Low-Dose Oral Natural Interferon Trials
Closed 1 July 2010
Summary of Results
Natural Interferon-Alpha is not the recombinant interferon ordinarily prescribed for cats. It is cultured from actual human cell lines rather than reproduced by recombinant DNA technology. See Interferons and FIV and entries on the Gingivostomatitis and Upper Respiratory Infection pages.
Clinical staging is a matter of some uncertainty with FIV, especially when available information varies among a number of individual owners and when no single knowledgeable
and experienced person is making the clinical judgments. For purposes of this file, recurrent
or refractory pathologies characteristic of cats with FIV infection or constellations of
problems associated with FIV are assumed to justify the label “ARC” (AIDS-Related
Complex). Cats who don’t meet these criteria but who have shown otherwise unexplained
lymphadenopathy and/or vague signs of disease, including recurring fever are categorized as
“PGL” (Persistent Generalized Lymphadenopathy). Cats whose blood work and/or clinical
health suggest deep immune suppression are categorized as “AIDS.”
1)
Cat. Huckleberry [m], born c. 1999 No Further Reports
Owner. Karin Gulbran, U.S.
Disease Status. Neuro-AIDS
History. Huckleberry was rescued as a kitten. Possibly the stress of a new cat in the household
triggered seizures and fever (106 F) in Huckleberry in July of 2006, at which time he was
diagnosed FIV+ by Elisa. There are several possible avenues of infection, some recent, some
not. How long he has been FIV+ is unclear. His CBCs were normal, and toxoplasmosis
was ruled out. Several more episodes of seizure, fever, and depression followed, but no
definitive veterinary diagnosis (“fever of unknown origin”) was forthcoming. It was
unknown if these symptoms were the result of FIV-related neurological inflammation. Prednisone
seemed to be successful in controlling symptoms, but was felt to be an imperfect solution in the
long term.
Natural Interferon Therapy. On September 23, 2006, Huckleberry began a regimen of dilutenatural interferon-α (Alferon), 50 IU daily (seven days on, seven days off), distributed on oral
tissue. Prior to treatment, prednisone was gradually withdrawn, but treatment was begun with
several days of overlap. The initial treatment period of Alferon was extended to compensate for
the overlap. On December 10 dosage was reduced to 25 IU out of the owner’s belief that a
smaller dosage will have optimal benefit. For a one-month period, spanning April and May 2007
Huckleberry received no interferon owing to supply problems. In mid-November 2007, after a
two-week weaning off period on half-dosage, Huckleberry began a trial stoppage of
phenobarbital. Alferon was suspended at that time because of demands on the owner’s time and
was not resumed.
Outcomes. On or about October 11, 2006, Huckleberry had another episode of seizure and high
fever (106 F) during which he injured a leg. Phenobarbital was prescribed to control seizures.
There have been no further actual seizures to date. However, on 3 November 06 Huckleberry
showed discomfort and fever. He was put on antibiotics. Urinalysis for possible bladder
infection revealed only proteinuria (+2). During the 06 holiday period the owner was absent.
Three interferon dosages were missed by caretakers. An episode occurred which a cat sitter
described as follows: “ . . . he suddenly looked at her like he had never seen her before, hissed,
and started to hide. He quickly snapped out of it.” Sitter described behavior as like his “seeing
ghosts.” A second episode occurred in the presence of the owner on 10 January 2007 and
resolved spontaneously within 24 hours. Temperature was not taken in either case, so it is
unknown whether any fever accompanied these episodes. In early February, a probable cat fight
produced depressive-seclusive behavior and evident pain. An outbreak of feline acne occurred
during in January 07, followed by some scratching & hair loss but both resolved or nearly so in
the spring, probably because of dietary adjustment. At the end of the one-month dosing lapse,
Huckleberry showed behavior similar to his earlier bouts of fever, although temperature was not
taken. Within two days of reinstituting Alferon therapy, behavior was normal and has remained
so during the period of administration. Huckleberry was feeling and acting normally at the time therapy was
discontinued. In March 2010 Huckleberry again experienced neurological events that included not only paranoid and seclusive behavior, but ataxia (impaired coordination) and weakness in the hind quarters. The owner speculates that stress was once again a trigger. Seizure medications were temporarily helpful, but Huckleberry died in July, 2010.
Discussion. Uncertainty about the time of Huckleberry’s initial infection and the relation or lack
of relation of his seizures, fevers, and depression to it is unresolvable. If the
assumption is made that Huckleberry was FIV+ for a number of years prior to the first seizure
episode, then there are at least some grounds for seeing natural interferon as beneficial for him,
since the general trend was away from these episodes. The recurrence of symptoms after several years does not of itself argue that cessation of all therapy -- including interferon therapy -- was a mistake, but certainly raises the possibility. In the absence of competing explanations, it must be assumed that FIV is responsible for the neurological symptoms and that one of two scenarios was at work: (1) the first episodes dating from 2007 were connected with initial (acute) infection and the 2010 episode with chronic infection or (2) both are connected to chronic infection. Stress as a potential trigger for FIV disease expression, including neurological symptoms, has been well documented.
2)
Cat. Simon [m], born c. 1990 No Further Reports
Owner. Karen Hipp, U.S.
Disease Status. ARC
History. Simon was a stray, rescued in 1996. He was diabetic, a problem well-controlled by
homeopathics after a period on insulin. He was diagnosed FIV+ by Elisa in September 2005
after having previously tested negative. In February 2006 he began to suffer from stomatitis and
faucitis. Despite various treatments with antibiotics, antivirals, anti-inflammatories, and
homeopathics, his stomatitis at the time of beginning natural interferon therapy was very severe.
He subsisted largely through syringe-feeding.
Natural Interferon Therapy. On October 18, 2006, Simon began a regimen of dilute natural interferon-α (Alferon), 50 IU. daily (seven days on, seven days off), distributed on oral tissue. Concurrently, he was treated with metacam, coloidal silver, amantadine, and other natural remedies the use of which preceded interferon therapy. Us of Alferon ceased on 9 January 2007.
Outcomes. As of 23 November, there was no change in Simon’s condition. His mouth area
continued to be very painful and inflamed, and for this reason distributing the interferon in the
gum area proved difficult. Doxycycline and niacinamide were added to his
treatment regimen with positive results that seem more likely to be owing to them than to the
Alferon. However, by January of 07, the improvement had pretty much vanished. Minor
episodes of sneezing occurred in early January, but without discharge or fever. On 9 January 2007 the owner
stopped giving Alferon and began giving 1.5 ml of oral prednisolone, which was reduced several
days later to 1.25ml (3.75mg). Within several days, the owner reported , “I already do see a
difference.”
Discussion. Natural interferon provided no visible benefit for Simon. His age and the
previously refractory nature of his stomatitis may be mitigating factors, but Simon’s experience
provides no grounds for seeing natural interferon as a significant therapy for at least some types
of stomatitis. It is well-established that FIV is an exacerbating factor in the expression of oral disease.
3)
Cat. Sammy [m], born c. 1998-2001 No Further Reports
Owner. Kelly Lane, U.S.
Disease Status. PGL or Asymptomatic
History. Sammy was trapped-neutered-released by the eventual owner in 2002. At that time he was diagnosed FIV+ by Elisa. In 2005 he was rescued and taken in by the owner to become part of a large feline population. He suffered
from a URTI in 2005 following rescue, but showed no recurrent or refractory FIV-related symptoms. Beginning in
November 2005 he exhibited persistent marble-size swelling of the submandibular lymph
nodes. Relation to the earlier URTI or to exposure to the larger feline population is unknown. Whether there was generalized lymphadenopathy is unclear. Sammy received dilute recombinant interferon-α orally for a period of about two weeks without effect.
Natural Interferon Therapy. On or around 11 October 2006, Sammy began a regimen of dilute natural interferon-α (Alferon), IU daily (seven days on, seven days off), distributed on oral tissue. Therapy was suspended in October 2007.
Outcomes. After 1 week of treatment with Alferon, lymphatic swelling was no longer evident or
palpable. (Both the lymphadenopathy and its disappearance were confirmed by Sammy’s vet.) In
early January 2007, Sammy contracted a URTI already contracted by other cats in the household.
Symptoms were stuffy nose, inflamed eyes, swelling of submandibular lymph nodes. After
treatment with clavamox and topical antibiotic for eyes, symptoms eventually resolved. As of late June 2007, Sammy registered a 1 ½ pound weight drop from December 2006, possibly as a result of his earlier infection and/or seasonal variability. Eventually he regained his lost weight.
Discussion. Given that Sammy’s lymphadenopathy existed for some time but did not recur at
all during the period when he has received Alferon, natural interferon appears to have been a
beneficial therapeutic agent. However, the natural process of clearing a community-derived infection cannot be entirely discounted.
4)
Cat. Boris [m], born c.1993. No Further Reports
Owner. Alma Williams, U.S.
Disease Status. ARC
History. Boris was with the owner since birth by a pregnant stray, and spent a period of his
earlier life out of doors, where he presumably contracted the virus by bite wound. In 2004, he
tested FIV+ by Elisa subsequent to development of stomatitis; diagnosis was confirmed by
Western Blot. Treatment with Lactoferrin, recombinant oral interferon, and antibiotics (clavamox and clindamycin) was followed by full mouth extraction and, sometime later, by laser
ablation of ulcerated tissue. There was no improvement of the stomatitis. Bartonella henselae
infection was confirmed in late 2004 and treated with azithromycin, again without improvement
of the stomatitis. In 2004, Boris experienced two short bouts of rectal inflammation and
diarrhea. In 2005 he was diagnosed with sporotrichosis, but was unable to tolerate medication.
Cutaneous nodules were successfully treated with topically applied Monistat. Despite extensive
treatment with antibiotics, supplements, steroids, anti-inflammatories, and immune modulators
(pentoxyfylline), stomatitis did not improve more than transiently.
Natural Interferon Therapy. On 3 November 2006, Boris began a regimen of dilute natural interferon-α (Alferon), 50 IU daily (seven days on, seven days off), distributed on oral tissue. He was being concomitantly treated with Olive Leaf, Lactoferrin, l-lysine, CoQ 10, and essential fatty acids, all of which had been part of the treatment regimen prior to beginning Alferon.
Metronidazole and low-dose prednisolone were stopped at the time Alferon was begun. In mid-January 2007 interferon therapy was suspended.
Outcomes. It was extremely difficult to properly administer Alferon to Boris. He recoiled when
administration was attempted as if the fluid itself were painful. He might not have been getting a
consistent dosage, and in the absence of other therapeutic support, his oral inflammation seemed
worse. Beginning on Dec 2, the interferon was mixed as a diluting agent with powdered bovine
lactoferrin. The result was better tolerated when administered. However, there was no
improvement in Boris’ oral inflammation; if anything, it worsened. Minor episode of sneezing
in early January, quickly resolved. In early January 2007, the owner reported serum chemistries
indicating chronic renal failure (BUN/169. Creatinine/5.8. Phosphorus/13.3). Hydration with
lactated Ringers solution was begun. CBC showed high neutrophils and low lymphocytes,
indicating an infection, but of unknown origin and of unknown relation to renal values. The
presumed infection seemed to clear by March 2007, but Boris remained "tired." In April 2007 Boris died. His deteriorating renal function clearly played a role, though the exact cause of death was not determined.
Discussion. It is possible that Boris’s age and CRF compromised the ability of his immune
system to respond to Alferon. The period of administration was relatively brief and circumstances of administration were not optimal, but his experience provides no reason for seeing natural interferon therapy as an effective therapeutic agent in the treatment of at least some types of stomatitis.
5)
Cat: Dorje [m], born 2006 No Further Reports
Owner: Karen Eckhoff, U.S.
Disease Status: Uncertain, possible vertical infection.
History: Dorje was adopted from a shelter. At his post adoption veterinary visit he was screened
FIV positive by Elisa, with the result subsequently confirmed by Western Blot. A retest at six
months was likewise positive. His age suggests the possibility that he was infected maternally in
utero or subsequently; however, scarring about the ears leaves open the possibility of infection by
wound at an early age. An upper respiratory infection that existed prior to adoption failed to
resolve satisfactorily despite repeated rounds of antibiotics.
Natural Interferon Therapy. On 12 December 2006, Dorje began a regimen of dilute natural
interferon-α (Alferon), 50 IU daily (seven days on, seven days off), distributed on oral tissue.125 mg l-lysine bid, which was begun prior to starting interferon therapy, was continued. Lysine was discontinued and Lactoferrin (62.5 mg twice daily) added on 5 February 2007. Subsequently, more supplements were added. In addition to a multivitamin, he now received 100iu Vitamin E twice a week, and 75mg NAC and 62.5mg Vitamin C twice a day (total 150mg and 125mg,
respectively). He began the NAC and Vitamin C on March 9, 2007, and the vitamin E has been
given since February 18, 2007. Lysine was restarted in April 2007. L-Carnitine replaced Vitamin C for a time in May 2007, but Vitamin C subsequently replaced L-Carnitine. After a hiatus
of several months in early winter during which supplements were not given, Dorje began again
getting them, although he resisted eating the food to which they have been added. In February
2009 the owner stopped administering Alferon and all other supplements for economic reasons.
Outcomes. The owner reported some reduction in lymphatic swelling at the end of the first week
of administration and possible improvement in URTI symptoms. Upon Dorje’s return from
boarding at a vets (during which lysine was stopped) during the second off-admin week, URTI
seemed worse again, with some depression exhibited. During February and March, upper
respiratory symptoms waxed and waned, though the owner reports that “sneezing subsided
somewhat” and that Dorje was now active and playful. A mid-April veterinary checkup found
Dorje’s lymph nodes normal and only slight nasal congestion. The vet conjectured that the
lymphadenopathy thought to exist by the owner was probably nonexistent. The vet (holistic)
approved Dorje’s regimen of supplements and speculated that a change of food might have
helped to relieve allergy with a possible role in the URTI. A late summer 2008 checkup found
him well and normal in all regards. He remained outwardly normal and energetic until cessation of therapy. The
owner reported at one point that he seemed more active and energetic during “on” weeks of
interferon, although his veterinarian reported that his teeth had an unusual buildup of plaque for
his age.
Discussion. The recurrence of URTI symptoms of uncertain etiology during the administration
period of Alferon and the occurrence of the period of best health after a number of other
supplements were begun cloud the case for judging natural interferon therapy an unequivocal
success. Since it is uncertain whether lymphadenopathy existed at the beginning of therapy,
it is difficult to assess the effectiveness of the interferon in that regard. Attribution of URTI to food allergy is unusual, but further clouds assessment. It is possible, but not conclusively so, that
the state of Dorje’s good health after spring 2007 owed something to Alferon.
Continued good health during a hiatus from supplements but continuation of interferon may or
may not be significant.
6)
Cat. Zouzou [m], born c. 1994 No Further Reports See Reports: Bud's Therapy and Other Cats
Owner. Marcel Blanc, France
Disease Stage. Late ARC or early AIDS
History. Zouzou was taken in as a stray in January of 2005. In March 2005 he was treated for an epithelioma (a type of cancer) of the ear that was probably FIV-related. After suffering bouts of
gingivitis, including the loss of two canines, Zouzou was diagnosed by Elisa as FIV+ in August,
2005. The finding was confirmed by PCR in October 2005. CBC showed lymphopenia (
low lymphocytes) and anemia. A prognosis of 6-12 months to live was given. Kidney values on
serum chemistries showed marginal BUN and creatinine, suggesting possible initial stages of
chronic renal failure. From November 2005 to December 2006, Zouzou was successfully maintained with a combination of HIV antiretroviral drugs, Feline Omega Interferon, and several supplements. Hematology normalized, gingivitis was well-controlled, and overall clinical health improved considerably. During this period a very small epithelioma of one ear did occur, and was treated successfully. (See Reports . . .)
Natural Interferon Therapy. On 17 January 2007, Zouzou began a regimen of dilute natural interferon-α (Alferon), 25 IU. daily (seven days on, seven days off), distributed on oral tissue. NAC, which had been used the previous year and stopped, was restarted at about the same time. On
May 31, 2007, Zouzou began 0.5 mg Methyprednisolone given orally each day in a gelatin capsule, along with 250 mg daily of Niacinamide and (somewhat later) 50mg of Selenium, these in addition to his established regimen of Alferon and supplements (Vitamin A, Vitamin C, and NAC). On June 25, dosage of methylprednisolone was raised to .75 mg daily because of unresponsive oral inflammation. In
early August, unfavorable test results led to dropping Niacinamide, Selenium, and NAC from the
treatment regimen and tapering off Vitamin C with a view to stopping it; Emtricitabine, an antiretroviral drug which had been continued at reduced dosage to maintain a weakened strain of virus, was
discontinued. At the same time, Olive Leaf (300mg daily) was begun and Alpha Lipoic Acid shortly thereafter. In late September, Zouzou began taking the anticancer drug Gleevec, which has also shown in studies an ability to inhibit HIV replication in macrophages.
Low-dose methylprednisolone was stopped in order to avoid interactions with the Gleevec. Gleevec was
stopped because of rising liver-associated values. It could not be restarted because of a potential
drug interaction with heart medication. Alferon was discontinued in December 2007 near time of death.
Outcomes. Zouzou died on 9 December 2007 of lung edema secondary to heart disease. His decline was sudden in onset. Following is a record of Zouzou’s blood values from the period immediately preceding initiation of natural interferon therapy until death.
---------------Viral Load/RNA----Viral Load/DNA----W(hite)BC----Lymphocytes----Hematocrit----CD4:8
12/2006--------45,000/ml----------------34,000/ml----------8,860/mm3--------6,379/mm3-----------44.5
04/2007--------50,000/ml----------------70,000/ml---------15,200/mm3-------6,384/mm3-----------36.3
05/07------------------------------------------------------------9,910/mm3--------2,973/mm3-----------31.6--------- .1
08/07(early)---309,000/ml---------------20,300/ml---------10,380/mm3-------1,042/mm3 ----------40.7----------.1
08/07(late)----106,000/ml----------------18,100/ml---------10,180/mm3--------814/mm3------------27.6---------.25
09/07------------------------------------------------------------7,900/mm3--------1,975/mm3-----------19.3
12/07-----------47,610/ml-----------------18,410/ml---------11,400/mm3-------2,300/mm3-----------25.2
Viral Load. The PCR assay done about three months after beginning oral
interferon showed a doubling of proviral (DNA) load from that done in the month immediately preceding the beginning of the drug, and an assay after that showed a largejump in free virus (RNA) with a curiously low count of provirus (DNA). The steep decline in RNA and DNA viremia measured by the final viral load test probably owed much to cancer therapy, but fell so much that olive leaf and ALA almost certainly had a role, as well. The decline in proviral DNA from 8/07 forward was certainly related to the decline in lymphocytes generally. Hematology. After the end of NRTI therapy, the lymphocyte-neutrophil differential varied considerably. A series of CBCs showed a tendency to inversion of the normal neutrophil dominance, but there was twice a correction. It is unclear to what extent–if any–these variations were owing either to therapeutic agents (feline interferon in the first case, Alferon
thereafter) or clinical factors, such as gingivitis or primary immune activity directed at FIV. Red
blood cells (as indicated by hematocrit) had been within the normal range since the beginning of
antiretroviral therapy. The decline in hematocrit beginning in August 2007 was almost certainly
owing to cancer. However, after starting Gleevec, hematocrit climbed to 31.9 (10/31), indicating
a favorable impact of the drug and/or limb amputation on anemia. After Gleevec was stopped,
hematocrit fell to 25.2. Immune testing done in May and August 2007 showed a very low
CD4:CD8 ratio of .1 The testing was done with an immunochemistry method to assess a
CD4/CD8 ratio through counting CD4 antibody reacting patches and counting CD8 antibody
reacting patches. The CD4/CD8 ratio so obtained mirrors only crudely the real CD4/CD8 ratio
obtained through counting the individual CD4 or CD8 lymphocytes by flow cytometry. A third immune test done in early September 2007 showed a rise in ratio to .25. In the absence of absolute figures, the full significance of these surprisingly low ratios is unclear. Clinical. Shortly before
the time that oral interferon therapy was begun, Zouzou began to show signs of a return of
gingivitis. In January 2007 a veterinary visit revealed two areas of inflammation. In the months
that followed, despite oral interferon therapy and repeat courses of clindamycin and metacam,
mild to moderate gingivitis remained a problem. Apparent improvement of gingivitis with the
addition of low-dose methylprednisolone was noted almost immediately, but by mid-June signs
of increasing discomfort were reappearing, only to decrease and disappear entirely by the end of
June, probably in response to an increase in dosage. No further symptoms of gingivitis appeared
for the rest of Zouzou’s life. The owner observed no side effects of the oral
natural interferon or of the low-dose methlprednisolone. In August 2007, following noticeable
swelling, a diagnosis of osteosarcoma in one hind leg was confirmed. Amputation of the leg
took place on 11 September 2007. Histological analysis of associated lymph nodes showed
metastasis of a particularly virulent form of osteosarcoma. The owner elected not to have
chemotherapy done, but began use of the anticancer drug Gleevec. In November 2007,
echocardiography led to a diagnosis of hypertrophic cardiomyopathy, the left ventricular wall
being found to be very thickened, the left ventricular cavity almost nonexistent, and the left
atrium maximally dilated. In mid-November, an episode of lung edema (no doubt associated
with cardiac disease) occurred and was resolved with diuretics. Zouzou died on 9 December
2007 of lung edema secondary to heart disease. His decline was sudden in onset.
Discussion. Beneficial effects of the oral natural interferon-α were undemonstrated and must have been
subtle over time if they occurred at all. Low-dose methylprednisolone was effective with regard
to gingivitis. It seems likely that cancer had a major role in the viremia and declining immune
status which occurred subsequent to beginning low-dose steroid therapy, but there are no grounds for
concluding that the therapy was as successful in controlling primary FIV infection as it was the
oral inflammation secondary to it. Based on Zouzou's experience, it is impossible to say whether low-dose steroids and low-dose interferon are a compatible or incompatible combination. The final two viral load assays may validate the ability of olive leaf (in conjunction with the antioxidant alpha lipoic acid) to significantly impact viral
burden. Because the only T cell testing took place in the months prior to diagnosis of cancer, it is
difficult to know whether the overall control of Zouzou’s viral burden was reflected in
improvements in the immune cells most immediately impacted by FIV. It is also difficult to say
whether the development of cancer and heart disease owed anything to FIV infection–with which
increased risk of organ failure and many forms of cancer are associated–or to any therapeutic
agents.
7)
Cat. Zuzu [m], born c. 2002-03 No Further Reports
Owner. Patrizia and Andor Ginder, Botswana
Disease Stage. ARC/AIDS
History. Prior to his rescue in January 2006 Zuzu was a neighborhood stray, though he seemed to be accustomed to human contact. He tested negative for FIV at in January 2006. After Gasha, a prexisting cat in the household, died of FIV/FeLV/FIP/Hemobartonella in July 2006, Zuzu was
retested for FIV and FeLV by Elisa. This time he tested positive for FIV. It is therefore
possible that Zuzu’s infection was of recent origin and that Gasha was the source. He was
clinically healthy from the time of adoption. Baseline bloodwork showed normal red values
(HCT 44.2%, HGB 13.4g/dl) but a low white cell count (2400). An evidently faulty CBC in May
2007, showed abnormally low values. However a retest showed normal white counts (7600); red
cells remain in the vicinity of the baseline test (HCT 40.3%, HGB 12.8g/dl). Immune testing was
done at that time, viral load testing shortly thereafter. Results were consistent with chronic FIV infection. Virus was identified as Clade A. Results
follow:
--------------------------------------Reference values -----May, 2007
T-cells - ------------------------------(58-77%)----------------51%
CD4+ cells - -------------------------(26-42%)---------------22.5%
CD8+ cells ---------------------------(18-36%)---------------25.5%
Ratio CD4+/CD8+ -------------------(.81-2.00)---------------0.88
B-cells –-------------------------------(14-33%)---------------29.5%
T-cells-------------------------------- (996-3164)-------------734.5M/l
CD4+ cells--------------------------- (468-1638)-------------324 M/l
CD8+ cells----------------------------(311-1338)-------------367 M/l
B-cells------ --------------------------(252-1068)-------------424.8 M/l
Proviral Load --------------------------------------------------45,500 DNA/ mil cells
Free Viral Load-------------------------------------------------17, 800 RNA/ml plasma
Natural Interferon Therapy. On 12 August 2007, Zuzu began a regimen of dilute natural interferon-α (Alfaferone), 50 IU daily (seven days on, seven days off), distributed on oral tissue. On 19 August, 1 20mg capsule of Moducare daily was begun, followed on 1 September by 125 mg of Ester C twice daily and Vitamin E 100mg twice weekly. Vitamins C and E are given in alternate months.
Outcomes. Zuzu remained in good health until May, 2009, when he ran a high fever, which was attributed to a bacterial infection. The illness resolved with antibiotic therapy (Synulox). New viral load and immune status testing were placed on indefinite hold because of legal difficulties in exporting blood for testing to Germany. On 12 September, 2009 Zuzu began to show subtle symptoms of a reduced appetite and activity. Several days later he was taken to a local vet, who found fever (>40 C) and elevated WBC with left-shift, indicating acute infection. Antibiotics (Synulox) were again administered, in addition to ketoprofen for fever. Response to therapy was poor. On 17 September Synulox was discontinued and doxycycline and metronidazole begun. Response to therapy remained poor. On 23 September Zuzu was admitted to the Academic Veterinary Hospital in Pretoria, South Africa. Amoxcilin clavulanate and enrofloxicin, ketofen (ketoprofen) and IV fluids were administered. Fever resolved, but Zuzu stopped eating, and clinical signs continued to deteriorate. Ultrasonography was unremarkable save for “mildly increased cortical echogenicity” in the kidney, which the ultrasonographer interepreted as evidence of “mild chronic renal disease.” Hematology revealed neutropenia (2590) with severe degenerative left shift, severe thrombocytopenia, and moderate lymphopenia. Serum chemistry showed severe hypoalbuminaemia, moderate hypergammaglobulinaemia, mildly elevated urea, and severely elevated ALT (1071 U/L) with normal ALP and GGT. Urinalysis revealed proteinuria with red and white blood cells and casts. Culture was negative. Diagnosis was acute pyelonephritis. On 25 September Zuzu deteriorated to a moribund state. His clinical signs included hypothermia, bradycardia, pale yellow mucous membranes and multifocal neurological signs. Immediate resuscitation therapy was initiated. The attempt was not successful and Zuzu died. A post mortem was performed. The report reads as follows. “A stored serum sample was sent for Toxoplasmosis gondii titres and was negative on a screening dilution of 1:50. There was pronounced icterus of all the mucous membranes and the subcutaneous fat. Samples of all organs, except the brain, were sent for histopathology. The findings on organ histopathology included an acute pyelonephritis together with shock lung and an acute embolic myocarditis. The fluid aspirated from the abdomen and the thorax post mortally did not shed more light on the antemortal causal agent. Comments: The severe leukopaenia can be attributed to the FIV status of Zazu, however with the cystitis and pyelonephritis this haematology picture may well have been the indication of sepsis. It is however very difficult to postulate as to why Zazu, although previously treated with a variety of antibiotics still succumbed to Systemic inflammatory response syndrome (SIRS) and Multiple organ dysfunction (MODS). The primary trigger in SIRS AND MODS is often eliminated, it is however the bodies inappropriate reaction that leads to the patients demise.”
Discussion. The timeline of Zuzu's mortal illness is consistent with acute pyelonephritis. That is, the bloodwork done on 14 September showed an elevated white count with left shift, the left shift indicating excessive demand on bone marrow for new cells to deal with acute infection. This bloodwork--and a fever over 40 C.--is consistent with acute pyelonephritis, or inflammation of the lower kidney owing to bacterial infection. The subsequent leukopenia (a shift from excess to dearth of white cells) with further degenerative left shift, neutropenia, and extreme thrombocytopenia (dearth of neutrophils and platelets) in the bloodwork of 23 September indicates that sepsis had occurred in the interim; that is, that bacteria had entered the blood stream and that septic shock and systemic inflammatory response (SIRS) followed from it, which included adherence of mature neutrophils to blood vessel walls, resulting in a low absolute neutrophil count and predominance of immature neutrophils. Multiorgan failure is a direct consequence of sepsis and accounts for the compromise of liver, lungs, and heart indicated in bloodwork and PM. As noted on the report, SIRS involves an exuberant and inappropriate immune response; it is a not uncommon consequence of sepsis. The observation of the post mortem report regarding attribution of severe leukopenia to FIV status seems unwarranted in light of the fact that WBC was elevated, not depressed, at the outset of presentation. The most common causes of pyelonephritis are (1) ascending infection from the lower urinary tract and (2) obstruction within the kidney, such as might, for instance, be caused by kidney stones. It has also been noted, however, that bloodborne bacteria lodging in the kidney can also be a cause. It is unclear what the cause was in Zuzu's case. The Merck Veterinary Manual lists immunosuppression as a predisposing factor to development of pyelonephritis. The only detail out of keeping with a diagnosis of acute pyelonephritis is the negative result of the urine culture. In the case of acute (rather than chronic) pyelonephritis, a positive culture is more usual than not. A relationship of Zuzu’s May 2009 illness to his FIV status is uncertain, but probable in light of his subsequent--and this time fatal--infection. As to the role of FIV in Zuzu's final illness, the nonresponse to therapy, including aggressive antibiotic therapy is not inconsistent with deteriorating immunity, a working definition of AIDS sometimes being “when antibiotics no longer work.” However, given the presence of sepsis (which is inherently life threatening) and the significant threat posed by acute pyelonephritis, it is hard to say with certainty that FIV was the key factor, though this seems more likely than not, particularly if the infection of May, 2009 is viewed as “a shot across the bow.” It is clear that sepsis rather than pyelonephritis was the proximate cause of death since extensive destruction of kidney capacity does not appear to have been present. A minor but surprising detail of the ultrasonography report was the mention of mild chronic renal failure. Zuzu was young to be experiencing even mild renal failure, but this has been reported as a feature of chronic FIV infection. However, this finding may simply have been a mistaken interpretation of changes in the kidneys owing to pyelonephritis.
One cannot know whether Zuzu would have suffered other health problems or an earlier demise in the absence of interferon therapy (in conjunction with the phytosterol and vitamin supplements he received.) He was healthy for nearly two years after beginning therapy as an asymptomatic cat. However, the therapeutic program did not ultimately prevent illness or death.
8)
Cat. Carlo [m], born c. 1995 No Further Reports See Reports: Bud's Therapy and Other Cats
Owner. Ulrike Roediger, Germany
Disease Status. ARC
History. Carlo was a stray, who has been part of his owner’s household since 1996. For about
the first four years of this period he was an outdoor cat. During this period he suffered lung
inflammation, which was successfully treated with antibiotics. In May, 2004 he began to show
dermatologic disorders (dandruff, hair loss) at the base of the tail which did not resolve, despite
testing and treatment. In June 2004 Carlo tested positive for FIV. Oral inflammation resolved
after dentistry. Beginning in November 2004, Carlo received a series of 5 injections of feline
omega interferon with a view to improving his general condition. Deterioration continued. By January 2005 he was showing continued dermatitis, lymphadenopathy (swollen lymph nodes) from the submandibular area to the base of the spine, and
general fatigue and depression. From April 2005 through September 2006, the owner, inspired by theories of Dr. Alfred
Plechner, began giving monthly depo injections IM. Lymphadenopathy began to recede in April 2006. Carlo gained weight excessively throughout 2006, partly as a result of improved food consumption, partly as a side effect of
steroid use. Tapering of steroid dosage brought weight under control, and he slimmed down
from 7.5 kg to 6.4kg. In October 2006, oral prednisolone at a dosage of .5 mg daily was substituted for monthly injections. Concurrently, Carlo began receiving olive leaf and small doses of niacinamide supplements, followed by Vitamin C, Vitamin H, Vitamin B-complex and B-12,,
thistle oil, and silymarin (for liver health) throughout 2007. Carlo showed illness and loss of appetite
in early June 2007, which clindamycin cleared up. The problem of hair loss proved recurrent into 2008, with sections of the abdomen and hindquarters denuded. In April 2008, Carlo began to display a limp in the left foreleg.
For a time in early 2008, Carlo was less active than normal, despite a dental cleaning and
removal of a bad tooth.
Therapy. On 9 May 2008, Carlo began a regimen of dilute natural interferon-α (Alfaferone), 50 IU daily (seven days on, seven days off), distributed on oral tissue. Lactoferrin was added to the existing treatment regimen shortly before the interferon. In Novermber 2008, both lactoferrin and Alfaferone were discontinued, although other elements of pre-interferon therapy continued.
Outcomes. Clinical. A limp that began in April 2008 gradually improved and appeared to be a mechanical injury. For several weeks, vomiting occurred the morning following administration of Alfaferone, necessitating its suspension. Resumption went without incident. Similarly, in November Carlo experienced bouts of itching following several administrations of Alfaferone. Whether this was coincidental is unclear. However, administration ceased for good owing to a fear that Carlo was allergic to the human origin of the interferon. Hematology. Blood work from 20 May 2008 showed a healthy WBC and HCT. (For selected bloodwork, see Reports . . .) A slight elevation of T4 was of uncertain significance. A November 2008 check of renal values was normal. Carlo was eating normally and, apart from his skin problems, feeling well, and
maintaining normal weigh at the time of cessation of Alfaferone.
Discussion. Mild side effects are occasionally noted anecdotally for oral interferon. Vomiting is
a significant and unusual side effect. The likelihood is that this reaction to natural interferon, if
there was a causal link, was peculiar to Carlo because of his allergy profile. Whether low-dose
Alfaferone and low-dose prednisolone are an effective combination is difficult to judge from
Carlo’s experience, although it is unlikely that addition of the former lessened the demonstrated
effectiveness of the latter. By the same token, a decline in clinical health that took place in the
months following the end of interferon therapy may or may not have had anything to do with the
cessation.
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Summary of Results
The following report was forwarded to the team that conducted the study which occasioned this trial.
Dear Dr. Amadori,
This response has been five years in the making, as your attached message indicates. You were kind enough to respond back in 2005 to my inquiries about the study of Alfaferone for FIV in which you participated. Specifically, I was curious why you had chosen a natural interferon for the study. Subsequent to your response, I began an on-line forum, FIV-HealthScience. An early project during the first year of the group (August, 2006 forward) was to track the experience of members who chose to try natural interferon-a as an FIV therapy in as formal a trial as was possible under the circumstances. It may be that you are no longer as interested in the subject now as you were in 2005, but I am writing to report on the results in the event that it has even mild curiosity value for you now. Such a report was part of the plan back in 2006. The actual case histories can be accessed at http://www.fivtherapy.com/fiv_infntrials.htm. I include a synopsis of the results here.
They rise to nowhere near the standards of a formal scientific trial, as you can imagine. They were dependent on the reportage of individual owners without a background in veterinary medicine. Staging of infection involved some guesswork. Most participants co-administered other agents concurrently with the oral interferon; some of these were supplements, but two people attempted low-dose (< 1mg daily) steroid therapy at some point during the period of interferon administration. In a few cases there were interruptions in therapy, and several people had administration difficulties because of cats with severe oral inflammation. One person (whose cat had numerous allergic issues) stopped administration earlier than planned because of a possible allergic reaction (it was speculated) to the human origin of the drug (as unlikely as that seems given the level of dilution) or to some component of the diluent. Two people chose to use a 25 IU dosage instead of a 50 IU dosage in deference to other sources (Cummins, Weiss et al) who believed that a greater dilution was optimal with natural interferon.
Eight cat owners and eight cats participated in the trial. The last person still administering natural interferon lost the cat receiving it in September, 2009, but was very late in reporting the details. Of the eight cats, one (1) was classed asymptomatic at the outset of the trial and four (4) as ARC. Two (2) were classified very tentatively as PGL, in one case because the lymphadenopathy could not be confirmed as generalized; in the other because symptoms were solely neurological, but the circumstances of infection left unclear whether this was an after effect of acute infection or a first symptom of chronic infection. In the second case, subsequent events indicated development of probable neuro-AIDS. The last cat (1), which was evidently vertically infected, defied classification because of lack of sufficiently verified information regarding symptoms and a possible allergy component.
Of the aforementioned cats, none with oral inflammatory disease (two severe and one moderate) experienced any benefit whatever. The cat who was asymptomatic at the beginning of the trial experienced a serious but responsive bacterial infection 21 months into therapy and a fatal infection four months later. One ARC stage cat experienced a significant spike in viral load during the period immediately following the beginning of therapy. The cat with neurological symptoms experienced no clear benefit from the interferon during the period following initiation of therapy, although anti-inflammatory and anti-seizure medications were effective. Only one cat clearly improved in the period immediately following initiation of therapy; this was a cat with submandibular lymphadenopathy; a second cat (the vertically infected cat with possible allergies) may have experienced improvement. In several cats, extended benefit over time, while possible, was not clearly demonstrated. Whether the asymptomatic cat who eventually succumbed to infection would have experienced health problems sooner without the interferon is impossible to say.
In summary, no dramatic benefits were evident. It seemed pretty clear that significant oral inflammation was unaffected by the interferon, although two of the three cats so afflicted had outworn numerous other therapies prior to attempting interferon and the owner of one of these (probably foolishly) stopped using antibiotics at the beginning of the period of administration. The one unequivocal success (resolution of submandibular lymphadenopathy) may or may not have involved an FIV-related condition. Of the nine cats, three (2 in S. Africa, 1 in Germany) received Alfaferone, six (5 in the U.S., 1 in France) received Alferon.
Interest remains strong among people with FIV+ cats, both sick and well, for effective therapies. Thank you again for your long-ago feedback and for having participated in a study that seemed to have the actual well-being of cats behind it, as opposed to having half an eye to HIV.
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