Antimicrobial 7: Agents for Helminth Infections Flashcards
What are 2 groups of helminths?
Transmission?
- Nemathelminthes (nematodes, roundworms)
- Platyhelminthes
- Trematodes (flukes)
- Cestodes (tapeworms)
Direct ingestion is a common way to become infected.
• Eggs/larvae in feces of infected humans can enter
soil and eventually become ingested by an
secondary/intermediate host (e.g. cattle, pigs)
What are the 2 Intestinal worms?
- Tapeworms (Taenia saginata, Taenia solium,
Hymenolepsis nana, Diphyllobothrium latum)
– Humans become infected by eating raw or
uncooked meat that happens to contain larvae.
– Intermediate hosts are different for different
species and include cattle, pigs, insects, fish. - Intestinal Roundworms (Ascaris lumbricoides
(roundworm) , Enterobius vermicularis (threadworm),
Trichuris trichura (whipworm ), necator americanus,
Ancylostoma duodenale (hookworms))
– Infection by roundworm, threadworm and
whipworms commonly occurs through
undercooked/contaminated food.
– Infection by hookworms usually occurs when larvae
penetrates the skin.
What are the other 3 worms other than intestinal worms?
- Flukes
• Live and mate in the veins/venules of the bladder or
gut wall
• Eggs laid pass into the bladder or gut, and trigger
inflammation in these organs, resulting in hematuria
and loss of blood in faeces. - Tissue Roundworms
• Live in the lymphatics, connective tissues or
mesentery of the host - Hydatid tapeworms
• Dogs are the primary host and sheep are the
intermediate hosts
What are the 3 Helminth related diseases?
- Elephantiasis
– Hugely swollen legs, caused by obstruction of
lymphatic vessels by filariae - Onchocerciasis (river blindness)
– Microfilariae in the eye
– A leading preventable cause of blindness in Africa
and Latin America - Guinea Worm disease
– Larvae released from crustaceansin wells and
waterholes are ingested by humans. The larvae
then move from the intestinal tract to the tissues
where they mature and mate.
– Gravid female migrate to the subcutaneous tissue
of the leg or foot and may protrude through an
ulcer in the skin.
– Worm may be up to 1 meter in length. Removal can
be surgically or via slow mechanical winding, but
must ensure the worm does not break, as remains
would putrefy!
– No effective drug treatments. Clean drinking water
or filtering larval-contaminated water through nylon
mesh tights for prevention.
Anthelmintics drugs
See slide 12 for details
Anthelmintics drugs
See slide 12 for details
Benzimidazoles
What drugs are Benzimidazoles? (3)
Mebendazole
tiabendazole
albendazole
Benzimidazoles
MOA
AE
- Inhibits the polymerization of helminth β- tubulin, and
therefore interfering with microtubule-dependent
functions (e.g. glucose uptake) - GI disturbances
Nitazoxanide
Characteristics
MOA
Nitazoxanide is an oral antiparasitic and antiviral agent. It’s metabolite tizoxanide is active and this agent is approved for the treatment of giardiasis and cryptosporidiosis.
Proposed MOA is due to inhibiting
pyruvate:ferredoxin oxidoreductase (PFOR) enzyme-dependent electron transfer, which is important for parasite anaerobic energy metabolism
Praziquantel
MOA
Binds to the consensus protein kinase C-binding sites in a β-subunit of schistosome voltage-gated calcium
channels. This induces Ca 2+ influx causing a rapid and prolonged contraction of the musculature, resulting in eventual paralysis and death of the worm.
-The tegument of the parasite is also disrupted,
unmasking novel antigens and therefore, making the
parasite more susceptible to immune responses.
Praziquantel
AE
- Dizziness
- abdominal distress
- headache, urticaria, nausea
- Minimal side effects; may be more frequent in
patients with heavy worm load
Piperazine
Characteristics
MOA
AE
• treat infections with the common roundworm
(A.lumbricoides) and threadworm (E.vermicularis)
• Reversibly inhibits neuromuscular transmission
in the worm, likely through inhibiting GABA at GABA-
gated chloride channels in the nematode muscle.
• GI disturbances, urticaria, bronchospasm
Diethylcarbamazine
Characteristics
MOA
AE
• Derivative of Piperazine. Effective in filarial infections
by B.malayi, W. bancrofti, L.loa
• Effective in removing microfilariae from bloodstream,
but has limited effect on adult worms in lymphatics
• Exact mechanism: unknown
• Proposed mechanisms:
- By changing the parasite (e.g. alteration in helminth
surface membrane) such that it becomes
susceptible to the host’s immune response
- Interfering with helminth arachidonate metabolism
• GI disturbances, joint pain, headache, weakness
• Allergic side effects related to the products of the
dying filariae are common; Can last 3-7 days.
Niclosamide
Characteristics
MOA
AE
• Widely used in combination with praziquantel to treat
tapeworm infections
• Diminishes potential of the inner mitochondrial
membrane and inhibit/uncouple oxidative
phosphorylation.
• For T. solium only, drug is given followed by a
purgative 2 hours later in case tapeworm segments
releases ova.
• Nausea, vomiting, pruritis, light-headedness
Levamisole
Characteristics
MOA
AE
• Effective in treatment of infections by the common
roundworm (A. lumbricoides)
• Nicotine-like action: stimulates and subsequently
blocks neuromuscular junctions; paralyzed worms
expelled in the feces.
- Has been withdrawn from North American markets
- agranulocytosis
- CNS, GI disturbance
Ivermectin
Characteristics
• First choice for treatment of many filarial infections.
• Drug of choice for elephantiasis.
• Drug of choice for onchocerciasis.
• Also active against some roundworms but not
hookworms.
Ivermectin
MOA
AE
• Semisynthetic agent derived from avermectin (natural
substance).
• Kills the worm by opening glutamate-gated chloride
channels and increasing Cl- conductance; binding to
GABA receptors or novel allosteric sites on
acetylcholine nicotinic receptor cause increase in
transmission resulting in motor paralysis
- Skin rash/itching
- Post-treatment encephalopathy.
Summary
____: Inhibits polymerization of helminth β-tubulin, hence interfering with microtubule-dependent functions (e.g. glucose uptake)
Benzimidazoles
Summary
____: Induces a influx of Ca 2+ causing a rapid and prolonged contraction of the musculature, resulting in eventual paralysis and death of the worm.
Praziquantel
Summary
____: Reversibly inhibits neuromuscular transmission in the worm, likely through inhibiting GABA.
Piperazine
Summary
____: Derivative of Piperazine.
Effective in removing microfilariae from
bloodstream, but has limited effect on adult
worms in lymphatics.
Exact mechanism unknown.
Diethylcarbazine
Summary
____: Inhibit/uncouple oxidative phosphorylation.
Niclosamide
Summary
____: Blocks neuromuscular junctions; results in paralyzed worms .
Levamisole
Summary
____: Increases Cl - conductance and increases transmission resulting in motor paralysis.
Ivermectin
