06-02-23 - Anti-helminthics and Anti Protozoals

Question 1

Learning outcomes

Answer 1

• List the drugs active against intestinal protozoan organisms and the way in which they work
• Demonstrate knowledge of methods of controlling protozoan infections
• Demonstrate understanding of the main helminthic pathogens and the way in which they cause disease
• Recognise the clinical manifestations of infection associated with intestinal helminths
• List the main anti-helminthic drugs and the way in which they work
• Demonstrate understanding of methods of controlling helminth infections

Question 2

What are protozoa?

What are 4 examples of types of protozoa?

Answer 2

• Protozoa are a group of single-celled eukaryotes, either free-living or parasitic, that feed on organic matter such as other microorganisms or organic tissues and debris
• 4 examples of types of protozoa:
  1) Amoebas
  2) Flagellates
  3) Ciliates
  4) Sporozoans

Question 3

What are 2 protozoal infections of the small intestine?

What is 1 protozoal infection of the large intestine?

Answer 3

• 2 protozoal infections of the small intestine:
  1) Giardia lamblia
  2) Cryptosporidium parvum
• 1 protozoal infection of the large intestine?
  1) Entamoeba histolytica

Question 4

What is G lamblia (Giardia lamblia)?

How is it treated?

Answer 4

• G lamblia (Giardia lamblia) is an Intestinal trophozoite
• It is treated with metronidazole or tinidazole (single dose)

Question 5

What are 3 proposed drugs in the treatment of Cryptosporidium parvum?

What groups might these drugs not work in?

Answer 5

• 3 proposed drugs in the treatment of Cryptosporidium parvum:
  1) Paromomycin
  2) Nitazoxanide
  3) Spiramycin
• Limited evidence that any of these drugs have an impact on the severity or duration of diarrhoea in the most immunocompromised patients

Question 6

What is amoebiasis?

How is amoebiasis treated?

How does chronic infection change the course of treatment?

How are amoebic abscesses treated?

Answer 6

• Amoebiasis, or amoebic dysentery, is an infection of the intestines caused by a parasitic amoeba Entamoeba histolytica
• Amoebiasis is treated with metronidazole
• In chronic infection, cysts will survive and cause relapse and are resistant to metronidazole
• Chronic infection needs treatment with diloxanide furoate
• Amoebic abscess requires treatment with metronidazole at higher and longer doses

Question 7

What are 4 common features of amoebiasis?

Answer 7

• 4 common features of amoebiasis:

1) Cysts resistant in the environment

2) Replicative stage is damaging to gut epithelium e.g causing villous atrophy and colitis

3) Passed out in much higher numbers

4) Although it is a cycle, without any intervention = exponential growth, leading to increase symptoms in patient
* This will reach a point where either the immune system can clear the infection, or the patient dies from organ complications

Question 8

What is metronidazole?

What is their mechanism of action?

What do protozoa is it active against?

Why is it useful against liver amoebic liver abscesses?

What side-effect is common?

What can it cause when mixed with alcohol?

Answer 8

• Metronidazole is originally an antiprotozoal agent
• Under anaerobic conditions it generates toxic radicals that damage bacterial and protozoal DNA
• Metronidazole is 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
• Metronidazole causes an acute nauseous reaction with alcohol

Question 9

What type of medical is Diloxanide furoate?

What are 3 common side effects of Diloxanide furoate?

What well tolerate is Diloxanide furoate?

What list is it part of?

Answer 9

• Diloxanide furoate is a luminal amebicide, meaning it kills amoeba in the lumen of the intestine
• 3 common side effects of Diloxanide furoate:
  1) Flatulence
  2) Itchiness
  3) Hives
• Diloxanide furoate is usually well tolerated with minimal toxicity
• It is on WHO essential medicines list

Question 10

What type of medication is Paromomycin?

How is it administered?

How is it absorbed?

In what stage does it kill amoeba?

What are 5 side-effects of Paromomycin?

Why do these side-effects occur?

Answer 10

• Paromomycin is an aminoglycoside
• It is administered orally
• Paromomycin is not absorbed from the GI tract, but is absorbed through the blood
• Kills amoebic cystic stage, which is very useful as it is highly resistant
• 5 side-effects of Paromomycin:
  1) Abdominal cramps
  2) Diarrhoea
  3) Heartburn
  4) Nausea
  5) Vomiting
• These side-effects can occur because paromomycin can build up in the GI tract and cause toxicity

Question 11

What does oral dehydration therapy (ORT) involve?

What % of acute diarrhoea cases can be treated with oral rehydration solution (ORS)? How does ORS work?

Answer 11

• Oral Rehydration Therapy (ORT) Involves the replacement of fluids and electrolytes lost during diarrheal illness
• 90-95% of cases of acute, watery diarrhoea can be successfully treated with an oral rehydration solution (ORS)
• ORS works by increasing the reabsorption of fluids and salts into the intestinal wall

Question 12

What are the 4 ingredients in the UNICEF / WHO Recipe for oral rehydration solution (ORS)?

What other ingredients can also be added?

Answer 12

• 4 ingredients in the UNICEF / WHO Recipe for oral rehydration solution (ORS):
  1) Glucose (anhydrous) 13.6g / L
  2) Sodium chloride 2.6g / L
  3) Potassium chloride 1.5g / L
  4) Trisodium citrate dihydrate 2.9g / L
• In addition, fruit juices, coconut water, and other indigenous solutions can adequately approximate ORS

Question 13

What are 4 ways Protozoal Infections of the GI Tract can be prevented?

Answer 13

• 4 ways Protozoal Infections of the GI Tract can be prevented:
  1) Improved hygiene and water supplies
  2) Eating only freshly prepared food served hot
  3) Avoiding salads and fruit which cannot be peeled
  4) Avoiding tap water and ice cubes

Question 14

Describe the flowchart of helminths for nematodes (in picture)

Answer 14

Question 15

Describe the flowchart of helminths for cestodes (in picture)

Answer 15

Question 16

Describe the flowchart of helminths for trematodes (in picture)

Answer 16

Question 17

What is a disease vector?

What is the degree of exposure related to?

What are 4 different vectors for helminth infections?

Answer 17

• A disease vector is any living agent that carries and transmits an infectious pathogen to another living organism
• The degree of exposure to disease is largely related to geographical orientation
• 4 different vectors for helminth infections:

1) Flies
* Vector for Onchocerciasis
* Onchocerciasis is an infection caused by the parasitic worm Onchocerca volvulus

2) Aedes mosquito
* Vector for Filariasis
* Filariasis is a parasitic disease caused by microscopic, thread-like worms

3) Crysops
* Vector for Guinea worm
* Dracunculus medinensis is a nematode that causes dracunculiasis, also known as guinea worm disease

4) Snails
* Vector for Schistosomiasis, Capillaria, Fasciola

Question 18

What are 3 modes of entry for helminths?

Where is their localization from these entry points?

Answer 18

• 3 modes of entry for helminths and where they localise:

1) Mouth
* Can be from eggs or larvae in water, food or intermediate host
* Localise in the internal organs or intestines

2) Bite of insect vector
* Larvae enter the skin
* Localise in the dermal and lymphatic tissues

3) Penetration
* Larvae burrow through the skin
* Localise in the blood vessels (around intestine or bladder)

Question 19

Schistosoma spp:
* Pathophysiology – life stage of interest (1)
* Clinical features – symptom/feature (3)
* Treatment – drug (1)

Answer 19

• Schistosoma spp:
• Pathophysiology (2)
  1) Eggs are deposited in smallest venule that can accommodate the female worm
  2) Pathology is primarily related to sites of egg deposition, number of eggs deposited and host reaction to egg antigens
• Clinical Features (3)
  1) Affected by numerous factors (penetration, eggs)
  2) Papular rash may develop, associated with pruritus
  3) Granulomas replaced by collagen, scarring
• Treatment (1)
  1) Praziquantel, taken for 1 - 2 days

Question 20

Filariasis:
* Pathophysiology – life stage of interest (3)
* Clinical features – symptom/feature (2)
* Treatment – drug (3)

Answer 20

• Filariasis:
• Pathophysiology – life stage of interest (3)
  1) [Infected] Aedes mosquito bite→ larvae
  2) Larvae→ lymphatics→ adult maturation→♀ microfilariae
  3) Lymphatic obstruction
• Clinical features – symptom/feature (2)
  1) Asymptomatic
  2) Swelling, abscess, enlarged lymph node(s)
• Treatment – drug (3)
  1) Diethylcarbamazine (DEC)
  2) Ivermectin, albendazole and DEC
  3) Surgery

Question 21

Trichuris trichiura (Whipworm)
* Pathophysiology – life stage of interest (3)
* Clinical features – symptom/feature (3)
* Treatment – drug (2)

Answer 21

• Trichuris trichiura (Whipworm)
• Pathophysiology – life stage of interest (3)
  1) Ingestion of eggs from soil
  2) Larvae→cecal epithelium→90 days;adults→eggs→faeces
  3) Worms remain embedded
• Clinical features – symptom/feature (3)
  1) Asymptomatic
  2) Dysentery/diarrhoea
  3) Colitis
• Treatment – drug (2)
  1) Mebendazole
  2) Albendazole

Question 22

Hookworm (Ancylostoma and Necator)
* Pathophysiology – life stage of interest (3)
* Clinical features – symptom/feature (4)
* Treatment – drug (1)

Answer 22

• Hookworm (Ancylostoma and Necator)
• Pathophysiology – life stage of interest (3)
  1) Larvae penetrate the skin (foot) from soil
  2) Larvae→lungs (blood)→alveoli→ epiglottis→ swallowed
  3) In bowel adults develop, feed on blood, live ≥ 2 years.
• Clinical features – symptom/feature (4)
  1) Asymptomatic
  2) Pruritic papulovesicular rash
  3) ~Löffler syndrome
  4) GI disturbance
• Treatment – drug (1)
  1) Albendazole and mebendazole

Question 23

Pinworm (Strongyloides stercoralis)
* Pathophysiology – life stage of interest (4)
* Clinical features – symptom/feature (4)
* Treatment – drug (1)

Answer 23

• Pinworm (Strongyloides stercoralis)
• Pathophysiology – life stage of interest (4)
  1) Larvae penetrate skin
  2) Larvae→ Duodenum mucosa;adults→♀ eggs→ stool
  3) Disruption of small intestinal mucosa; villous atrophy
  4) Marked loss of elasticity of intestinal wall
• Clinical features – symptom/feature (4)
  1) Dysentery (persistent in immunocompromised hosts) &Dehydration
  2) Malabsorption syndrome
  3) Anal pruritis
  4) Association with appendicitis
• Treatment – drug (1)
  1) Ivermectin / Albendazole

Question 24

(Pinworm/)Threadworm (Enterobius vermicularis)
* Pathophysiology – life stage of interest (4)
* Clinical features – symptom/feature (4)
* Treatment – drug (1)

Answer 24

• (Pinworm/)Threadworm (Enterobius vermicularis)
• Pathophysiology – life stage of interest (3)
  1) Inhalation/ingestion of eggs
  2) Eggs hatch (S intestine)→adults→ mating→ migration
  3) Female migrates to anus at night to lay approx. 10,000 eggs, which may develop to infective stage within hours
• Clinical features – symptom/feature (3)
  1) Asymptomatic
  2) Intense itching (nocturnal)
  3) secondary bacterial infection – mild catarrhal inflammation and diarrhoea, slight eosinophilia
• Treatment – drug (3)
  1) Mebendazole
  2) or Pyrantel pamoate
  3) or Albendazole

Question 25

Difference between threadworm and pinworm

Answer 25

* Difference between threadworm and pinworm: * Strongyloides stercoralis is a human pathogenic parasitic roundworm causing the disease strongyloidiasis. Its common name in the US is threadworm. In the UK and Australia, however, the term threadworm can also refer to nematodes of the genus Enterobius, otherwise known as pinworms. [1] * Best to refer to each as their proper name to avoid confusion

Question 26

What are 3 space occupying lesions (atypical presentations)?

Answer 26

* 3 space occupying lesions (atypical presentations – parasite ending up in wrong place): 1) Eggs in the wrong place 2) Cysticercosis causing CSF obstruction 3) Ascaris causing intestinal obstruction

Question 27

What are 4 different features in the pathogenesis of helminth infections? How can they each be treated?

Answer 27

* 4 different features in the pathogenesis of helminth infections and how they are treated: 1) Inflammation * Treated using Anti-inflammatory eg., steroids 2) Competition for nutrients * Reduce worm burden and support nutrition 3) Space occupying lesions * Surgery, decompression 4) Stimulation of fibrosis * Helminth eradication and treatment of secondary effects

Question 28

What drug is used to treat cestodes infecting the intestinal tract? What types of drugs may be used in conjunction with this?

Answer 28

* Cestodes infecting the intestinal tract are treated using praziquantel * Remember the problems of cysticercosis where it is necessary to continue anti-epileptic drugs and combine anti-helminthic treatment with steroids

Question 29

What drug is the most effective agent against nematodes infecting the intestinal tract? What drug was previously used? What drugs are rarely used? What must we also engage with as part of the treatment for intestinal nematodes?

Answer 29

* Ivermectin is the most effective agent against nematodes infecting the intestinal tract * Albendazole was used liberally until Ivermectin was shown to be superior * Levamisole and piperazine are rarely used * 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) * This means trying to ensure the patient is carrying out good hygiene, preparing food properly, and not drinking unclean water etc.

Question 30

What is the mechanism of action of Praziquantel?

Answer 30

* The mechanism of action of Praziquantel: probably increases calcium permeability of membranes depolarising them * May interfere with purine synthesis

Question 31

28) What 6 conditions can Praziquantel be used to treat?

Answer 31

* 6 conditions can Praziquantel be used to treat: 1) Hydatid disease 2) Cysticercosis 3) Schistosomiasis 4) Clonorchis 5) Fascioliasis 6) Paragonimiasis infection

Question 32

Where is Praziquantel absorbed? What is the dose needed? What is it on? Does it have first pass effect? What systemic concentrations does it need to be effective? How is it excreted? What is the half-life of Praziquantel like?

Answer 32

* Praziquantel is well absorbed orally * The dose used is 20 mg/kg * It is on WHO essential medicine list * Praziquantel significant first pass effect * Low systemic concentrations are needed for praziquantel to be effective * Praziquantel is excreted in the kidneys * It has a short half-life

Question 33

What are 11 symptoms of Praziquantel? What are 3 contraindications of Praziquantel?

Answer 33

* 11 Symptoms of Praziquantel: 1) Dizziness 2) Headache 3) Drowsiness and somnolescence (drowsiness) 4) Rarely seizures 5) Abdominal cramps 6) Nausea 7) Diarrhoea 8) Transient asymptomatic rise in transaminases (enzymes) 9) Urticaria 10) Rash 11) Pruritis (itching) * Interacts with rifampicin (decreased concentrations), carbamazine, phenytoin (reducing praziquantel bioavailability)

Question 34

What 7 nematode infections can Albendazole be used to treat? What protozoa can Albendazole be used to treat? What 2 cestode infections can Albendazole be sued to treat? What are 2 other similar mediations to albendazole? What list is Albendazole part of?

Answer 34

* 7 nematode infections can Albendazole be used to treat: 1) Trichiuriasis 2) Filariasis 3) Enterobius Infection 4) Ascariasis 5) Hookworm 6) Toxocariasis 7) Strongyloidiasis * Albendazole can be used to treat the protozoa giardia * 2 cestode infections can Albendazole be sued to treat: 1) Neurocysticercosis 2) Hydatid disease * 2 other similar mediations to albendazole: 1) Mebendazole 2) Thiabendazole * Albendazole is on the WHO essential medicine list

Question 35

What are 4 steps in the mechanism of action of Albendazole?

Answer 35

* 4 steps in the mechanism of action of Albendazole: 1) Binds to colchicine sensitive receptor or tubulin 2) This prevents polymerisation into microtubules 3) Impaired glucose uptake and depleted glycogen stores 4) Degenerative changes appear in the worm

Question 36

Where is Albendazole concentrated? Why can this be problematic? What are 6 symptoms of Albendazole?

Answer 36

* Albendazole is concentrated in semen * This may be problematic as Albendazole can be teratogenic (cause congenital disorders) 6 symptoms of Albendazole: 1) Persistent sore throat 2) Headaches dizziness 3) Seizures 4) Acute liver failure (due to pre-existing conditions/extreme cases) 5) Aplastic anaemia 6) Marrow suppression

Question 37

What is the mechanism of action of Piperazine (MOA)? Where in the body is it active? What is it metabolised by? What 2 infections is Piperazine used to treat? What are 3 side-effects of Piperazine?

Answer 37

* Mechanism of action (MOA) - Piperazine has agonist activity against the gamma butyric acid receptor, paralysing muscular activity * Piperazine is orally active * It is metabolised by the liver * 2 infections Piperazine is used to treat: 1) Ascariasis 2) Enterobius infection * 3 side-effects of Piperazine: 1) GI tract upset 2) Hypersensitivity (rare) 3) Dizziness (rare)

Question 38

What 2 worms is Pyrantel used to treat? What is the mechanism of action of Pyrantel? Where is it poorly absorbed? What does this provide? How is it excreted? What medications is pyrantel antagonistic with? When should we avoid using Pyrantel? When can it cause intestinal obstruction?

Answer 38

* 2 worms Pyrantel is used to treat: 1) Hookworms 2) Roundworms * MOA - Pyrantel Causes depolarising neuromuscular blockade * Pyrantel is poorly absorbed, which provides selective toxicity * It is Excreted unchanged in the faeces * Pyrantel is antagonistic with piperazine * We should avoid Pyrantel in pregnancy, as it can pass into the placenta * Can cause intestinal obstruction if there is a heavy worm load – may require surgery

Question 39

What list is Levamisole on? What receptors does it act on? What helminth infections can it be used to treat? How quickly is Levamisole absorbed? Where should it be used cautiously? What are 3 side-effects of Levamisole?

Answer 39

* Levamisole is on the WHO List of essential medicine * Levamisole is a Nicotinic acetylcholine receptor antagonist * Can be used to treat Ascariasis and mixed ascaris hookworm infection * Levamisole is rapidly absorbed * It should be used cautiously in pregnancy * 3 side-effects of Levamisole: 1) Abdominal pain 2) Nausea 3) Vomiting

Question 40

What list is Diethyl carbamazine part of? What is it a derivative of? What is its mechanism of action? What infection is it used to treat? What are 3 side-effects of Diethyl carbamazine?

Answer 40

* Diethyl carbamazine Is on WHO essential medicine list * Diethyl carbamazine is a piperazine derivative * MOA - Inhibits arachidonic acid making parasites more susceptible to immune attack * Diethyl carbamazine is used to treat Filaria infection * 3 side-effects of Diethyl carbamazine: 1) Increase in inflammation 2) Caution Mazzotti reaction (life-threatening) 3) Loss of site in onchocerciasis

Question 41

What is the MOA of Ivermectin? What 4 conditions is Ivermectin active against?

Answer 41

* MOA of Ivermectin: * Ivermectin binds glutamate-gated chloride leading to an 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. * 4 conditions is Ivermectin active against: 1) Filarial worms 2) Lice 3) Scabies 4) Bed bugs

Question 42

What 2 groups is Ivermectin being used eradicate? Why is the use of Ivermectin complicated? What 3 things does Ivermectin increase the risk of absorption of across the BBB?

Answer 42

* Ivermectin is currently being used for eradication of lymphatic filariasis and onchocerciasis * Ivermectin contraindicated in children < 5 or breast-feeding mothers * The use of Ivermectin is complicated due to it causing CNS depression both the worm and the host * 3 things Ivermectin increases the risk of absorption of across the BBB: 1) HIV protease inhibitors 2) Calcium channel blockers 3) Glucocorticoids

Question 43

What 3 processes does Niclosamide inhibit? What is the only infection Niclosamide is used for? What are 4 side-effects of Niclosamide?

Answer 43

* 3 processes Niclosamide inhibits: 1) Glucose uptake 2) Oxidative phosphorylation 3) Anaerobic metabolism * Niclosamide is used for the treatment of tape worm (type of flatworm) infections only * 4 side-effects of Niclosamide: 1) Dizziness 2) Skin rashes 3) Drowsiness 4) Perianal itching

Question 44

What are 3 prevention and control measures for intestinal helminths?

Answer 44

* 3 prevention and control measures for intestinal helminths: 1) Vector control for filariasis 2) Meat inspection for cysticercosis 3) Sanitation and hygiene for intestinal nematodes