Malaria Flashcards
what mosquito carries plasmodia
anopheles
plasmodium is a _____
protozoan
species plasmodium
vivax, ovale, malariae, falciparum
which species have low parasite burden
vivax, ovale, malariae
which species have high parasite burden
falciparum
vivax, ovale, malariae cause
mild anemia
which species relapse
vivax, ovale
which species cause severe anemia
falciparum
what does falciparum cause
severe anemia
cerebral and multi-organ symptoms
high-fatality rate
Most common
vivax, falciparum
most deadly
falciparum
relapses
vivax, ovale
life cycle of plasmodium falciparum
mosquito digestive tract –> sporozoites in mouth –> hepatic cell in mammal –> schizonts which multiply –> merozoites burst out of cell –> ring form into RBC –> trophozoite –> schizonts –> merozoites, continue in that cycle
morphology: P. falciparum
lots of rings
crescent-shaped gametocytes
morphology: P. malariae
“rosette” arrangement of merozoites
morphology: P. ovale
enlarged red cells
Schuffner’s dots
morphology: P. vivax
Schuffner’s dots
enlarged red cells
P. falciparum is able to infect ____ (special)
red cells of any age
P. falciparum causes what kind of red blood cell pathology
“rosettes” – abnormal binding to endothelium
blood flow is impeded
main cause of death in children = cerebral ischemia
P. falciparum and cytokines
Stimulates high production of cytokines
TNF, INF-Υ, IL-1
suppress red cell production, cause fever, tissue damage, and red cell binding to endothelium
malaria: what happens in the patient
spleen becomes enlarged
liver enlarged/pigmented
brain vessels get plugged
heart/lungs maybe involved
spleen pathology
enlarged
parasites in red cells
super-active macrophages
if chronic: fibrosis, grayish color
brain vessels pathology
red cell rosettes
hypoxia around vessels
eventual, ischemia
incubation
1-2 weeks
prodrome
flu-like illness
paroxysms
fever/chills, sweating, myalgia
quotidian
daily
falciparum
tertian
every 48 hrs
vivax, ovale
quartan
every 72 hrs
malariae
host resistance (2 ways)
inherited red cell alterations
partial immune-mediated resistance
inherited red cell alterations
Hemoglobinopathies (e.g., sickle cell)
Thalassemias
G6PD deficiency
RBC antigens (ABO, Duffy)
partial immune-mediated resistance
Develops over time in patients in endemic areas
Reduces severity of disease
P. falciparum uses antigenic variation
blood type and binding
O - least adhesive (cannot bind to endothelium)
A and or B most
diagnosis
sxs and hx
ID plasmodia in red cells on regularly-stained blood smear (gold standard)
rapid immunochromatographic tests sometimes used (quicker but less accurate)
The science that deals with drugs, their sources, appearance, chemistry, actions, mechanism of action and use
pharmacology
The practical branch of medicine dealing with the treatment of disease
therapeutics
best plan for malaria
DON’T GET BIT
use of netting and insect repellents
avoid areas and exposure during high insect activity
plan B
prophylaxis
treat active malaria
use radical cure if indicated
considerations in treatment?
which area? resistance? persistent hepatic forms? clinical status of disease?
which species have resistance?
falciparum, vivax
which ones have latent forms
ovale, vivax
what treats latent malaria
primaquine
best choice suppressive prophylaxis - prevention of malaria
alternative?
chloroquine
atovaquone/proguanil
best choice suppressive prophylaxis - prevention of malaria in CHLOROQUINE RESISTANT
alternative?
atovaquone/proguanil
doxycycline or mefloquine
treatment of acute attack for all plasmodium except resistant
oral chloroquine
treatment of acute attack for chloroquine resistant P. falciparum
quinine sulfate + doxycycline
alternative: atovaquone/proguanil OR artemether/lumefantrine or Mefloquine
treatment of acute attack for chloroquine resistant P. vivax
Quinine sulfate + doxycycline
alternative: mefloquine
treatment of severe disease
parenteral
quinidine gluconate + doxycycline
alternative: artesunate + oral drug when tolerated
radical cure
primaquine phosphate
which drugs act at primary liver stage
pyrimethamine/sulfadoxine
atovaquone/proguanil
primaquine
what drugs act at hypnozoite stage
primaquine
what drugs act RBC asexual stage
all (chloroquine, mefloquine, quinine, quinidine….) but primaquine
what drugs act at RBC gametocyte
chloroquine
quinine, quinidine
artesunate
primaquine
chloroquine basis for selectivity
The parasitized RBC concentrates Chloroquine at least 25 fold more than unparasitized RBC. Chloroquine accumulates in the acid pH of the food vacuole.
chloroquine mechanism
parasite digest hgb and makes FPIX which is toxic - parasite heme polymerase turns it to hemozoin (not toxic)
chloroquine binds to FPIX and prevents conversion to hemozoin
adverse effects chloroquine
low dose prophylaxis - no tox
acute attack doses:
dizziness, headache, itching, vomiting, skin rashes
difficulty in visual accommodation
large doses for prolonged periods can cause severe eye damage and even blindness
main AE chloroquine
eye issues
what is more toxic than chloroquine but no resistance yet
quinine, quinidine
mechanism quinine/quinidine
parasite digest hgb and makes FPIX which is toxic - parasite heme polymerase turns it to hemozoin (not toxic)
chloroquine binds to FPIX and prevents conversion to hemozoin
AE quinine
Acute attack doses – Cinchonism
tinnitus, blurred vision, nausea,
headache, decreased hearing acuity
permanent damage to vision, balance and hearing can result
Anti-arrhythmic drug that blocks Na and K currents
quinidine
quinine used in
Used in chloroquine resistant P. falciparum
quinidine used in
Intravenous for severe malaria
AE quinidine
Cardiac problems - so patients need cardiac monitoring
mefloquine mechanism
Disrupts sequestration of heme as hemozoin (same as chloroquine)
AE mefloquine
Sometimes nausea, vomiting, dizziness, visual or auditory disturbances
May cause disorientation, hallucinations and depression
main AE mefloquine
neuropsychiatric reactions
indications mefloquine
Indicated only for the treatment and prevention of Chloroquine resistant P. falciparum
atovaquone given with
proguanil
atovaquone MOA
unique
Depolarizes parasitic mitochondria and inhibits their electron transport
proguanil given w/
atovaquone
proguanil MOA
metabolite of proguanil inhibits dihydrofolate reductase
selective for the plasmodial enzyme
Enhances the mitochondrial toxicity of atovaquone
Reduces the frequency of atovaquone resistance
proguanil not active against
hepatic stages of P. vivax or P. ovale
A/P onset
slow
A/P effectiveness against exo-erythrocytic forms
unclear
Proguanil concentrates in erythrocytes
A/P use
replacing mefloquine for prophylaxis
AE of A/P
GI disturbances
Artemisinins and combinations
+mefloquine
+lumefantrine
don’t use alone (resistance)
mechanism artemisinins
Heme iron in the malarial pigment acts on the drug to produce free radicals that damage parasite proteins
Inhibits a calcium ion ATPase in P. falciparum
artemisinins onset and efficacy
rapid and potent activity against even multi-drug resistant organisms
lumefantrine mechanism
unknown
lumefantrine effective against
erythocytic stage
give lumefantrine with
artemether
Rapid initial reduction in parasite biomass afforded by artemether and subsequent clearance of remaining viable parasites by the more slowly eliminated lumefantrine
primaquine use
Drug of choice to eliminate hepatic forms of P. vivax and P. ovale
Eradicates hypnozoite forms dormant in liver
Some prefer to wait for the low risk of relapse rather than face potential side-effects of the drug.
mechanism primaquine
Unknown
Possibly by generation of reactive oxygen species or by interfering with electron transport in the parasite
AE primaquine
occasional GI distress, nausea, headache, pruritis, leukopenia
Hemolytic anemia in people with a glucose-6-phosphate dehydrogenase deficiency
