Cology of infectious

• Helminths


  Worms with many cells
• Major groups of helminths

  • Nemathelminths (nematodes, roundworms)
  • Platyhelminths (flatworms)
  • Trematodes (flukes)
  • Cestodes (tapeworms)
• Intestinal helminthic parasites


  • Ascaris lumbricoides (roundworm)
  • Trichiuris trichiuria (whipworm)
  • Ancylostoma duodenale
  • Necator americanicus (hookworms)
• Intestinal helminths rarely cause death, but have chronic and insidious effects on health and nutritional status, impair physical and mental growth of children, thwart educational achievement, and hinder economic development
• Helminth life cycle


  1. Infection of host

  2. Harboring sexually mature form

  3. Eggs/larvae pass out and infect secondary host
• Humans are generally the primary (definitive) host for helminth infections, harbouring the sexually mature form that reproduces
• Encysted larvae may lodge in the muscles, viscera, eye or brain, leading to cysticercosis
• Anthelminthic drugs


  Act by paralysing the parasite, damaging the worm so the immune system can eliminate it, or altering its metabolism
• Drugs effective against one type of worm may be ineffective against others due to varying metabolic requirements
• Drugs must be able to penetrate the tough exterior cuticle of the worm or gain access to its alimentary tract
• Many helminths possess active drug efflux pumps that reduce the concentration of the drug in the parasite
• Classifications of anthelminthic drugs

  • Benzimidazoles
  • Praziquantel
  • Piperazine
  • Niclosamide
  • Diethylcarbamazine
  • Levamisole
  • Ivermectin
• Benzimidazoles


  Examples: mebendazole, thiabendazole, albendazole

  Act by inhibiting the polymerisation of helminth β-tubulin, interfering with microtubule-dependent functions
• Benzimidazoles


  • Selective inhibitory action, 250-400 times more effective in helminths than mammalian tissue

  Effect takes time to develop, worms may not be expelled for several days

  Cure rates generally 60-100% with most parasites
• Mebendazole


  Only 10% absorbed orally, but fatty meal increases absorption

  Rapidly metabolised, products excreted in urine and bile within 24-48 hours

  Given as single dose for threadworm, twice daily for 3 days for hookworm and roundworm
• Thiabendazole


  Rapidly absorbed, very rapidly metabolised and excreted in urine

  Given twice daily for 3 days for guinea worm and Strongyloides, up to 5 days for hookworm and roundworm
• Albendazole


  Also poorly absorbed, but absorption increased by food, especially fats

  Extensively metabolised by first-pass to sulfoxide and sulfone metabolites, former likely active
• Benzimidazole unwanted effects


  Few with albendazole or mebendazole, occasional gastrointestinal disturbances

  More frequent but transient with thiabendazole, including gastrointestinal, headache, dizziness, drowsiness, allergic reactions

  Mebendazole should not be given to pregnant women or children under 2
• Praziquantel


  Highly effective broad-spectrum anthelminthic, drug of choice for schistosomiasis and cysticercosis
• Praziquantel mechanism of action

  Disrupts Ca2+ homeostasis in parasite by binding to calcium channels, inducing influx, contraction, paralysis and death

  Also disrupts tegument, unmasking antigens and increasing susceptibility to host immune response
• Praziquantel pharmacokinetics


  Well absorbed orally, rapidly metabolised to inactive metabolites, plasma half-life 60-90 min
• Praziquantel unwanted effects


  Minimal side effects, usually transitory and rarely clinically important

  Effects may be more marked in heavy worm load due to products from dead worms

  Considered safe for pregnant and lactating women
• Piperazine


  Susceptible infections: roundworm, threadworm

  Acts by reversibly inhibiting neuromuscular transmission, probably via GABA-like action

  Paralysed worms expelled alive by normal intestinal peristalsis
• Piperazine is given orally and some, but not all, is absorbed