Anti-helminthics and Anti-Protozoals Flashcards
Name some SI protozoal infection of the GI tract?
- Giardia lamblia
- Cryptosporidium parvum
Name a LI protozoal infection of the GI tract?
- Entamoeba histolytica
What are the 2 stages of the Gardia lamblia life cycle?
- Trophozoite
- Cyst
What are the features of the trophozoite stage of the G. lamblia stage?
- Flagellated and bi-nucleated
- Lives in the upper part of the SI
- Adheres to brush border of epithelial cells
What are the features of the cyst stage of the G. lamblia stage?
- Formed when trophozoite forms resistant wall
- Passes out in stools
- Can survive for several weeks
How are intestinal trophozoite infections treated?
Single dose metronidazole or tinidazole
Explain the life cycle of C. parvum
- Asexual and sexual development within host
- Ingestion of resistant oocysts
- Release of infective sporozoites in SI
- Invasion of intestinal epithelium
- Division to form merozoites which re-infect cells
- After sexual phase, oocytes released
What can the presentation of C. parvum infection be like?
Painful, watery diarhoea for a week or more
What drugs have been suggested to work against Cryptosporidial infection?
- Paromomycin
- Nitazoxanide
- Spiramycin
Limited evidence that it works for very immunocompromised patients
Describe the life-cycle of Entomaeba histoltica
- Transmitted through contaminated food/water or anal sexual activity
- Cysts pass through stomach and and excyst in the SI giving rise to progeny
- Adhere to epithelial cells and cause damage mainly through cytolysis
- After mucosal invasion, cysts invade RBCs giving rise to amoebic colitis
- Trophozoite stages live in colon and pass out as resistant, infective cysts
Where is entomaeba histolytica prevelant?
Tropical and sub-tropical countries (> 50% of population)
What is intestinal amoebiasis treated with?
- Metronidazole (chronic infection cysts survive and are resistant)
- Amoebic abscess (e.g liver abcess) requires treatment with metronidazole at higher and longer doses
- Chronic infection needs treatment with diloxanide furoate
What is metronidazole used to treat and how does it work?
- Antiprotazoal agent
- Active against Entamoeba histolytica and Giardia lamblia
- Penetrates well into tissue - hence its value in amoebic liver abscess
- Under anaerobic conditions it generates toxic radicals that damge bacterial and protozoal DNA
What are some of the side-effects of metronidazole?
- Metallic taste is common and can be hard to tolerate
- Cause an acute nauseous reaction with alcohol
What is Diloxanide furoate?
- A luminal amoebicide
- Does not get out of gut
- Irradicatess amoebes
- irrradicates cystic form
- Usually well tolerated
- Flatulence, itchiness and hives are associated with use
What other drug has a very similar affect to diloxanide?
Paromomycin (adverse events do include diarrhoea, heartburn, nausea and vomiting)
What is Oral Rehydration Therapy?
- Involves the replacement of fluids and electrlytes lost during diarrheal illness
- Solution increases the resorption of fluids and salts into intestinal wall
What percentage of cases of acute, watery diarrhoea can be successfully treated with an oral rehydration solution (ORS)?
90 - 95%
How can protozoal infections of the GI tract be prevented?
- Improving 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 3 main classes of helminths?
- Nematodes (roundworms)
- Cestodes (tapeworms)
- Trematodes (flukes)
What are the 2 main classes of nematodes?
- Blood and tissue
- Intestinal
Give some examples of blood and tissue nematodes?
- Brugia
- Wucheraria
- Onchocerca
- Mansonella
- Loa loa
- Toxocara
Give some examples of intestinal nematodes?
- Ascaris
- Hookworm
- Enterobius
- Trichiuris
What are the 2 main types of Cestodes?
- Taenia
- Echinococcus
Give 2 examples of Taenia Cestodes
- Taenia solium
- Taenia saginata
Give 2 examples of Echinococcus Cestodes
- Echinococcus granulosus
- Echinococcus multilocularis
What are the 3 main places trematodes can be found?
- Lungs
- Liver
- Blood
What trematode can be found in the lung?
Paragonomiasis
What trematodes can be found in the liver?
- Opisthorcis (fish)
- Fasciola (sheep)
What trematodes (flukes) can be found in the blood?
- Schistosoma mansoni
- Schistosoma haematobium
- Schistosoma japonicum
Give some examples of helminthic vectors and what helminths are carried in them?
- Flies: Onchocerciasis
- Aedes mosquito: Filariasis
- Crysops: Guinea worm
- Snails: Schistosomiasis, Capillaria, Fasciola
Describe the Schistosomiasis life cycle
- Human intestine or bladder
- Eggs in urine or faeces are released in water
- Eggs hatch in water
- Become miracidium
- Enter snails (complex life-cycle in the snail)
- Cercariae exit the snail (thermotropic, negatively geotropic and phototropic)
- Enter skin and migrate through body into bladder or intestine
What are the pathological mechanisms of helminthic infections?
- Inflammation
- Competition for nutrients
- Space occupying lesions
- Stimulation of fibrosis
Give some examples of paraistes where inflammation is the main pathogenic mechanism?
- Filariasis
- Onchocerciasis
- Toxocariasis
- Cysticercosis
- Schistosomiasis (can get bladder cancer and bladder fibrosis)
- Enterobius
What part of filaria and onchocerca cause inflammation?
- Wolbachia bacteria which live inside them
- They control the gender of filaria, kill of males
What happens when e. coli / wolbachia / gram -ve bacteria are killed in the blood?
LPS causes shock - killing filaria can cause this
What can the inflammation caused by filiaria cause in the lymphatics?
Elephantiasis
What can competition for nutrients by helminths cause?
- major threat to health
- Intellectual development slowed due to less micronutrients
- More severe with poor nutrition
What are the clinical features of Trichiuris?
- Vague abdominal symptoms
- Trichiuris dysentery syndrome
- Growth retardation
- Intellectual comprimise
Micronutrient deficiency
Mucosal integrity
What are examples of space occupying lesions?
- Eggs in the wrong place
- Cysticercosis causing CSF obstruction
- Ascaris causing intestinal obstruction
- Hydatid cyst in the liver
What is Trichuris trichiura?
- Whipworm
- Can live for 3 yrs in gut
- Acquired through ingesting eggs on vegetables
- 10,000 eggs produced daily
- 800 million cases worldwide
Where are enterobius vermicularis found?
- Anus (causes intense itching and possible secondary bacterial infection)
- Female lays 10,000 eggs here at night which may develop into infective stage in hrs
What type of helminths are Enterobius vermicularis?
- Threadworm
- Small cylindrical nematodes < 1 cm
What type of worm is strongyloides stercoralis?
Pinworm
How does strongyloides stercoralis affect the intestines?
- Disruption of SI mucosa
- Villous atrophy
- Marked loss of intestinal wall
What are the clinical manifestations of strongyloides stercoralis?
- Dysentery (persistant in immunocompromised hosts)
- Dehydration
- Malabsorption syndrome
- Anal pruritis
- Association with appendicitis
How are helminth infections treated?
- Inflammation is treated with anti-inflammatory e.g steroids
- Competition for nutrients is treated by reducing worm burden and by supporting nutrition + surgery, decompression
- Helminth eradication is important + treating secondary effects (essential when fibrosis occurs as a result of infection)
What drug is used to treat cestode infection?
- Praziquantel
- Anti-epileptic drugs plus anti-helminthic treatment with steroids
What does praziquantel do?
- Likely increases calcium permeability of membranes depolarising them
- May interfere with purine synthesis
- Treat cestode, schistosomiasis
- Clonorchis, fascioliasis and paragnomiasis infection
Where is praziquental excreted?
Kidneys
What is albendazole used to treat?
- Nematode infection
- Some protozoa such as giardia
What is the mode of action of albendazole?
- Binds to colchicine sensitive receptor or tubulin
- Prevents polymerisation into MTs
- Impaired glucose uptake and depleted glycogen stores
- Degenerative changes int the worm
What can the side-effects of albendazole be?
- Relitavely safe drug
- Relatively common
- Conc in semen therefore may be teratogenic
- Persistant sore throat
- Headaches, dizziness and seizures
- Acute liver failure
- Aplastic anaemia and marrow supression
What is piperazine used to treat?
Ascariasis and enterobius infection
What can pyrantel be used to treat?
Hookworms and roundworms
- Causes depolarising neuromuscular blockade
- Can cause intestinal obstruction
What can ascaris be mixed with to treat hookworm infection?
Levamisole
What can dithyl carbanasine be used for?
- Diagnostically, kills microfiliaria of oncoserca
- Causes worms to go to skin and can be seen in biopsy
What can ivermectin be used against?
- Filarial worms, lice, scabies, bed bugs
- Complicated CNS depression
What is the drug of choice to treat nematodes?
Albendazole
What control measures can be taken to prevent intestinal helminths?
- Vector control for filariasis
- Meat inspection for cysticercosis (white spots on meat)
- Sanitation and hygiene for intestinal nematodes
