P falciparum ; serious complications and deaths. Drug resistance ;notably with P falciparum.

sporozoites ; invade liver cells - exoerythrocytic

stage tissue schizonts ; Merozoites;-erythrocytes; clinical illness gametocytes develop in erythrocytes --mosquitoes;sporozoites.

 P falciparum and P malariae, only one cycle of liver cell invasion and multiplication occurs, ceases in 4 weeks, Thus, treatment that

eliminates erythrocytic parasites P vivax and P ovale , a dormant hepatic stage, the hypnozoite, is not eradicated by most drugs, relapses occur after therapy directed against erythrocytic parasites. Eradication of both erythrocytic and hepatic parasites is required to cure these infections A fifth species, P knowlesi

Drug

Class

Use

Chloroquine

4-Aminoquinoline

Treatment and chemoprophylaxis of infection with sensitive parasites Treatment of infection with some chloroquine-resistant P falciparum strains and in fixed combination with artesunate Treatment of P falciparum infection in fixed combination with dihydroartemisinin Oral and intravenous1 treatment of P falciparum infections

Amodiaquine1

4-Aminoquinoline

Piperaquine1

Bisquinoline

Quinine

Quinoline methanol

Quinidine

Quinoline methanol

Intravenous therapy of severe infections with P falciparum Chemoprophylaxis and treatment of infections with P falciparum

Mefloquine

Quinoline methanol

Primaquine

8-Aminoquinoline

Radical cure and terminal prophylaxis of infections with P vivax and P ovale; alternative chemoprophylaxis for all species Treatment of infections with some chloroquine-resistant P falciparum, including combination with artesunate; intermittent preventive therapy in endemic areas Treatment and chemoprophylaxis of P falciparum infection Treatment (with quinine) of infections with P falciparum; chemoprophylaxis

Sulfadoxine-pyrimethamine (Fansidar)

Folate antagonist combination

Atovaquone-proguanil (Malarone) Doxycycline

Quinone-folate antagonist combination Tetracycline

Halofantrine

Phenanthrene methanol
Amyl alcohol

Treatment of P falciparum infections

Treatment of P falciparum malaria in fixed combination with artemether (Coartem Treatment of P falciparum infections; oral combination therapies for uncomplicated disease; intravenous artesunate for severe disease

Lumefantrine1

Artemisinins (artesunate, artemether,1 dihydroartemisinin1)

Sesquiterpene lactone endoperoxides

Drugs for the Prevention of Malaria

Drug Use2 Adult Dosage3

Chloroquine

Areas without resistant P falciparum

500 mg weekly

Malarone

Areas with chloroquineresistant P falciparum

1 tablet (250 mg atovaquone/100 mg proguanil) daily 250 mg weekly

Mefloquine

Areas with chloroquineresistant P falciparum

Doxycycline

Areas with multidrugresistant P falciparum

100 mg daily

Primaquine4

Terminal prophylaxis of P vivax and P ovale infections; alternative for primary prevention

52.6 mg (30 mg base) daily for 14 days after travel; for primary prevention 52.6 mg (30 mg base) daily

 1Recommendations may change, 2Areas without known chloroquine-resistant P falciparum are Central America west of the Panama Canal, Haiti, Dominican Republic, Egypt, and most malarious countries of the Middle East. Malarone or mefloquine are currently recommended for other malarious areas except for border areas of Thailand, where doxycycline is recommended. 3For drugs other than primaquine, begin 12 weeks before departure (except 2 days before for doxycycline and Malarone) and continue for 4 weeks after leaving the endemic area (except 1 week for Malarone). All dosages refer to salts. 4Screen for G6PD deficiency before using primaquine.

 Children, clindamycin instead of doxycycline along with main quinine/quinidine for falciparum
artemisinin derivatives are increasingly the

international standard of care mefloquine and halofantrine, both of which have toxicity concerns Malarone, which may occasionally fail

Clinical Setting

Drug Therapy1

Alternative Drugs

Chloroquine-sensitive P falciparum and P malariae infections

Chloroquine phosphate, 1 g, followed by 500 mg at 6, 24, and 48 hours or Chloroquine phosphate, 1 g at 0 and 24 hours, then 0.5 g at 48 hours

P vivax and P ovale infections

Chloroquine (as above), then (if G6PD normal) primaquine, 52.6 (30 mg base) for 14 days Malarone, 4 tablets (total of 1 g atovaquone, 400 mg proguanil) daily for 3 days or Mefloquine, 15 mg/kg once or 750 mg, then 500 mg in 68 hours or Coartem (coartemether 20 mg, lumefantrine 120 mg), 4 tablets twice daily for 3 days

Uncomplicated infections with Quinine sulfate, 650 mg 3 times daily for 37 days chloroquine-resistant P falciparum plus one of the followingDoxycycline, 100 mg twice daily for 7 days or Clindamycin, 600 mg twice daily for 7 days

Severe or complicated infections with P falciparum3

Artesunate, 2.4 mg/kg IV, every 12 hours for 1 day, then daily for two additional days; follow with 7 day oral course of doxycycline or clindamycin or full treatment course of mefloquine or Malarone

Artemether, 3.2 mg/kg IM, then 1.6 mg/kg/d IM; follow with oral therapy as for artesunate

or

Quinidine gluconate,2 10 mg/kg IV over 12 hours, then 0.02 mg/kg IV/min

or

15 mg/kg IV over 4 hours, then 7.5 mg/kg IV over 4 hours every 8 hours

CHLOROQUINE
highly effective blood schizonticide moderately effective against gametocytes of P

vivax, P ovale, and P malariae but not against P falciparum. Chloroquine is not active against liver stage parasites. Heme to hemozoin prevented, heme toxicity Resistance high-pfalci, low-vivax, mutation of a transporter PfCRT, reversed by verapamil, desipramine, and chlorpheniramine

 drug of choice in the treatment of nonfalciparum and sensitive falciparum malaria

Terminates fever, 24-48h

Clears parasitemia 48-72 h

artemisinin-based combination therapies to

treat falciparum malaria amebic abscesses that fail initial therapy with metronidazole Chloroquine is considered safe in pregnancy and for young children.

 Antipyretic
Antiinflammatory dmard,discoid lupus,

phototoxicity piperaquine combined with dihydroartemisinin in coformulated tablets excellent efficacy and safety for the treatment of falciparum malaria, without apparent drug resistance. Piperaquine has a longer half-life (~ 28 days) than amodiaquine (~ 14 days), mefloquine (~ 14 days), or lumefantrine (~ 4 days)

WHO Recommendations for the Treatment of Falciparum Malaria.

Regimen

Notes

Artemether-lumefantrine (Coartem, Riamet)

Coformulated; first-line therapy in many African countries

Artesunate-amodiaquine (ASAQ, Arsucam)

Coformulated; first-line therapy in many African countries

Artesunate-mefloquine

Standard therapy in parts of Southeast Asia

Artesunate-sulfadoxine-pyrimethamine

First-line therapy in some countries; efficacy low compared with other regimens in some areas

Amodiaquine-sulfadoxine-pyrimethamine

Less expensive; recommended as an interim option when efficacy established and other regimens are not available

QUININE & QUINIDINE

first-line therapies for falciparum malaria

severe disease toxicity may complicate therapy Resistance to quinine is uncommon but may be increasing. highly effective blood schizonticide against the four species of human malaria parasites gametocidal against P vivax and P ovale but not P falciparum

 not active against liver stage parasites

mechanism of action of quinine is unknown Not used for other species

Doxy/clinda duration reduced to 3 days

intravenous artesunate alternative a daily dose of 325 mg is effective for

chemoprophylaxis Babesiosis q+clinda Hypoglycemia insulin release Given in pregnancy too; contracts uterus

Blackwater fever; hemolysis & hemoglobinuria Warfarin digoxin Not with mefloquine MEFLOQUINE only be given orally a single-dose treatment; weekly for cp not active against hepatic stages or gametocytes. mechanism of action of mefloquine is unknown. resistance appears to be uncommon severe or complicated malaria, quinine, quinidine, and artemisinins are more rapidly active, and drug resistance is less likely artesunate plus mefloquine showed excellent antimalarial efficacy seizures and psychosis cardiac arrhythmias and bradycardia Used in pregnancy & childen