Unit 3 Flashcards
1
Q
What are protozoa?
A
Protozoa are single-celled organisms from the Protista kingdom. They live in water, soil, or inside other organisms. Protozoa can move independently, using structures like flagella or cilia. Some are harmless, while others cause diseases like malaria. They can reproduce through cell division and play roles in ecosystems and the food chain.
2
Q
What is the global impact of malaria?
A
Malaria is caused by infection with protozoan parasites of genus Plasmodium
Malaria is a vector-borne disease
3.2 billion people live in at-risk areas (tropical and subtropical countries)
> 249 million human malaria cases in 2022
~608,000 deaths annually –> predominantly children <5 years in Africa
Every 2 minutes, a child DIES from malaria
3
Q
Where is the major malarial burden?
A
The major malarial burden lies in Africa with 93% of all cases and 94% deaths
Nigeria alone making up 26% of all cases and 31% of all deaths
4
Q
What are the human-infecting plasmodium parasites?
A
- Plasmodium falciparum
- Plasmodium vivax
- Plasmodium malariae
- Plasmodium ovale curtisi
- Plasmodium ovale wallikeri
- Plasmodium knowlesi
5
Q
What is plasmodium falciparum?
A
The cause of 99% of all malaria cases in sub-saharan Africa
6
Q
What is plasmodium vivax?
A
The predominant malaria parasite in the Americas
7
Q
What is plasmodium knowlesi?
A
Zoonotic parasite
Zoonotic malaria is increasing exponentially in Malaysia
In 2018 no human malaria but 4131 cases of Monkey malaria
- Zoonotic malaria is a severe public health threat in South East Asia
8
Q
What are the symptoms of malaria?
A
Mild/uncomplicated:
- Cyclical fever and chills
- Headaches, body aches
- Nausea and vomiting
- Enlargement of spleen and liver
- Mild jaundice
Severe:
- Severe anaemia and haemoglobinuria
- Acute respiratory distress syndrome (ARDS)
- Renal impairment
- Metabolic acidosis, hypoglycaemia
- Cerebral malaria (impaired consciousness, seizures, coma)
9
Q
What is the lifecycle of plasmodium parasites?
A
- 10-100 sporozoites injected with the saliva during a mosquito feed
- Sporozoites injected into the skin enter the circulatory system and are transported to the liver (<1hr)
- In the liver sinusoid the motile sporozoite exit the circulation and start invading hepatocytes
- Replication - Liver stage merozoites invade the erythrocytes, in which they replicate, exit and reinvade fresh erythrocytes
–> Cycle - Blood stage cycle causes all symptoms of malaria:
- At low % some parasites become gametocytes (sexual stages)
- Gametocytes taken up with blood meal form a zygote, from which after replication 1000 sporozoites emerge - salivary gland.
10
Q
What is the history of the zoonotic plasmodium parasite - Plasmodium knowlesi?
A
First discovered in 1931 in a macaque imported from Singapore to India
In 1932 it was established that P.knowlesi can be infectious to humans under experimental conditions
Named after Robert Knowles, Director of the Calcutta School of Tropical Medicine
First natural human infection was an American soldier in 1965, returning from Malaysia.
2004 Professor Singh described that cases in Malaysia were misdiagnosed as P.malariae, were actually P.knowlesi
= Significant to human malaria transmission in Malaysian Borneo
Cases reported from Malaysia, Indonesia, Brunei, Myanmar, Thailand, Vietnam, Laos, Singapore, Philippines, Cambodia
11
Q
What are the Wildlife Reservoirs and vector for Plasmodium knowlesi?
A
WILDLIFE RESERVOIRS:
Macaca fascicularis (long-tailed Macaque)
Macaca nemestrina (southern pig tailed macaque)
Macaca leonina (northern pig-tailed macaque)
VECTOR:
Anopheles leucosphyrus group:
- An.dirus, An.cracens, An.latens, An.balabacensis, An.introlatus
12
Q
Is the emergence of human infections with monkey malaria (P.knowlesi) an adaptation to a new host (=human):
A
Yes and no!!
Phylogenetic studies estimate the ancestral parasite population to have evolved at 98,000 - 478,000 years ago, predating human arrival in South East Asia at ~60,000 years ago
P.knowlesi shows extremely high prevalence in Macaques, suggesting that currently there is a greater transmission intensity of P.knowlesi by vectors between wild Macaques, than from Macaque to human
–> It is unlike the evolution of P.falciparum
Instead, extensive deforestation started migration of long-tailed Macaque from forested to semi-urban areas and plantations, triggering mosquitoes to follow their host, adapting to fringes and farm areas.
Significantly associated with increased risk of zoonotic malaria
Age, sex, travel to forest areas, houses >1m off ground, contact with Macaques, occupation such as farm or plantation worker.
AND human malaria elimination campaign was successful:
- Reduced heterologous immunity in population
- Deforestation causes reduced biodiversity and with it potentially dead-end hosts, therefore resulting in higher prevalence of P.knowlesi in macaques with spillover into humans = dilution effect
13
Q
Is zoonotic malaria becoming a problem?
A
YES
Although Malaysia has entered elimination phase for Malaria control, zoonotic malaria is increasing exponentially and becoming a significant public health problem affecting primarily farmers and plantation workers as mosquitoes are exophilic, active at night/dusk.
Potentially a similar development seen with other monkey malaria parasites:
- P.cynomolgi in macaques in South East Asia
- P.simium in howler monkeys in Brazil
14
Q
What is cryptosporidium?
A
A protozoan parasite belonging to the phylum Apicomplexa
Cause of diarrhoeal disease in most mammalian and bird species
Transmitted through faecal-contaminated water, food and environments
8 cryptosporidium species can infect humans, but the most prevalent/virulent are
- The zoonotic C.parvum and the anthroponotic C.hominis
Infection is initiated when sporozoites released from oocysts in the intestinal tract invade mucosal epithelial cells
Symptoms in an immunocompetent individual are self-limiting (1-2 weeks)
Lack of effective treatment options
15
Q
What is the cryptosporidium life cycle?
A
- Infection starts when a host ingests thick-walled sporulated oocysts of Cryptosporidium, which contain 4 banana-shaped sporozoites. These oocysts are small 4-6µm
- During excystation, sporozoites leave the oocyst, which happens in the small intestine. Temp 37 degrees celsius and acidic conditions trigger a parasite protease cascade necessary for excystation. Free sporozoites are motile and bind to epithelial cells mediated by proteins from the apical organelles, likely involving thrombospondins
- The sporozoite differentiates into type 1 meront. Mitosis (merogony) results in 8 merozoites
- Type 1 merozoites are released and attach to new epithelial cells. These go on to produce more type 1 moronts in a series of asexual cycles; some type 1 merozoites however invade new enterocytes and develop to a type 2 meront. Merogony in the type 2 meronts forms 4 type 2 merozoites. These reinvade epithelial cells to form either a macrogamont or a microgamont. Each microgamont replicates to produce 16 microgametes (no flagellum!), rod-shaped 1.4 x 0.5µm long. The microgametes exit the host cell and fertilise adjacent macrogamont to form a zygote
- The zygote develops into an oocyst, and then undergoes sporogamy, whilst it is still attached to the enterocyte. The oocyst differentiates to become a thin-walled oocyst or a thick-walled oocyst. Once they have differentiated the oocyst detaches into the lumen. Thick-walled oocysts are excreted with the stool whereas thin-walled oocysts can reinfect the mucosal lining in the gut.
16
Q
What is the prevalence and disease burden of Cryptosporidium in cattle?
A
C.parvum is one of 4 species infecting cattle, as well as zoonotic pathogen
C.parvum is widespread and the major cause of calf enteritis, with 28-30% prevalence in pre-weaned calves in the UK
It is a pathogen to 155 species of mammal, not only human and cattle
17
Q
What is the prevalence and disease burden of cryptosporidium overall?
A
C.parvum contaminated soil in water catchment areas is a public health concern, given its zoonotic potential
In the UK between 2000-2003, six drinking water associated Cryptosporidiosis outbreaks were reported.
Besides livestock, C.parvum is also prevalent in wildlife (red and roe deer) in the UK
Two approved veterinary therapeutic treatments are Halofuginone Lactate given preventative at birth or paromomycin given preventative after diagnosis
18
Q
What does Halofuginone lactate do, when can it be given?
A
Halofuginone lactate cannot be given if diarrhoea symptoms have been present for 24hrs.
It does not cure the disease but is able to reduce the symptoms and reduce oocyst shedding.
Mechanism is unknown but it appears to affect the free sporozoites and merozoites
19
Q
What does paromomycin do?
A
It is a non-absorbable amino glycoside (originally approved by FDA against amebiasis).
Its use in AIDS patients appeared only slightly improved over placebo. Whereas, treatment in calves at much higher mg/kg seemed to have some effect and reduce oocyst shedding
20
Q
What are the key factors for global success of cryptosporidiosis?
A
PATHOGENIC FACTORS:
- Specificity to host
- Ability to persist
- Zoonotic agent
- Difference in species/genotype infectivity
ENVIRONMENTAL FACTORS:
- Waterhead security
- Season
- Water sanitation
- Geographic clusters
- Temporal clusters
- Climate and meteorology
HOST FACTORS:
- Food preparation
- Access to water
- Sanitary bathroom habits
- Access to toilet paper
- Proximity to livestock
- Age
- Immune-impairment
- Travel
- Gender
21
Q
How is Cryptosporidiosis diagnosed?
A
Routinely oocyst detection in faeces is carried out by microscopy of faeces samples stained with acid fast dye
Antigen test (ELISA or dipstick)
Molecular detection by PCR (also allows for speciation)
22
Q
How is Cryptosporidiosis treated?
A
Nitazoxanide = FDA approved anti-cryptosporidial drug, but not commercially produced and effective in shortening period of diarrhoea and reducing oocyst shedding
—> PREVENTION
23
Q
What are some Cryptosporidiosis prevention strategies in livestock?
A
Supporting calves from birth (hydration; steam cleaning and disinfection (hydrogen peroxide)) and deep straw beds
Therapeutic treatment of calves with approved drugs
Separating infected calves until oocyst shedding stops
24
Q
What are some Cryptosporidiosis prevention strategies in the environment?
A
Reduce stocking density of cattle
Heat-treat/compost manure before use and anaerobic digestion of slurry
25
What are some Cryptosporidiosis prevention strategies in humans?
Protecting water catchment areas, surveillance of water quality and water treatment (heating, UV)
Good personal hygiene, hygienic food prep
26
What is MIC?
Minimum inhibitory concentration
27
What is MBC?
Minimum bactericidal concentration (<0.01% of the viability of the inoculum remains)
28
What is the principle of antibiotic spectrum?
Narrow spectrum
- E.g. penicillin G (original penicillin) mainly against streptococci
Intermediate
- E.g. Vancomycin active against Gram-positive bacteria
Broad spectrum
- Several classes/phyla
- E.g. Carbapenems active against Gram + and Gram -
29
What are Carbapenems?
A class of b-lactams with broad spectrum activity (compared to penicillin and cephalosporins). Their chemical structure makes them resistant to most b-lactamases, one of the main resistance mechanisms against b-lactams (e.g. imipenem)
Mode of action: Binds to PBP (penicillin binding proteins) and inhibits cell wall synthesis
Effective against Gram +, Gram - and anaerobes. Used as a last resort for bacterial infections because:
1. Broad spectrum and therefore likely to generate resistance in broad spectrum of pathogens
2. Poor oral uptake, given IV for serious infections
Resistance to carbanepems recently reported
30
How do antimicrobials work?
Target inhibition, by binding tightly to an important target the drug gets in the way of an important cell process and limits growth or kills the cell
Target corruption, by corrupting an important process the presence of the drugs leads to an accumulation of errors in an important cell process, limiting growth or killing the cell
31
What are some antibacterial targets for different antibiotics?
Folate metabolism:
- Sulfonamides
- Trimethoprim
Cell-wall biosynthesis:
- ß-lactams
- Glycopeptides
- Cephalosporins
Protein biosynthesis:
- Macrolides
- Tetracyclines
- Aminoglycosides
- Oxazolidinones
DNA replication and repair:
- Fluoroquinolones
32
What is peptidoglycan?
The basic component of the bacterial cell wall that surrounds and protects most bacteria
33
What is the structure of peptidoglycan?
Peptidoglycan is formed of linear chains of two alternating amino sugars, N-acetylmuramic acid (NAM) and N-acetylglucosamine (NAG) connected by a glycosidic bond.
Each NAM is attached to a short (4- to 5- residue) amino acid chain, containing D-alanine, D-glutamic acid and meso-diaminopimelic acid in the case of Eschericia coli (a Gram negative bacteria) or L-alanine, D-glutamine, L-lysine, and D-alanine in the case of Staphylococcus aureus (a gram positive bacteria)
Cross-linking between amino acids occurs with the help of the enzyme transpeptidase and results in a 3-dimensional structure that is strong and rigid.
Peptidoglycan is constantly being broken down, recycled and renewed as bacteria grow and divide.
34
Why is peptidoglycan important for antibiotic therapy (inc. examples)?
Because peptidoglycan is unique to bacteria, the enzymes that synthesise it are some of the most important targets for antibiotic therapy.
Beta lactase (e.g. penicillin) inhibit cell wall synthesis by stopping activity of transpeptidase (Penicillin Binding Protein)
Glycopeptides (e.g. vancomycin) (intermediate spectrum, only G+) inhibit cell synthesis by binding to the amino acids within the cell wall preventing the addition of new units to the peptidoglycan
NB Beta lactams can differ in spectrum of activity due to structural differences.
35
What do we know about bacterial DNA replication and repair as antibacterial targets?
DNA gyrase is involved in dsDNA unwinding (along with Helicase) during DNA replication and transcription. It is present in bacteria but not in humans so is a good target for antibiotics.
Fluoroquinolones (broad spectrum) bind to DNA gyrase and stop them from unwinding DNA, so that stops DNA replication and transcription
Rifampicin (rifamycins; broad spectrum) bind and inhibit RNA polymerase thus preventing transcription initiation. It cannot stop elongation of mRNA once binding to the template-strand of DNA has been initiated
Rifampicin inhibits only prokaryotic DNA-primed RNA polymerase
36
What do we know about bacterial protein synthesis as antibacterial targets?
Protein synthesis occurs in the ribosome, which is made up of two subunits that assemble around the start of an mRNA to initiate protein synthesis. The small subunit is where codons are translated into amino acids, and the large subunit links the amino acids together into a polypeptide chain
Tetracycline and streptomycin (amino glycoside; intermediate spectrum against G-) bind to 30s ribosomal subunit to prevent initiation of protein synthesis
Chloramphenicol and erythromycin (macrolide; broad spectrum) both bind to the 50s ribosomal subunit, preventing peptide bond formation and hence elongation step of protein synthesis
Linezolid (an oxazolidinone, synthetic antibiotic; intermediate spectrum against G+) binds to 50s of ribosome and prevents tRNA from entering the ribosome to initiate translation
Linezolid is used to treat MRSA and VRE infection (ie. severe infections caused by gram +ve resistant to other antibiotics), relatively new, discovered in 1990s. Big advantage of linezolid is high bioavailability - almost 100% of the drug reaches the bloodstream when given orally, as if it was given intravenously. It is also readily distributed to most tissues in the body.
37
What do we know about bacterial metabolism as antibacterial targets?
Folate biosynthesis to make folic acid, needed for bacterial growth and replication. Two enzymes in this biosynthesis pathway are targets: Dihydropteroate synthase and dihydrofolate reductase.
Trimethoprim (broad spectrum) inhibits DHFR by resistance to its action develops quickly when it is used alone so it is usually combined with a sulphonamide (broad spectrum).
Another example of antimetabolite are purine or pyrimidine analogues, but they can't be used as therapeutics because:
1. They will be toxic to host too! Hence used only in cancer because worth the side effects
2. Are large molecules that penetrate/taken up poorly by bacterial cells
May be considered if found one that was specifically incorporated by bacterial polymerases but not mammalian polymerases. E.g. AZT is nucleoside analogue, which inhibits viral reverse transcriptase once it is incorporated. Also inhibits human DNA polymerase during cell division, but has approximately 100-fold greater affinity for viral reverse transcriptase. But this accounts for toxic effects of AZT on cardiac and skeletal muscles.
38
What is a historical perspective on the problem of antibiotic resistance?
1930s and 1940s:
- Sulphonamide and penicillin resistant Staphylococcus aureus
1970s:
- Penicillin resistant Neisseria gonorrhoeae (PPNG)
- ß-lactamase producing Haemophilus influenzae
Late 1970s to 1980s:
- Methicillin resistant Staphylococcus aureus (MRSA)
- Multi-drug resistant (MDR) Mycobacterium tuberculosis
1980s to 1990s:
- Common enteric and non-enteric Gram -ve bacteria, Shigella sp., Salmonella sp., E.coli etc
- Antimicrobials in farming
39
Why do we need to talk about managing antibiotic resistance?
To put it bluntly, what we're doing isn't working.
Marked increases in both GP and GN resistance in the past 10-20 years
40
What are some examples of problematic resistant bacteria?
- MRSA
- ß-lactamase producing enterobacteriaceae
- Vancomycin resistant Enterococcus faecium and Pseudomonas aeroginosa
- Acinetobacter baimannii
41
What are some ways bacteria can become resistant to these drugs?
Innate resistance
Acquired resistance
- Mutation
- Acquisition of new genes
42
What are some mechanisms of resistance?
1. Drug inactivation
2. Uptake/excretion alteration
3. Target modification
43
What is transduction in antimicrobial resistance mechanisms?
Bacteriophages (viruses that infect bacteria) mediate transfer via transduction, whereby DNA from a donor bacterium is packaged into a virus particle and transferred into a recipient bacterium during infection.
44
What is conjugation in antimicrobial resistance mechanisms?
The mechanism of gene transfer responsible for the most concerning aspects of antimicrobial resistance.
A sex pilus (small tube) forms between two bacterial cells through which a plasmid is transferred from one to the other
45
What is transformation in antimicrobial resistance mechanisms?
Some bacteria are able to take up free DNA from the environment and incorporate it into their chromosome
46
What happens in drug inactivation?
Enzymatic hydrolysis of the ß-lactam ring:
- If the bacterium (usually gram -ve) produces the enzyme ß-lactamase or the enzyme penicillinase, the enzyme will break open the ß-lactam ring go the antibiotic, rendering the antibiotic ineffective.
- Penicillinase was the first ß-lactamase to be identified: it was first isolated by Abraham and Chain in 1940 from Gram-negative E.coli even before penicillin entered clinical use
Recent example: New Delhi metal-beta-lactamase, 2009 New Delhi. Resistant to broad range ß-lactams (carbapenems).
Cephalosporins also have ß-lactam ring but that is slightly different to penicillin. However, the ß-lactam ring can also be hydrolysed.
NB. Methicillin no longer manufactured because more stable and active b-lactams such as oxacillin (antibiotic susceptibility testing), flucoxacillin and dicolxacillin (therapy) are used
Enzymes catalyse covalent modification of amino or hydroxyl functions, leading to a chemically modified drug which binds poorly to ribosomes
The aninoglycoside antibiotic kanamycin can be enzymatically modified at three sites by three kinds of enzymatic processing - N-acetylation
O-phosphorylation or O-adenylylation - to block recognition by its target on the ribosome
47
What are some methods of altered drug uptake in drug resistance?
Efflux pumps
- Tetracyclines, fluoroquinolones, ß-lactams, macrolides
Porin mutations
- Gram negatives
- Mostly ß-lactams
Reduced outer membrane permeability
- P.aeruginosa, E.coli O157:H7
- Aminoglycosides, quinolones
48
What do efflux pumps do?
Active transport to remove antibiotics from inside of cells
49
How does reduced membrane permeability occur?
Changes to membrane proteins, molecular mechanisms not really known
50
What happens with porin mutations?
Gram negative cell envelope have inner and outer membrane, where channels known as porins are.
Porins are for influx of compounds, and adaptation to reduce influx of antibiotics through porins results in resistance
51
What are some target modifications that occur in drug resistance?
ß-lactams:
- Altered penicillin-binding proteins
- E.g. MRSA
Glycopeptides (vancomycin, teicoplanin):
- Altered ribosome (streptomycin resistance)
Macrolides, licosamides, streptogramines:
- Altered ribosome (23S rRNA)
52
How do ß-lactam antibiotics act?
By inhibiting the synthesis of the peptidoglycan layer of bacterial cell walls. The peptidoglycan layer is important for cell wall structural integrity, especially in Gram-positive organisms.
The final transpeptidation step in the synthesis of the peptidoglycan is facilitated by transpeptidases known as penicillin-binding proteins (PBPs).
PBPs bind to the D-Ala-D-Ala at the end of muropeptides (peptidoglycan precursors) to crosslink the peptideglycan.
ß-lactam antibiotics mimic this site and competitively inhibit PBP cross linking of peptidoglycan.
53
What is the action of Vancomycin?
Alteration to the terminal amino acid residues of the peptidoglycan subunits, normally D-alanyl-D-analine, which vancomycin binds to.
54
What is the action of aminoglycosides?
Alter ribosome binding site where streptomycin normally binds. Resistance to streptomycin can occur by this mechanism since this agent binds to a single site on the 30S subunit of the ribosome.
Resistance to the other ahminoglycosides by this mechanism is uncommon since they bind to multiple sites on both ribosomal subunits.
55
What is the action of macrolides?
Most frequently found mechanism of macrolide binding site modification is dimethylation of a single 23S rRNA nucleotide, A2058, by Erm-type methyltransferases
A2058 is also intimately involved in the binding of lincosamides and streptogramin B. Hence, Erm-based methylation (termed MLSB resistance) renders the cell resistant to at lease three unrelated classes of antibiotics
56
How does exposure to antibiotic cause bacteria to become resistant?
Induced resistance:
- Inheritance of adaptively acquired characteristics. Antibiotics somehow direct mutations
OR
Selected resistance:
- Antibiotics do not direct mutation, but select for mutants
Resistance is selected by presence of antibiotic:
- Drug-resistant mutants shown to appear spontaneously rather than being directed by the presence of the drug.
57
How do we determine if mutants appear before or after addition of selective agent?
Grow several cultures without selective agent, then add agent to all cultures at the same time measure percentage of resistant mutants in each culture.
INDUCED RESISTANCE:
- Mutants appear only in response to a selective agent
- Each bacterium will have the same chance of becoming a mutant after antibiotic is added, so same percentage of bacteria should become resistant in all cultures
SELECTED RESISTANCE:
- Mutants appear prior to addition of selective agent
- Number of mutant bacteria will vary among the cultures
58
What are the factors affecting rate of resistance emergence?
1. Complexity of resistance mechanism (i.e. point mutation in rpoB conferring resistance to rifampin vs multiple gene product interaction for vancomycin resistance)
2. Fitness cost. Resistance requires changes that are too damaging for bacterium to survive
3. Compensatory mutations - mutations that compensate for reduction in fitness affect population-wide resistance emergence. Depends on level of drug used.
4. Opportunities for HGT, somewhat dependent on ability to persist and/or colonise new host (e.g. bacteria that can colonise hospitalised patients can increase in resistance in a short timescale)
5. Intensity of selective pressure imposed by antimicrobial agents.
59
What are factors determining the rate of decline in resistance?
1. Fitness cost and compensatory mutations
2. Interventions to control resistance (change in antibiotic use policies, interventions to reduce transmission)
60
What are some risk factors for antimicrobial resistance?
Overuse in clinical settings:
- Non-completion of whole course
Use in agriculture:
- Prophylaxis
- Growth promotion
Lack of use of effective preventative measures:
- Handwashing
- Patient isolation
61
What are some sources of selective pressure?
Widespread, inappropriate use of antibiotics;
- Up to 50% of antibiotics are prescribed unnecessarily
- Half of patients do not finish prescribed course
- 63% of vancomycin orders were inconsistent with CDC guidelines
Use of broad spectrum antibiotics:
- 70% consumed by animals
- 30% consumed by humans
62
How is antimicrobial resistance spread?
Migration:
- Economic, socio-political and climatic push and pull factors
Environmental:
- Human and animal hospital sites as reservoirs for C.difficile and MRSA
Diagnostics:
- Asymptomatic infection contributes to spread (C.diff and TB)
- Improved diagnostics to detect latent TB
63
What are human factors contributing to spread of antimicrobial resistance?
Migration:
- Is a key epidemiological determinant for TB in low-burden European countries, and transfer of hypervirulent Clostridium difficile and MRSA
64
What is the example of MDR- and XDR-TB, and treatment approach?
Effective treatment regime for TB involves a two/three-drug combination that:
- Lasted 4-6 months
- Reduced relapses
- Eliminated antibiotic resistant strains
Three drug combination:
SM (streptomycin) + INH (isoniazid) + either thioacetazone or PZA (pyrazinamide) or RMP (rifampicin)
Resistant strains were almost always resistant to only one of the three available drugs
65
What is the origin of antibiotics?
Antibiotics - "against life"
Penicillin:
- 1928
- Staphylococcus aureus
- Alexander Flemming
- Florey and Chain
Sulphonamide:
- 1932
- Gerhard Domagk
- Streptococcus pyogenes
66
What makes a good target?
Effective against bacteria
Not toxic to humans/animals
Process that are different in bacteria and humans/animals
67
What happened in the changes in intestinal flora of farm personnel after introduction of Tetracycline-supplemented feed on a farm:
Within 5 months after chickens on a farm were fed Tet-supplemented feed, 31.3% of weekly faecal samples from farm dwellers contained >80% TetR bacteria (p<0.001)
The resistant bacteria contained transferable plasmids that encoded for multiple antibiotic resistance.
68
How are resistant microorganisms spread?
Antibiotics --> Someone gets antibiotics and develops resistant bacteria in the gut.
1. They spread resistant bacteria in the general community
and/or
2. They get care at a hospital, nursing home or other care facility --> Resistance bacteria spread to other patients, either directly or indirectly via surfaces in the facility and unclean hands of healthcare providers
Antibiotics --> Animals take antibiotics and develop resistant bacteria in their guts
1. Drug-resistant bacteria can remain on meat from animals. When not handled or cooked properly, the bacteria can spread to humans
and/or
2. Fertiliser or water containing animal faeces and drug-resistant bacteria is used on food crops. These bacteria can remain in the human gut.
69
What is the history and timeline of resistance?
Penicillin was available in 1942 and S.aureus resistant to it occurred in the same year.
1950s-1970s: Chloramphenicol, tetracycline, erythromycin resistance
1960s: ß-lactamase resistant penicillins available
1970s-1980s: MRSA, MDR M.tuberculosis, Penicillin resistant N.gonorrhoeae (PRNG), ß-lactamase producing H.influenzae
1980s-1990s: Common enteric and non-enteric gram negative bacteria, (e.g. Shigella sp., Salmonella sp., E.coli etc), Antimicrobials in farming
1997 Vancomycin resistant Enterococcus
2002 Vancomycin resistant S.aureus
70
Why did resistance to vancomycin take longer to emerge?
Because it was restricted, expensive, and earlier on had poor oral uptake and had to be given intravenously.
Also because vancomycin resistance requires several genes that work together to create a resistant phenotype.
i.e. enzymes for synthesis of low-affinity precursors, in which the C-terminal D-Ala residue is replaced by D-lactate (D-Lac) or D-serine (D-Ser), thus modifying the vancomyin-binding target; and for elimination of the high-affinity precursors that are normally produced by the host, thus removing the vancomycin-binding target.
71
How can we manage antibiotic resistance?
Low income countries
1. Health-Care facilities:
- Implementation of antimicrobial stewardship programs and infection control measures
- Universal screening of patients for MDRB upon administration
- Evaluation of duration and regimes of antibiotic treatment
- International harmonisation of breakpoints
- Development of rapid and affordable diagnostic technologies
- Active surveillance
- Re-launching discovery and development of new antimicrobial drugs
- Reinforce international/national regulations
2. Community setting and industry:
- Educational programmes for prescribers and users
- Assessing antibiotic consumption
- Assessing prevalence of MDR strains
- Update local antibiotic prescribing guidelines
- Active surveillance
- Improved sanitation
- Reinforce international/ national regulations
3. Food and water sources:
- Assessment of antibiotic concentrations of sewages and wastewater treatment plants
- Improved sanitation of industrial systems
- Decontamination of hospital sewage water
- Reinforce international/ national regulations
4. Farm animals and agriculture:
- Banning/regulating antibiotic use as growth promoters
- Improving farm biosecurity
- Enforcing joint surveillance systems in humans and animals
- The harmonisation of epidemiological cut-off values
- Reinforce international/ national regulations
Generation - receptor of MDRB
Other humans
72
What do we know about antibiotics and novel antibiotics?
-Members of each antibiotic class share a common core structure (e.g. beta-lactam ring in cephalosporins)
- Most chemical scaffolds from which today’s antibiotics are derived were introduced between the mid-1930s and the early 1960s
-Aside from the introduction of carbapenems in 1985, all antibiotics approved for clinical use between the early 1960s and 2000 were synthetic derivatives of existing scaffolds
-Just four such scaffolds—cephalosporins, penicillins, quinolones, and macrolides—account for 73% of the antibacterial new chemical entities filed between 1981 and 2005
73
What are some new vaccination strategies?
Recombinant protein vaccines against C.dificile
Intranasal vaccination for protection against adult TB
Vaccines targeting resistant genotypes in combination with antibiotics against drug-sensitive genotypes (MRSA biofilm infections)
Recombinant protein vaccine candidate IC84 is based on two truncated forms of TcdA and TcdB.
Intranasal vaccination by different antigen formulations has shown promising results in the augmentation of immunity and the combat of the pathogens at the site of infection.
Route of immunization dictates location of TB-reactive T cells, which predicts the protective outcome of vaccine-elicited immunity.
MRSA: vast number and transient expression of virulence factors in the infectious course of this pathogen have made the discovery of protective antigens difficult. In addition, MRSA biofilm growth involves cells growing at different rates and composed of divergent cell populations, making it difficult to develop a vaccine that represent such different cell types.
Multicomponent vaccine (4 antigens) was coupled with vancomycin treatment in a biofilm model of chronic osteomyelitis in rabbits cleared infection in 87.5% of treated rabbits.
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What do we know about Novel Antimicrobials?
Phage therapy:
- Whole phage or purified components of phage
Peptides and bacteriocins:
- Produced by animal, plant and bacteria as host defence molecules to combat infections
- Usually target cytoplasmic membrane. E.g. buforin II peptide isolated from the stomach of the Asian toad Bufo bufo gargarizans
Buforin II has been used as a wound-healing agent in traditional Korean medicine.
Antisense agents:
- Synthetic antisense agents that silence genes essential for bacterial survival
Probiotics:
- Live microorganisms that have health benefits
Prebiotics:
- Non-digestible carbohydrates that help growth or activity of probiotic bacteria in the gut
Phytotherapy:
- Plant extracts in natural form
75
What are the US national goals Sept, 2014:
1. Slow emergence of AMR
2. Strengthen National One-Health surveillance efforts
3. Advance development of rapid diagnostic tests to identify and characterise AMR
4. New antibiotics, therapeutics and vaccines
5. Global effort on AMR prevention, surveillance, control and antibiotic R&D
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What are the key aims of the UK strategy and what are they underpinned by?
PREVENT
- People from being infected - infection prevention and control
PRESERVE
- The antibiotics we have - good stewardship
PROMOTE
- Development of new antimicrobials, new approaches, better diagnostics - the independent review by Jim O'Neill
UNDERPINNED BY:
- Surveillance
- R&D
- One Health Approach
- International Collaboration
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What is the Canadian AMR response?
ACTION 1:
- Establish and increase surveillance in both animal and human settings
ACTION 2:
- Promote appropriate antibiotic use in animal and human settings
ACTION 3:
- Work with animal agriculture sector (antibiotic stewardship in Veterinary Medicine)
ACTION 4:
- Promote innovation
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What is the WHO draft global action plan?
Five strategic objectives:
1. Improve awareness and understanding of antimicrobial resistance
2. To strengthen knowledge through surveillance and research
3. To reduce the incidence of infection
4. To optimise the use of antimicrobial agents
5. To develop the economic case for sustainable investment that takes the account of the needs of all countries, and increase investment in new medicines, diagnostic tools, vaccines and other interventions
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What are the 7 areas in which actions are most necessary in the Action plan against the rising threats from AMR (EU communications)
- Making sure antimicrobials are used appropriately in both humans and animals
- Preventing microbial infections and their spread
- Developing new effective antimicrobials or alternative for treatment
- Cooperating with international partners to contain the risks of AMR
- Improving monitoring and surveillance in human and animal medicine
- Promotion research and innovation
- Improving communication, education and training
80
What are three perspectives from which to consider Zoonotic disease control?
Socio-economics and livelihoods
Decision making drivers at household and community level
Anthropogenic drivers of disease
81
What is One Health?
The health of humans, animals and ecosystems are interconnected
82
What are the One Health lines of inquiry?
Infectious disease research:
- Pathogenic microorganisms, host-pathogen interactions, endemic, epidemic, pandemic, zoonotic
Epidemiology:
- Study of the distribution and patterns of disease in defined populations
Public health:
- Health of a population. Entire spectrum of health. and well-being ~ Not only disease
Socio-economics:
- Interaction between economic activity and social processes/characteristics
Community:
- Shared identity, locality, interact with each other, similar values, norms
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What are Zoonoses?
Diseases transmitted between vertebrate animals and humans
E.g.
Source - Incubator - Indicator
Wildlife - Livestock/pets - Human
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What percentage of diseases are zoonoses?
Approximately 75% of recently emerging infectious diseases affecting humans are diseases of animal origin
85
What do we know about the emergence of zoonoses?
Environmental changes, human and animal demography, pathogen changes and changes in farming practice lead to the emergence of zoonotic diseases
Social and cultural factors such as food habits and religious beliefs play a role in the emergence of zoonotic diseases
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What is the impact of zoonoses?
Human and animal morbidity/mortality
Cost:
- Humans - DALYS (years of life lost to premature mortality or disability)
- National/international economic losses e.g. trade, movement restrictions
- Impact on public health structures
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What are some etiologies of zoonotic diseases?
Viral zoonoses:
- Rabies, Milker's nodules, Rift valley fever, Ebola etc
Bacterial zoonoses:
- Antrax, Tuberculosis, Brucellosis
Rickettsial zoonoses:
- Q-fever, Scrub typhus, Rocky Mountain spotted fever
Parasitic zoonoses:
- Trichinellosis, Hydatidosis, Cysticercosis
Mycotic/Fungal zoonoses:
- Tinea/Ringworm infection, Aspergillosis
Protozoan zoonoses:
- Trypanosomiasis, Leishmaniasis
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What are endemic vs emerging zoonoses?
Endemic:
- Constant presence of diseases or infectious agents within a given geographic area or population group
Emerging disease:
- A new infection resulting from the evolution or change of an existing pathogen or parasite resulting from the evolution or change of an existing pathogen or parasite resulting in a change of host range, vector, pathogenicity or strain; or
- The occurrence of a previously unrecognised infection or disease
Re-emerging disease - an already known disease that either shifts its geographical setting or expands its host range, or significantly increases its prevalence
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What are the factors in endemic disease?
Weak/deficient health systems - lack of investment nationally and internationally
Poor assessment systems - reliance on metrics that overlook the full cost of disease - the dual burden of human and livestock disease and its actual cost
Poor awareness amongst communities
Poor sanitation
Poverty - competing livelihood demands and priorities
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What are the 7 facts of neglected zoonotic diseases?
1. Massively under-reported
2. Cause significant human morbidity and mortality
3. Impose a dual burden on humans and animals
4. Are ancient diseases, often eliminated in wealthy countries
5. Control at source when feasible is highly cost-effective
6. Pose no potential for global spread
7. Affect poor and marginalised communities
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What are actors in disease control?
Inter-sectoral collaboration
- National health systems
- Private sector
- International organisms
- Research
- Communities
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What are pragmatic 'One Health' interventions?
Design of interventions to mitigate on-going burden of disease
Strengthening institutions, leadership, building trust through common good
Interventions that prevent infection at source likely to provide a broader 'safety net' than reliance on clinical management of human cases alone e.g. linking medical and veterinary surveillance
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What is community participation?
A process in which people take part in decision making in the institutions, programmes and environment that affect them
Health programmes and policy are often defined at regional and national levels, but prevention and intervention take place at the community level
Community context has been identified as an important determinant of health outcomes
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What do we know about Sub-Saharan Africa?
Around 70% of population (half a billion people) are dependent on agriculture and livestock
Infectious disease remains the major constraint to livestock productivity on the sub-continent
Predominant farming system is small-holder crop-livestock
Prevailing systems are vulnerable to ecosystem change and evolve in the face of it
This can involve encroachment on wildlife habitats, resulting in increased contact between livestock/companion animals and wild species.
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What do we know about changing livestock systems?
Shifts from traditional pastoralism with greater reliance on crops
Increasing pressure on grazing lands
Changing patterns of demand for meat and milk
Increasing complexity of milk and meat value changes
96
What are common endemic livestock diseases?
Tick-borne diseases:
- Anaplasmosis
- Babesiosis
- Ehrlichiosis
Trypanosomiasis
Helminths
CBPP - Contagious bovine pleuropneumonia
Brucellosis
Rift Valley fever
Pest de Petits ruminants (PPR)
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What do we know about the epidemiology of Trypanosomiasis?
Evident in around 10 million km^2 in 37 African countries and a major constraint to the development of livestock production and mixed farming
One of the most ubiquitous and important constraints to agricultural development in the sub-humid and humid zones of Africa
Direct impacts on livestock management and productivity, human settlement, human welfare
Poor surveillance and diagnosis
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What do we know about Trypanosomiasis, the disease?
Human African Trypanosomiasis - Sleeping sickness
Animal African trypanosomiasis - 'Nagana'
Vector: Glossina tsetse fly
Protozoan parasite - Trypanosoma
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What do we know about the different trypanosomiasis strains?
HUMANS:
Trypanosoma brucei rhodesiense - Eastern and Southern Africa - acute
Trypanosoma brucei gambiense - West Africa - chronic
ANIMALS (Cattle, Goats, Sheep):
Trypanosoma congolense - East Africa
Trypanosoma Vivax - West Africa
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What do we know about One Health and the Environment?
Intergovernmental Panel on Biodiversity and Ecosystem services report (2019)
95% of the Earth's land surface has some indication of human modification
Climate change
And biodiversity loss = growing threats
IPBES (2019) found that:
- 75% of global land surface is already significantly altered
- 66% of oceanic areas are experiencing increasing cumulative impacts from human activities
- Over 85% of global wetland area has been lost
95% = some indication of human modification, and 84% has multiple human impacts
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What do we know about biodiversity loss?
Livestock make up 62% of the world's mammal biomass; humans account for 34% and wild mammals just 4%
Domestic poultry are 71% of bird biomass
Extinctions: Huge rise in extinction rate
- 100 to 1000 fold compared to background
Cascading effects of extinction:
- Impacts on ecosystems
- Impacts on human wellbeing
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What has climate change led to?
Anthropogenic greenhouse gas emissions causing the "greenhouse effect"
Global heating
Changes to precipitation
Increase in extreme weather events
Ocean acidification
Sea level change
Huge impacts for biodiversity and human communities
103
What is pathogen pollution?
The act of biodiversity loss exposes people to novel viruses and pathogens
"Pathogen pollution" = human mediated transport of pathogens
Biodiversity loss - through habitat loss, degradation and fragmentation - exposes people to novel viruses and pathogens
104
What is disease spread in degraded habitats?
Risk of disease spread appears higher in human dominated and simplified habitats (Morand, 2018)
Recent study by Gibb et al. 2020 - demonstrates how global land-use changes favour zoonotic reservoirs and increase the risks of zoonotic diseases
Habitat degradation also releases sequestered carbon - increasing climate change
MORAND:
Habitat fragmentation that leads to increased edge, and increasing contacts between different communities of reservoirs and vectors, should increase disease transmission and pathogen prevalence.
GIBB:
More effective zoonotic host species might be generally more likely to persist in disturbed ecosystems, because certain trait profiles (for example, 'fast' life histories and higher population densities) correlate with both reservoir status and reduced extirpation risk in several vertebrate taxa (rodents, birds, bats)
105
What do we know about land use change and disease outbreaks?
Land use change has been estimated to be linked to 31% of outbreaks of emerging infectious diseases
- E.g. HIV, Ebola, and Zika viruses - which are considered connected to anthropogenic changes in tropical rainforests
15% of emerging diseases linked to agricultural changes - e.g. increases intensification
Virus transmission risk highest from animals that have adapted to human-dominated landscapes (Kreuder Johnson et al 2020)
- With domesticated species, primates and bats identified as carrying the greatest risk of zoonotic virus transmission
106
What do we know about ecosystem disease regulation?
Ecosystem service of disease regulation - natural biodiversity limits the exposure and impact of many pathogens through a dilution or buffering effect
This limits opportunities for pathogen spillover from wildlife to people
Still controversial, and probably not universal.
107
What is dilution effect?
More biodiversity means more hosts that aren't infected/good at infecting vectors
Leads to less risk of disease transmission to humans. Because animals spread zoonotic pathogens unequally, changes in the balance of reservoirs vs. non-reservoirs in a habitat affect the risk of spillover to a human.
Compared to a reservoir animals, non-reservoir animals make fewer copies of a pathogen and do not spread it as efficiently.
When biodiversity is high, a disease gets diluted among non-reservoirs.
Lyme disease - white-footed mice host via ticks
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How does biodiversity affect West Nile virus?
West Nile virus - infects bird and mammals. It has become established in birds and mosquitoes in North America. West Nile virus infections tend to be high where bird diversity is low. Bird species in which West Nile virus grows best - Crows, Jays, Finches, Sparrows and Thrushes - can be found in low biodiversity communities like cities.
Birds that don't grow the virus as well - Coots, Quail, Pheasants, Woodpeckers, and Parakeets - are generally only found in communities with high biodiversity like forests. In high biodiversity communities, West Nile virus gets diluted, and the overall amount of virus per bird is lower.
Naturally high levels of biodiversity, predators and competitors often keep super spreader species at lower abundance. So protecting naturally high levels of biodiversity is critical for mitigating pathogen transmission and spillover.
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What is buffering effect?
Buffering effect = more distance between people and wildlife - reduced in degraded habitats (agricultural overlap, hunting etc...)
110
What do we know about Wildlife trade and disease transmission?
Wildlife trad and wild meat consumption
- Often blamed or associated with disease transmission
Calls for bans
But wildlife is an essential source of income and sustenance for many people.
Ensuring that legal wildlife trade is sustainable as well as safe from disease risk will support food security for communities that rely on wildlife, and help to reduce the need for large-scale land-use changes.
111
What are some stats on Wildlife trade?
Bans are a food security risk in 15 countries
Need an extra ~124,000km2 agricultural land to replace wild meat protein with livestock
Land use change could drive >260 species towards extinction, globally
Global bans on wildlife trade fail to target the causes of disease emergence and harm the livelihoods and food security of millions of people.
112
Are trade or movement bans sometimes useful?
January 2016 - the USA banned the import of salamanders following the emergence of B.salamandrivorans to protect the native wildlife from this novel pathogen
This occurred after it was discovered in Europe - infecting and killing both captive and wild salamanders
Traded for pets but so far has been kept out of the US
113
What do we know about wildlife as a source of disease?
Wildlife implicated in many emerging zoonotic diseases
Including Ebola, Marburg Virus, HIV, Sin Nombre virus, Nipah Virus, Hendra virus and Manangle virus, West Nile virus, Lyme disease, Middle East respiratory syndrome (MERS), and avian influenza
But many zoonotic diseases pass to humans from livestock or other domestic animals
114
Biodiversity - risk or at risk?
Biodiversity and protected areas themselves are not an inherent risk for pathogen spill over
Human changes to ecosystems - and changes in contact between species - create the conditions associated with zoonotic disease risk
Risk monitoring and mitigation
Disease screening and risk assessment before reintroduction/release
Built in risk monitoring and mitigation, particularly at interfaces where wildlife-human or wildlife-domestic animal contact occurs that could lead to spill over
115
What do we know about risk assessments for Wildlife trade?
The Hazard Analysis and Critical Control Points System (HACCP) identifies hazards and their risks to human health
- Developed from the 1960s onwards
Endorsed by the food and agricultural organisation, World Organisation for Animal Health and WHO
Exclude practices that pose high health risks and increase compliance with existing legal systems and criteria
Strong controls to manage health risks from wildlife trade will help efforts targeting illegal and unsustainable practices too
Trade and consumption of kangaroo meat from Australia has an HACCP-based risk management system in place for international export and domestic consumption
116
What do we know about using ecology for Lyme disease control/risk management?
Lyme disease caused by bacteria (Borrelia burgdorgeri) carried by ticks in the genus Ixodes
Pass through vertebrate hosts in larval stages
White-footed Mouse (Peromyscus leucopus) is the most abundant and best spreader of the bacteria
Jones et al. 1998 - added acorns to the forest floor to stimulate a mast-year for oak trees
One year later, mouse populations increase in abundance and then spirochete bacteria in ticks increase
Can predict high risk years in advance based on acorn crop
117
What do we know about bats as wildlife reservoirs?
Bats are reservoir hosts of many zoonotic viruses
- Including Nipah and Hendra viruses, SARS-like coronaviruses and possibly also MERS coronavirus
Do bats have a disproportionate number of emerging zoonoses compared with other mammalian groups?
- A hypothesis that has been supported by two separate analyses of mammal virus datasets
Understanding why and how spillover from bats to humans occurs is important
- Why bats host so many zoonotic pathogens that cause lethal diseases in humans
Need an understanding of the ecology of the pathogen and its natural host(s) and of human-host interactions to help stop future spillovers
118
What do we know about bats and Hendra virus and preventing risk of spillovers?
Monitoring climate and food shortages can help predict risk of spillovers
Winter flowering of trees in fragments of forest seems to prevent spill over
119
What do we know about Bats and Nipah virus?
Study identified the intensification of the pig industry as the driver of the zoonotic emergence of Nipah virus in Malaysia
- These results informed government policies
- Since then no further Nipah virus disease outbreaks have occurred in Malaysia
Transmission from flying foxes to pigs is thought to occur via saliva on fomites (discarded fruit pulp) or via faecal or urine contamination of pigsties
Pigs act as amplifier hosts, enabling infection of humans via droplet transmission during respiratory infections. The risk of direct transmission from bats to humans in Malaysia is believed to be low
Dual use of agricultural land (for pigs and mangos) and increases in production, resulted in the direct overlap of mango production and livestock rearing and therefore produced a pathway for a virus circulating in flying foxes to infect an intensively managed commercial pig population
Policy = to separate pigs from bats via the removal of fruit trees from pig farms and the relocation of farms away from forested areas
120
What is the source for Nipah virus infection in India and Bangladesh?
Different! Palm sap contaminated with bat urine
121
What do we know about Wildlife Conservation and One Health?
One health became quite anthropocentric, placing nature at the service of humans - but nature can also benefit from One Health approaches as disease is a risk to wildlife populations
Die-offs in wildlife
- Canine distemper in African Lions (Panthera Leo) in the Serengeti
- Rabies in Ethiopian Wolves
- Chytridiomycosis in amphibians globally
- Pilchard herpesvirus disease in Australasia
- West Nile virus in corvids and other birds in New York
Disease can be an issue for Wildlife conservation
122
What do we know about extinction from disease?
Pathogens implicated for the first time in species extinctions, or near-extinctions
- Canine distemper in the black-footed ferret (Mustela nigripes)
- Chytridiomycosis in the sharp-snouted day frog (Taudactylus acutirostris)
- Steinhausiosis in the Polynesian tree snail, Partula turgida
Some, but not all may benefit from a One Health Approach
123
What do we know about bTB?
bTB is in many wildlife species - Badgers and TB in the UK
Also spread to Africa - with movement of cattle
South Africa - African buffalo, Greater kudu, Lion, Eland, Warthog, Bushpig, Large spotted genet, Leopard, Spotted Hyaena, Cheetah, Chacma baboon, impala and honey badger
African buffalo can act as maintenance host of M.bovis and allow bovine tuberculosis to spread in large ecosystems without cattle
Bovine TB was found to be driving social changes within lion prides which contributed to lower lion survival and breeding success. A faster territorial male coalition turnover - leads to greater frequency of infanticide
Other species may get bTB through scavenging, e.g. hyaenas, cheetahs, leopards, warthog
Conservation efforts in endangered species impacted, and free exchange of genetic resources between conservation areas reduced
124
What do we know about bTB in Wildlife?
1 in 7 Rhinos in Kruger park have bTB
Not impacting population levels yet
Infections could lead to death with additional stress (e.g. drought)
But - impacts movement of animals. Positive animals can't be moved between areas
Reduces genetic connectivity between populations
125
What do we know about gorillas and One Health?
Conservation through Public Health - founded by Gladys Kalema-Zikusoka, Lawrence Zikusoka, and Stephen Rubanga in 2002
Special focus on the endangered mountain gorilla in Uganda
Started with a scabies case in the gorillas - which came from humans
"It made me realise that you can't protect the gorillas if you don’t think about the people living around the park, who have very little health care" - Gladys Kalema-Zikusoka
TB in the human and cattle community - concerned about passing to the gorillas. Ebola is also a risk (seen in Congo)
Gorilla species is endangered, around 600 adults left
126
What do we know about Branches of work in Gorillas and One Health?
Wildlife health monitoring
- Including monitoring mountain gorillas for infection by human diseases and possible treatment (foecal and blood samples)
Improving human health
- and family planning in the vicinity of gorilla habitat to protect gorillas from disease and to benefit local communities
Livestock health
- promotion and disease surveillance warnings
Information, education and communication projects
- in remote areas to benefit local communities
127
What do we know about Rabies and One Health?
Rabies kills around 60,000 people annually
Easily preventable through annual or biannual mass vaccination of dogs
Many countries spend lots on post-exposure prophylaxis
One Health Approach could be beneficial
Humans and livestock/ domestic animals at risk
Wildlife can also carry and suffer from rabies (bats, carnivores)
128
What do we know about Ethiopian wolves and rabies?
Rabies (and canine distemper virus) cause outbreaks in Ethiopian wolf populations
Wolf populations are very small (<500 adults in the world)
Recovery can be slow due to the breeding system of the species
Virus spillover from domestic dogs
Main areas of action
- Control diseases in domestic dogs
- Reduce dog-wolf contact
- Increasing capacity to detect outbreaks
- Vaccinating wolves (preventative measure and emergency vaccination in response to a confirmed epizootic)
Vaccinate dogs against CDV and rabies
- Over 3000 dogs a year in the settlements around wolf habitat to reduce risk of transmission
Disease alert networks
- Improve the ability to detect, diagnose and contain outbreaks
