A 3 year old male in Ghana presents with fever, headache and cough for three days. His RDT is shown. He tolerates food by mouth. What is the recommended treatment?
Artemether-lumefantrine is the choice in Ghana. (Coartem)
A patient presents with fever, chills, headache, myalgias, diarrhea, mild anemia, mild thrombocytopenia and tolerates oral medications. He is diagnosed with uncomplicated malaria. How does his condition differ from severe malaria?
Severe malaria: can’t take oral meds, organ failure (cerebral malaria, renal failure, shock, DIC, cardiorespiratory failure and severe anemia are all precipitated by hyperparasitemia > 5% and Hgb < 7). Acidosis and hypoglycemia are also seen in severe malaria.
Species of malaria responsible for the largest burden of mortality
Where do different drugs act to control malaria infection?
1) Tissue schizonticide: tx for active liver stage, Atovoquone-Proguanil and Primaquine. 2) Blood schizonticide: kills malaria in blood and treats symptoms, Mefloquine, Doxycycline, Chloroquine, Atovoquone-Proguanil, Artemisinins, Quinine. 3) Gametocytocide: prevents transmission to mosquitos, Artemisinins, Primaquine. 4) Anti-hypnozoite: prevents dormant relapsing by P. vivax and P. ovale: Primaquine.
What drugs work the fastest in killing malaria parasites? How do you utilize this?
Give the most rapid acting drug when people are sicking and a slower acting drug to mop up the rest of the parasites. Artemisinins > Quinine > Atovaquone-Proguanil = Mefloquine > Tetracycline, Clindamycin, TMP-SMX
What anti-malarial drugs work by impairing intra-parasitic heme polymerization into hemozoin, resulting in parasite death due to inability to deal with excess iron?
Quinolines: Chloroquine, Hydroxychloroquine, Quinine, Quinidine, Mefloquine, Lumefantrine and Primaquine.
Drug of choice for all malaria species except for P. falciparum?
Chloroquine. Much of the P. falciparum in the world has become resistant to chloroquine.
Tinnitus, headache, nausea, bitter taste and dysphoria…all side effects of oral quinine.
Use of quinidine in the US
Drug of choice for IV therapy in severe P. falciparum infection.
Original use of quinidine
Anti-arrhythmic, prolongs QT interval.
Anti-malarial drug with a 3 week half life used to treat chloroquine resistant P. falciparum? Why does this cause sleep disturbance, hallucinations and depression?
Mefloquine. It has CNS side effects because it can cross the BBB.
Region of the world with mefloquine resistance?
Anti-malarial drug that is treatment of choice for soldiers that get malaria in Liberia, has a 4.5 day half life, has lots of side effects (to include QT prolongation) and should be taken with food to enhance absorption?
Lumefantrine (a component of coartem)
Why do artemisinins kill more parasites per dose than chloroquine and quinine?
They act on parasites at all stages of development where the chloroquine and quinine drugs act more on sequestered parasites.
2 drugs in the artemisinin class? How do they work?
Coartem (artemether-lumefantrine, po) and IV artesunate (drug of choice for severe malaria in rest of world). These drugs are endoperoxides that are cleaved and produce free radicals that rapidly kill the blood parasites.
Half-life of artemisinins
A few minutes, out of the body within an hour.
Anti-malarials that target folate production? Why are they not widely used? When is it preferred?
Proguanil and Sulfadoxine-Trimethoprim. These drugs block dihydropteroate synthase and dihydrofolate reductase. Resistance is widespread due to point mutations in DHPS and DHFR. It is preferred in kids and pregnant women.
Anti-malarial active against the liver and the blood stages that targets the mitochondrial electron transport chain.
Half life of atovaquone
Malarone. Use? Resistance?
Atovaquone-proguanil. Effective for treatment and prophylaxis. Resistance develops easily due to single point mutations.
Antibiotics used to treat malaria
Doxycycline, tetracycline, clindamycin, azithromycin. These work against the “apicoplast”, which is responsible for cell division and replication. This presents the healthy daughter cells to come out with the next generation and work very slowly.
Why might it be more difficult to diagnose someone with malaria that received ciprofloxacin prophylaxis for traveler’s diarrhea?
They are also anti-malarial and will make the infection less severe.
Drugs recommended for malaria in pregnancy?
Quinine + clindamycin, mefloquine, chloroquine, artemisinins (avoid 1st trimester)
Anti-malarial drugs that are more active against relapsing malaria caused by P. vivax or P. ovale?
Primaquine (8-aminoquinolone). It is more active in the liver and less active in the blood. Consequently it is used with chloroquine, quinine or mefloquine to treat the blood infection. It is also a gametocide that prevents secondary infection of mosquitos.
What must you do before prescribing primaquine?
Test for G6PD to avoid hemolytic anemia.
Why does primaquine typically fail?
It is cleared rather quickly and people feel better and don’t follow through because their blood acting drugs are working well. Also some people don’t metabolize the drug.
IV drug of choice that has replaced quinidine for sever malaria
A 25 year old is going on a 2 week safari to western Kenya. What is the most appropriate chemoprophylactic?
1) Prevent mosquito bites 2) Atovaquone-proguanil is 1st line, doxycycline is only effective if you take it every day, chloroquine has many resistant strains, mefloquine has CNS side effects.