parasitic infections Flashcards
what are the Main Anti-protozoal Drugs
examples of each
Toxoplasmosis: pyrimethamine, sulphadiazine, clindamycin, clarith/ azithromycin
Anti-amoebics: Tinidazole, metronidazole, diloxanide furoate
Anti-malarials: chloroquine, proguanil, atovaquone, artemisinins, doxycycline
what are parasites?
Living organism requiring intimate prolonged contact with another living organism to meet some of its basic nutritional needs
organisms of varying complexity from unicellular protozoa to complex multicellular helminths
what are examples of endo parasites and ectoparasites
Endoparasites
Protozoa
Helminths
Ectoparasites
Lice
Leeches
Scabies
Fleas
what is Protozoa
Unicellular eukaryotic organisms
Means “first animal”
Feed on bacteria and particles of nutrients
during growing stage
~20,000 different species but relatively few cause disease
Diverse structure, most inhabit water/soil
Some use insect vectors, others environment (e.g. water-borne)
Important for travel medicine as many infections from tropics
what are protozoal infections
Protozoal Infections include:
Malaria (top right image)
Intestinal infections – Amoebic dysentery, toxoplasmosis and cryptosporidiosis
what are the causes of malaria
how is it transmitted
what are the main 4 types
diagnosis
symtpoms
preventions
treatment
Cause: parasitic protozoa “Plasmodium”
Infects human and insect (mosquito) hosts alternately
Latest data are 2020, 241 million cases, mostly in Africa and mostly P. falciparum
627,000 deaths, more than two-thirds in <5yrs
UK cases are imported: 1719 in 2019, mainly P. falciparum
4 main types: P. falciparum, P. vivax, P. ovale and P. malariae
Most important types: P. falciparum most common in Africa and e.g. eastern Mediterranean with P. vivax common in South East Asia & Americas
P. falciparum is considered most serious (e.g. cerebral malaria)
Other types typically give less severe disease
P. vivax and ovale can lay dormant in liver – relapse
Diagnosis: usually blood film microscopy and/or antigen-based rapid diagnostic tests (RDT)
SYMPTOMS
For uncomplicated malaria, commonly have a mix of:
Fever, chills, headaches, sweating, nausea, vomiting, aches and general feeling unwell
May have bouts of shivering, fever and sweats that occur for a few hours every 3 or 4 days but less common
More severe malaria is an emergency and can include a range of serious effects such as cerebral malaria and other organ and metabolic damage
PREVENTION
-anti-marial drugs
mosquito nets
covering
permethrin
TREATMENT
Vaccines
1. RTS,S (P. falciparum) – blocks liver infection
Work began in late 1987
Clinical trials in children and infants, including large Phase III 2009-14
39% & 29% decrease malaria & severe malaria cases (respectively) 5-17mo old
July 2015 EMA approval (MOSQUIRIX)
Pilot in Ghana, Kenya, Malawi>800,000 children since 2019
Recommended by WHO on 6th Oct 2021 for more widespread use
- R21 (P. falciparum)
Recent trial in ~450 showed ~80% effectiveness
Larger trial currently underway
Both protein-based vaccines with adjuvant
Recent trial showed combining vaccine + chemoprevention effective reducing incidence, severe malaria and death
Malaria transmissionand life-cycle
Human Stages:
Mosquito bites / feeds, injects sporozoites
Infect liver cells
Develop to schizont
Schizont rupture and
Release merozoites that infect erythrocytes to become immature trophozoites of which…
Some mature and generate schizonts that rupture (feed back to 5)
Whilst some generate gametocytes that are ingested by mosquitos
To 12. are stages of reproduction in mosquito
Malaria Prophylaxis & Treatment uk
pregnancy
Prophylaxis
Depends on area visiting (risk) but commonly:
Doxycycline (POM)
proguanil + atovaquone (Malarone) – (P – Maloff Protect/POM - Malarone)
Mefloquine (POM)
Pregnancy: If cannot avoid travel, possible options: proguanil, chloroquine, mefloquine
Treatment (for uncomplicated cases)
1st choice is chloroquine for non-falciparum (P. malariae, P. ovale, P. vivax)
Chloroquine resistance common in most P. falciparum strains.
First line preference is:
Artemether + lumefantrine (Riamet)
[or dihydroartemisinin (aka artenimol) + piperaquine], if not available then:
Quinine + Doxycycline (or clindamycin),
Proguanil + atovaquone (Malarone),
Pregnancy: Quinine + clindamycin
Severe/complicated falciparum: Artesunate IV (initially)
Amoebic Dysentery & Amoebiasis
what is it
transmission
causes
treatment
Disease of tropics
~50 million cases/year
100,000 deaths
Transmission: Faecal-oral
Cause: Entamoeba histolytica
Commonly asymptomatic
Mild diarrhoea to severe dysentery
Extra-intestinal infections include liver abscesses
Digests (liquifies) human host cells (colon wall, neutrophils, liver cells)
Treatment:
Often self-limiting
Metronidazole (first line, acute invasive amoebic dysentery) or
Tinidazole followed by paromomycin/diloxanide furoate or other drugs active against cysts in the lumen
Toxoplasmosis
causes
symptoms
treatment
Cause: Toxoplasma gondii
Human exposure common (e.g. cat faeces or infected meat, unwashed fruit/vegetables)
Significant proportion adult population seropositive
Risk of developing disease low
Symptoms usually mild in healthy people
A few hundred reported cases in UK annually
Can be life threatening if immunocompromised
Also serious congenital infection:
Retinochoroiditis, seizures, and mental retardation.
Treatment: Often self-limiting
Most often pyrimethamine plus sulphadiazine (see malaria for mechanisms)
Alternative plus clindamycin, clarithromycin or azithromycin
Toxoplasmosis
causes
symptoms
treatment
Cause: Toxoplasma gondii
Human exposure common (e.g. cat faeces or infected meat, unwashed fruit/vegetables)
Significant proportion adult population seropositive
Risk of developing disease low
Symptoms usually mild in healthy people
A few hundred reported cases in UK annually
Can be life threatening if immunocompromised
Also serious congenital infection:
Retinochoroiditis, seizures, and mental retardation.
Treatment: Often self-limiting
Most often pyrimethamine plus sulphadiazine (see malaria for mechanisms)
Alternative plus clindamycin, clarithromycin or azithromycin
Cryptosporidiosis
causes
transmission
symptoms
treatment
Cause: Cryptosporidium parvum
~30% of western population seropositive
A notifiable infection in UK, a few thousand cases per year reported
Transmission:
Typically spread from water (swimming lakes / pools)
Contaminated foods / surfaces, common after flooding (also in UK)
No insect vector
Completes life cycle in human host, cysts passed out in faeces into water
Symptoms: Most common symptom watery diarrhoea, others include:
Dehydration, weight loss, stomach cramps or pain, fever, nausea, vomiting
Some people asymptomatic
Usually 1-2 weeks, cyclical - feel better, then worse again
Treatment:
Self-limiting but dangerous immunocompromised e.g. HIV/children/pregnancy
Usually don’t treat “normal” patients. Nitazoxanide (US, immunocompetent)
Helminths
parasitic worms
how does it reproduce
transmission
where does species attach to
what do they feed off
immune response
Most species attach to intestinal tract
Digestive enzymes dissolve worm egg shell, release the worm
Worm protected from digestive enzymes by external keratin layer
Helminths feed off host
take nourishment / protection
disrupts hosts’ nutrient absorption,
causes weakness / disease
Can be asymptomatic for months/yrs
Immune response to worm infection in humans is via T-helper cells
results in inflammation of the gut
results in cyst-like structures forming around the egg deposits throughout the body
Cestodes
causes
symptom
treatment
Cause: 2 subclases Cestoda
Cestodaria
Less common, unusual
Eucestoda - Most common, widespread
Taenia solium (pork tapeworm)
T. saginata (beef tapeworm)
Diphyllobothrium latum (fish tapeworm)
Head (“scolex”) which attaches to host
Neck, which differentiates into segments
Proglottids are body segments
Each male / female sex reproductive structures which can leave the host (faeces) and infect others
symptoms
Vary depending on infecting species, often:
upper abdominal discomfort
diarrhoea
loss of appetite
often asymptomatic
If untreated can cause intestinal blockages
Treatment:
Use Taenicides: niclosamide or praziquantel, unlicensed - Named patient basis
Nematodes: Pin/Threadworm
causes
diagnosis
treatment
Cause:
Enterobius vermicularis
Live ~6 weeks, lay eggs on perianal skin (up to 20,000/night)
Also secretes substances with eggs causes itching
Scratch, transmit under nails etc
Continued infection if eggs swallowed, worm released by digestive juices
Don’t enter blood, seldom serious except sleep-disturbance from itchiness/ crawling sensation
Diagnosis: Seeing worms in perianal region or “scotch tape test”
Sellotape around anus in morning, stick worms/eggs, look by microscope
Pinworms up to 13mm long, one side convex, other flat, colourless shell
Treatment: Mebendazole and good hygiene
Nematodes: Hookworm
causes
symptoms
treatment
Cause: 2 species infect humans:
Ancylostoma duodenale - Acquired by ingestion
Necator americanus - Acquired by penetration through skin
Found in upper small intestine, hook on and draw blood
Symptoms: Usually asymptomatic
Can lead to iron-deficient anaemia
Diarrhoea, nausea, vomiting
Can get severe local irritation from larvae in skin
Treat with cryotherapy
Treatment: Mebendazole or Albendazole (unlicensed alternative)
Nematodes: Whipworms
causes
symptoms
diagnosis
treatment
Cause: Trichuris trichiura - Infection by ingestion of eggs
Eggs hatch in the small intestine,
Move into wall of the small intestine and develop
When adult, thinner end (front) burrows into large intestine, thicker end hangs into the lumen for mating
The females can grow to 50 mm (2 inches) long
Symptoms: Light infestations are frequently asymptomatic
Heavy infestations may have bloody diarrhoea.
May lead to iron-deficiency anaemia
Diagnosis: Infestation is detectable by stool examination
Treatment: Mebendazole
Nematodes: Ascaricides‘roundworm’
cause
symptom
treatment
Cause: Common roundworms - Ascaris lumbricoides
Up to 25% world (1 billion) infected
Up to 50 cm long
Common where poor sanitation & human faeces used to fertilise
Ascaris takes most of its nutrients from the partially digested host food in the intestine
Symptoms: can be asymptomatic for long periods
As larval stages travel through the body, may cause:
visceral damage, peritonitis and inflammation
enlargement of liver or spleen, toxicity, pneumonia
Heavy infestation may cause nutritional deficiency
Other complications, sometimes fatal, include:
Obstruction bowel by a bolus of worms (esp. children)
Obstruction bile or pancreatic duct
Treatment: First line - Mebendazole (levamisole alternative)
Good hygiene: e.g. Scrub nails, bath after waking to remove eggs laid in night
Eggs can survive outside body
Treat with mebendazole (100mg)
Threadworms - single dose (6mo +)
Roundworm, whipworm, hookworms - b.d., 3 days (1yr +)
Roundworm alternative single dose 500mg (2yrs +)
Note: none recommended in pregnancy
Trematodes: Flukes
causes
treatment
Cause:
Blood flukes (schistosomiasis / bilharziasis)
Schistosoma mansoni
Africa & America
S. japonicum
Far East
S. hematobium.
Africa
Tissue flukes e.g.:
Liver fluke - Clonorchis sinensis
Lung fluke - Paragonimus westermani
Treatment: Praziquantel
what is Schistosomicides
symptoms
treatment
Male and female (unlike other trematodes); adult flukes 10-20 mm long
Symptoms:
Penetration of cercariae causes transient dermatitis (swimmers’ itch).
due to physical damage to the skin by proteases and other toxic substances secreted by the cercaria
also get host immune response
S. japonicum & S. mansoni
Dermatitis, abdominal pain, bloody stool, peri-portal fibrosis, hepato-splenomegaly, CNS effects
S. hematobium
Dermatitis, urogenital cystitis, urethritis and bladder carcinoma
Treatment:
with praziquantel (named patient basis), 20 mg/kg either twice or three times in a day depending on type (japonicum 3 times)
Head Lice & Scabies
treatment and their mao
Head lice common parasite children (pediculus humanus - capitis)
Treatment: Dimeticone lotion or liquid (live lice/eggs) –
works by suffocating lice
Wet combing mechanical removal
Scabies is common skin parasite (Sarcoptes scabiei)
Treatment: Permethrin 5% cream (or malathion) - topically,
ivermectin (oral, if doesn’t respond)
Mechanisms of action
Permethrin disrupts sodium channels, leading to paralysis
Ivermectin, increases inhibitory neurotransmission again
leading to paralysis and death
Pyrimethamine moa
inhibits DHFR
Sulphadiazine moa
Sulphadiazine inhibits DHPS (a sulphonamide)
Clindamycin, clarith/azithromycin moa
inhibit protein synthesis
Tini/metroni-dazole moa
inhibit nucleic acid synthesis via generation damaging nitroso radicals
Diloxanide possibly functions as chloramphenicol
moa of doxycline
Doxycycline inhibits protein synthesis
Proguanil moa
Proguanil inhibits DHFR
Antimalarial Mechanisms of Action and Resistance
Target:
heme detoxification [(hydroxy)chloroquine, quinine (also binds DNA), mefloquine, primaquine]
folate and pyrimidine biosynthesis [proguanil, sulphonamides, pyrimethamine]
electron transport [atovaquone, proguanil]
Protein synthesis [doxycycline, clindamycin]
Protein damage by free radicals [artemisinins]
Widespread resistance to antifolates and chloroquine (P. falciparum)
Resistance emerging to drugs in ACT in south-east Asia and some evidence in WHO Africa region
what does Chloroquine do?
Chloroquine interferes with heme detoxification
what is the function of Atovaquone
Atovaquone inhibits mitochondrial electron transport
what is the function of Artemisinins
Artemisinins (DHA) damage proteins and inhibit proteasome (not fully understood
