1) Tuberculosis (caused by members of the mycobacterium complex)

2) Rapidly growing mycobacterium

3) Leproid syndromes in animals (similar to leprosy in humans)

1) TB (M.tuberculosis complex)
2) Leprosy (M.leprae and M.lepromatosis)

3)Buruli Ulcer (M.ulcerans)- mainly seen in Africa with a few hotspots in Australia

-Leprosy starts in the respiratory tract and disseminates hematogenously to skin and peripheral nerves

-Tropism for Schwann cells (peripheral nerves)

-Will not grow on synthetic media (however rapidly growly mycobacterium can grow on normal blood agar, leproid organisms will NOT grow this media)

-Host adapted? Armadillo? Rodents? (likely reservoir host interacts with cats and allows them to get the disease)

-Reductive evolution

-dorsal ear fold tends to be affected, symmetrical or asymmetrical lesions

-common in dogs kept outdoors

-flies or other biting insects pick up bacteria in the environment and it inoculates in dogs, incubation period a couple of months then lesions develop into granulomas into SQ space

-common in Brazil, Australia, Europe, and the US

-cannot grow organisms in vitro (disease of microbiology- need PCR to detect organisms)

-most dogs will clear organisms with the immune response of the host

-negative stained Bacilli in Diff Quik or Acid-fast on Zeehl Nielson stain

-Diagnose with FNA (negative stained on acid-fast) and biopsy with PCR analysis to confirm the diagnosis

-usually will self resolve over two months without any treatment

-When treatment is needed, usually a combination of Rifampicin, Clarithromycin +/- Pradofloxacin

-SQ in an anatomical location with a predisposition for the face (nasal and ocular structures, may include conjunctiva, keratitis, etc)

-Mycobacteria Tarwin, M.lepraemurium(***Most common spp.), and M.visible

(strong geographic tropism of disease)

-M.lapraemurium has crossed over from rats to cats via interaction (lesions tend to be on lip, face, or limbs from hunting rats due to inoculation)

-Lumps on the skin of the cat, negative stained bacilli with Diff Quik in macrophages or outside macrophages, acid-fast staining (Ziehl-Neelsen stain or modified Ziehl Neelsen Wade-Fite stain) results from the presence of membrane glycolipids

-Cats have skin lesions all over (liver and spleen included)

-Mycolic lipids and ester in the cell wall cause mycobacteria to repel Romanowsky type stain

-large number of epithelioid macrophages with intracellular pathogens

-older immunosuppressed cats (FIV+, early renal insufficiency, etc) -cats develop granulomas of the subcutis and skin (single or multiple skin nodules and may be ulcerated)

-Red squirrels and other rodents are definitive hosts for these leprosy like organisms

-disease of antiquity (pattern of disease depends on reservoir host and how it interacts with cat and dependent on vector involved)

-Triple therapy (Rifampin, Clarithromycin and Pradofloxacin) responsive- some don't respond to drugs or often develop other diseases a year or two later 

-Gram-positive

-Bacilli (rods)

-Acid-fast (AFBs)

-Waxy cell wall (mycolic acids)

-Survive and multiply in phagocytes

-Robert Koch's contribution

-taxonomy used to be based on phenotypic characteristics (ie. growth rate and pigmentation)--->slow vs. rapid growers, not appropriate for 'non-culturable' organisms

-DNA sequencing of genomic regions varies between species (16S rRNA gene) molecular characterization used now

-Divide mycobacteria into rapid growers and slow growers

-Rapid growers are more like pyogenic organisms and give rise to pyogranulomatous inflammation with sinuses that drain watery pus

-Slow growers tend to produce more granulomatous inflammation with nodules to tumor-like masses

-Tuberculosis refers to infections with slow growers adapted to a mammalian host (reductive evolution)

-But, we don't know how to get many of them to grow in the lab, and these are almost always slow growers

-Inherited or immune defect

-Have disease in one or another or both body cavities

-Severe interstitial lung pattern characteristic 

-May have one large popliteal lymph node

-Often have increased ALT and liver involvement

-Hair often fails to re-grow after clipping

-can be cured by timely therapy with rifampicin and clarithromycin (and sometimes clofazimine)

-Always attempt culture- M.avium, M.tuberculosis, M.genavense, M.marinum will often grow if given enough time

-Submit FRESH tissue on an ice block for culture and PCR

-Can do PCR of FFPE tissue (not optimal)

-MALDI-tof

-BACTEC system or equivalent highly suitable- may fastidious bugs grow to a limited extent but DNA is there

-M.smegmatis and M.fortuitum

-We now have, ie. M.smegmatis species complex consisting of M.smegmatis sensu stricto, M.goodii, and M.wolinskyi

-relies on biochemical testing and PCR sequence

-little or no importance TO DATE

-due to M.smegmatis, M.fortuitum, M.chelonae and other RGM

-inguinal fat pad in cats (and other sites)

-subcutis of the chest wall in dogs

-obese animals predisposed

-follows trauma that penetrates fatty tissue and where dirt contaminates the wound

-much more common in cats than dogs- over 50 cats and 3 dogs over a 10 year period

-more common in certain geographic regions (ie. Australia)

-localized disease caused by saprophytic mycobacteria in immune-competent hosts

-non-healing wounds

-atypical cat bite wounds

-"pepper-pot" draining sinuses

-thickening/hardening of subcutis

-DDx Nocardia infections

-Can look identical to RGM infections

-Cytology, Gram stain, and culture will differentiate them

-Most are caused by N.nova in Australia

-Need very similar approach, but very different susceptibility patterns

-Can be in fatty subcutis or distal extremities

-Nocardia is a filamentous organism that is Gram-positive so the cytology is quite different. Sometimes look like negative filaments if stained with Diff Quik (rather than Gram stain)

-Approach is similar but needs a different antibiotic plan to treat Nocardia vs. RGM (therefore important to diagnose properly

-FNA---> cytology and culture 

-sample intact lesion, not draining material

-Use U/S to guide the FNA

-culture around cephalosporin disk

-tell lab what you are chasing!!!

-FNA is stained with a modified acid-fast stain and Grams stain (not Diff Quik)

-Often affect obese cats

-Live in soil, water environments

-culture and susceptibility testing

-E tests are good for determining MICs

-try doxycycline and pradofloxacin Australia or clarithromycin and pradofloxacin (in the USA)

-slowly increase the dose to the highest tolerated level

-assess the response

-surgery if refractory (some cases require referral)

-clarithromycin unreliable for most M.smegmatis strains, but good for M.fortuitum and M.chelonae

-Consider clofazimine or linezolid for refractory cases

-Doxycycline 5mg/kg with food twice daily

-Baytril is good for RGM in dogs, but contraindicated in cats (Retino-Toxicity)

-Fluoroquinolones are not monotherapy because resistance develops

-Clarithromycin or azithromycin (latter less effective but can be given once daily)

-Rifampicin-Tricky (watch the liver) and does not work for Rapidly Growing Mycobacterium (intrinsic resistance)

-Clofazimine-good for expensive; hard to get (WHO tries to reserve for human leprosy)

-Moxifloxacin (human fluoroquinolone)

-"Kissing cousin" to pradofloxacin

-Made by Bayer

-Avelox 

-enhanced activity against Gram positives and anaerobes

-No retino-toxicity

-Excellent for rapidly growing mycobacteria, TB and possibly feline leprosy

-Dose is 10 mg/kg orally once daily

-Affordable in the cat

-veterinary drug (Bayer)

-similar to moxifloxacin

-Has become key drug in rapidly growing mycobacterium infections

-combine with doxycycline or clarithromycin

-No risk of retinotoxicity

-Best FQ for mycobacteria!

M.microti is the skin infection transferred to cats from voles

-No infection from M.microti from cats to humans.

-In Siamese, (acromelanotic) so when skin gets warm at hair follicles, they lose pigmentation in that region

-Wear gloves when handling pus and draining tracts- humans get infected

-Mycobacterium bovis is a slow-growing aerobic bacterium and the causative agent of tuberculosis in cattle.

-It is related to Mycobacterium tuberculosis, the bacterium which causes tuberculosis in humans.

-M.bovis may jump the species barrier and cause tuberculosis-like infection in humans and other mammals. (spread person to person when people with the disease cough or sneeze

-M.bovis causes cutaneous lesions in cats.

-M.bovis may affect humans as well (mostly M.tuberculosis).

-There are 6 cases of cats affecting people worldwide over the past 150 years.

-TB in cats: most cats will not cough.

-Feline tuberculosis- adult cats, male predisposition, no breed disposition, FELV/FIV neg, low Vit D

-Hunting cats (badgers contaminate environment- usually infected by rodents with M.bovis or microti), cat-to-cat

-Tuberculosis (M.tuberculosis, M.bovis and M.microti) 

-Non-tuberculosis mycobacteriosis (Non-tuberculous mycobacteriosis, Feline leprosy syndrome, and Canine leproid granuloma syndrome).

-Vast majority of clinical signs are cutaneous, lymphadenopathy (submandibular, Prescapular and popliteal), respiratory signs, arthritis, ocular signs, weight loss, GI signs. Possible transmission through commercial raw food

-Diagnosis (clinical signs, hematology, serum biochem (high calcium), radiology/CT, cytology/histopath, serology, ID TT test, IFN gamma test, Culture/PCR

-Radiology reveals chest, abdomen, and skeleton pathology (and are not specific for tuberculosis)- diffuse interstitial pulmonary pattern, few cats with pulmonary TB show consistent clinical signs. -patchy, diffuse, and interstitial pulmonary changes.

-transfer <5yr, pregnant, chemoTx, HIV, DM, etc. then counsel against treating animal.  

-ITALY prohibits treating M.bovis in any patient other than humans (need to euthanize cats for small nodules on skin).

-Treatment (wound dehiscence), Use of rifampicin (only drug that can be given for feline TB that will work on non-dividing mycobacteria).

- Better resolution when 3 drugs for 3 months minimum and 2 months beyond clinical resolution. Rifampicin-pradofloxacin-azithromycin OR Rifampin-isoniazid-ethambutol

-Vitamin D supplementation?

-Potential prognosis (~40% remission and 70% are long term remission)

• Unique composition of cell wall is composed of mycolic acids
• Also contains glycolipids (eg. diacyltrehaloses, polyacyltrehalose, lipomannan, lipoarabinomannan, mannose-capped-LAM, sulfolipids and trehalose-6,6'-dimycolate)
• pathogen alters its metabolism of fatty acid to survive conditions in the host that reflected in an altered cell wall composition in terms of lipids