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Malaria is infection with Plasmodium sp. Symptoms are fever (which may be periodic), chills, sweating, hemolytic anemia, and splenomegaly. Diagnosis is by seeing Plasmodium in a peripheral blood smear. Treatment and prophylaxis depend on the species and drug sensitivity and include chloroquine, quinine, the fixed combination of atovaquone and proguanil, mefloquine, doxycycline, and artemisinin derivatives. Patients infected with P. vivax and P. ovale also receive primaquine to prevent relapse.

Malaria is endemic in Africa, much of South and Southeast Asia, North and South Korea, Mexico, Central America, Haiti, the Dominican Republic, northern South America (including northern parts of Argentina), the Middle East (including Turkey, Syria, Iran, and Iraq), and Central Asia. There are 300 to 500 million infected people worldwide, with 1 to 2 million deaths yearly, most in children < 5 yr in Africa. Malaria once was endemic in the US but has been virtually eliminated. About 1500 cases/yr occur in the US. Nearly all are acquired abroad, but a small number result from blood transfusions or rare autochthonous transmission by local mosquitoes that feed on infected immigrants.

Pathophysiology

The Plasmodium species that are spread among humans are

• P. falciparum
• P. vivax
• P. ovale
• P. malariae

Also, simian malaria has been reported in humans; P. knowlesi is implicated most often. Whether P. knowlesi is transmitted from human to human via the mosquito, without the natural intermediate monkey host, has not been determined.

The basic elements of the life cycle are the same for all Plasmodium sp. (see Fig. 1: Extraintestinal Protozoa: Plasmodium life cycle) Transmission begins when a female Anopheles mosquito feeds on a person with malaria and ingests blood containing gametocytes. During the following 1 to 2 wk, gametocytes inside the mosquito reproduce sexually and produce infective sporozoites. When the mosquito feeds on another human, sporozoites are inoculated and quickly reach the liver and infect hepatocytes. The parasites mature into tissue schizonts within hepatocytes. Each schizont produces 10,000 to 30,000 merozoites, which are released into the bloodstream 1 to 3 wk later when the hepatocyte ruptures. Each merozoite can invade an RBC and there transform into a trophozoite. Trophozoites grow and develop into erythrocyte schizonts; schizonts produce further merozoites, which 48 to 72 h later rupture the RBC and are released in plasma. These merozoites then rapidly invade new RBCs, repeating the cycle. Some trophozoites develop into gametocytes, which are ingested by an Anopheles mosquito. They undergo sexual union in the gut of the mosquito, develop into oocysts, and release infective sporozoites, which migrate to the salivary glands.

Fig. 1
Plasmodium life cycle The malaria parasite life cycle involves 2 hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host. Sporozoites infect liver cells. There, the sporozoites mature into schizonts. The schizonts rupture and release merozoites. This initial replication in the liver is called the exoerythrocytic cycle. Merozoites infect RBCs. There, the parasite multiplies asexually (called the erythrocytic cycle). The merozoites develop into ring-stage trophozoites. Some then mature into schizonts. The schizonts rupture, releasing merozoites. Some trophozoites differentiate into gametocytes. During a blood meal, an Anopheles mosquito ingests the male (microgametocytes) and female (macrogametocytes), gametocytes beginning the sporogonic cycle. In the mosquito's stomach, the microgametes penetrate the macrogametes, producing zygotes. The zygotes become motile and elongated, developing into ookinetes. The ookinetes invade the midgut wall of the mosquito where they develop into oocysts. The oocysts grow, rupture, and release sporozoites, which travel to the mosquito's salivary glands. Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle.

With P. vivax and P. ovale (but not P. falciparum or P. malariae), tissue schizonts may persist as hypnozoites in the liver for up to 3 yr. These dormant forms serve as time-release capsules, which cause relapses and complicate chemotherapy because they are not killed by most antimalarial drugs, which typically act on bloodstream parasites.

The pre-erythrocytic (hepatic) stage of the malarial life cycle is bypassed when infection is transmitted by blood transfusions, by sharing of contaminated needles, or congenitally. Therefore, these modes of transmission do not cause latent disease or delayed recurrences.

Rupture of RBCs during release of merozoites is responsible for the clinical symptoms. If severe, hemolysis causes anemia and jaundice, which are worsened by phagocytosis of infected RBCs in the spleen. Anemia may be severe in P. falciparum or chronic P. vivax infection but tends to be mild in P. malariae infection.

Falciparum malaria: Unlike other forms of malaria, P. falciparum causes microvascular obstruction because infected RBCs adhere to vascular endothelial cells. Ischemia develops with resultant tissue hypoxia, particularly in the brain, kidneys, lungs, and GI tract. Hypoglycemia and lactic acidosis are other potential complications.

Resistance to infection: Most West Africans have complete resistance to P. vivax because their RBCs lack the Duffy blood group, which is required for the attachment of P. vivax to RBCs; many African Americans also have such resistance. The development of Plasmodium in RBCs is retarded in patients with hemoglobin S, hemoglobin C, thalassemia, G6PD deficiency, or elliptocytosis.

Previous infections provide partial immunity. Once residents of hyperendemic areas leave, acquired immunity wanes over time (months to years), and symptomatic malaria may develop if they return home and become reinfected.

Symptoms and Signs

The incubation period is usually 12 to 17 days for P. vivax, 9 to 14 days for P. falciparum, 16 to 18 days or longer for P. ovale, and about 1 mo (18 to 40 days) or longer (years) for P. malariae. However, some strains of P. vivax in temperate climates may not cause clinical illness for months to > 1 yr after infection.

Manifestations common to all forms of malaria include

• Fever and rigor—the malarial paroxysm
• Anemia
• Jaundice
• Splenomegaly
• Hepatomegaly

The malarial paroxysm coincides with release of merozoites from ruptured RBCs. The classic paroxysm starts with malaise, abrupt chills and fever rising to 39 to 41° C, rapid and thready pulse, polyuria, headache, myalgia, and nausea. After 2 to 6 h, fever falls, and profuse sweating occurs for 2 to 3 h, followed by extreme fatigue. Fever is often hectic at the start of infection. In established infections, malarial paroxysms typically occur about every 2 to 3 days depending on the species; intervals are not rigid.

Splenomegaly usually becomes palpable by the end of the first week of clinical disease but may not occur with P. falciparum. The enlarged spleen is soft and prone to traumatic rupture. Splenomegaly may decrease with recurrent attacks of malaria as functional immunity develops. After many bouts, the spleen may become fibrotic and firm or, in some patients, becomes massively enlarged (tropical splenomegaly). Hepatomegaly usually accompanies splenomegaly.

P. falciparum causes the most severe disease because of its microvascular effects. It is the only species likely to cause fatal disease if untreated; nonimmune patients may die within days of their initial symptoms. Patients with cerebral malaria may develop symptoms ranging from irritability to seizures and coma. Acute respiratory distress syndrome (ARDS), diarrhea, icterus, epigastric tenderness, retinal hemorrhages, algid malaria (a shocklike syndrome), and severe thrombocytopenia may also occur. Renal insufficiency may result from volume depletion, vascular obstruction by parasitized erythrocytes, or immune complex deposition. Hemoglobinemia and hemoglobinuria resulting from intravascular hemolysis may progress to blackwater fever (so named based on the dark color of the urine), either spontaneously or after treatment with quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
. Hypoglycemia is common and may be aggravated by quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
treatment and associated hyperinsulinemia. Placental involvement may lead to spontaneous abortion, stillbirth, or sometimes congenital infection.

P. vivax, P. ovale, and P. malariae typically do not compromise vital organs. Mortality is rare and is mostly due to splenic rupture or uncontrolled hyperparasitemia in asplenic patients. The clinical course with P. ovale is similar to that of P. vivax. In established infections, temperature spikes occur at 48-h intervals. P. malariae infections may cause no acute symptoms, but low-level parasitemia may persist for decades and lead to immune complex–mediated nephritis or nephrosis or tropical splenomegaly; when symptomatic, fever tends to occur at 72-h intervals.

In patients who have been taking chemoprophylaxis (see Extraintestinal Protozoa: Chemoprophylaxis), malaria may be atypical. The incubation period may extend weeks after the drug is stopped. Those infected may develop headache, backache, and irregular fever. Parasites may initially be difficult to find in blood samples.

Diagnosis

• Light microscopy of blood (thin and thick smears)
• Sometimes rapid blood assays that detect Plasmodium antigens or enzymes

Fever and chills (particularly recurrent attacks) in a traveler returning from an endemic region should prompt immediate assessment for malaria. Most cases occur within the first 6 mo, but onset may take up to 2 yr or, rarely, longer.

Malaria is typically diagnosed by finding parasites on microscopic examination of thick or thin blood smears. The infecting species (which determines therapy and prognosis) is identified by characteristic features on smears (see Table 1: Extraintestinal Protozoa: Diagnostic Features of Plasmodium Species in Blood Films). Blood smears should be repeated at 4- to 6-h intervals if the initial smear is negative.

Thin blood smears stained with Wright-Giemsa stain allow assessment of parasite morphology within RBCs and determination of percentage parasitemia. Thick smears are more sensitive but more difficult to prepare and interpret as the RBCs are lysed before staining.

Commercial rapid assays have been developed to diagnose malaria based on the presence of certain plasmodium antigens or enzymatic activities. Assays may involve detection of a histidine-rich protein 2 (HRP-2) associated with malaria parasites (especially P. falciparum and P. vivax) and detection of plasmodium-associated lactate dehydrogenase (pLDH). However, the rapid tests are no more sensitive for detecting low levels of parasitemia than evaluation of a blood smear by an experienced microscopist and do not detect dual infections.

PCR and species-specific DNA probes may be used but are not widely available. Serologic tests may reflect prior exposure and are not useful in the diagnosis of acute malaria.

Table 1
Diagnostic Features of Plasmodium Species in Blood Films Characteristic Plasmodium Sp* Vivax Falciparum Malariae† Infected RBCs enlarged Yes No No Schüffner's dots‡ Yes No No Maurer's dots or clefts No Yes§ No Multiple infections in RBCs Rare Yes No Rings with 2 chromatin dots Rare Frequent No Crescentic gametocytes No Yes No Bayonet or band trophozoites No No Yes Schizonts present in peripheral blood Yes Rare Yes Number of merozoites per schizont (mean [range]) 16 (12–24) 12 (8–24)¶ 8 (6–12) *RBCs infected with P. ovale are fimbriated, oval, and slightly enlarged; the parasites otherwise resemble P. vivax. † P. knowlesi is morphologically similar to P. malaria and has been confused with it. ‡ Schüffner's dots are best seen when the blood smear is stained with Giemsa, not Wright's stain. § This feature is not always visible. ¶ Schizonts are trapped in viscera and usually are not present in peripheral blood.

Treatment

• Antimalarial drugs chosen by known resistance patterns of strain in area of acquisition

Malaria is particularly dangerous in children < 5 yr (mortality is highest in those < 2 yr), pregnant women, and previously unexposed visitors to endemic areas. In case of a febrile illness during travel in an endemic region, prompt professional medical evaluation is essential; when this is not possible, self-medication with atovaquone-proguanil Some Trade Names

can be used pending evaluation.

If P. falciparum is suspected, therapy should be initiated immediately, even if the initial smear is negative. P. falciparum and, more recently, P. vivax have become increasingly resistant to antimalarial drugs. Recommended dosages of antimalarial drugs are listed in Table 2: Extraintestinal Protozoa: Treatment of Malaria and Table 3: Extraintestinal Protozoa: Prevention of Malaria. Common adverse effects and contraindications are listed in Table 4: Extraintestinal Protozoa: Adverse Reactions and Contraindications of Antimalarial Drugs.

Table 2
Treatment of Malaria This table is presented as a PDF and requires the free Adobe PDF reader. Get Adobe Reader

Table 3
Prevention of Malaria Preferences Druga (Oral) Adult Dosage Pediatric Dosage Chloroquine-sensitive areas Drug of choice Chloroquine Some Trade Names ARALEN Click for Drug Monograph phosphateb 500 mg (300 mg base) po once/wk 5 mg/kg base (up to 300 mg base) po once/wk Chloroquine-resistant areas Drug of choice Atovaquone/proguanil Some Trade Names MALARONE Click for Drug Monograph c 1 adult tablet once/day 5–8 kg: 1/2 pediatric tablet once/day 9–10 kg: 3/4 pediatric tablet once/day 11–20 kg: 1 pediatric tablet once/day 21–30 kg: 2 pediatric tablets once/day 31–40 kg: 3 pediatric tablets once/day > 40 kg: 1 adult tablet once/day Or Doxycycline Some Trade Names PERIOSTAT VIBRAMYCIN Click for Drug Monograph d 100 mg po once/day 2 mg/kg (up to 100 mg) po once/day Or Mefloquine Some Trade Names LARIAM Click for Drug Monograph b,e 250 mg po once/wk 5–10 kg: 1/8 tablet once/wk 11–20 kg: 1/4 tablet once/wk 21–30 kg: 1/2 tablet once/wk 31–45 kg: 3/4 tablet once/wk > 45 kg: 1 tablet once/wk Alternative Primaquine Some Trade Names No US trade name Click for Drug Monograph f 30 mg base po once/day 0.6 mg/kg base po once/day aSee Table 4: Extraintestinal Protozoa: Adverse Reactions and Contraindications of Antimalarial Drugs for adverse reactions and contraindications. bThe drug is begun 1 to 2 wk before travel and continued weekly during the stay and for 4 wk after leaving. c Atovaquone/proguanil Some Trade Names MALARONE Click for Drug Monograph is available as a fixed-dose combination tablet: adult tablets (250 mg atovaquone Some Trade Names MEPRON Click for Drug Monograph /100 mg proguanil) and pediatric tablets (62.5 mg atovaquone Some Trade Names MEPRON Click for Drug Monograph /25 mg proguanil). To enhance absorption, patients should take the drug with food or a milky drink. Atovaquone/proguanil Some Trade Names MALARONE Click for Drug Monograph is begun 1 to 2 days before travel and continued during the stay and for 1 wk after leaving. dThe drug is begun 1 to 2 days before travel and continued during the stay and for 4 wk after leaving. Use of tetracyclines is contraindicated in pregnancy and in children < 8 yr. eResistance to mefloquine Some Trade Names LARIAM Click for Drug Monograph has been reported in some areas (eg, Myanmar borders with Thailand, China, and Laos; Thailand-Cambodia border southern Vietnam; in these areas, atovaquone-proguanil Some Trade Names or doxycycline Some Trade Names PERIOSTAT VIBRAMYCIN Click for Drug Monograph should be used for prophylaxis. Many experts no longer recommend mefloquine Some Trade Names LARIAM Click for Drug Monograph because of its potential for serious neuropsychiatric effects. Mefloquine Some Trade Names LARIAM Click for Drug Monograph has not been approved for use during pregnancy. The drug is not recommended for patients who have conduction disorder, active depression, or a history of seizures or psychosis; if patients have a psychiatric disorder, the drug should be used cautiously. f Primaquine Some Trade Names No US trade name Click for Drug Monograph begun 1 day before travel and continued until 3 to 7 days after leaving provides effective prophylaxis against chloroquine Some Trade Names ARALEN Click for Drug Monograph -resistant P. falciparum. In some studies, primaquine Some Trade Names No US trade name Click for Drug Monograph was less effective against P. vivax. Taking the drug with food can reduce the severity of nausea and abdominal pain. Primaquine Some Trade Names No US trade name Click for Drug Monograph is contraindicated during pregnancy. Adapted with permission from The Medical Letter on Drugs and Therapeutics. The Medical Letter, Inc., August 2004 and updated based on Treatment Guidelines from The Medical Letter 5 (supplement): e6–e8, 2007; last modification July 2009.

Table 4
Adverse Reactions and Contraindications of Antimalarial Drugs Drug Adverse Reactions Contraindications Artemether/lumefantrine Headache, anorexia, dizziness, asthenia (usually mild) With lumefantrine, prolonged QT interval Pregnancy category C (the drug should be used only if potential benefit justifies potential risk to fetus) Artesunate As with artemether As with artemether Atovaquone/proguanil Some Trade Names MALARONE Click for Drug Monograph GI disturbances, headache, dizziness, rash, pruritus Pregnancy category C (the drug should be used only if potential benefit justifies potential risk to fetus) Hypersensitivity, breastfeeding*, severe renal impairment (creatinine clearance < 30 mL/min) Chloroquine Some Trade Names ARALEN Click for Drug Monograph phosphate Chloroquine Some Trade Names ARALEN Click for Drug Monograph HCl Hydroxychloroquine Some Trade Names PLAQUENIL Click for Drug Monograph sulfate GI disturbances, headaches, dizziness, blurred vision, rashes or pruritus, exacerbation of psoriasis, blood dyscrasias, alopecia, ECG changes, retinopathy, psychosis (rare) Hypersensitivity, retinal or visual field changes Clindamycin Some Trade Names CLEOCIN Click for Drug Monograph Hypotension, bone marrow toxicity, renal dysfunction, rashes, jaundice, tinnitus, Clostridium difficile infection (pseudomembranous colitis) Hypersensitivity Doxycycline Some Trade Names PERIOSTAT VIBRAMYCIN Click for Drug Monograph GI upset, photosensitivity, vaginal candidiasis, C. difficile infection (pseudomembranous colitis), erosive esophagitis Pregnancy, children ≤ 8 yr Halofantrine Some Trade Names HALFAN Prolongation of PR and QT intervals, cardiac arrhythmia, hypotension, GI disturbances, dizziness, mental changes, seizures, sudden death Cardiac conduction defects, familial QT prolongation, drugs that affect QT interval, hypersensitivity Pregnancy category C Mefloquine Some Trade Names LARIAM Click for Drug Monograph Bad dreams, neuropsychiatric symptoms, dizziness, vertigo, confusion, psychosis, seizures, sinus bradycardia, GI disturbances Hypersensitivity, history of seizures or psychiatric disorders, cardiac conduction disturbances or arrhythmia, co-administration of drugs that may prolong cardiac conduction (eg, β-blockers, Ca channel blockers, quinine Some Trade Names QUALAQUIN Click for Drug Monograph , quinidine Some Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph , halofantrine Some Trade Names HALFAN ), occupations requiring fine coordination and spatial discrimination in which vertigo may be life threatening, 1st trimester of pregnancy Quinine Some Trade Names QUALAQUIN Click for Drug Monograph sulfate Quinine Some Trade Names QUALAQUIN Click for Drug Monograph dihydrochloride GI disturbances, tinnitus, visual disturbances, allergic reactions, mental changes, arrhythmias, cardiotoxicity Hypersensitivity, G6PD deficiency, optic neuritis, tinnitus, pregnancy (relative contraindication), past adverse quinine Some Trade Names QUALAQUIN Click for Drug Monograph reaction (continuous ECG, BP [when drug is given IV], and glucose monitoring recommended) Quinidine Some Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph gluconate Arrhythmias, prolonged Q-Tc interval, hypotension Hypersensitivity, thrombocytopenia (continuous ECG, BP, and glucose monitoring recommended) Primaquine Some Trade Names No US trade name Click for Drug Monograph phosphate Severe intravascular hemolysis in people with G6PD deficiency, GI disturbances, leukopenia, methemoglobinuria Concomitant quinacrine, potentially hemolytic or bone marrow suppressing agents, G6PD deficiency, pregnancy (because the G6PD status of the fetus is unknown) Pyrimethamine Some Trade Names DARAPRIM Click for Drug Monograph -sulfadoxine Erythema multiforme, Stevens-Johnson syndrome, toxic epidermal neurolysis, urticaria, exfoliative dermatitis, serum sickness, hepatitis, seizures, mental changes, GI disturbances, stomatitis, pancreatitis, bone marrow toxicity, hemolysis, fever, nephrosis Hypersensitivity, folate deficiency anemia, infants ≤ 2 mo, pregnancy, breastfeeding * Proguanil is excreted in human milk; whether atovaquone Some Trade Names MEPRON Click for Drug Monograph is excreted in human milk is unknown. Safety and effectiveness of these drugs have not been established in children who weigh < 5 kg.

Treatment of the acute attack: Chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
is the drug of choice against P. malariae, P. ovale, and chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-sensitive P. falciparum and P. vivax. Chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
resistance is common among P. falciparum strains throughout endemic areas, with the exception of Central America north and west of the Panama Canal, Mexico, Haiti, the Dominican Republic, Paraguay, northern Argentina, North and South Korea, Georgia, Armenia, most of rural China, and some Middle Eastern countries; current location of resistant strains is available from the CDC at http://cdc-malaria.ncsa.uiuc.edu/. Chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
resistance is not always complete, but chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
should be used only for malaria acquired in areas where Plasmodium sp are known to be sensitive.

Artemisinin derivatives, particularly artemether and artesunate and also the new synthetic arteether, are used globally for the treatment of acute malaria in regions where chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-resistance is present. They are usually used in combination with a second drug (eg, lumefantrine); in areas where artemisinins were used as monotherapy for many years (China, Viet Nam, along the Thai-Cambodian border), resistance to artemisinins has been confirmed in P. falciparum. Artemisinin derivatives act more rapidly than other drugs and are well tolerated. Although artemisinins are embryotoxic and associated with a low incidence of teratogenicity in animals, they have not been reported to cause birth defects in humans. They are a pregnancy category C drug.

Uncomplicated chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-resistant malaria can also be treated with atovaquone-proguanil Some Trade Names

. Quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
plus doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
has long been used for uncomplicated and complicated chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-resistant infections, but quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
is associated with frequent side effects. If the patient is pregnant, quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
plus clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
can be used. Mefloquine Some Trade Names
LARIAM
Click for Drug Monograph
is another option, but adverse effects are common.

IV quinidine Some Trade Names
CARDIOQUIN
QUINAGLUTE
Click for Drug Monograph
, quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
dihydrochloride, or artesunate (available from the CDC) is used in patients unable to take oral drugs. If quinidine Some Trade Names
CARDIOQUIN
QUINAGLUTE
Click for Drug Monograph
or quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
is used, hemodynamic and ECG monitoring is required; the infusion is slowed or temporarily suspended if the QT interval is > 0.6 sec or the QRS widens > 25% beyond baseline. Parenteral therapy should be continued until oral drug is tolerated. It is customary to supplement quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
and quinidine Some Trade Names
CARDIOQUIN
QUINAGLUTE
Click for Drug Monograph
with doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
or clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
to prevent late recrudescences. These antibiotics act too slowly to be used alone for the treatment of acute malaria. Halofantrine Some Trade Names
HALFAN

(not available in the US) may prolong the QT interval and has been associated with sudden death.

Patients with falciparum malaria must be monitored closely for hypoglycemia and proper hydration. Exchange transfusions have been used in some patients with high parasitemia to remove infected RBCs, but there is no uniform agreement on this approach. After successful treatment, patients usually improve in 24 to 48 h, but symptoms can persist for 5 days with P. falciparum.

Chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-resistant P. vivax is common in Papua New Guinea and Indonesia. It is treated with quinine Some Trade Names
QUALAQUIN
Click for Drug Monograph
plus doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
or with mefloquine Some Trade Names
LARIAM
Click for Drug Monograph
.

Curative therapy for hypnozoites: The hypnozoite stage must be eliminated from the liver with primaquine Some Trade Names
No US trade name
Click for Drug Monograph
to prevent relapses of P. vivax or P. ovale malaria. Primaquine Some Trade Names
No US trade name
Click for Drug Monograph
may be given simultaneously with chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
or afterward. Some P. vivax strains are less sensitive and require repeated treatment with higher doses. Primaquine Some Trade Names
No US trade name
Click for Drug Monograph
therapy is not necessary for P. falciparum or P. malariae because these Plasmodium sp do not have a persistent hepatic phase.

Prevention

Prophylactic antimalarial drugs and insect repellants reduce but do not eliminate risk of malaria. Vaccines are under development, but none is currently available.

Prophylaxis against mosquitoes includes using permethrin Some Trade Names
ELIMITE
NIX
RID SPRAY
Click for Drug Monograph
- or pyrethrum-containing residual insecticide sprays (which have prolonged duration of action) on clothing or in homes and outbuildings, placing screens on doors and windows, using mosquito netting (preferably impregnated with permethrin Some Trade Names
ELIMITE
NIX
RID SPRAY
Click for Drug Monograph
or pyrethrum) around beds, using mosquito repellents such as DEET (diethyltoluamide), and wearing protective clothing, especially between dusk and dawn, when Anopheles mosquitoes are active.

Chemoprophylaxis: Regimens and dosing vary by geographic location and patient characteristics (see Table 3: Extraintestinal Protozoa: Prevention of Malaria). Information for travelers is available from the CDC at http://www.cdc.gov/malaria/travel/index.htm.

If exposure to P. vivax or P. ovale is intense or prolonged or if the traveler was splenectomized, a 14-day prophylactic course of primaquine Some Trade Names
No US trade name
Click for Drug Monograph
phosphate on return helps reduce the risk of recurrence. The major adverse effect is hemolysis in people with G6PD deficiency. G6PD levels should be determined before the drug is used.

Malaria during pregnancy poses a serious threat to both mother and fetus. Chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
can be used in areas where Plasmodium sp are susceptible. In general, pregnant women should avoid travel to chloroquine Some Trade Names
ARALEN
Click for Drug Monograph
-resistant areas. The safety of mefloquine Some Trade Names
LARIAM
Click for Drug Monograph
during pregnancy has not been documented, but limited experience suggests that it may be used when the benefits are judged to outweigh the risks. Doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
, atovaquone-proguanil Some Trade Names

, and primaquine Some Trade Names
No US trade name
Click for Drug Monograph
should not be used during pregnancy. Artemisinins have short half-lives and are not useful for prophylaxis.

Last full review/revision December 2009 by Richard D. Pearson, MD

Content last modified December 2009