Mimeo Report VY70-1
TIL ETIOLOGY OF PATHOLOGIC
CHANGiS IN CANINE HifA TLORMi DISEASE
Richard E. Bradley, D.V.i., Ph.D.
Department of Veterinary Science
University of Florida
Gainesvillc, Florida 32601 U.S.A.
A Portion of This Paper 'as
Presented at the Fourth International
Conference of the Vorld Association
for the Advancement of Veterinary
Parasitology, Glasgow, Scotland,
August 26-2d, 1969
Canine hea-rt.orm disease hae been recognized as a clinical entity
by veterinarians for many years. The current :ilnocledge of methods for
diagnosis and treatment of this disease was surmumarized in the proceed-
ings of a symposium held at the University of Georgia, Athens, Georgia,
in 1967. This information was recently published and is available for
reference (Jackson, R.F., et al., 1969).
The etiological agent of canine heartwoim disease is the nematode,
Dirofilaria immitis. The adult stage of this filarial worm inhabits the
heart and adjacent large blood vessels of the definitive host, the dog.
Although a considerable amount of information has been published
about certain aspects of the biology of the parasite and the clinical
signs associated with an infection of the adult parasites, very little
is known about the pathologic changes within the host during the prepa-
tent period. Similarly, little is known of the effects of a long-lived
adult infection and the microfilaremia that accompanies it.
This report is concerned with the causes of pathologic changes
that occur in naturally-infected dogs due to patent infection with
D. immitis and in non-infected dogs that were transfused with D. immitis
I. Biology of the Parasite, Dirofilaria immitis.
The filarial worm, Dirofilaria immitis, was first described by
Gruby and Delfond in 1843 and named by Leidy in 1856. The life
cycle of this parasite was described by Fulleborn in 1908, who
shoved the requirement for a suitable mosquito intermediate host
for successful completion of the cycle. Other workers, starting
vith Breinl (1921), described developing filarial larvae from dog
and cat fleas (Ctenocephalides canis and C. felis, respectively),
thus giving support to the theory that several blood-sucking ar-
thropods were suitable vectors of D. immitis. This proposal of
multiple vectors received continued support until Newton and bright
(1956) described the presence of another filarial parasite of dogs
in the United States belonging to the genus Dipetalonema. The reve-
lation of existence of two filarial worms in dogs in the U.S. clari-
fied the confusion of multiple vectors, since dog and cat fleas are
apparently the vectors of Dipetalonema sp. and not of D. nimmitis.
However, restriction of D. immitis vectors to only mosquitoes
has not helped the confused state of incidence and distribution of
this parasite. Although some authors (Hu, 1931; Summers, 1943;
Kartman, 1953; Bemrick and Sandholm, 1966) state that various mos-
quitoes are suitable vectors of this parasite and give a list of
genera, species, and varieties, it has been our experience that
laboratory transmission of D. immitis is not readily accomplished.
Another relatively unknown feature of the biology of Dirofilaria
immitis is the incidence of the parasite and the epizootiology of
clinical heartworm disease, which is reported by practicing veteri-
narians to be quite high. The incidence of D. immitis may be meas-
ured by microscopic examination of blood samples and identification
of any microfilariae present from representatives of the dog popula-
tion in an area. These data may also be obtained at necropsy of a
sample of the dog population. However, by either method, valid data
a.e difficult to obtain and published information on the true epi-
zootiology of canine heartworm disease and the incidence of the para-
site is scanty. The recent report of Thrasher and Clanton (1968) rep-
resents an important first step in obtaining statistically valid and
scientifically sound data on incidence of D. immitis in dog popula-
tions in Georgia. Also in 1968, we conducted an incidence study in
Hlillsborough County (Tampa), Florida, utilizing the necropsy method
for determining incidence of the parasite. Although, admittedly,
precise history is lacking on the dogs, some interesting facts
were revealed; a summary of results of the survey iL presented in
Table I. The most striking feature of the study was the fact that
two-thirds of the dogs with D. immitis had less than 10 adult para-
sites. This finding was in contrast to the fact that the Hills-
borough County area has a heavy hosquito population vell-distribu-
ted among all species reported from Florida and the U.S. as suc-
cessful vectors of D. immitis. It should follow that the area is
enzootic for D. immitis infection and that native dogs would presumably
be exposed to a high degree of infection since mosquito populations are
present during the entire year. But the small numbers found in our
sample may indicate that an inhibitory mechanism is operating at some
stage in the life cycle which limits the number of adult D. immitis
present in a dog at any one time. Otto (Jackson, R.F., ct al. 1966)
and others have attributed this inhibition to an immune mechanism op-
erating in the dog host. Such may well be the case, but one cannot
overlook the indirect evidence that there are many factors that may be
exerted on the population of mosquito vectors in enzootic areas to
actually limit the exposure of dogs to infective larvae. Research a-
long this line has not been pursued with D. immitis. Attempts are cur-
rently being made in our laboratory to develop satisfactory serologic
methods of identification of filarial larval stages found in wild-
caught mosquitoes as a means of studying the infectivity rates of mos-
quitoes and thus the efficiency of transmission to the definitive host.
II. Pathologic changes during the prepatent period of D. immitis infection
In recent years, attention has been directed to possible changes
that occur in dogs infected with developing larvae of D. immitis. How-
ever, experimental data utilizing laboratory infected dogs is very limi-
The report of Kume and Itagaki (1955), which traced the course
of larval migration and development to completion, did not include data
on cellular changes along the migratory route. There have been addition-
al reports of experimental infections of dogs in the laboratory (Webber
and Hauking, 1955; Newton, 1957; Sawyer and Weinstein, 1963; neston, 1968),
but none have contained information on host response during prepatency
of the successful infections.
The only report dealing with changes in the host during the prepa-
tent period of experimentally-induced D. immitis infections has been that
of Pacheco (1966). He attempted to quantitate the immune response in
dogs that were inoculated with infective D. immitis larvae and reported
a rise in antibody detectable by indirect hemagglutination (IIA) by two
weeks after inoculation. Complement-fixing antibodies were detectable
at three months post-inoculation and the general pattern was a rise in
detectable antibody to a peak at approximately the time that patency of
the infection would occur. After that time, he reported that the titer
diminished to an undetectable level at about nine months post-inoculation.
However, there are several unanswered questions in Pacheco's report such
as prior and concomitant experience of his experimental dogs with other
helminth parasites and, perhaps the most important of all, confirmation
of completion of the D. immitis life cycle by either demonstration of
circulating microfilariae or necropsy data on the number of adult para-
sites that developed from the inoculations with infective D. immitis
larvae in his experimental doss.
A recent report that contained information on successful laboratory
infections of experimental dogs with D. immitis is by Tulloch et al.
(196J). The design of the experiment, however, was to evaluate a
program of preventive drug therapy and attention vas not devoted
to pathologic changes except to those seen at necropsy.
III. Pathologic changes during the course of patent infections with D.
immitis in dogs.
A sizeable number of reports on gross and microscopic lesions
attributed to the adults of D. immitis have been published. Compre-
hensive studies on pulmonary arterial lesions have been reported by
Adcock (1961), on hepatic lesions by von Lichtenberg et al. (1962),
and on general pathologic changes by Winter (1959) and others. All
infected subjects in these studies were naturally-infected and no
information of the length of the patent period, the number of infec-
tive larvae that the dogs had been exposed to, or the dynamics of the
parasite population was presented.
In the report by Tulloch et al. (196J), microscopic lesions in
the lung and liver tissues of the infected control (non-medicated)
dogs confirmed the descriptions of changes in these tissues by ear-
lier workers except for the appearance of an eosinophilic granuloma
in the kidney of one dog.
The effects of microfilaremia on infected dogs, either direct
or indirect, have not been extensively studied. There have been
suggestions of pathologic effects by several authors, but experimen-
tal proof has not been offered.
Uong (1964 a, b) reported on studies designed to determine the
mechanisms that control the level of microfilaiemia in dogs naturally-
infected with D. immitis and laboratory-infectod with Brugia pahangi
and the relationship to the immunologic responses of the host. How-
ever, although cellular or tissue responses to microfilaremia were
not reported, one of the significant contributions from these papers
was a technique for separating microfilariae from whole blood compo-
nents, following the method originally proposed by Yaegcr (1i60) for
A report that directly implicates microfilariae as being respon-
sible for "transfusion reactions" in dogs was made by Ota et al. (1962).
They reported that transfusing dogs with homologous blood containing
microfilariae produced a true anaphylaxis based on a filarial antigen-
antibody reaction. In a carefully-designed series of experiments, they
conclusively showed that the anaphylactic reaction occurred only in
cases where the transfused blood contained microfilariae. Similar re-
actions occurred in dogs injected intravenously with extracts of adult
D. immitis. The report did not include microscopic changes in tissues
after the reaction occurred, but the clinical signs and gross lesions
at necropsy were those generally accepted as due to anaphylactic shock
hypotensionn, increased portal venous pressure, and hepatic congestion
manifested as a swollen, firm, dark purple-colored liver at necropsy).
ImTARIALS AITD I;THODS
Experimental design. To study the effects of adult D. immitis,
naturally-infected dogs were necropsied and both gross and microscopic
In order to study the effects of microfilariaa and microfilaremia,
large quantities of microfilariae were separated from whole blood of
naturally-infected dogs and transfused into non-infected dogs held in
isolation from exposure to D. immitis infection. Clinical and necrop-
sy observations were made on the recipient dogs. Lesions were recor-
Natuially-infected dogs. iMixed breed dogs, obtained from a li-
censed animal dealer, and shown to have D. immitis microfilaremia by
microscopic examination of the blood were used. All animals were ex-
amined clinically and treated for intestinal helminths with appropri-
ate anthelmintic drugs, when diagnosed.
The dogs vere housed in individual outdoor, concrete-floored,
wire runs, roofed for weather protection. Feed consisted of free-
choice Gaines meal; drinking water was likewise free-choice.
Non-infected dogs. The principals in this phase of the study
were pedigreed Beagles obtained at weaning time from a commercial
colony maintained in an area in the United States known to be free
of D. immitis. This factor is monitored in all dogs in the colony
on a regular basis by microscopic examination of blood samples for
microfilariae. Fecal examinations for helminth ova are also done
on a regular basis and records show the colony to be essentially
helminth-free and totally D. immitis-free.
The experimental dogs were housed in Rockefeller-type isolation
rooms, double-screened, air conditioned, and entered only through a
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double-door entry room. Protective clothing and rubber boots were
donned in this area prior to entering the isolation room; insecti-
cide spray and scrubbing with disinfectant was done as a routine to
prevent entry of mosquitoes into the animal quarters. All entry of
feed, utensils, instruments, etc., and removal of waste materials
was similarly under strict regulation.
The dogs were housed together as litters until the time of es-
trus of the females approached, at which time they were separated by
sexes. Feeding consisted of a commercially-manufactured dog food pel-
let (Gaines meal) which was "self-fed" from hanging feeders; drinking
water was provided ad libitum. All dogs were vaccinated against dis-
temper-hepatitis and rabies, at the proper times, using modified live
Preparation of microfilariae for transfusion. Heparinized whole
blood was collected under aseptic conditions from naturally-infected
dogs treated as outlined by Wong (1966 b). Slight modifications of
Long's method inclu:jd the collection of 300 ml. quantities of blood
and, after adding the phytohemagglutinin, the resulting mixture was
placed in conical, screw-capped, 26 mm. x 151 mm. glass centrifuge
tubes. The routine of washing and centrifugation (refrigerated cen-
trifuge, 1100 r.p.m. at 10 C.) was then completed. The total number
of microfilariae in the final sample was estimated by counting those
present in a measured amount and multiplying by the total volume.
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Viability of the microfilariae was estimated by observing the rate of
movement and the percentage moving per low power (lOx) microscope
field. The microfilariac were then suspended in 50 ml. Krebs solution
and injected intravenously into the recipient dog over a period of ap-
proximately 10 minutes time.
Necropsy procedures and tissue preparation. The techniques des-
cribed by Jones and Gleiser (1954) for canine necropsies were follow-
ed. Tissues for histopathological examination were preserved in buf-
fered 10 formalin (pH 7.0). These were embedded, sections cut at
lO0 and mounted and stained with hematoxylin and eosin or vasson's
trichrome stain, as described by Thompson (1966).
RESULTS AND DISCUSSION
Natural infection with adult D. immitis. Fr'om necropsy examina-
tion of Id naturally-infected dogs, varying degrees of pathologic
lesions were found.
The primary lesions occurring in the heart and pulmonary arter-
ies included varying degrees of cellular changes ranging up to vil-
lous projections of the intima into the lumen of the pulmonary vessels.
In some cased of this series with villous projections of the intima
of the pulmonary arteries, endothelial proliferation in the smaller
arterioles was also seen. These microscopic lesions were also seen
accompanying the gross lesions of a roughened rugosese") appearance
of the lining of the pulmonary artery. Furthermore, this combination
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of gross and microscopic leoioiu vas invariably fi'oue in dogs harboring
large numbers (30 or more) of adult D. immitis which usually extended
from the heart into the pulmonary arteries.
The hepatic lesions seen in this series of necropsies varied from
gross lesions of swollen, discolored livers to microscopic lesions of
advanced cavernomatous changes in the hepatic trinity. However, as a
general rule, the gross appearance of the liver was essentially normal,
but microscopic lesions were readily detected. These varied from cen-
trolobular congestion to cavernomatous formation in the hepatic trinity.
Specific lesions in other tissues from these naturally-infected
dogs were not detected. 1.Iicrofilariae vere invariably found in all or-
gans examined microscopically, but specific cellular changes attribu-
table to these larval forms could not be seen.
The lesions described from the present series are in full agreement
with the published accounts by Henningar and Ferguson (1957), Winter
(1959), Adcock (1961), and von Lichtenberg et al. (1962).
Perhaps the most plausible explanation of the lesions seen in con-
junction vith adult D. immitis infections is that of chronic irritation
by a foreign body. It is not difficult to accept this theory where one
sees large numbers of parasites in situ. Since much of the chronic fi-
brosis and sclerosis is irreversible, it also follows that the lesions
persist in the affected dog although the parasites may be removed (spon-
taneously, surgically, or by drug treatment). Furthermore, no doubt
these types of lesions may be seen in many other disease processes and
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there is little evidence to indicate that any of them arc specific
for D. immitis infection. One exception to this statement may be
in lives changes, especially the "terminal li.ver failure syndrome"
described by von Lichtenbe-r; ut al. (3.962) and confirLmed by Savyer
and Veinstein (1963) which vill be discussed bulou..
T-ansfusion of non-infected dogs with D. immitis microfilariae.
The injection of approximately 3.5 million D. imilrtis microfi.ariae
into a non-infected dog resulted in the rapid onset of an anaphylac-
tic-like reaction (immediate vomition and defucation, muscle tremors
followed by clon'c spasms, rapid and shallow breathing, undetectable
carotid pulse, tetanic spasms of the muscles) and death. Attempts at
artificial respiration and the use of chemical. ;timulants were unsuc-
cessful and death occurred within 10 minuteL after the completion of
the injection of the .nic-ofilariae.
At necropsy, the g'oss lesions were those gcnexaclly ascribed
to anaphylaxis, i.e. edematous lungs, severe coigest'on of the 1'ver
and kidneys, etc. No adult or immature helm'.nth parasites were found
in the intestinal tract. Microscopically, the primary lesson was
that of centrolobular de eneaat'on and necroosij of the liver; a few
mici-ofilariae were seen in lung capillaries.
Thiu preliminary findinii of a "transfusion j.eaction" to a sus-
pension of D. immitis microfil.aiae is significant in that it may
indicate a role of circulating microfilariae in the canine heartworm
There can be several explanations given for this reaction, each
of which must be confirmed by additional experimentation.
First, the "transfusion reaction" may be a simple reaction to
foreign protein. Such a non-specific reaction could be initiated by
dead microfilariae present in the total injected number. No doubt
a percentage of the microfilariae uere adversely affected by the sep-
aration procedures in preparation for injection.
Secondly, the reaction could be due to prior sensitization of
the recipient dog with helminth antigens. This could be a signifi-
cant finding, if shown to be a consistent occurrence since it could
help to explain the apparent limitation of development of adult D. t,:
imiLtis in some dogs by an "interference phenomenon" between intes-
tinal or other helminths concurrently infecting the dog and infective
D. immitis larvae that were injected into it by a mosquito vector.
The same sort of phenomenon could explain some of the spontaneous
deaths of adult D. immrtis in dogs heavily infected with other hel-
minths. Of course, a main point for discussion would be to explain
how juch a cross-reaction could occur in only one direction, with
the effect exerted only on the D. immitis adults or larvae, if such
is the case.
A third explanation for the "transfusion reaction" may lie in
the basic nature of the dog's physiological and anatomical make-up.
According to Walker et al. (1960), the dog has one or more "hepatic
sphincters" that may be located in specific areas of the hepatic
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venous system or may be, in fact, an innate ability of vasoconstriction
for its entire hepatic venous system.
Essex et al. (1931) observed an anaphylactic-like effect following
injection of helminth extracts into dogs, noting the similarity of the
reaction to that following injections of rattlesnake venom. Essex and
Thomas (1950) investigated the location of the "hepatic sphincter" in
dogs by using a vinyl acetate injection mass into the hepatic venous
system. They concluded that there were not sphincterss" as such, but
a general venous constriction in the dog liver following injections of
helminth extracts. They also pointed out that this phenomenon was much
more pronounced in the dog than in the cat, rabbit, or rat.
Roche e Silva and Grana (1946) reported that injections of Ascaris
sp. extract into the dog elicited an anaphylactic-like reaction. The
gross appearance of tho liver in such cases was that of extreme dis-
tention and congestion, indicating that the anaphylactic-like mecha-
nism was operating.
Grana (1947) reported confirmation of this phenomenon with either
Ascaris sp. extract of hydatid fluid both in vivo and in vitro, using
intact dogs or isolated, perfused dog livers, respectively.
These findings agree directly with the report of Ota et al. (1962)
who observed anaphylactic-like reactions in dogs receiving D. immitis
microfilaria-containing whole blood transfusions. Furthermore, our
findings in the present study lend further support to the proposal
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that microfilariae are, in fact, etiological agents of some of
the pathologic changes in canine heartworm disease.
This line of reasoning on the development of liver patho-
logy is also in direct agreement with the proposed "terminal
liver failure syndrome" of von Lichtenbcrg et al. (1962). In
this report, the authors have postulated that the pathogenesis
of severe liver pathology described from their experimental
dogs vas primarily due to impaired circulation and chronic pas-
sive liver congestion. No doubt that impaired circulation may
contribute to the overall pathogenesis, but there is also evi-
dence from our preliminary study and from the other reports of
the effects of helminth extracts and microfilariae on hepatic
venous circulation that direct effects on the liver may also be
contributing to the clinical syndrome of heartworm disease. Con-
tinued studies are currently under vay in our laboratory to fur-
ther elucidate the mechanism of pathogenesis. It is hoped that
the improved method for obtaining microfilariae from infected
blood reported by Greenough and Buckner (1969) will expedite
such studies by providing larger numbers of microfilariae for
transfusion into experimental dogs produced in a carefully-con-
trolled (helminth-free) environment.
The author wishes to thank Dr. Ronald F. Jackson for help in
planning and execution of the research project from which this pa-
per has come. Thanks arc also due Dr. Robert H. Busch, .i.A.C.V.P.,
for help in necropsies and interpretation of histopathological ma-
terials. Also contributing to the success of the project have been
graduate students, Dr. Henry Carwile, Dr. T.K.S., kiukkur, and 1.ki.
David Weiner. The technical assistance of iir. Louis 2rgle, Mr.
lick Jattuso, fiirs. Lois Rogow, and ;-I. Jan Zvilling is also grate-
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Summary and Conclusions
The pathologic changes of canine heartworm disease described
by previous authors as attributable to adult D. immitis infection
were confirmed. These changes are thought to be due to the mechani-
cal irritation of the lining of the heart and adjacent blood vessels
which leads to the progressive development of fibrotic and oclero-
tic elements in the vessel walls. The latter changes may ulimate-
ly lead to other disease processes including elevated blocd pres-
sure, cardiac enlargement, pulmonary edema, and others.
The pathologic changes due to microfilaremia have been char-
acterized as similar to anaphylaxis. Although only preliminary
experimental evidence was available, correlation with published
reports on the hepatic venous circulation of the dog support this
theory. The microfilaremia that accompanies a population of adult
D. immitis in the heart and adjacent vessels in a dog may thus
play a role in the pathogenesis of canine heartuorm disease.
Adcock, J.L. 1961. Pulmonary arterial lesions in canine di ofilariasis.
Am. J. Vet. Res. 22:655-662.
Bcmrick, 1;.J. and H.A. Sandholm. 1966. Aedes vexans and other potential
mosquito vectors of Dirofilaria immitis in Minnesota. J. Parasitol.
Breinl, A. 1921. Preliminary note on the development of the larvae of
Dirofilaria immitis in the dog fleas Ctenocephalus canis and
Ctenocephalus felis. Ann. Trop. Med. Parasitol. 14:3d9-392.
Essex, H.E., J. Q;arkowitz, and F.C. iann. 1931. Physiologic responses
and immune reactions to extracts of certain intestinal parasites.
Am. J. Physiol. 9d:13-24.
Essex, IH.. and V.D. Thomas. 1950. The response of the hepatic venous
circulation to certain substances given intravenously. Iayo Clinic
Fulleborn, F. 1906. Uber versuche an hundefilarien und desen ubertragung
durch mucken. A.ch. Schiff. Trop. Hyg., Beihft. 12:6-43.
Grana, A., F.C. i;nn and H.E. Essex. 1947. Influence on the liver on the
shock produced by extracts of certain parasites. Am. J. Physiol.
Greenough, Y.B. and D. Buckner. 1969. Removal of microfilariae from
unanesthetized dogs by continuous flow centrifugation. Trans. Royal
Soc. Trop. :;ed. Hyg. 63:259-262.
Hu, S.I.K. 1931. Studies of host-parasite relationships of D. immitis
Leidy and its culicine intermediate hosts. Am. J. Hyg. 14:614-629.
Hennigar, G.R. and R.:. Ferguson. 1957. Pulmonary vascular sclerosis
as a result of Dirofilaria immitis infection in dogs. J.A.V.M.A.
Jones, T.C. and C.A. Gleiser. 1954. Veterinary Neciopsy Procedures.
J.B. Lippincott Co., Philadelphia, Pa.
Ka_'tman, L. 1953. Factors influencing infection of the mosquito with
Dirofilaria immitis (Leidy, 1856). Axp. Parasitol. 2:27-7d.
Kume, 5. and S. Itagaki. 1955. On the life-cycle of Dirofilaria immitis
in the dog as the final host. British Vet. J. II1:16-24.
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Jackson, R.F., ...F. Jackson, J.C. lorsan and G.F. Otto. 1969. Heartuorm
Disease in the Dog: Report of L. Symposium. J.A.V...A. 154:369-397.
von Lichtenberg, F., R.F. Jackson and G.F. Otto. 1962. Hepatic lesions
in dogs with dirofilariasis. J.A.V.M..A. 141:121-128.
Newton, W!.L. and 1..H. Right. 1956. The occurrence of a dog filariid
other than Dirofilaria immitis in the United States. J. Parasitol.
Newton, I:.L. 1957. experimentall transmission of the dog heartworm,
Dirofilaria immitis, by Anopheles quadrimaculatus. J. Parasitol.
Newton, W.L. 1968. Longevity of and experimental infection with
Dirofilaria immitis in a dog. J. Parasitol. 54:187-133.
Ota, Y., R.C. Camishion and J.H. Gibbon. 1962. Dirofilaria immitis
(heartuorms) and Dipetaloncma species as causes of "transfusion
reaction" in dogs. Surgery 51:518-526.
Pacheco, G. 1966. Progressive changes in certain serological responses
to Dlirccfilaria immitis infection in the dog. J. Parasitol.
Roche t Silva, IM. and A. Grana. 1946. Anaphylaxis-like reactions
produced by ascaris extracts. Arch. Surg. 52:713-728.
Sawyer, T.K. and P.P. .:einstein. 1963. Experimentally induced canine
dirofilariasis. J.A.V..i.A. 143:975-97d.
Summers, ,..A. 1943. experimental studies on the larval development
of Difofilaria ii.tis in certain insects. Am. J. Hyg. 37:173-178.
Thompson, S.1,. 1966. Selected Histochemical and Histopathological
i.ethods. Chas. C. Thomas, Springfield, Ill.
Thrasher, J.P. and J.h. Clanton, Jr. 1963. 2pizootiological observa-
tions of canine filariasis in Georgia. J.A.V...A. 152:1517-1520.
Tulloch, G.S., G. Facheco, H.UI. Casey, and -:.S. Bills. 1968. Preventive
Chemotherapy of canine dirofilariasis with dietbylcarbamazine
(SA;.I-TR-d-,-5). School of Aerospace iMedicine, U.S. Air Force,
Brooks Air Force Base, Texas.
Walker, '..F., J.S. iahcdonald and C. Pickard. 1960. Hepatic vein sphinc-
ter mechanism in the dog. Brit. J. Surge. 48:213-220.
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W.ebber, W.A.F. and F. HawkinG. 1955. Experimental maintenance of
Dirofilaria repens and D. immitis in dogs. xp. Parasitol.
Winter, H. 1959. The pathology of canine dirofilariasis. Am. J.
Vet. Res. 20:366-371.
Wong, M.M. 1964a. Studies on microfilaremia in dogs. I. A search
for the mechanisms that stabilize the level of microfilaremia.
Am. J. Trop. Med. Hyg. 13:57-65.
V.ong, ii.i. 1964b. Studies on microfilaremia in dogs. II. Levels
of microfilaremia in relation to immunologic responses of the
host. Am. J. Trop. ;.:ed. Hyg. 13:66-77.
Yaeger, R.G. 1960. A method of isolating trypanosomes from blood.
J. Parasitol. 46:28d.
Incidence of Dirofilaria immitis in Dogs from
Hillsborough County, Florida: 8 Samples (Feb.-Apr., 1968)
1. Total examined 255
2. Total infected 74 (32.4,;)
3. Range of D. immitis county
in infected dogs:
1 10 : 49
10 20 : I6
20 50 : 4
50 or morc : 3
4. iean 12.1/dog