Ectoparasites Part A

Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 Learning Objectives
• To recognise the signs and symptoms of an
ectoparasite infestation
• To relate their biology to infestation and its control
• To be aware of their global importance and threat
• To understand their associated treatments:
• Physical
• Pharmacological
• Hygiene
 E
ctoparasite ↑

Signs and symptoms of infestation: -

general
Generic2
• - signs and symptoms
– Itching
– Scratching
– Bites
-

– Soreness ->
possibility reinfestation]
of
reoccureness
of

Inot life threateningI

that

• Generally
infection
is caused by
parasites

– Infestation not infection

- -

• But
– 2ParasitesI are hosts for transmitted pathogens and diseases
– Mild to severe discomfort
– Secondary infection from scratching
– Public health issues, contagious
- -

– Social stigma
-
 Ectoparasites infestation Symptoms.
-> itching

-> soreness

- Scratching
->
bites

ofreinfestation]
Not-life threatenings -->
possibility reoccureness
infection
of
that
is caused by
parasites

transmitted
pathogenes are
disease
hosts for
pathogenes and

infestation causes discomfort e.g. itching

secondry infection because of scratching the infected

arech
 [Ticks, mites, fleas and liceI
• What are they: phylum Arthropoda
Fleas and liceI
–[
– Class Insecta
-

– 6 legs
– Wingless
– [Ticks and mitesS
– Class Arachnida
-

– 8 legs
– Spiders, scorpions
-

• Different life cycles

• What do they do
– All blood sucking parasites
– Live on skin: ectoparasites
-

– Tend to be host specific i.e. human

-

Lice are the most common ectoparasite in UK

• &->

– others have
ent greater socioeconomic impact
off
days
work
Ticks
Biology: Life-cycle of tick three host
not just fluffy animals but also man
overwinter survival

-
Tick distribution
 Ticks: [Ixodes ricinusI

• Climb tall grass and shrubs; “questing”

– Attach to a passing host
– Hiking
– Playing in long grass
• Inspect skin at end of day
– Check for ticks
 Ticks: Signs
the arm - move to
armpits
• Move up body
on

• Warm, sweaty places Fresh vs fed tick

– Exposed limbs
• Top of legs
-

• Top of arms
-

• buttocks
- In reality
– Neck
-

• Do not itch
-

• Visual examination
-

–[only way to detect3

-
 Ticks: treatment
• No pharmacological treatment
• Physical Removal
– Use of tweezers or Tick Card see
– http://www.lymediseaseaction.org.uk/about-ticks/tick-removal/
infection
– Do not squeeze or crush body
grisk
of

– Do not leave head behind

– Do not burn off or use other noxious means
– Keep tick for positive identification
– Probably Ok if removed within 24 hrs of attachment?
Ectoparasites Part B
Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 Global importance and threat
Possible consequences of tick bite:
infection
• UK and Europe bacterial
Lyme disease,
– En I signs and symptoms
– Issue leaflet

• UK and Europe
– Tick-Borne Encephalitis
-
 Lymes disease
• Bacterial disease carried by tick
– ESpirochetes Borrelia burgdorfiI
• Symptoms:
– Bulls eye rash (not always)
e n

– Flu like symptoms feeling discomfort

-
of

• Tired and general malaise

• “Great imitator”
– Seek clinical help Imidiatly
-
erythema migrans (EM):Not hot, itchy or scaly
– Incubation 2-100 days erythema for red and migrans for spreading
• Epidemiology
– >8000 serologically confirmed cases in 2019
– 14% world population has had Lymes disease!
• Treatment
– Oral antibiotic:5-
doxycycline
Lyme disease: -

Bacterial infection carried outby ticks

I
Spirochetes Borrelia burgdorfi

Symptoms o

red patches
swollen eye like

flue like
symptoms
whatto do

seek clinical
immedial help.
Treatment

oral antibiotics-> doxycycline

 European B. burgdorfi distribution

Prevention: awareness, cover up, topical insecticides

 Tick-Borne Encephalitis
• Viral disease carried by tick
– Flavivirus
-

– Infects Brain
-

• Symptoms:
jimdiate
– Seek[
Clinical help j

• Mortality up to&
2%
• Death possible within
-

7 days of neurological symptoms

• Epidemiology
• Russia & Europe 5000-7000 cases p.a., mandatory surveillance
- -

• Now in UK see NHS

• Vaccination: FSME-Immun and Encepur
specially if at risk, Vaccine available on NHS at cost
-

• -

• For some countries routine vaccination

• E.g. Latvia, Switxerland
-

• Travel guidance
TBE average annual incidence rate per
100000 in the EU/EFTA (2012)

Prevention: cover up, topical insecticides

Activity: Watch these three videos to
show the impact of Lyme disease.
Can you recognise the common signs and symptoms
that the disease displays?
Matt Dawson case study
Lyme disease has 'dominated' my life
Woman bedridden for two years by Lyme disease from tick bite
Ectoparasites Part C Scabies
Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 Scabies: Sarcoptes scabiei
• Sarcoptic Mange in dogs
• Signs and symptoms
– epidermal skin infestation
– feed on tissue and fluids
– characterized by superficial burrows and pruritus
e n

(intense itching)
– > 300 million cases worldwide
-

• Scabere “to scratch"

-

• Like skin fold

– Fingers
– Buttocks
– Breasts
 Scabies: signs & symptoms
• Intense pruritus
e ->

• Visual signs
• Ensure not
-

• impetigo or Eczema
-

• Burrow markings
-

• Ink test, “wake” sign

• Skin biopsy: scabies mites
• Too small to be seen
Scabies: similar signs
• impetigo

• Eczema
 Skin biopsy
(low sensitivity aids positive identification with mite or egg)
 Scabies
• Highly contagious
-

• 1/1000 see GP per month in UK

e n

• Spread directly :
-

• touching infested person's skin

-

• picking up the mites under the fingernails

-

• scratching
o n

• Spread indirectly by fomites (objects):

• keyboards, toilets, clothing, towels, bedding, furniture
• anything
-
that the mite may be rubbed off onto
• Survive up to 14 days away from a host
• But less than 36 hours in absence of human skin debris
• Symptoms develop after[3-4 weeksI infestation
-
 Those at most risk
• Institutional settings-close contact
– Barracks and dormitories
– Elderly people – those who live in nursing homes
– Children – in schools and nurseries
• Overcrowded situations
• Young mothers
– from close contact with infested children
• Sexually active: considered as STD
 Pharmacy and therapeutics
• Resistant to soap and water, even scrubbing
– Consider mite location within skin
• Can be infected indefinitely
– Consider Life cycle- reinfestation
-

• Family and sexual partners need to be treated

- e n

– Consider reinfestation
-

• Clothes, towels and bed linen disinfected

- -
e

• Hot wash >60°C to kill parasite- reinfestation

-IS

• Use insecticides: acaricides

-

– kill arachnid sub class Acari: ticks and mites

-

– 1st lined
-
5% Permethrin cream I
– 2nd line [0.5% Malathion lotionI
-

– Oral[Ivermectin
-- (200mg/kg) “crusted scabies”
– Benzyl benzoate less effective than above
-

• unknown action!
-
 Pharmacy and therapeutics
• 1st line treatment [Permethrin cream 5% (Lyclear)I
• Whole body!
• Lyclear for scalp
• 2nd line treatment[Malathion lotion 0.5% (Derbac-M)I
• used if permethrin ineffective: resistance
• Itching treated with
• crotamiton (Eurax)
• sedating antihistamine
-

• Acquired immunity
• Secondary infestations
• Reduced parasite burden
e

• Can eliminate second infestation

-
 Ectoparasites Part D
How do drugs for scabies work?
Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 animal function leads
paralyse
How does [permethrinI work? to death

• Permethrin
– Synthetic pyrethroid
• Similar to natural pyrethrins from [
Chrysanthenum flowersI
• Example of [ion channel agonistI
• [Acts on nervous system of animalI
– [Neurological toxinI
-
&
• Blinds to voltage-gated -
Na+ channels
• Prolong Na+-channel activation
-

– prevent inactivation and deactivation

Paralyses animal function leading to deathI
•-
[Na+ channel
inactivation3

O
Na+ ion channel

Lipid bilayer

Vm Activation gate
60
30
Inactivation gate
Vm (mV)

0
-30
-60
Na+ -90
0 50 100 150 200
Time (ms)
 Na+ channel
inactivation

Na+ ion channel

Lipid bilayer
th
binds to
Thin
permiactivation gate
Vm -
Activation gate
60
30
Inactivation gate
Vm (mV)

0
-30
-60
Na+ -90
0 50 100 150 200
Time (ms)
How does permithin has no affecton humans?
humans has differentsquence at the binding site
to insects and organisms
compare sequence in other
Mechanism of pyrethroid
[
-
resistanceI

Super-kdr
Knockdown resistance (kdr)
 Why are insects more susceptible?I
I
harmed
Courtesy of Dr I Mellor SoLS easly

• A major reason is
the -
sequence of the
domain II S4-S5
-
linker at the super-
e

kdr site-(M918).
-

918
DIIS4-S5 linker
Drosophila-para NLLISIMGRTMGAL • Methionine Sulphur side chains
Super-kdr NLLISITGRTMGAL • Threonine Polar side chains
874
Rat NaV1.2 NMLIKIIGNSVGAL • Isoleucine Non Polar side chains
 Structural-functional role of mutations
918
DIIS4-S5 linker
Drosophila-para NLLISIMGRTMGAL • Methionine Hydrophobic side chains
Super-kdr NLLISITGRTMGAL •Threonine Polar uncharged side chains
Rat NaV1.2 NMLIKIIGNSVGAL • Isoleucine Polar uncharged side chains
874

• Methionine Hydrophobic side chains

Thioether sS/Π interaction with aromatic groups.
Pyrethroids leads to binding and toxicity?

•Threonine, polar uncharged side chains

Chiral side chain
No binding

• Isoleucine, non polar branched chain

Chiral side chain
No binding
 Contraindications
1
-D as

• Due to L
absorbtion of topical cream minimalI - >

• Breast feeding
– No evidence of risk, but do [
remove cream from nipple!
• Itching may persist up to [
3 weeks post treatmentI
• Animal material and faeces remain in skin
• Suspect treatment failure if
– Itching
-
persists⑧
> 6 weeks
– Faeces remain in skin
-

– New burrows appear

-

§ Why is this?
– Treatment non-compliance
• Once overnight complete coverage
reinfestation
• Repeat one week later, why? preven
-

– Treatment of personal close contacts?

• Prevent re-infestation
-

– Drug Resistance
– Genotype animal for permethrin drug resistance
 Ectoparasites Part E
How do drugs for scabies work?
Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 How does [malathion work?
I

• Malathion
AnticholinesteraseI
–[
• Organophosphorous compound
Neurological toxinI
–[ the animal leads to death
Paralyses
• Acts on nervous system of animal
-

• Irreversibly binds to and blocks cholinesterase

• Promotes all [cholinergic neurotransmissionI
– Acetylcholine is used as neurotransmitter
• Post-ganglionic neuronal excitation
• Continuous muscle excitation and contraction
Action of anticholinesterase

ACh ACh

A + Ch A + Ch
Anti-ChE
ACh ACh
AChE AChE
Target tissue Target tissue
 SoContraindications3
• Malathion low toxicity to man
• Only with repeated exposure, over dose
-

– Ingestion and subsequent metabolism to the far more toxic malaoxon

– Chlorination of water promotes oxidation to malaoxon

-
->

– Malathion Malaoxon
-

• Anticholinesterase effects in man

– Parasympathomimetic, promotes muscarinic transmission
– Neuromuscular, promotes nicotinic transmission at skeletal muscle
-

– CNS, promotes central cholinergic neurotransmission

-
Sites of cholinesterase action
 Malathion/Malaoxon poisoning
• Muscarinic (parasympathetic) effects include:
– Miosis (pupillary constriction)
--

– Salivation
-
– Sweating
-

– Bradycardia (slowing of heart rate)

-

• Nicotinic (skeletal muscle, SkM) effects include:

-

– Fasciculation (twitching of SkM)

- -

• -
Spontaneous release of ACh
– Paralysis
-

• Depolarizing neuromuscular block

• Central nervous system symptoms include:
anxiety
– -
restlessness
– -
– Dizziness
-

• All effects due to heightened C

ACh action
 Ectoparasites Part F
How do drugs for scabies work?
Fleas, Lice, Ticks and Mites

Dr Paul A Smith FSB

School of Life Science
 How does Iivermectin work?I
• Ivermectin
– Used for crusted scabies
– Macroyltic lactone
e

• Derived from Streptomyces bacterium

• Example of ion channel agonist animal
deat
• Act on nervous system of animal Paralyse
to
reads

– LNeurological toxinI
• Binds to and activates GluCl ion channels
– Glutamate-gated chloride channels
– member of the Cys-loop ligand-gated ion channel family
– Also GABAARs and nACHRs in vertebrates
• ↳GluCl are specific to invertebrate3,58
– Found in muscle and nerves
– Not found in man
• Causes persistent opening of ion channel
• Paralyses animal function
 Glutamatergic synaptic transmission:
ionotropic events - hyperpolarization

glutamate gated
chloride channel

Out Cleft
Post-synaptic membrane
In

Cl-- K+ Glutamate or ivermectin

 [Contraindications for IvermectinI
• Oral administration not topical
• Does not cross blood brain barrier of humans
-

– P-Glycoprotein
-

– Multi-drug-resistance (MDR1) gene

--

• In man it modulates, not activate, nAChR and GABAAR

- -

• Not given to
– Children under age of⑧
5
– Body weight ⑧
<15 Kg
– Breastfeeding
– Hepatic or /and renal diseases
-
-
Complications of scabies3
2 -

• Secondary infection
e n

• Staphylococcus: Impetigo
• Treat with antibiotics
• Social stigma
• Pyschological harm: guilt and shame
-

• Crusted scabies
– Extreme infestation
• Thousands to millions of parasites
– Does not itch
-

– Thick warty crusts

-

– Immuno-deficient
-
– Young, elderly, HIV, chemotherapy
-

– Treated with Ivermectin

-
 Prophylaxis
d and preventionI
Sharing of clothing,-
• - towels, bed linen
• Dirty hotels and accomodation
and under fingernails
-

•-General hygiene Waste hand

 Prophylaxis and prevention
• Sharing of clothing, towels, bed linen
• Dirty hotels and accomodation
• General hygiene