Malaria Drugs and Vaccines Derek Cervenka and Peter Knopick Parasitology 460/462

Overview  Modes of attack for the different drug types  Intracellular  Blocks the food source for the parasite  Extracellular  Blocks the newly formed merozoites from escaping the cells  Resistance to these drugs is a big problem  Most used in a “cocktail”

Chloroquine aka: Aralen  Affects all forms of malaria but P. Falciparum has grown a large resistance.  Taken orally once a week on the same day to keep a regular schedule.  Can be used as a prophylactic before going into an infected area.  This does not work for Vivax or Malarliae, its not effective against the exoerythrocytes types.  Was the drug of choice for most malarial treatments  Now only effective in some parts of Central America, the Middle East, and parts of the Carribean.  This is due mainly to resistances being formed by the parasite

Chloroquine Cont.  How it works  Kills off the sporozoites before they infect red blood cells  Helps to control the merozoites once they are releases from the red blood cells  Side effects  Nausea, diarrhea, dizziness, sleep disturbances, stomach aches, headaches, blurred vision or light flashes  Most of these go away directly after nonuse of the drug

Amodiaquine aka: Camoquin, Flavoquine  Affects all forms of malaria however just as with Chloroquine resistances have been noted around the world.  Taken as a mixture of Amodiaquine and Artesunate in tablet form  2 pills of each are taken twice a day for three days.  A full regiment for the drug only takes 3 days.  Used in treatment of acute cases where Chloroquine and other drugs have a resistance built up.  Tends to kill more invasive types (like P. Falciparum) easier than other drugs.

Amodiaquine Cont.  How it works  Works as a very strong schizonticide  Binds and accumlates in the lysosomes of red blood cells.  This causes the hemoglobin within the cell to change in a way so that the parasite can longer consume it  Since malaria can’t use it’s energy source it dies out  Side Effects  nausea, vomiting, diarrhea, vertigo and lethargy.  Abdominal pain, headache and photosensitivity have also been reported. When given for long periods, it sometimes causes corneal deposits, visual disturbances and a bluish/grey coloring of the finger nails and skin.

Mefloquine aka : Lariam®  Used as preventative and in the treatment of chloroquine-resistant falciparum malaria  Developed during the Vietnam War  As a preventaive, take once a week, 1-3 weeks before traveling to an area where malaria is common, continuing 4 weeks after you return from the area.

Mefloquine Cont.  How it works  There is no definitive answer on this however most drugs work on two different methods  Side effects  nausea, vomiting, diarrhea, loss of appetite, chills or fever, muscle aches or weakness, severe depression, anxiety, paranoia, insomnia or abnormal dreams, headache, dizziness or drowsiness

Artemisinin  Easily affects all types of malaria  Has very little to no resistance built up in the world  This means it’s the worlds go-to drug on tough strains and recurring infections  Taken usually as a mixture with other less potent drugs  Usually in table form and taken during short intervals  First discovered as an herbal remedy in early Chinese medicine  It is an extract from the Artemisia Annua plant  Was first used as a treatment for fevers 1000 years ago

Antimalarial combination therapy “Antimalarial combination therapy is the simultaneous use of two or more blood schizontocidal drugs with independent modes of action and thus unrelated biochemical targets in the parasite.” -WHO

Artemisinin Cont.  How it works  Binds to the outside of infected red blood cells and blocks receptors  These receptors are used by the parasite to release the new merozoites  Basically acts as a net to catch and keep control of the new merozoites  Side Effects  Very few side effects  Slight headaches nausea may occur