Lecture 4 - Zoonoses Flashcards
What is a zoonotic infection?
Azoonosis(pluralzoonoses) orzoonotic diseaseis aninfectious diseaseof humans caused by apathogen(an infectious agent, such as abacterium,virus,parasiteorprion) that canjumpfrom a non-human (usually avertebrate) to ahuman.
When from humans to other animals, that’s reverse zoonosis
Zoonoses (UK)
Animal influenza - livestock, humans
Anthrax - livestock, wild animals, environment
Brucellosis - Cattle, goats, sheep, pig
Leptospirosis - Rodents, ruminants
Lyme disease - ticks, rodents, sheep, deer, small mammals
Leptospira
Gram negative, obligate aerobe spirochete
Helicoidal protoplasmic cylinder (2 axial filaments (Between cylinder & envelope)
motile
Transverse division
Oxidase, catalase and peroxidase positive
Optimal pH: 7.2 to 7.4
Size:
6 to 20 μm in length & 0.1 μm in diameter
coils are 0.2 – 0.3 μm in overall diameter & 0.5 μm in pitch
Ultrastructure
Outer envelope (3-5 layers, cell wall composed of polysaccharide & peptidoglycan, alanine, glutamic acid, diaminopimetic acid, muramic acid)
Hooked end(s)
Virulent Leptospira
Antigenic structure:
>250 serovars determined by microscopic agglutination assay
Determinants of virulence:
- Soluble hemolysin
- Endoflagellum
- Metallopeptidases
- Collagenase
- Resistance to oxidative stress
OmpA Loa22 (lipoprotein, function unknown)
Cell-mediated sensitivity reactions
Haem oxygenase
Endotoxin (LPS)
LPS Target: renal tubular Na,K-ATPase and H,K-ATPase activities
What species causes Weil’s disease
Leptospira interrogans
What species causes Hardjo disease
Leptospira borgpetersenii
Leptospira interrogans
Clinical Infection – Leptospirosis or Weil’s disease
Leptospirosis is a zoonotic disease caused by Leptospira interrogans, of which only some strains are pathogenic.
Leptospira interrogans serogroup icterohaemorrhagiae is the main serovar causing human disease.
Transmission
- A wide range of host reservoirs
- Humans risk : direct or indirect contact with infected animals or animal products
- Also from infected soil, food and water through a break in the skin and mucous membranes
- Readily killed by >60oC, detergents, desiccations & acids
Pathogenesis of Leptospira interrogans
Migration from bloodstream into lungs, liver, kidneys andcerebrospinal fluidto cause aggravation of disease
Renal injuries: Interstitial nephritis with associated glomerular swelling & hyperplasia, thickening of basement membranes & tubules Renal failure
Hepatic injuries: hepatocellular disease due to vasculitis
Meningitis
Symmetric pretibial rash
Clinical manifestation period:
Incubation period (10-12 days)
Sudden chills with fever, chills, headache, conjunctival suffusion, myalgia, GIT symptoms
1st leptospiremic stage - Defervescence (abatement of fever)- 2nd leptospiremic stage
Reside/avoid macrophages inducing high level of cytokines which causessepsis-like symptoms which is life-threatening instead of helping to fight against the infection
Leptospira treatment
- Antibiotics treatment within first 2 days e.g. penicillin, streptomycin, tetracycline, erthyromycin
- Serovar-specific vaccine
- Prophylaxis with short/long-term tetracycline
Leptospira infections in 2014
Cases in 2014: 76
Occupational exposure - 76% animal, 24% water
22 cases were from abroad
South East Asia,
Central America
and the Caribbean, and France.
Mainly male
Age 19-67
Recreational water exposure
Leptospira infections in 2010
10 infections were occupational
4 livestock farmers ( sheep or cattle)
2 abattoir workers ( cattle and pigs),
1 carpenter repairing a river bank,
a gamekeeper with exposure to multiple animal species,
a building worker who encountered stagnant water on a building site and
a rowing instructor who died following immersion in the river Thames.
10 Non-occupational activities:
3 were fishing in inland waters,
1 postman who reared poultry in his back garden and was exposed to rodents,
1 man who kept pet rats,
3 people who were clearing out sewers, guttering and a rat-infested house,
1 who was bitten by a mouse,
1 recreational canoeist and
2 infections no risk factor information
What is lyme disease
- Discovered 1977
- Most common borne tick/insect disease in US/Europe
- ~300,000 americans and ~85,000 europeans develop lyme disease
- Fastest growing vector borne disease in US
Lyme disease can affect people of all ages.
Named after the town of Lyme, Connecticut where it was first described in 1976.
The oldest known case was the Tyrolean Iceman, a 5,300-year-old Copper-age mummified individual, discovered in the Italian Alps.
What causes lyme disease
Borrelia burgdorferi - A bacterial spirochete
Predominant in North America,, but also exists in Europe
Human beings become infected after being bitten by hard-bodied ticks ( Ixodes species ) that are infected with B. burgdorferi.
Other insects that feed on animal blood may be involved.
When treated early, patients are expected to recover fully but, if left untreated, the infection can spread to the joints, heart and nervous system
Borrelia burgdorferi
Helical cell shape
Periplasmic flagella
Flagellar insertion points are located near the termini of the spirochaete.
Bundles of flagella wind around the flexible, rod-shaped protoplasmic cylinder of Borrelia and overlap in the middle.
The outer membrane constrains the flagellar bundles within the periplasm.
Movement of B. burgdorferi
B. burgdorferi bacteria can move along the sides of blood vessels to spread throughout the body without getting swept away by the force of rushing blood (catch bonds; protein called BBK32).
Genome of B. burgdorferi
- Unique genome
- Large linear chromosome (901,725bp with ~853 coding genes)
21 other linear and circular plasmids (an additional 533,000 bp of DNA).
The genomic organization of B. burgdorferi is unique due to the high number of plasmids.
Some strains lacking a complete set of plasmids are unable to successfully infect their host,
One plasmid named lp25 has been found to be necessary for Borrelia infection
Sequenced genome does not contain any obvious genes coding for pathogenesis,
therefore, the mechanisms of B. burgdorferi infections are unknown.
Lacks iron containing enzymes and iron containing proteins in electron transport
uses Manganese instead
circumvents bodies defence mechanisms ie. no free iron in tissues and fluids
Ticks that carry Lyme disease
Black-legged tick (USA)
European tick
Lone-star tick (USA)
Rocky mountain tick (USA)
B. burgdorferi: life cycle
Uninfected larval ticks acquire B. burgdorferi by feeding on infected small wild mammals, primarily rodents.
Spirochaetes multiply and persist in the midguts of infected ticks through the moult to the nymphal stage.
When infected nymphal ticks feed, the spirochaetes migrate from the midguts to the salivary glands, from where they can be transmitted to a naive mammalian host.
Lyme Disease in the UK
~2000 undiagnosed cases
Emergence of Lyme disease
A major reason for the rise in Lyme incidence:
- More deer
- Surbanization: living closer to animals
- Climate change
two-fold:
helping ticks reproduce,
and helping them live in more parts of the US
Lyme Disease: Signs and Symptoms (stage 1)
Two stages of Lyme disease:
Stage 1 (Early stage) – 3 to 30 days after bite.
Flu-like symptoms develop within 7 – 14 days.
Symptoms include fatigue, headache, fever and chills, muscle and joint pain, nausea, vomiting, dizziness and a non-productive cough.
Skin lesion(s) may appear as a small red circular rash around the bite and expand.
Secondary skin rashes appear in nearly 80% of individuals with Lyme disease.
Lyme Disease: Signs and Symptoms (stage 2)
Stage II (Late) – May occur weeks or months after the onset of Lyme disease.
Severe headache and neck pain or stiffness.
Arthritis will develop in 60% of patients, weeks or months after infection (rarely more than 2 years).
Fifteen percent of people infected with Lyme disease develop neurological symptoms, including psychiatric problems.
B. burgdorferi Infection cycle
Tick salivary protein binds and protects Lyme disease agent Borrelia burgdorferi.
As an infected tick feeds, B. burgdorferi migrates from gut to the salivary glands and is transmitted through the saliva to a vertebrate host.
At the same time, B. burgdorferi undergoes a dramatic switch in the major surface protein from OspA (blue bacteria) to OspC (red bacteria).
Osp A. protects the tick in the gut (vaccine target)
Decreasing OspA/Increasing OspC allows detachment from the gut to flow into the tick’s salivary glands.
B. burgdorferi encounters the tick protein Salp15 in the salivary glands, and Salp15 binds to OspC (protection).
In the presence of neutralizing antibodies from an immune vertebrate host, B. burgdorferi with both OspC and Salp15 on their surface preferentially survive, relative to those in which either Salp15 or OspC is missing.
