial a e t Ehrlichia chaffeensis that is gn closely related to E. canis (16). Although considered rare, a n m e of clinical cases of HME associated with myocardial u br changes have been described in h m n (17-20). A recent case u as report has documented severe myocarditis and congestive heart failure in a h m n patient diagnosed with h m n monocytic u a u a ehrlichiosis. The patient recovered promptly after the initiation of treatment with doxycycline (19). Myocardial cell infiltrates with e e a have been observed with E. chaffeensis infections dm in man (21). It has been suggested that macrophages activated by Ehrlichia species through the effects of interferon-y may
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ARTICLES T be 1. Hematological results al S q e ta h m t l gc lfindingsd c m ni g the subclinical e u ni l e aoo i a o u e tn sa e of CME, the chronic p n yo e i ds a e and the tg a c t p nc i e s r c v r p a e at r te t e t wt Doxycycline. e o ey h s fe r am n ih
Date/Parameter
H m t ci e ao rt Eyho ye rt r cts H m go i e o l bn MCV MCH MCHC R tc l c t s ei uo ye Paees ltlt MPV L u o ye e k cts N ur p is e to hl Lm h cts y p o ye M n cts o o ye Eosinophils B s p is a o hl nr = no r s l e ut
Units
%
17 Mar 06
45.8 6.93 13.9 66.1 20.1 30.4 nr 175 7.5 6.24 4.54 0.95 0.56 0.28 0.03
7 Jul 06 37.4 6.82 13.8 54.8 20.2 36.9 0.19 117 19.5 5.62 4.22 1.05 0.17 0.16 0.02
13 Oct 06
29.2 5.27 11.3 55.2 21.4 38.7 1.45 174 16.3 4.50 2.22 1.57 0.62 0.07 0.02
24 Oct 06
40.4 6.56 13.2 61.6 20.1 32.7 0.68 356 11.5 7.70 5.56 1.17 0.52 0.35 0.01
2 Nov 06
48.7 7.53 14.9 64.7 19.8 30.6 0.19 393 11.5 6.02 5.04 0.51 0.19 0.24 0.04
x 10/ul g/Dl u
3
6
Pg
% %
x lOVul u
3
x lOVul x 10/u xlV Ou x 107u x 107u xlV Ou
3
Normal ange 37-55 5.5-8.5 12.0-18.0 60-77 19.5-24.5 32-36 0.0-1.5 200-500 5-15 6-17 3-11.5 1.0-4.8 0.15-1.35 0.01-1.25 0-0.5
RFRNE EE E C S
1. H r s S., T. W n r and H. Bark, C nn m n c tc am , a e, a i e o o yi ehrlichiosis u d t . C m e d Cont. Educ. Prac. Vet. 19: p ae o p n . 4 14 4 1997 3-4. 7. 2. W n r T, S. H r s H. Bark, E. Bogin, Y. Avidar, and a e, am , A. Keysary, C aa t rz to of the subclinical p a e h r cei ai n hs of c nn ehrlichiosis in e p rm nay i f ce b a l aie x ei e t l ne t d e ge d g . Vet. Parasitol. 69: 3 71 . 1997 os 0-7 8. 3. W n r T, A. Keysary, E. S aa a i H. Bark, and S. a e, h r b n, H r s C nn m n c tc ehrlichiosis - an o eve . Isr. am , a i e o o yi vriw J. Vet. Med. 54: 1 31 6 1999 0-0. 9. 4. H r s S., PH. Kass, E. Ke e t and T. W n r C nn am , l m n, a e, a i e m n c tc ehrlichiosis: a r to p ci e su y of 100 o o yi er s e tv t d cases, and an epidemiological i v si ai n of po n si n e tg to r g o tc indicators for the ds a e Vet. Rec. 141: 3 03 1997 ies. 6-. 5. Leiva, M., C. N r no and M.T. P n , O ua sg s of 10. aa j , ea c lr in c nn m n c tc ehrlichiosis: a r to p ci e su y in a i e o o yi er s e tv t d d g fo Barcelona, Spain. Vet. O hh l o. 8: 3 79 . os r m p t am l 8-3 20 05 6. H r s S., R. Ofri, I. Aizenberg, and T. W n r A ue am , a e, c t bi d e s a s cae wt m n co a g m o ah ln n s s o i t d ih o o l n l a m p t y
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i d c d by Ehrlichia canis infection. Vet. Parasitol. 78 n ue 1 56 . 1998 5-0 Gould, D.J., K. M r h , H. Rudorf, and S.M. Crispin up y C nn m n c tc ehrlichiosis pe e tn as a ue a i e o o yi r s ni g ct bi d e s 36 m nh at r i p rai n i t the UK. ln n s o t s fe m ot to no Small. Anim. Pract. 41: 2 35 2 0 6 - . 00 B c a a , J.W. and J. Bucheler, V re r l s ae s se uhnn et ba c l y t m m a ue c nn h at size in r do r p s JAVMA. es r a i e e r a i ga h . 1 49 1995 9-. W n r T, S. H r s F. J n ea , H. Bark, A. Keysa a e, am , o g j n and A.W. Cornelissen, Significance of serological testin for ehrlichial ds a e in d g wt special e p a i iess o s ih m h ss the da n ss of c nn m n c tc ehrlichiosis c u e ig oi a i e o o yi a sd Ehrlichia canis. Vet. Parasitol. 95: 1-15. 2001 H r s S., M. K n y L. Miara, I. Aizenberg, T. W n am , e n, a and S. S a , C m ai o of sm la e u splenic s m h w o p rs n i ut n o s a PCR wt bo d s m l PCR for da n ss and te t e ih l o a pe ig oi r am of e p rm na Ehrlichia canis infection. Antimicrob x ei e t l A e t C e oh r 48: 4 8 - 0 2 0 g ns h m t e. 4 89 . 0 4
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11. Sklyar, E. and G. Hollander, Is this atrial parasystole, 18. atrial dissociation, or an artifact? J. Electrocardiol. 40: 133-4. 2007 12. Chung, K.Y., TJ. Walsh, and E. Massie, A Review of 19. Atrial Dissociation, with Illustrative Cases and Critical Discussion. Am. J. Med. Sci. 250: 72-8. 1965 13. Hildebrandt, P.K., D.L. Huxsoll, J.S. Walker, R.M. 20. Nims, R. Taylor, and M. Andrews, Pathology of canine ehrlichiosis (Tropical Canine Pancytopenia). Am. J. Vet. Res. 34: 1309-1320. 1973 21. 14. Waner, T, Y. Avidar, S. Harms, R. Zass, and E. Bogin. Activities and isoenzymes patterns of creatine kinase and lactate dehydrogenase in beagle dogs artificially infected with Ehrlichia canis. . In Vllth Congress of the 22. International Society for Animal Clinical Biochemistry. 1994. Guelph, Canada. 15. Diniz, P.P., H.S. de Morais, E.B. Breitschwerdt, and D.S. Schwartz, S m Cardiac Troponin I Concentration in em Dogs with Ehrlichiosis. J. Vet. Intern. Med. 2008 16. Anderson, B.E., J.E. Dawson, D.C. Jones, and K.H. 23. Wilson, Ehrlichia chaffeensis, a new species associated with h m n ehrlichiosis. J. Clin. Microbiol. 29: 2838-42. u a 1991 17. Wiliams, J.D., R.M. Snow, and J.G. Arciniegas, Myocardial involvement in a patient with h m n u a ehrlichiosis. Am. J. Med. 98: 414-5. 1995
Vanek, N.N., S. Kazi, N.M. Cepero, S. Tang, and J.H. R H m n ehrlichiosis causing left ventricular dilatation a u a dysfunction. Clin. Infect. Dis. 22: 386-7. 1996 Stone, J.H., K. Dierberg, G. Aram, and J.S. Dumler, H m n monocytic ehrlichiosis. JAMA. 292: 2263-70. u a 2004 Paddock, CD. and J.E. Childs, Ehrlichia chaffeensis: prototypical emerging pathogen. Clin. Microbiol. Rev. 37-64. 2003 Walker, D.H. and J.S. Dumler, H m n monocytic an u a granulocytic ehrlichioses. Discovery and diagnosis of emerging tick-borne infections and the critical role of pathologist. Arch. Pathol. Lab. Med. 121: 785-91. 1997 Lee, E.H. and Y. Rikihisa, Anti-Ehrlichia chaffeensis antibody complexed with E. chaffeensis induces pote proinflammatory cytokine mRNA expression in h m u a monocytes through sustained reduction of IkappaB-alph and activation of NF-kappaB. Infect. Immun. 65: 28901997 Ismail, N., L. Soong, J.W. McBride, G. Valbuena, J.P Olano, H.M. Feng, and D.H. Walker, Overproduction TNF-alpha by CD8+ type 1 cells and down-regulation of IFN-gamma production by CD4+ Thl cells contribu to toxic shock-like syndrome in an animal model of fa monocytotropic ehrlichiosis. J. Immunol. 172: 1786-800 2004
ERTM R AU
Histophilus somi in Israel
In a recently published abstract (1) we stated that "H. somni wasfirstdescribed in Israel in 1991, from a case of bo mastitis. Further cases were not reported until 2002". In fact, as pointed out by Dr. A. Grinberg, who isolated and publish abovementioned case, the microorganism was isolated in 1993 from cases of calf pneumonia and s m n of clinically h ee bulls (2). Moreover, the microorganism was isolated from the lungs of a calf diagnosed histo-pathologically as being afflic Trombotic Meningoencephalitis, in 1994 (3). All these cases occurred in the northern region of Israel. Unfortunately these r were overlooked due to the limitations of electronic bibliographic searches.
Prof. D. Elad Kimron Veterinary Institute, Israel 1. Blum S, Freed M, Zukin N, Friedman S, Elad D. Histophilus somni: a new, uninvited resident in Israel. Isr. J. Vet. 63:49,2008. 2. Grinberg A, Khatib N, Kosak A, Ziv G. Haemophilus somnus infection in cattle in Israel -firstreport. Israel. Isr. J. Med. 48:61-64,1993. 3. Grinberg A, Kosak A, Khatib N, Samish M, Bar D, Nyska A. Infectious Thrombotic Meningoencephalitis in a calf diagnosed case in Israel. Isr. J. Vet. Med. 49:20-22, 1994. Volume 63 (4) 2 0 08 website: www.isrvma.org
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