Treatment of Protozoal and Helminthic Infections Flashcards
What is the Treatment of G. lamblia
- Intestinal trophozoite is treated with metronidazole or tinidazole (single dose)
What is the Cryptosporidium treatment and what are the issues associated with this?
- Drugs have been proposed for use: paromomycin, nitazoxanide and spiramycin
- Limited evidence that any of these drugs have an impact on the severity or duration of diarrhoea in the most immunocompromised patients
What is the treatment for intestinal infection of amoebiasis?
treatment with metronidazole
What is the treatment for chronic infection of amoebiasis?
- Chronic infections need treatment with diloxanide furoate
What does amoebic abscess require treatment with?
metronidazole at higher and longer doses
Describe metronidazole and its mechanism of action
- Originally an antiprotozoal agent
- Under anaerobic conditions it generates toxic radicals that damage bacterial and protozoal DNA
- Active against Entamoeba histolytica and Giardia lamblia
- Penetrates well into tissue – hence its value in amoebic liver abscess
- A metallic taste is common and can be hard to tolerate
- Cause an acute nauseous reaction with alcohol
What is the mechanism of action of Diloxanide furoate and what is its functions
- A luminal amoebicide
- Flatulence, itchiness, and hives associated with use
- Usually well tolerated with minimal toxicity
- On WHO essential medicines list
Describe Parmomycin’s action
- An aminoglycoside
- Given orally
- Not absorbed from the GI tract
- Kills amoebic cystic stage
What are the adverse effects of paromomycin?
abdominal cramps, diarrhoea, heartburn, nausea and vomiting
What are the non pharmacological treatment methods for prevention of protozoal infections of the GI tract
- Improved hygiene and water supplies
- Eating only freshly prepared food served hot
- Avoiding salads and fruit which cannot be peeled
- Avoiding tap water and ice cubes
What are the main types of blood and tissue and intestinal nematodes?
Blood and tissue
- Brugia, Wucheraria, Onchocerca, Mansonella, Loa Loa, Toxocara
Intestinal
- Ascaris, hookworm, enterobius, trichiuris
What are the main types of cestodes?
Taenia
- sodium and saginata
Echinococcus
- granulises, multilocularis
What are the main types of trematodes?
Lung = paragonomiasis Liver = Opisthorcis, fasciola Blood = S.mansioni, S.haematobium, S.japonicum
Describe 4 different types of vectors
- Flies: Onchocerciasis
- Aedes mosquito: Filariasis
- Crysops: Guinea worm
- Snails: Schistosomiasis, Capillaria, Fasciola
What are the clinical features of Trichiuris?
- Vague abdominal symptoms
- Trichiuris dysentery syndrome
- Growth retardation
- Intellectual compromise
o Micronutrient deficiency
o Mucosal integrity
What are the main effects of Strongyloides stercoralis?
- Disruption of small intestine mucosa
- Villous atrophy
- Marked loss of elasticity of intestinal wall
What are the clinical manifestations of S. stercaralis?
- Dysentery (persistent in immunocompromised hosts)
- Dehydration
- Malabsorption syndrome
- Anal pruritis
- Associated with appendicitis
Treatment when pathogenesis is inflammation
- Anti-inflammatory e.g. steroids
What are the main pathological mechanisms of of helminths?
- Inflammation
- Competition for nutrients
- Space occupying lesions
- Stimulation of fibrosis
Examples where inflammation is the main pathological mechanism
- Filariasis
- Onchocerciasis
- Toxocariasis
- Cysticercosis
- Schistosomiasis
- Enterobius
Examples where competition for nutrients is the main pathological mechanism
- Hookworms
- Ascaris
- Tapeworms
- Trichiuris trichiura
- Major threat to health
- More severe with poor nutrition
- Intellectual development may be slowed
What helminths use space occupying lesions as their pathological mechanism?
- Eggs in the wrong place
- Cysticercosis causing CSF obstruction
- Ascaris causing intestinal obstruction
What is the treatment when competition for nutrients is the pathological mechanism?
- Reduce worm burden and support nutrition
What is the treatment when space occupying lesions is the pathological mechanism?
Surgery, decompression
What is the treatment when stimulation of fibrosis is the pathological mechanism?
- Helminth eradication and treatment of secondary effects
What is the treatment for cestodes?
praziquantel
o Remember the problems of cysticercosis
o Where it is necessary to combine anti-epileptic drugs and combine anti-helminthic treatment with steroids
What is the treatment for nematodes?
o Albendazole is the most effective of agents
o Levamisole and piperazine are rarely used
o Remember that a single dose or course of treatment is rarely enough as you must engage with the family and the environment (NB Enterobius infection)
When is Praziquantel used?
- Hydatid disease
- Cysticercosis
- Schistosomiasis
- Clonorchis, fascioliasis and paragonimiasis infection
How is Praziquantel excreted?
kidneys
What is the mechanism of Praziquantel ?
- Not fully known; probably increases calcium permeability of membranes depolarising them
- May interfere with purine synthesis
What is the effects of Praziquantel ?
- On WHO essential medicines list
- Significant first pass effect
- Low systemic concentrations
- Short half life
What are the SE of Praziquantel ?
o Dizziness, headache, drowsiness and somnolescence, rarely seizures
o Abdominal cramps, nausea and diarrhoea
o Transient asymptomatic rise in transaminases
o Uticeria, rash and pruitis
What does Praziquantel interact with?
o Interacts with rifampicin (decreased concentrations), cabamazine, phenytoin (reducing praziquantel bioavailability)
What type of drug is Albendazole?
- A benzimidazole
- WHO essential medicine list
What is Albendazole used in the treatment of?
- Treatment of nematode infections: trichiuriasis, filariasis, enterobius infection, ascariasis, hookworm, toxocariasis, strongyloidiasis
- Treatment of some protozoa: giardia
- Treatment of some cestode infections: neurocysticercosis and hydatid disease
What is the mode of action of Albendazole?
o Binds to clchicine sensitive receptor or tubulin
o This prevents the polymerisation into microtubules
o Impaired glucose uptake and depleted glycogen stores
o Degenerative changes appear in the worm
What are the side effects of Albendazole?
o Concentrated in semen and may be teratogenic
o Persistent sore throat
o Headaches, dizziness, seizures
o Acute liver failure
o Aplastic anaemia and marrow suppression
Outline the drug piperazine
- Agonist activity against the gamma butyric acid receptor paralysing muscular activity
- Orally active
- Metabolism in liver
- Variable half life
- Used to treat ascariasis and enterobius infection
- SE include GI tract upset and rarely hypersensitivity, dizziness
What is pyrantel used in the treatment of?
- Treatment of hookworms and roundworms
Outline the action of the drug pyrantel
- Causes depolarising neuromuscular blockade
- Poorly absorbed providing selective toxicity
- Excreted unchanged in the faeces
- Antagonistic with piperazine
- Avoid in pregnancy
- Can cause intestinal obstruction if there is a heavy worm load
Outline the drug levamisole
- WHO list of essential medicines
- Nicotinic acetylcholine receptor antagonist
- Ascariasis and mixed ascaris hookworm infection
- Rapidly absorbed
- Caution in pregnancy
- Abdominal pain, nausea and vomiting are reported
Outline the drug Diethyl carbamazin
- A piperazine derivative
- WHO essential medicine list
- Inhibits arachidonic acid making parasites more susceptible to immune attack
- Filaria infection
- Associated with increase in inflammation: caution Mazzotti reaction, loss of site in onchocerciasis
What is the mechanism of action of Ivermectin?
binds glutamate-gated chloride increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell resulting in paralysis and death of the parasite either directly or by causing the worms to starve.
what is Ivermectin active against?
- Active against filarial worms, lice, scabies and bed bugs
- Currently being used for eradication of lymphatic filariasis and onchocerciasis
When is ivermectin contraindicated?
- Contraindicated in children < 5 or breast feeding mothers
Outline nicloasmide
- Inhibits glucose uptake, oxidative phosphorylation and anaerobic metabolism
- Used for the treatment of tape worm infections only
- Causes dizziness, skin rashes, drowsiness and perianal itching.
Prevention and control of intestinal helminths
- Vector control for filatiasis
- Meat inspection for cysticercosis
- Sanitation and hygiene for intestinal nematodes
