Bacterial Disease Flashcards
What is procalcitonin and what is it used for
A peptide precursor protein of calcitonin produced by thyroid parafollicular C cells. In physiological conditions it is rapidly converted to calcitonin by intracellular processes, meaning serum levels are very low.
During inflammation or bacterial infections endotoxins and inflammatory cytokines stimulate non parathyroid organs to produce PCT (which cannot be converted in these locations).
So plasma PCT levels rise rapidly during infection and remain elevated provided there is ongoing stimulus
What occurs to PCT levels during viral infections
There is not generally an increase that is seen with bacterial infections. because IFN and Th cells inhibit production
So PCT can be used to differentiate bacterial from viral infections in humans.
Evidence for PCT in cats
2 JFMS studies one for detection of bacterial infection, another comparison for viral and bacterial infection
1) significant increase in PCT and neutrophils in infected cats compared to healthy controls. Sens 70%; Spec 94%
2) Serum PCT and microRNA of PCT increased significantly more in bacterial vs viral infection cats. Did not differ by the location of the infection
Evidence for PCT in dogs
JVIM 2020 study - PCT increased significantly from baseline after LPS injection compared to placebo.
Returned to baseline after 48h
May be useful biomarker of sepsis.
Ehrlichia - pathogenesis and pathophysiology, diagnostic sens/spec
Transmitted by feeding of R linnaei in Australia (currently WA, SA maybe NT and QLD)
Infection of monocytes to evade immune detection, sequestered in spleen and liver where it replicates
Causes type II reaction to produce antiplatelet antibodies in 60%
Also type III MPGN, uveitis, IMPA
Also reported to cause hyperviscosity syndromes
Acute phase predominated by fever, malaise and thrombocytopenia
Chronic phase (does not occur in all infected but also seeing more rapid progression in Aust dogs) - bone marrow aplasia, type III dz, lymphocytosis. Recent study documented higher incidence of CKD in dogs with prior exposure to Ehrlichia in endemic areas.
Dx: demonstration of morula in monocytes, acute and convalescent IFA serology - some cross-reactivity with other dz like anaplasma. May not see seroconversion with chronicity
IDEXX 4dx ELISA - low PPV due to low disease prevalence in Aust currently.
Also note can have asymptomatic carriers.
PCR of blood, liver, spleen aspirates can also be diagnostic but low sensitivity (higher for organ aspirates). Confirms active infection
Ehrlichia Tx recommendations
4 weeks of doxycycliine - ACVIM adn Vet J reviews.
Can use splenic aspirates to confirm resolution/clearance but no test is perfect for this. Serology not useful as will remain positive.
A recent study experimentally infected dogs then treated and then immunosuppressed and no recrudescence was seen
Anaplasmosis - spp, clinical signs, diagnosis
A phagocytophilum has more systemic clinical sign so ffever, conjunctivitis, and lymphadenopathy. Not found in Aust. Infects neutrophils and may cause immune suppression
A platys is present in northern A, transmitted by tick. Only clinical signs may be mild and cyclical thrombocytopaenia which is not always symptomatic.
Dx is with documentation of seroconversion on acute/conv IFA titres, also IDEXX 4Dx ELISA can demonstrate exposure. Both may be negativ ein early disease.
PCR of blood, spleen or BM sens/spec unknown but may be useful in acute phase
Bartonella - epidemiology, transmission, significance dogs vs cats
B henselae principal reservoir host is cat and is transmitted by fleas which can likely spread to dogs
Other spp not currently reported in Aust. but there are multiple strains of B henselae (and immunity is not cross-protective)
Older patients are more likely to be seropositive, and younger cats bacteraemic
Wide study of role in multiple dz in cats has failed to identify causality, but immunocompromise may result in inflammatory disorders
Clinical disease is considered rare in naturally infected cats
In dogs there may be more evidence for disease association but still common to have serological conversion in absence of clinical signs. Thought to be associated with IMPA in dogs.
An association of B henselae and culture negative endocarditis was reported in one small study (though not all dogs tested) Usually affected dogs are afebrile and involves aortic valve.
Because of limitations of serology culture is the preferred diagnostic test but can take several weeks. PCR is faster. Both have low sensitivity.
Recommended treatment and indications for Bartonella
In cats not recommended to treat as clinical disease is unlikely. Though if immunocompromised may develop (not proven)
Similarly in dogs only treat if strong suspicion is cause of disease and positive PCR or culture or histo showing pyogranulomatous disease.
Combination of doxy, rifampin and quinolones used in people but ability of these to clear infection is not known (and whether or not that is necessary is also unknown)
Treatment may also be indicated in pets of immunocompromised humans. Esp young cats which have been more implicated in zoonotic transmission (probably because they are bacteraemic)
Borrelia burgdorferi epidemiology, pathogenesis, pathophysiology
2018 ACVIM consensus
Found in USA and Europe, transmitted by Ixodes spp ticks. Not been identified in Aust ticks. Wildlife reservoirs perpetuate high tick infection rate. Transovarial tick infection does not occur.
Requires long feeding time to transmit
Bacteria change expression of surface proteins to enable transmission from OspA to C. Replicates at site of tick attachment then disseminates.
B.b evade host immune detection by outer surface protein modification and metamorphosis to resistant form. May also interfere with B cell maturation/proliferation.
Only ~10% of dogs show clinical signs of infection, which may persist for >1yr. Seropositivity may persist for years.
Disease caused by Borrelia
Borreliosis = Lyme disease
Not thought to occur in most infected dogs
In a small subset can develop Lyme polyarthritis or Lyme nephritis
Most studies show no association of seropositivity and clinical signs.
CS: lethargy, painful joints, swelling; mild-moderate thrombocytopaenia, anaemia and leukocytosis
Lyme nephritis may cause hypoalbuminemia, metabolic acidosis, hyperphosphataemia
So far unable to prove nephritis in seropositive dogs is CAUSED by the Borrelia - cannot determine if Ab complexes in MPGN are due to Borrelia or not.
Seems Retriever breeds are overrepresented though
Diagnosis of Borrelia
Serology - indicates exposure but not infection/clinical disease, paired serology is not recommended as the disease progression is slow and seroconversion may not occur.
Serology to detect OspC antibodies may be falsely positive following vaccination
C6, VlsE are not affected by vaccination status.
Due to pathogen variance in antigens, development of serological response occurs in phases (ie not all antigens displayed at once so wont have all the antibodies following initial infection).
Quantitative serology may be useful inf tracking response to therapy or reinfection but there is no published evidence documenting this. Though magnitude of C6 quantitative serology did correspond with circulating Ag-Ab complexes. Though high titres did not correspond with development of illness.
Renal histopathology - MPGN on biopsy in conjunction with seropositivity
Most do not have concurrent Lyme arthritis
Testing seropositive dogs for proteinuria at routine screening is recommended
Indications to treat Borrelia and drugs used
Vast majority of seropositive dogs will never develop clinical disease so it is challenging to know when to treat. Also many dogs remain positive on tissue PCR so duration of treatment is not understood nor is whether clearance of the organism is necessary
In a patient that is proteinuric and seropositive treatment with doxycycline could be undertaken (provided other causes of PLN are excluded). If there is severe persistent disease then biopsy and possible immunosuppression (after other standard PLN treatments are undertaken without effect) is indicated. Prognosis is guarded to poor
For Lyme Arthritis - doxycycline. unknown dose or duration but most Tx for 4 weeks. Though clearance of the organism is not documented in these cases
Borrelia Vaccination concerns
2018 ACVIM consensus
- future sensitisation and aggravation of type 3 disease (MPGN). We dont know which Borrelia antigens contribute to this due to difficulty studying natural infections
- vaccinated dogs have reduced risk of developing clinical signs - consistent across studies but all were small with risk of biases
- can cause false positive on serological tests
- lack of field efficacy studies
- seroconversion was not a criteria of successful vaccination
Causes of tuberculoid mycobacterial lesions, pathogenesis and their Tx
M bovis; M tuberculosis from people, M microti from rodents
Spillover infections in dogs and cats
Bacteria are phagocytosed by macrophages but cannot be destroyed, instead replicate intracellularly before cell death and release of more bacteria triggering bigger immune response -> granuloma
Route of infection determines where lesions are found, most common: GIT, Resp, Skin +/- draining LNs
Case series of intestinal M bovis in UK cats fed raw diet
Tx - triple therapy rifambin, clarithromycin, fluoroquinolone
In addition to Sx if possible
