Unit 2 - Malaria Flashcards
why did reported malaria cases reach a 40-year high in 2011?
first and second generation immigrants from malaria-endemic countries returning to their “home” countries to visit friends and relatives tend not to use appropriate malaria prevention measures, and thus are more likely to be infected
what are the 5 different human forms of malaria? information on them?
P. vivax - wide distribution, involved in relapses
P. falciparum - most lethal and most common, much resistance to major drugs
P. malariae - less common, may cause asymptomatic infections that can last for decades
P. ovale - least common, involved in relapses
P. knowlesi - originally believed to infect only monkeys
-can reproduce every 24 hours in blood, which makes any possible infection more lethal
-human infections first reported in Malaysia and Philippines
what are the clinical signs of malaria?
- periodic episodes of chills and fever
- hepatosplenomegaly
- identified parasites in blood smears
malignant tertrian
- agent
- frequency of occurrence
- latency after infection
- frequency of febrile paroxysms
- severity
AKA estrivoautumnal
- P. falciparum
- most common
- 12 day latency
- irregular febrile paroxysms
- most severe
tertrian malaria
- agent
- frequency of occurrence
- latency after infection
- frequency of febrile paroxysms
- severity
- P. vivax
- less common
- 26 day latency
- febrile paroxysms every 2 days
- mild severity
quartan malaria
- agent
- frequency of occurrence
- latency after infection
- frequency of febrile paroxysms
- severity
- P. malariae
- least common
- 18-40 day latency
- febrile paroxysms every 3 days
- intermediate severity
what are the three types of malaria treatment?
- prophylaxis
- treatment of acute attack
- radical cure
what are anti-malarial drugs to know?
- quinoline derivatives
- artemisinin compounds
- antifolates
- antibiotics
- “Other”
what are the quinoline derivatives?
- quinine/quinidine
- chloroquine
- mefloquine
- primaquine
all have the quinoline ring structure
what is special to know about quinine/quinidine?
since 1991, it is th eonly parenteral antimalarial available for us in the US
what is special to know about chloroquine?
it is used for prophylaxis and treatment of acute attacks, but many strains have developed resistance (only few places are not resistant)
how do parasites gain immunity to drugs?
they get point mutations such that PfCRT is able to expel chloroquine through energy-dependent efflux mechanism
-but this can be countered by positively charged amantadine that binds the pore, preventing efflux
what is special to know about mefloquine?
used for prophylaxis and treatment of acute malaria attacks, but resistance is increasing
-also dangerous effects to the nervous system
what is the supposed method of action of anti-malarial drugs?
accumulate in parasite’s food vacuoles and disrupt heme polymerization to hemozoin (which is benign to parasite)
- causes oxidative damage membranes and digestive processes
- since the drugs are basic, and the food vacuole is acidic, it will also induce Fe trapping
what is Chloroguanide (Proguanil)?
the only DHF reductase inhibitor still used for malaria
-currently used as combo therapy with Atovaquone
what is Atovaquone?
napthoquinone that depolarizes parasitic mitochondria and inhibits their electron transport (low incidence of resistance)
-used in combo therapy with Proguanil/Chloroguanide for prophylaxis and treatment of malaria from P. falciparum, including chloroquine-resistant strains
what is the mechanism of Artemisinin compounds?
structurally similar to thapsigargin, which is highly specific inhibitor of sarcoendoplasmic reticulum Ca++ ATPase (pump) SERCA
-most recent studies show that when activated, artemisinins act by specifically and selectively inhibiting SERCA of P. falciparum
what is lumefantrine/benflumetol?
aminoalcohol class used in combo with artemether -resistance to artemiesins develops rapidly, so want to use lumefantrine to prevent it
what is primaquine?
only drug that inhibits exoerythrocytic schyzogony
=forms quinoline-quinone intermediates that oxidize schizont membranes
-used for prophylaxis and prevention of relapses (as the parasite may stay latent in the liver for long periods of time)
what is the overall approach to malaria prevention?
- assess risk of malaria exposure
- obtain detailed itinerary
- identify zones of resistance
- review accommodations
- discuss planned activities - discuss antimosquito measures
- chemoprophylaxis
- review symptoms of malaria with patient before departure
what is the chemoprophylaxis of choice if one is going to a chloroquine-sensitive zone?
chloroquine
what is the chemoprophylaxis of choice if one is going to a chloroquine-resistant zone?
Mefloquine, doxycycline, atovaquone-proguanil
what is the chemoprophylaxis of choice if one is going to a mefloquine-resistant zone?
doxycycline, atovaquone-proguanil
what is the chemoprophylaxis of choice if it’s terminal prophylaxis?
primaquine
what happened when irradiated sporozoites were delivered via mosquito bites to volunteers?
when subsequently challenged with infected mosquitoes, the volunteers were protected
what is special about immune globulin purified from blood of individuals who were life-long residents of malarious regions?
highly effective against blood stage form of parasite
what is special about humans living in malaria-endemic regions exposed to repeated infections?
natural protection from severe disease
how does one treat severe malaria?
- IV quinidine gluconate + antibacterial
- should be given in ICU, monitoring cardiac function, parasitemia, glucose, Hg, electrolytes - IV artesunate + Atovaquone-proguanil, doxycycline (clindamycin if pregnant), or mefloquine
- exchange blood transfusion (if parasite desnity >10%, altered mental status, pulmonary edema, renal complications), but usually the first two are enough
what is treatment of uncomplicated malaria in chloroquine sensitive strains of P. falciparum, malariae, or knowlesi?
main: chloroquine phosphate (as malariae and knowlesi have no known resistance in humans)
second: hydroxychloroquine
what is treatment of uncomplicated malaria in chloroquine sensitive strains of P. vivax and ovale?
Main: chloroquine phosphate + primaquine phosphate
second: hydroxychloroquine + primaquine phosphate
what is treatment of uncomplicated malaria in chloroquine resistant strains of P. falciparum?
Main: atovaquone-proguanil
second: Artemether-lumefantrine, quinine sulfate + antibiotic, or mefloquine
what is treatment of uncomplicated malaria in chloroquine resistant strains of P. vivax
Main: quinine sulfate + either doxycycline or tetracycline + primaquine phosphate
Second: atovaquone-proguanil + primaquine phosphate, or mefloquine + primaquine phosphate
what is the radical cure?
for eradication of persistent exoerythrocytic parasites after clinical cure of acute attack by P. vivax or P. ovale
-primaquine phosphate is drug of choice
what drugs target parasite cytosol?
antifolates
what drugs target parasite apicoplast?
antibiotics inhibiting protein translation (tetracycline, doxycycline)
what drugs target parasite lysosomal food vacuole?
- quinolines interact with heme and hematozoin
- peroxides oxidoreductively generate free radicals
what drugs target parasite plasma membrane?
vaccines interact with surface antigens
what drugs target parasite mitochondria?
atovaquone inhibition of cytochrome C reductase
what are side effects of chloroquine?
itching (Africans), retinitis (rare)
what are side effects of quinine/quinidine?
cinchonism, hypotension, hypoglycemia, abortion, arrhythmias
what are side effects of primaquine?
hemolysis (patients with G6PD deficiency), methemoglobinemia, fever, nausa, vomiting
what are side effects of doxycycline?
photosensitivity
what are side effects of proguanil?
rare side effects
what are side effects of artesunate?
neurotoxicity, prolongation of QT interval
