Lecture 4 - Revision Flashcards
What is a zoonotic disease?
- Human disease caused by pathogen that jumps from non-human to a human
- Reverse zoonosis is caused by a pathogen that jumps from a human to non-human
What are the disease specific priorities to improve health caused by zoonosis
- Vaccination development
- Diagnostics
- Implement research
- Epidemiology
- Existing drugs
Macro priorities of zoonosis treatment
Cost effective interventions
Analysis of livestock dependencies
Sanitation and water
Surveillance and mapping
Cross sectional collaboration for research
Gender dimensions
Lyme disease resevoirs
Ticks, rodents, deer, sheep, small mammals
Leptospirosis reservoirs
Rodents and ruminants
Leptospira physiology
Gram negative
Obligate aerobe spirochete
Helicoidal protoplasmic cylinder (2 axial filaments (between cylinder and envelope))
Motile
Transverse division
Oxidase, catalase and peroxidase positive
7.2-7.4 pH
6-20um in length, 0.1um in diameter
Coils are 0.2-0.3um in diameter and 0.5um in pitch
Ultrastructure of Leptospira
- Outer envelope (3-5 layers, cell wall composed of peptidoglycan, alanine, glutamic acid, diaminopetric acid, muramic acid)
- Hooked ends
Determinants of virulence in leptospirosis
- > 250 serovars
Determinants of virulences: - Soluble hemolysins
- Endoflagellum
- Metallopeptidases
- Collagenase
- LPS target: renal tubular Na,K-ATPase and H,K-ATPase
What strain causes Weil’s disease
Leptospira interrogans
What strain causes Hardjo disease
Leptospira borapetersenii
Examples of intermediate Leptospira
L. fainei
L. broomii
Examples of non-pathogenic Leptospira
L. biflexa
L. meveri
Virulence associated genes in pathogenic, intermediate and saprophytic Leptospira
Pathogenic strains have the most virulence genes
All intermediates and pathogens have LipL32
All strains tested have Haem oxygenase, Loa22, and Perioxidase
Only pathogens have genes that encode for protein families, and toxins
What kind of infection does Leptospira interrogans cause and what is the most pathogenic serotype in humans?
Clinical infection - Leptospirosis or Weil’s disease
Zoonotic, where some strains pathogenic
Serogroup icterohaemorrhagiae mainly causes human disease
Transmission of Leptospira interrogans and how is it killed?
- Wide range of host reservoirs
- Human risk- direct or indirect contact with infected animals/animal products
- Also infected soil, food and water through break in skin and mucous membranes
- Killed by >60oC, detergents, desiccations & acids
What can Leptospirosis cause?
- Migration from bloodstream into lungs, liver, kidney, cerebrospinal fluid:
- Interstitial nephritis with associated glomeular swelling leads to renal failure
- Hepatic injuries due to vasculitis
-Meningitis
- Symmetric pretibial rash
Clinical manifestation of Leptospirosis
Incubation period is 10-12 days
Sudden chills, fever, headache, myalgia, GIT symptoms
1st leptospiremic stage - Defervescence - 2nd leptospiremic stage
Reside/avoid macrophages that induce high levels of cytokines that cause sepsis-like symptoms
Stages of infection by Leptospires
- Entry through skin - penetrate epidermis and reach the dermis containing structural proteins like collagen and fibronectin.
- Invasion into bloodstream - Bacteria migrate to blood vessels crossing cell-cell junctions. Cytokine and antimicrobial peptides are produced.
- Evasion of immune system - Proteases secreted and complement regulators degrade and attack the complement system
- Leptospira binds plasminogen, leading to fibrin, fibronectin and clot degradation
- Red blood cells destroyed via haemolysin secretion
- Extracellular matrix degraded by enzymes
- Macrophages release ROS and RNS, triggering inflammation and worsening tissue damage
How to treat Leptospira?
Antibiotic treatment 2 days after onset - Penicillin, Streptomycin, tetracycline trc
Serovar-specific vaccine
Prophylaxis with short/long-term tetracycline
Leptospira cases in 2014
76
79% caused by animal exposure
24% were caused by water
22 cases aborad in South East Asia, Central America, Carrabean and France
Mainly males affected and aged 19-67
Recreational water exposure
Leptospira infections in 2010
- 4 livestock farmers
- 2 abattoir workers
- 1 carpenter
- 1 Gamekeeper
- 1 building worker
- 1 rowing instructor
- 3 fishers
- 1 postman
- 1 man who kept pet rats
- 3 sewer cleaners
- 1 bitten by mouse
- 1 recreational canoeistt
What is Lyme disease
- Discovered 1977
- Most common tick/insect-borne disease in US/Europe:
- 300,000 Americans and 85,000 Europeans develop lyme disease
- First described in Lyme, Connecticut in 1976
- Oldest case was Tyrolean Iceman, 5,300 year old copper age mummy
What causes lyme disease
Borrelia burgdorferi - bacterial spirochete
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Predominant in North America, but also exists in Europe
Humans bitten by hard-bodied ticks (lxodes species) infected with B. burgdorferi
Other insects that feed on animal blood may be involved
- Patients fully recover when treated early, but can spread to joints, heart and nervous system if left untreated
