Is CRGV (Alabama Rot) the result of radiation poisoning? by Laura Holm

Alabamarot.co.uk received an email today from Laura Holm of Anderson Moores Veterinary Specialists in Winchester. Laura wrote:

“I have come across comments indicating that people are concerned about CRGV being the result of radiation poisoning. All possibilities are being carefully considered, but the histopathological changes seen with CRGV are different from those seen in the kidney following radiation damage – namely with CRGV, the glomerular capillaries specifically are targeted, whereas with radiation nephropathy, the vessels throughout the interstitium undergo damage.”

Could Alabama Rot be similar to Leishmaniasis?

2006 Frank Collins Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies, injecting the infective stage (i.e., promastigotes) from their proboscis during blood meals. Promastigotes that reach the puncture wound are phagocytized by macrophages ,and other types of mononuclear phagocytic cells, and inside these cells, transform into the tissue stage of the parasite (i.e., amastigotes), which multiply by simple division and proceed to infect other mononuclear phagocytic cells. Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. Sandflies become infected by ingesting infected cells during blood meals. In sandflies, amastigotes transform into promastigotes, develop in the gut, (in the hindgut for leishmanial organisms in the Viannia subgenus; in the midgut for organisms in the Leishmania subgenus), and migrate to the proboscis. See PHIL 3400 for a diagram of this cycle.
2006, Frank Collins. Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies…

Update 19th October 2016

Laura Holm of Anderson Moores Veterinary Specialists in Winchester today sent an email to alabamarot.co.uk. Laura wrote:

“I was looking at alabamarot.co.uk and noticed the thread about Leishmaniasis. I just wanted to let you know that we are confident that CRGV is not caused by the Leishmaniasis for a number of reasons: There are significant clinical differences between CRGV and Leishmaniasis. Additionally, Leishmaniasis can be readily diagnosed when a post mortem examination is conducted, and none of the dogs with CRGV had compatible post mortem findings.”

Could Alabama Rot be similar to Leishmaniasis?

Further to a comment yesterday by Margaret Hughes, I’ve published my draft post from June 8th 2015.

Canine Leishmaniasis (wikipedia) is:

“a zoonotic disease caused by Leishmania parasites transmitted by the bite of an infected phlebotomine sandfly… Symptoms include skin lesions and kidney injury.”

The life cycle of L. infantum with indication of proven and unproven non-sandfly routes of transmission to dogs.

Laura Holm and others said:

“Skin lesions are not commonly associated with AKI in dogs,
unless the AKI has resulted from immune-mediated disease
(Fournel and others 1992), certain neoplasms (Moore and others 1994), infectious diseases (Ferrer and others 1988) or vascular events, such as vasculopathy (Goldfarb and Adler 2001).”

The infectious disease reference by Ferrer and others 1988 is titled “Skin lesions in Canine Leishmaniasis”.  It was republished (preview) in 2008:

“Canine leishmaniasis is a severe, often fatal disease of the dog caused by the protozoan parasite Leishmania donovani”

The following report stated that 20 foxhounds dogs in New York died of Leishmania in 1999/2000:

” … due to infection with the protozoan parasite
Leishmania spp… The dogs had … clinical signs including wasting, hemorrhage, seizures, weight
loss, hair loss, skin lesions, kidney failure, and
swollen limbs and joints. Testing revealed that
42% of adult dogs at the kennel were
serologically positive for antibodies against
Leishmania, and the organism was isolated from
15 seropositive dogs.” (ref: vet.uga.edu)

Infection with Canine leishmaniasis induces:

“a cytokine response which results in over-exuberant antibody production. Excessive immune-complex formation results in the development of lesions in the kidneys, joints, eye and blood vessel walls.” (ref: Leishmaniasis.info)

Dogs can take several years to show symptoms after infection:

“After being bitten, there is an interval of one month to several years before dogs become ill. In these dogs, the parasite lies dormant, sometimes for years before a stressor allows the parasite to multiply and cause disease. In virtually all dogs, it spreads throughout the body to the internal organs such as the liver, kidney and spleen, causing a chronic, debilitating, and sometimes fatal disease, with many dogs dying of kidney failure.” (ref: yourvet)

Alabama Rot attacks the skin and kidneys only, not the liver or spleen. But could Alabama Rot be similar to Leishmaniasis?

Chris Street of AlabamaRot.co.uk talks to BBC Surrey

On 4th July 2016 Chris Street from AlabamaRot.co.uk talked to James Cannon & Suzanne Bamborough from the BBC Surrey breakfast show.

There have been several cases of Alabama Rot in Surrey in 2016 and in previous years (see map).

Listen (for 29 days) to the  top story from BBC Radio Surrey from from 01:00:18 to 01:00:57, 01:07:26 to 01:16:05 and then from 02:08:02.

Chris Street speaks from 02:13:15 to 02:16:07 about the Alabama Rot map, where he now walks his dog and what are the main symptoms of Alabama Rot to look out for. After 4th August listen to Chris here:

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surrey

bbc-radio-surrey

Donate to the Alabama Rot Research Fund (ARRF)

arrfLaunched on 16th June 2016, the Alabama Rot Research Fund (ARRF) aims to raise £240,000 to fund a PhD candidate and other research. The ARRF aim is to find the causes, prevention and treatments for Alabama Rot.

Donate to AARF here.

Alabama-320x185-worthington
David Walker (Anderson Moores) & Molly, Jessica Worthington, Heather Gould (New Forest Dog Group) and Laura Holm (Anderson Moores). Jessica a veterinary nurse raised an amazing £10,400 for the Alabama Rot Research Fund after her cocker spaniel Pippa died of Alabama Rot.

4th July 2016 update: Jessica Worthington, who lost her Cocker Spaniel to Alabama Rot, talks to ITV about her experience and raising money for ARRF.

What causes Alabama Rot? How can it be prevented? By Anderson Moores Veterinary Specialists.

David Walker and Laura Holm of Anderson Moores Veterinary Specialists update the Alabama Rot story (April 2016). Anderson Moores say:-

Is CRGV caused by E.coli? Faeces, skin lesions, and kidneys of dogs with CRGV have been tested for E.coli, which can cause a similar illness (haemolytic uraemic syndrome, or HUS) in people. No E.coli have been found. Kidneys from affected dogs have been tested for Shiga toxin produced by E.coli – NONE has been found. Blood from affected dogs has been tested for antibodies to E.coli which cause HUS – NONE have been identified. So can we completely exclude E.coli? – Unfortunately not quite yet, because these bacteria and their toxins can be very difficult to isolate / identify, however, it currently appears to be an unlikely cause. Investigations are ongoing …”

Anderson Moores ask:-

“What other possible causes for CRGV have been investigated?”

“Is it Leptospirosis? (Weils disease)
Most dogs with CRGV were negative when tested for Leptospirosis and many were vaccinated against Leptospirosis (which helps to protect against infection with Leptospira).
Additionally, most dogs which have Leptospirosis respond well to treatment, as opposed to the poor response to therapy seen with CRGV.”

“Is it Lymes Disease? (carried by ticks)
Ticks are active in Spring and Autumn, rather than Winter (so the wrong time of year for CRGV). Some signs of Lymes disease are similar, but most importantly, the microscopic changes (pathology) in the kidney are totally different from CRGV.”

“Giant Hogweed?
This grows in summer. It causes nasty skin lesions in sun light, but is not associated with acute kidney failure. Recent work by [a] senior botanist suggests that it is unlikely for any plants,
trees, fungi, or shrubs to cause CRGV.”

“Fish bacteria? (Aeromonas).
This is currently under investigation. Aeromonas produces a toxin (a bit like E.coli) which could cause CRGV. Aeromonas cause disease in fish, including skin lesions. There is a study checking for evidence of Aeromonas infection in dogs with CRGV.”

“Military Ordnance?
There has been no evidence for heavy metals, bacteria, or toxins in soil or water samples tested from the New Forest, and none identified in kidneys of affected dogs.”

“Radioactivity?
The clinical signs of CRGV are not consistent with radiation poisoning. Radiation would affect all dogs equally in an affected area, which is not what we see with CRGV.”

Anderson Moores say:-

“How can CRGV be prevented? As the cause remains unknown it is very difficult to advise how best to avoid CRGV.

Washing dogs after a walk (using tepid water) might be a sensible precaution but it is unknown as to whether this is either necessary or of any benefit (please do not use strong antiseptics / disinfectants or other chemicals to bathe dogs. This could be harmful.)

There is no evidence that dogs can catch CRGV from each other (dogs which walked together were more likely to all be affected than dogs which lived together but did not go on the same walks). There is no evidence that they can catch it from a place where an infected dog has been (e.g. the vets, the dog groomer, or the boarding kennel).

It is possible that there is an environmental ‘trigger’ but this is currently unknown. It is therefore up to each individual dog walker to decide whether to avoid certain types of terrain, or certain areas.”

For dog owners & vets: noticing signs & treatment of CRGV; CRGV-like diseases in humans.

Cutaneous and renal glomerular vasculopathy lesions present on the muzzle.
Cutaneous and renal glomerular vasculopathy lesions present on the muzzle.

Laura Holm of Anderson Moores Vet Specialists wrote “Noticing signs of CRGV in dogs to diagnose disease presence” in the Vet Times (March 21st 2016).

Cutaneous and renal glomerular vasculopathy lesion affecting forelimb digits.
Cutaneous and renal glomerular vasculopathy lesion affecting forelimb digits.

Laura Holm said that only a quarter of dogs with skin lesions go on to get acute kidney injury:

“Evidence suggests the median time from the onset of a skin lesion, to development of azotaemia [high blood Nitrogen levels], is 3 days (range 0 to 10 days) … There does, however, appear to be a subset of dogs that develop skin lesions without azotaemia (non-azotaemic CRGV) … with about 75% of cases remaining systemically well following development of skin lesions and only about 25% developing clinical signs attributable to AKI [Acute Kidney Injury].”

Blood clots result in skin ulcers and kidney failure:

“When microthrombi [small blood clots] occlude [obstruct] blood supply in dermal [an area below the skin] vessels, dermal cell death occurs and cutaneous ulceration [skin ulcers] develops, whereas microthrombi in the glomeruli [kidney capillaries] reduce glomerular blood supply and glomerular filtration rate, potentially causing azotaemia [high nitrogen levels in blood] and oliguria [production of small amounts of urine] or anuria [failure of kidneys to produce urine].”

Cutaneous and renal glomerular vasculopathy lesions on the body and limbs.
Cutaneous and renal glomerular vasculopathy lesions on the body and limbs.

Of the 75% dogs that have skin ulcers without kidney injury, the prognosis is excellent. Of the other 25% of dogs that have skin lesions and kidney injury, 85% die when treated at vets whilst slightly fewer (75%) die when treated at referral centres [eg Anderson Moores Vet Specialists in Winchester]:

“For CRGV cases that remain non-azotaemic [normal blood nitrogen levels], the prognosis is excellent. Although skin lesions may take weeks or months to heal, a full recovery should be expected.  Unfortunately, the prognosis is significantly less favourable in dogs with CRGV that develop AKI. Overall, more than 85% of CRGV cases with azotaemia have been euthanised or died… The outlook may be slightly better for cases managed in referral centres. Approximately 25% of azotaemic-suspected CRGV cases managed in referral centres have survived. However, no single therapy has been used more commonly in surviving cases and this figure is likely to reflect the more intensive monitoring and management generally possible in the referral setting.”

Laura Holm says that CRGV has not been reported in species other than dogs but CRGV-like diseases do occur in humans:

In humans a group of diseases exist that are characterised by thrombotic microangiopathy (TMA) [blood clots inside blood vessels] which bear some similarities to CRGV, namely: haemolytic uraemic syndrome (HUS) [anemia caused by destruction of red blood cells, acute kidney failure, and low platelet counts], atypical haemolytic uraemic syndrome (aHUS) [uncontrolled activation of the complement immune system that removes foreign particles] and thrombotic thrombocytopenic purpura (TTP) [microscopic clots that form in the small blood vessels].

But even in humans, the causes of CRGV-like diseases are poorly understood:

“Even in humans, the aetiopathogeneses [cause] of TMA illnesses are still relatively poorly understood. Definitive diagnosis can be challenging and treatment is not always successful.”

Reported by Chris Street BSc MSc at Alabamarot.co.uk (May 26th 2016)

References

Vet Times (March 21st 2016) article by Laura Holm.

Notes

Text in [ ] is by alabamarot.co.uk

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Fetcham Surrey – dog dies of confirmed CRGV.

Today Anderson Moores Vet Specialists report that sadly, one dog has been confirmed as having died as a result of cutaneous and renal glomerular vasculopathy (CRGV). The dog was from Fetcham, Surrey.

Our two Alabama Rot maps have been updated. The confirmed cases map gives the Fetcham, Surrey location (red drop). The all cases map includes the Fetcham location (red drop) and the three areas – Bookham Common, Polesden Lacey and Norbury Park (orange drops) where the dog was walked, according to Pet Doctors Fetcham.

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Is CRGV caused by Aeoromonas Hydrophila bacteria? – April 2016 update

Vet Fiona Macdonald
Vet Fiona Macdonald (Linkedin picture)

I reported in February 2015 on Fiona MacDonald’s hypothesis that CRGV might be caused by Aeoromonas Hydrophila bacteria.

In an update to her project, Fiona MacDonald wrote a letter in April 2016, to the New Forest Dog Owners Group (which provides some funds for her investigation project).

The project has two main lines of investigation, a serology test and a lesion swab culture, to see if the causal agent is Aeromonas hydrophila.

The swab of the lesion must be taken before the lesion is cleaned up because the disinfectant could kill the causative agent.

The serology ELISA test checks to see if any antibodies to Aeoromonas Hydrophila have been made by the infected dog. Twenty dogs with CRGV have been sampled for Aeoromonas Hydrophila.

Fiona Macdonald wrote about her project in the Vet Times (April 2016) and Veterinary Record here and here in 2015. They have had confirmed isolations of A hydrophila.

Letter to Vet Record May 2015

vet-record-fiona-macdonald-may2015

92% of all 121 Alabama Rot cases are in Winter or Spring

Of the 121 reported cases of confirmed, unconfirmed and suspected Alabama Rot between December 2012 and April 2016 (at 8th May 2016), 92% were reported in Winter (52%, 63 cases) and Spring (40%, 48 cases). Only 8% (10 cases) were reported in Summer (4%, 5 cases) or Autumn (4%, 5 cases).

75 confirmed cases (confirmed by dog post mortem) were analysed in another post dated 8th May 2016 indicating that 89% cases were reported in Winter or Spring.

This post with 121 analysed cases seems to strengthen the argument for a Winter / Spring seasonality to Alabama Rot. This 121 case analysis has 46 more cases (+60%) than the 75 confirmed cases.

alabamaRot-ALL-by-season
Winter (December, January, February), Spring (March, April, May), Summer (June, July, August), Autumn (September, October, November).

Chris Street of AlabamaRot.co.uk on 8th May 2016 analysed all confirmed UK Alabama Rot cases (between December 2012 and April 2016).

Data sources – Confirmed Cases UK map combined with Unconfirmed & Suspected cases (excludes confirmed cases) and cases-by-month spreadsheet.

Chart of All Alabama Rot cases by month between 2012 and 2016:

alabamaRot-ALL-cases-by-month

The monthly all cases were plotted by year:

alabamaRot-all-cases-by-month-by-year

The above chart shows the vast majority of Alabama Rot cases occur every year in Winter (December – February) and Spring (March – May).

Why donate to AlabamaRot.co.uk?

Your dog has skin lesions? Ask your vet to refer your dog to Anderson Moores Veterinary Specialists (01962 767920).