Chapter 248 MALARIA Flashcards
Responsible for nearly all deaths of malaria
Plasmodium falciparum
merozoites then invade the red blood cells (RBCs) and multiply
six- to twentyfold every 48 h
(P. knowlesi, 24 h; P. malariae, 72 h).
When the parasites reach densities of ~50/μL of blood or ____ the symptomatic stage of the infection begins.
(~100 million parasites in the blood of an adult),
In ____ infec- tions, a proportion of the intrahepatic forms do not divide immediately but remain inert for a period ranging from 3 weeks to ≥1 year before reproduction begins.
P. vivax and P. ovale
____, are the cause of the relapses that characterize infection with these two species.
hypnozoites
The swollen infected liver cells eventually burst, discharging motile _____ into the bloodstream.
merozoites
After entry into the bloodstream, merozoites rapidly invade erythrocytes and become ____.
trophozoites
By the end of the intraerythrocytic life cycle, the para- site has consumed two-thirds of the RBC’s hemoglobin and has grown to occupy most of the cell. It is now called a ______.
schizont
This zygote matures into an _____, which penetrates and encysts in the mosquito’s gut wall.
ookinete
to transmit malaria, the mosquito must survive for___
> 7 days.
potentially toxic heme is detoxified by lipid-mediated crystallization to biologically inert
hemozoin (malaria pigment)
The processes of cytoadherence, rosetting, and agglutination are central to the pathogenesis of
falciparum malaria.
Manifestation of severe falciparum malaria:
- Unarousable coma or severe malaria
- Acidemia or acidosis
- Anemia
- Renal failure
- ARDS
6: hypoglycemia - Hypotension
- Bleeding
- Convulsions
Coma is a characteristic and ominous feature of falciparum malaria and, despite treatment, is associated with death rates of ~20% among adults and 15% among children.
Cerebral Malaria
Most common funduscopic abnormalities include discrete spots of
retinal opacification (30–60%)
Approximately ____% of children surviving cerebral malaria—especially those with hypoglycemia, severe anemia, repeated seizures, and deep coma—have residual neu- rologic deficits when they regain consciousness;
10%
Chronic or repeated infections with P. malariae (and possibly with other malarial species) may cause soluble immune complex injury to the renal glomeruli, resulting in the nephrotic syndrome.
QuARTAN MALARIAL NEPHROPATHY
The diagnosis of malaria rests on the demonstration of asexual forms of the parasite in stained
peripheral-blood smears.
Repeat blood smears should be performed at least _____ for 2 days if the first smears are negative and malaria is strongly suspected.
every 12–24 h
Treatment Known chloroquine- sensitive strains of Plasmodium vivax,
P. malariae, P. ovale, P. knowlesi,
P. falciparumb
Chloroquine (10 mg of base/kg stat followed by 5 mg/ kg at 12, 24, and 36 h or by 10 mg/kg at 24 h and
5 mg/kg at 48 h)
or
Amodiaquine (10–12 mg of base/kg qd for 3 days)
Radical treatment for P. vivax or P. ovale infection
In addition to chloroquine or amodiaquine as detailed above,
primaquine (0.5 mg of base/kg qd in tropical regions and 0.25 mg/kg for temperate-origin P. vivax) should be given for 14 days to prevent relapse.
or
Artesunated (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days)e
Sensitive
P. falciparum malaria treatment
Artesunated (4 mg/kg qd for 3 days) plus sulfadoxine (25 mg/kg)/pyrimethamine (1.25 mg/kg) as a single dose
Or
Artesunated (4 mg/kg qd for 3 days) plus amodiaquine (10 mg of base/kg qd for 3 days)
Treatment for Multidrug-resistant P. falciparum malaria
Either artemether-lumefantrined (1.5/9 mg/kg bid for 3 days with food)
or
Artesunated (4 mg/kg qd for 3 days) plus mefloquine (24–25 mg of base/kg—either 8 mg/kg qd for 3 days or 15 mg/kg on day 2 and then 10 mg/kg on day 3)e
or
Dihydroartemisinin-piperaquined (2.5/20 mg/kg qd for 3 days)
Second-line treat- ment/treatment of imported malaria
Either artesunated (2 mg/kg qd for 7 days) or quinine (10 mg of salt/kg tid for 7 days) plus 1 of the following 3:
1. Tetracyclinef (4 mg/kg qid for 7 days)
2. Doxycyclinef (3 mg/kg qd for 7 days)
3. Clindamycin (10 mg/kg bid for 7 days)
or
Atovaquone-proguanil (20/8 mg/kg qd for 3 days with food)
Severe falciparum malaria
Artesunated (2.4 mg/kg stat IV followed by 2.4 mg/kg at 12 and 24 h and then daily if necessary)h
remains a first-line treatment for the non-falciparum malarias (P. vivax, P. ovale, P. malariae, P. knowlesi) except in Indonesia and Papua New Guinea, where high levels of resistance in P. vivax are prevalent.
chloroquine
World Health Organization (WHO) now recommends _____ as first-line treatment for uncomplicated falciparum malaria
artemisinin-based combinations (ACTs)
has therefore become the drug of choice for all patients with severe malaria everywhere.
Artesunate
total plasma concentrations of ___ for quinine and ____ for quinidine are effective and do not cause serious toxicity.
Quinine 8–15 mg/L
Quijidine 3.5–8.0 mg/L
Infections due to sensitive strains of P. vivax, P. knowlesi, P. malariae, and P. ovale should be treated with
oral chloroquine (total dose, 25 mg of base/kg) or with an ATC known to be efficacious for UNCOMPLICATED MALARIA
In areas with multidrug-resistant falciparum malaria (parts of Asia and South America, including those with mefloquine-resistant parasites; these regimens provide cure rates of >90%.
artemether-lumefantrine, artesunate-mefloquine, or dihydroartemisinin-piperaquine should be used;
is the only drug advised for pregnant women traveling to areas with drug-resistant malaria; this drug is generally considered safe in the sec- ond and third trimesters of pregnancy, and the data on first-trimester exposure, although limited, are reassuring.
MEFLOQUINE
Used for presumptive antirelapse therapy (terminal prophylaxis) to decrease risk of relapses of P. vivax and P. ovale
PRIMAQUINE
For prevention of malaria in areas with mainly
P. vivax
PRIMAQUINE
Prophylaxis in areas with chloroquine-resistant
P. falciparum
MEFLOQUINE
An alternative to chloroquine for primary prophylaxis only in areas with chloroquine-sensitive P. falciparumc or areas with P. vivax only
Hydroxychloroquine sulfate (PLAQUENIL)
Prophylaxis in areas with chloroquine- or mefloquine-resistant
P. falciparum
DOXYCYCLINE
Prophylaxis only in areas with chloroquine-sensitive P. falciparumc or areas with P. vivax only
Chloroquine phosphate (Aralen and generic)
Prophylaxis in areas with chloroquine- or mefloquine-resistant Plasmodium falciparum
Atovaquone- proguanil (Malarone)
is a fixed-combination, once-daily prophylactic agent that is very well tolerated by adults and children, with fewer adverse gastrointestinal effects than chloroquine-proguanil and fewer adverse central nervous system effects than mefloquine.
Atovaquone-proguanil (Malarone; 3.75/1.5 mg/kg or 250/100 mg, daily adult dose)
has been widely used for malarial prophylaxis because it is usually effective against multi- drug-resistant falciparum malaria and is reasonably well tolerated
Mefloquine (250 mg of salt weekly, adult dose)
Daily administration of ____ is an effective alternative to atovaquone-proguanil or mefloquine and is generally well tolerated but may cause vulvovaginal thrush, diarrhea, and photosensitivity and cannot be used by children <8 years old or by pregnant women.
doxycycline (100 mg daily, adult dose)
_____ taken with food), an 8-aminoquinoline compound, has proved safe and effective in the prevention of drug-resistant falciparum and vivax
Primaquine (daily adult dose, 0.5 mg of base/kg or 30 mg
True or false
Children born to nonimmune mothers in endemic areas (usually expatriates moving to malaria-endemic areas) should receive prophylaxis from birth.
TRUE
Travelers should start taking antimalarial drugs ____ before departure so that any untoward reactions can be detected and so that therapeutic antimalarial blood concentrations will be present when needed
2 days to 2 weeks
Antimalarial prophylaxis should continue for 4 weeks after the traveler has left the endemic area, except if ____ has been taken; these drugs have significant activities against the liver stage of the infection
atovaquone-proguanil or primaquine
chloroquine (a 4-aminoquinoline) act on the ____ stage of parasitic develop- ment
erythrocyte
inhibitors also inhibit preerythro- cytic growth in the liver (causal prophylaxis) and development in the mosquito (sporontocidal activity).
dihydrofolate reductase
DHR
Lumbar tap mean opening pressure
Approximately 180mmhg
