FIV and Hemobartonella
3. Connection to FIV
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Hemobartonella felis has recently been reclassified as three distinct parasitic organisms: Mycoplasma haemofelis, Mycoplasma haemominatum, and (as first reported in a 2006 Swiss study) Mycoplasma turicensis . All three are strange organisms (bacteria lacking a cell wall)
that attach to the surface of red blood cells rather than infect the cells themselves. M. turicensis and M.
haemominatum usually produce minimal disease. A 2003 study found a decided fall in hematocrit (red
cell volume) correlating directly with rises in the M. haemofelis copy number, whereas the values
of the cats infected with M. haemominatum remained within the reference range . However, whereas M. haemominatum is usually not associated with clinical disease, it does, according to several sources , cause anemia in cats carrying pre-existing FIV or FeLV infection, and anecdotal reports suggest a suboptimal response to standard therapy. Estimates of the prevalence of these mycoplasmas within feline populations vary. A recent U.S. study of 310 cats with regenerative anemia found “overall prevalences of Mhm, Mhf, and Mtc [mixed] infection were 23.2%
(72/310), 4.8% (15/310), and 6.5% (20/310), respectively” . An internal study performed at
Idexx Laboratories, screening samples from 303 cats with a hematocrit less than 25%, found 39
samples (13%), positive for M. haemofelis . “Feline hemoplasmas were detected in a total of 88
samples (or 29%); 13 samples had coinfections with two strains, and seven samples had
coinfections with all three strains” .
M. haemofelis can produce a life-threatening "hemolytic" anemia by provoking an autoimmune attack on the parasitized cells. Various mechanisms have been suggested to explain its
pathogenicity, and it is possible that several are involved. Antibody coating that marks cells for
destruction is known to take place. One proposal is that phagocytic scavengers called
macrophages destroy the cells in the spleen, liver, and bone marrow. It has also been proposed
that parasitized red cells sequestered in small blood vessels lose their normal shape, which allows
exposure to foreign antigens that incite a hemolytic response. Yet another suggestion is that the
red blood cell may be an innocent bystander of complement fixation . The complement system
is part of the nonspecific immune response that parallels and can be recruited to aid (“complement”) the
antibody response of the specific immune system.
Cats infected with M. haemofelis go through four phases of disease -- an asymptomatic phase following initial infection (2-21 days), an acute phase during which clinical signs occur (2-4
months), a recovery phase with mild anemia and minimal clinical signs, and a carrier phase that
may last for years . Many cats become lifelong carriers. Symptoms of acute infection include fever of variable magnitude, lethargy, and depression. Onset of symptoms is sometimes slow and progressive, sometimes rapid and usually
accompanied by jaundice. Cats at risk for the infection are disproportionately outdoor males since the primary modes of transmission appear to be bloodsucking insects and bites associated with fighting . This, of course, is the same group at
risk for FIV. The infection can also be passed from mother to offspring. Younger cats tend to suffer more severe anemia, possibly due to immunological immaturity 
Diagnosis has historically been difficult because the organisms cannot be cultured due to the lack of a cell wall. Routine bloodwork can be suggestive, but is not conclusive. A complete blood
count (see the page “FIV and the CBC”) can assess the extent of the anemia and provide clues to the cause. Reticulocytes
are immature red blood cells that are released from the bone marrow when certain regenerative
anemias are present, regenerative meaning that the bone marrow retains a capacity to
manufacture red cells. A high count of reticulocytes (immature red blood cells) is common with
hemobartonella because of the lysis of red cells going on, but may be inapparent at onset of
infection before the bone marrow has had adequate time to begin to respond (4 to 7 days) or may be masked by
concurrent illnesses that suppress bone marrow. It is particularly important to get a count of
aggregate (early immature) reticulocytes for any cat presenting with an unexplained anemia to
establish whether or not it is regenerative. However, many CBCs do not report on reticulocytes,
so the count must be requested separately. Red cell indices may show a low MCHC  (mean
cell hemoglobin content) and/or elevated MCV  (mean cell volume), the latter because
immature cells are larger than mature ones. In the early, acute phase of infection, white cell
counts may be normal or mildly elevated, with mild neutrophilia or monocytosis (elevations).
Serum chemistries are often unremarkable and may contain features expected with red cell
destruction: mild elevations of the liver enzymes ALT and AST, and elevated bilirubin (released
into the circulation when red cells are destroyed), which can show in eyes and gums as yellowish
jaundice if sufficiently pronounced .
Specialized testing is called for to nail down a diagnosis of hemobartonellosis. The Coombs Test, a blood test for presence of auto-antibodies, will usually establish whether an immune-mediated
process is taking place. In a recent study, only cats infected with M haemofelis (of the three hemobartonella organisms) registered positive Coombs tests . Examination of blood smears by microscopy has been the traditional standard for diagnosis. In fact, CBCs will often carry notations on whether blood parasites were
observed by the pathologist, along with notations on unusual red cell types–Howell-Jolly bodies,
spherocytes, anisocytosis, polychromasia, and hypochromasia–all of which are characteristic of
this type of infection . The different species of mycoplasmas can be distinguished by
microscopy. However, as already noted, cats infected with hemotropic mycoplasmosis alternate
phases when parasites are or are not present in the bloodstream in significant numbers.
Therefore, a negative test may not be conclusive. Daily sampling may be necessary before
organisms can be found. One study found, “Definitive cytological evidence of infection was seen
only on blood smears collected between days 25 and 29 from the M. haemofelis-infected cat” .
According to Idexx, “the number of infected cells fluctuates quickly (in some cases declining
from 90% to less than 1% in under 3 hours) and infection can easily be missed. False positive
results are also possible because feline hemotropic mycoplasmas can be difficult to differentiate
from precipitated stain, other drying or fixation artifacts, poorly staining Howell-Jolly bodies,
basophilic stippling, iron-positive inclusions, Cytauxzoon felis organisms and small Babesia
Fortunately, PCR technology, which looks for binding of pathogen DNA with a known test
DNA, can verify even trace amounts of mycoplasma DNA in blood samples. PCR not only
detects the presence of M haemofelis, but quantifies the result, allowing monitoring of response
to treatment . An in-house study by Idexx found that of 303 samples evaluated by routine
microscopic examination, 10 contained M. haemofelis. “All 10 of these samples were positive for
M. haemofelis by IDEXX RealPCR. In addition, 29 additional samples, for a total of 39 samples
or 13%, were positive for M. haemofelis by IDEXX RealPCR. . . . PCR is up to 10 times more
sensitive than microscopic evaluation and will have a significant impact on the diagnosis of
feline hemotropic mycoplasmosis” .
3. Connection to FIV
The relation of M. haemofelis to FIV has been a subject of some disagreement; an association with FeLV is more broadly recognized. A 2006 Swiss study found that retroviral infections generally (including FeLV and FIV) did not increase the prevalence of infection, and noted that retroviral infection was similarly prevalent in healthy and ill cats found positive for these mycoplasmas . Another 2006 article published in Veterinary Microbiology found no meaningful difference in the blood chemistries of FIV+ and FIV- cats deliberately infected with M. haemofelis . The Marvistavet site associates M. haemofelis only with FeLV and claims (without source citation) that FIV does not enhance the severity of hemotropic mycoplasma infection .
The preponderance of opinion, however, points to an association. HIV, it should be noted, has a strong association with the human-infecting counterpart of M haemofelis. Antech lists an association with FIV infection . A 2004 review calls it a pathogen in conjunction with retroviruses, FIV as well as FeLV, a connection stated again in a 2007 German study . Another review for the 27th WSAVA Congress states that concurrent infection with FeLV, FIP, and FIV will worsen the anemic state . Recent studies in the U.S., Brazil , and New Zealand  have all found a marked statistical correlation of mycoplasma infection and FIV. A 2012 study concludes that "Chronic FIV infection appears to modify the acute phase response to feline haemotropic mycoplasmas" [20, Korman].
The 2004 review notes that "an acute and life-threatening exacerbation of hemolytic anemia in carrier animals may be activated by concurrent disease, stress, and immunosuppression" . This reactivation threat has a familiar ring (See the “FIV and Toxoplasmosis” page). Human AIDS patients have been shown to be at special risk for various problems as a result of infection with a human
variety of this type of organism. M. haemofelis as a reactivated infection in cats with FIV has never been studied.
M. haemofelis is treated with glucocorticoids and antibiotics, though the former is somewhat controversial. If infection is suspected but diagnosis is uncertain or pending, prophylactic
treatment is prudent if symptoms are severe. In a recent studies, both Marbofloxicin (2 mg/kg PO q24
h)  and Enrofloxacin (5 mg/kg POd q24)  showed significant activity against M. haemofelis. In an earlier trial, azithromycin did not . Doxycycline has been regarded as the antibiotic of choice. “Doxycycline has less side effects than other tetracyclines in cats and so is preferred. Doxycycline should be given at 10 mg/kg, PO,
every 24 hours for at least 14 days. If administered for 28 days, more cats appear to stay
persistently PCR negative” . Imidocarb dipropionate (5 mg/kg, IM, every 2 weeks for at least 2
injections) has been used successfully when other drugs have failed . “If autoagglutination
[clumping of red cells due to antibody cross-linking] is evident, prednisolone is usually prescribed at 1 mg/kg, PO, every 12 hours for the first 7 days or until autoagglutination is no longer evident. Tetracyclines utilized to
date appear to lessen parasitemia and clinical signs of disease but probably do not clear the
organism from the body. In one study, experimentally infected cats treated with doxycycline
have apparent clinical response but the organism could still be detected by PCR when the cats
were given methylprednisolone acetate” . In a new (2009) head-to-head study with
doxycycline, a new quinolone antibiotic, Pradofloxacin, “ had anti-M hemofelis effects similar to
those of doxycycline. In addition, pradofloxacin may be more effective at long-term M hemofelis
organism clearance than doxycycline” . Blood transfusion can be given if clinically
 Barbara Willi, Felicitas S. Boretti, Claudia Baumgartner, Séverine Tasker, Bettina Wenger, Valentino Cattori, Marina L. Meli, Claudia E. Reusch, Hans Lutz, and Regina Hofmann-Lehmann. Prevalence, Risk Factor Analysis, and Follow-Up of Infections Caused by Three Feline Hemoplasma Species in Cats in Switzerland. Journal of Clinical Microbiology, March 2006, p. 961-969, Vol. 44, No. 3.
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