Protozoa and Helminths

Protozoa and Helminths

Protozoa and Helminths

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Protozoa Properties

  • Eukaryotic Microorganisms
  • Generally unicellular
  • Heterotrophic - needs organic substances
  • Often commensal
    • live in or on other organisms
  • Sometimes parasitic - life stages
  • Often live in aqueous environments
    • often motile
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Malaria

  • World Health Organisation priority disease
  • WHO figures released in February 2018
    • Estimated 216 million cases of malaria in 2016
    • Estimated 445,000 deaths
    • Africa region accounts for 91% of these deaths
    • Children are more at risk
  • Malaria mortality rates have fallen by 21% between 2010-2015, and by 31% in the WHO African Region
  • Malaria - Plasmodium
    • Plasmodium - ameboid intracellular parasites - P.vivax, P.falciparum, P.malariae
    • Transmitted through bite of Anopheles mosquito
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P. vivax Life Cycle

Malaria - Prevention

  • Mosquito control (insecticides, net, breading control)
  • Prophylaxis - choice based on many factors
    • risk of exposure
    • extent of drug resistance
    • efficacy of the recommended drugs
    • side effects of the drugs
    • patient-related factors (age, pregnancy, renal/hepatic impairment)
  • Prophylaxis 1-3 weeks before travel to endemic areas
  • Prophylaxis continues for up to 4 weeks after leaving endemic area
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Malaria - Prevention

  • Chloroquine
    • Prophylaxis not where falciparum malaria endemic (risk of resistance)
  • Mefloquine
    • Prophylaxis where falciparum malaria endemic
  • Doxycycline (tetracycline)
    • Prophylaxis where resistance to mefloquine and chloroquine
  • Malarone
    • Prophylaxis where falciparum malaria endemic including resistance to other antimalarial drug
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Malaria - Treatments

  • Quinine
    • Inhibits hemozoin biocrystallisation, which facilitates the aggregation of cytotoxic heme
  • Malarone
    • Interferes with two different pathways involved in biosynthesis of pyrimidines required for nucleic acid replication
    • Cytosine (C), Thymine (T), Uracil (U), are pyrimidine derivative
    • Atovaquone - inhibit electron transport chain
  • Riamet (artemether with lumefantrine)
    • Interferes with ability of malaria parasites to convert haem into haemozoin. This causes levels of the toxic haem to rise, which kills the bloos stages of the malaria parasites
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Cryptosporidiosis

  • Organism
    • Cryptosporidium parvum, hominis
    • Both aerobic and anaerobic metabolisms
  • Opportunistic infections
    • Faecal-oral
    • Water
  • Symptoms
    • Diarrhoea
    • Abdominal pain
    • Nausea
    • Severe crystosporidiosis in HIV patients
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Cryptosporidiosis

Cryptosporidiosis

  • Diagnosis
    • Organism in stool sample
  • Treatment
    • Fluid and electrolyte replacement
    • No licensed drugs in the UK
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Amoebic Dysentry (Amoebiasis)

  • Organism
    • Entamoeba histolytica
  • Disease
    • 400 million people infected worldwide
    • 70000 deaths per year world wide
    • Faecal-oral
    • Water
  • Diagnosis
    • Organism in stool sample
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Amoebic Dysentry (Amoebiasis)

  • Gastrointestinal infection that may or may not be symptomatic and can remain latent
    • Range from mild diarrhoea to dysentry with blood and mucus in the stool
  • Severe amoebiasis infections occur in two major forms:
    • Invasion of the intestinal lining causes amoebic dysentry or amoebic colitis
    • If the parasite reaches the bloodstream it can spread through the body, most frequently ending up in the liver where it causes amoebic liver abscesses
  • Life cycle: ingestion, cysts rupture, release amoeboid trophozoites, feeds on bacteria, reproduce asexually in colon, cause ulceration, can enter blood vessels
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Amoebic Dysentry (Amoebiasis)

Amoebic Dysentry (Amoebiasis): Treatments

  • Metrodinazole
    • Prodrug
    • Non-enzymatically reduced by reacting with reduced ferredoxin
    • Many of the reduced nitroso intermediates will form sulfinamides and thioether linkages with cysteine-bearing enzymes
    • Metronidazole metabolites are taken up into bacterial DNA and form unstable molecules
  • Tinidazole
  • Diloxanide fluorate
    • Unlicensed
    • Chronic amoebiasis
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Other Amoebal Diseases

  • Leishmaniasis
  • Giardiasis
  • Trypanosomiasis (sleeping sickness; Chagas' Disease)
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Helminths: Parasitic Worms

  • Flukes
  • Tapeworms
  • Roundworms
  • Threadworms
  • Hookworms
  • Whipworms
  • One billion people develop intestinal worm diseases globally every year
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Diseases and Routes of Infections

  • Causes a wide range of infections
    • Schistosomiasis (bilharzia)
    • Cysticercosis
    • Lymphatic filariasis (elephantiasis)
    • Onchocerciasis (river blindness)
  • Transmission routes
    • Schistosome or hookworm larvae directly penetrate the skin from infected water or soil
    • Filarial worms, such as Onchocerca, are transmitted by insect vectors
  • Inadequate sanitation is a major infection. Poverty and helminth infections are inextricably linked
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Symptoms

  • Stomach upset (abdominal pain, nausea or vomiting)
    • asymptomatic (a few roundworms)
    • reduced nutritional uptake
    • intestinal obstruction or bleeding
    • rectal prolapse
    • presence of a worm within vomit or stools
  • Flu-like symptoms
    • include fatigue or fever
    • anaemia
  • Skin rash
  • Breathing difficulties
    • if lungs infected
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Treatments - Anthelmintics

  • Depends on the worm
  • Mebendazole
    • Threadworm, roundworm (ascaris), whipworm infections
    • Inhibits the synthesis of microtubules, glucose uptake
  • Praziquantel
    • Tapeworm, whipworm, roundworm infections
    • Increases the permeability of the membranes of schistosome cells towards calcium ions, paralysing the parasite
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Treatments - Anthelmintics

  • Niclosamide
    • Taenicides (tapeworm infections) - unlicensed
    • Uncouples oxidative phosphorylation in the tapeworm
  • Ivermectin
    • Filaricide (named-patient basis) - unlicensed
    • GABA receptor, glutamate-gated chloride channels
  • Diethylcarbamazine
    • Filaricide (named-patient basis) - unlicensed
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