AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
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INTRODUCTION

Section 2 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Malaria is the most deadly vector borne disease in the world. Although devastating around many parts of the world, only about 800 cases (nearly all foreign-originating) are diagnosed in the US each year.

Four parasitic protozoa of the genus Plasmodium (Plasmodium ovale, Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum) cause human malaria. Of the 4 species, P falciparum causes the most severe morbidity and mortality.

All 4 species are transmitted through the bite of an infected female Anopheles species mosquito. Malaria also can be transmitted via a blood transfusion or congenitally between mother and fetus, although these forms of infection are rare.

At risk for contraction of malaria are nonimmune persons living in or traveling to areas of Central and South America, Hispaniola, sub-Saharan Africa, the Indian subcontinent, Southeast Asia, the Middle East, and Oceania. Of these areas, sub-Saharan Africa has the highest occurrence of P falciparum transmission to travelers from the US. Malaria-carrying Anopheles species mosquitoes tend to bite only between dusk and dawn.

Pathophysiology

The vector, the Anopheles species mosquito, passes plasmodia, which is contained in its saliva, into its host while obtaining a blood meal. Plasmodia enter circulating erythrocytes (RBCs) and feed on the hemoglobin and other proteins within the cells. One brood of parasites becomes dominant and is responsible for the synchronous nature of the clinical symptoms of malaria.

This protozoan brood replicates inside the cell. This replication induces RBC cytolysis and causes the release of toxic metabolic byproducts into the bloodstream; therefore, the host experiences flulike symptoms. These symptoms include chills, headache, myalgias, and malaise, and they occur in a cyclic pattern. The parasite also may cause jaundice and anemia. P falciparum, the most malignant of the 4 species of Plasmodium, may induce kidney failure, coma, and death. Malaria-induced death is preventable if the proper treatment is sought and implemented.

P vivax and P ovale may produce a dormant form that persists in the liver of infected individuals and emerges at a later time. Therefore, infection by these species requires treatment to kill any dormant protozoan as well as the actively infecting organisms.

Malaria-causing Plasmodium species metabolize hemoglobin and other RBC proteins to create a toxic pigment termed hemozoin (see Picture 3). The parasites derive their energy solely from glucose, and they metabolize it 70 times faster than the RBCs they inhabit, thereby causing hypoglycemia and lactic acidosis. The plasmodia also cause lysis of infected and uninfected RBCs, suppression of hematopoiesis, and increased clearance of RBCs by the spleen, which leads to anemia. Over time, malaria infection also causes thrombocytopenia and hepatosplenomegaly.

The morbidity and mortality caused by P falciparum are increased greatly over that caused by other Plasmodium species because of the increased parasitemia of P falciparum and its ability to cytoadhere. When an RBC becomes infected with P falciparum, it produces proteinaceous knobs that bind to endothelial cells. The adherence of these infected RBCs causes them to clump together in the blood vessels in many areas of the body, leading to much of the damage incurred by the parasite.

Frequency

United States

Although cases of malaria occur in some areas of the US in people who have not traveled outside the country and have no other known risk factors, malaria ceased to be an endemic disease to the country in the 1950s. Most cases of malaria reported by those living in the US are associated with recent travel to an endemic area.

International

Malaria remains an enormous international medical issue, with 300-500 million cases annually reported. It is most prevalent in rural tropical areas below elevations of 1000 m (3282 ft) but is not limited to these climates. P falciparum is found mostly in the tropics and, along with P vivax, accounts for 95% of malarial infections diagnosed worldwide. P vivax is distributed more widely than P falciparum, but it causes less morbidity and mortality.

Mortality/Morbidity

• Internationally, 3-3.5 million deaths occur annually. Of these deaths, the overwhelming majority is among children aged 5 years or younger, and 90% of the deaths each year are in rural sub-Saharan Africa.
• These deaths are unnecessary, since malaria is preventable and treatable. However, the lack of prevention and treatment due to poverty, war, and other economic and social instabilities in endemic areas results in millions of deaths each year.

Sex

Males and females are affected equally.

Age

• All ages are affected by malaria.
• Mortality is very high in children younger than 5 years.

CLINICAL

Section 3 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

Most patients live in or recently have traveled to an endemic area; however, a few cases are reported each year with no history of such travel.

• Determine the patient's immune status, age, allergies, other medical conditions, other medications, and pregnancy status.
• The patient usually remains asymptomatic for a week or more after the infecting mosquito bite.
• Clinical symptoms include the following:
• • Cough
  • Fatigue
  • Malaise
  • Shaking chills
  • Arthralgia
  • Myalgia
  • Paroxysm of fever, shaking chills, and sweats
• The classic paroxysm begins with a period of shivering and chills, which lasts for approximately 1-2 hours, and is followed by a high fever. Finally, the patient experiences excessive diaphoresis, and the body temperature of the patient drops to normal or below normal.
• Many patients, particularly early in infection, do not present the classic paroxysm but may have several small fever spikes a day.
• Maintain a high index of suspicion for malaria in any patient exhibiting any malarial symptoms and having a history of travel to endemic areas.
• Less common symptoms include the following:
• • Anorexia and lethargy
  • Nausea and vomiting
  • Diarrhea
  • Headache
  • Jaundice

Physical

• Physical signs that may be noted with malaria include the following:
• • Tachycardia
  • Fever
  • Hypotension
  • Signs of anemia
  • Splenomegaly
  • Icterus

Causes

• Malaria most often is caused by the bite of a female Anopheles species mosquito that is infected with 1 of the 4 species of the protozoan genus Plasmodium.
• • P vivax: If this kind of infection goes untreated, it usually lasts for 2-3 months with diminishing frequency and intensity of paroxysms. Of patients infected with P vivax, 50% experience a relapse in a few weeks to 5 years after the initial illness.
  • P ovale: These infections are similar to P vivax infections, although they are usually less severe. A P ovale infection often resolves without treatment.
  • P malariae: Those infected with this species of Plasmodium remain asymptomatic for a much longer period of time than those infected with P vivax or P ovale. Recrudescence is common in those infected with P malariae. It often is associated with a nephrotic syndrome, possibly resulting from deposition of antibody-antigen complex upon the glomeruli.
  • P falciparum: The most malignant form of malaria is caused by this species. Infection with P falciparum is not limited to RBCs of a particular age and, hence, represents the highest level of parasitemia among the 4 Plasmodium species. This species also causes vascular obstruction due to its ability to adhere to endothelial cell walls. This property leads to most complications of P falciparum infection. P falciparum can cause cerebral malaria, pulmonary edema, rapidly developing anemia, and renal problems.
• Other less common routes of infection are through blood transfusion and maternal-fetal transmission.

DIFFERENTIALS

Section 4 of 11  

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Other Problems to be Considered

African trypanosomiasis
Amebiasis and amebic liver abscess
Brucellosis
Cholera
Collagen vascular disease
Enteric fever
Epidemic or louse-borne typhus
Food-borne illness or toxin
Hodgkin disease
Relapsing fever
Poliomyelitis
Schistosomiasis (acute Katayama fever)
Seizure disorder

WORKUP

Section 5 of 11  

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Lab Studies

• Helpful studies include a CBC, electrolyte panel, renal function tests, pregnancy test, urinalysis, free serum haptoglobin, urine and blood cultures, and thick and thin blood smears.
• Laboratory diagnosis in the ED may be limited in hospitals that do not have personnel who are well acquainted with malaria or special tests for rapid detection of the disease.

Imaging Studies

• A chest x-ray may be helpful if respiratory symptoms are present.
• If CNS symptoms are present, a CT scan of the head may be ordered once the patient is stable to evaluate evidence of cerebral edema or hemorrhage.

Other Tests

• Microhematocrit centrifugation
• • Using this method with the CBC tube is a more sensitive method of detection of malaria infection.
  • However, microhematocrit centrifugation does not allow the identification of the species of Plasmodium. To determine that species, a peripheral blood smear must be examined.
• Giemsa-stained thick and thin peripheral blood smears
• • These smears are the criterion standard for malaria detection and should be sent to the laboratory immediately, since malaria is a potentially life-threatening infection.
  • When reading the smear, 200-300 oil-immersion fields should be examined (more if the patient recently has taken prophylactic medication, because this temporarily may decrease parasitemia).
  • One negative smear does not exclude malaria as a diagnosis; several more smears should be examined over a 36-hour period.
• Fluorescent dyes/ultraviolet indicator tests: Several different dyes allow laboratory results to be obtained more quickly. These methods require the use of a fluorescent microscope (QBC II System, Becton-Dickinson's Quantitative Buffy Coat [QBC] method).
• Polymerase chain reaction
• • Polymerase chain reaction (PCR) is a very specific and sensitive test for determining if the species of Plasmodium are present in the blood of an infected individual.
  • PCR is also very effective at detecting the Plasmodium species present in patients with parasitemias as low as 10 parasites/mL of blood.
• Rapid diagnostic tests (RDTs): ParaSight F, ICT-Malaria Pf, OptiMALr, and Kat-Quick kits (dipstick tests)
• • These tests are useful in detecting only P falciparum infections. It is based on antibody recognition of the HRP-2 antigen of P falciparum and, in most cases, it has been found to be as specific as microscopy studies. A false-positive result may occur up to 2 weeks or more after treatment due to persistence of circulating antigens.
  • It often is able to detect P falciparum in parasitemias that are below the threshold of reliable microscopic species identification.
  • The dipstick test is not as effective when parasite levels are below 100 parasites/mL of blood, and the test rarely is negative in those with high parasitemias. For these reasons, always confirm ParaSight F test results with a second type of screening test.
  • RDTs may not be available in the US due to lack of FDA approval. The World Health Organization's Regional Office for the Western Pacific (WHO/WPRO) provides technical information, including a list of commercially available malaria RDTs, at Malaria Rapid Diagnostic Tests.

TREATMENT

Section 6 of 11  

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• Medication
• Follow-up
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Emergency Department Care

• Assess airway, breathing, and circulation; intervene as necessary.
• If evidence of life-threatening hemolytic anemia is determined, establish large-bore intravenous (IV) lines, initiate fluid resuscitation, and administer transfusion of type-specific packed RBCs.
• Consider exchange transfusion for life-threatening complications.
• Monitor and treat hypoglycemia, as needed.
• Search for any signs of microvascular malarial complications.
• Laboratory analysis is helpful, although it is not always readily available to determine Plasmodium species, level of drug resistance, and degree of parasitemia. Obtain complete history for the laboratory.
• General hospital admission guidelines are as follows:
• • Patients with suspected or confirmed P falciparum infection
  • Children
  • Pregnant women
  • Immunodeficient individuals
• Intensive care unit admission guidelines are as follows:
• • Immediate life-threatening complications present, such as coagulopathy or end organ failure
  • Presence of signs and symptoms consistent with cerebral malaria (eg, altered mental status, repeated seizures, coma)
  • Patients who are nonimmune with a P falciparum parasitemia greater than 2% or who are semi-immune with a P falciparum parasitemia greater than 5%
  • Presence of any other severe malarial complications
• A reliable, semi-immune, adult patient with a P vivax, P ovale, or P malariae infection may be treated on an outpatient basis. Those treated as outpatients should have adequate follow-up care, including daily blood smears to confirm that the treatment is effective in decreasing parasitemia.
• If the infection is caused by an unidentified species or by mixed species, treat it as if it were caused by P falciparum. In the absence of known drug sensitivities, assume that the Plasmodium species in question is chloroquine resistant. If Southeast Asia is the origin of the infection, then assume mefloquine resistance.
• If a patient is diagnosed with P falciparum malaria with a parasitemia greater than 10% or if the patient is experiencing life-threatening complications (ie, coma, respiratory failure, coagulopathy, fulminant kidney failure), then investigate exchange transfusion as a treatment option. If transfusion is undertaken, it should continue until the parasitemia falls below 5%.
• Administer parenteral quinidine, quinine, or artemisinin therapy in conjunction with exchange transfusion to eradicate the protozoan from the blood stream.

Consultations

It is recommended that the emergency physician contact an infectious disease clinician or the pathologist when confronted with a possible case of malaria based upon history and physical examination to ensure proper identification and diagnosis.

• To aid in identification of the species of Plasmodium, also notify the pathologist of patient information, including the following:
• • Determine where the patient has traveled and when the patient returned home.
  • Determine if the patient has been diagnosed with malaria ever before. If so, find out which species of Plasmodium caused the previous infection.
  • Determine what medication or prophylaxis the patient has taken, and find out when the last dose was administered.
  • Determine if the patient has a history of blood transfusion or of nonsterile needle usage.
  • Identify the date and time that the patient's blood sample was drawn and determine what condition the patient was in at that time (eg, patient was symptomatic, any periodicity of symptoms).

MEDICATION

Section 7 of 11  

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Malaria treatment is not always straightforward and may be complex. Contacting the CDC for the latest treatment guidelines and drug regimens is advised. Not all recommended treatment regimens or drugs are included below. Treatment in pregnancy and complicated malaria requires specialized drug regimens. Consult the CDC as below.

Treatment regimens are dependent on the geographic derivation of infection.

Antipyretics, such as acetaminophen or NSAIDs, are indicated to reduce the level of discomfort caused by the infection and to reduce fever. NSAIDs should be used with caution if bleeding disorder or hemolysis is suspected.

For the most recent CDC recommendations concerning malaria treatment, call the CDC Malaria Hotline at (770) 488-7788 (M-F, 8 am-4:30 pm, eastern time). For emergency consultation after hours, call (770) 488-7100 and request to speak with a CDC Malaria Branch clinician.

Antimalarial drugs have a rich history, since malaria was possibly the first human infection to be treated pharmacologically. The Chinese used an extract from the sweet wormwood tree, while Peruvians used an extract from the bark of the cinchona tree. The active ingredient in these medications turned out to be artemisinin and quinine, respectively, which now comprise 2 of the 4 drug classes used to treat malaria. The 4 classes include the quinoline-related compounds, antifolates, artemisinin derivatives, and the antimicrobials.

No one drug that can eradicate all forms of the parasite's life cycle has been discovered or manufactured yet. Therefore, one or more classes of drugs often are given at the same time to combat malarial infection synergistically.

Beware of counterfeit antimalarial drugs being taken by patients that may have been purchased overseas or via the internet. They may not contain any active ingredients at all.

Drug Category: Antiprotozoal

Chloroquine remains the DOC if the patient is infected with a nonresistant strain of Plasmodium species. For chloroquine-resistant strains, a form of quinine is the drug next in line.

Drug Name	Clindamycin (Cleocin)
Description	Lincosamide useful as treatment against serious skin and soft tissue infections caused by most staphylococci strains. Also effective against aerobic and anaerobic streptococci, except enterococci. Inhibits bacterial protein synthesis by inhibiting peptide chain initiation at the bacterial ribosome where it preferentially binds to the 50S ribosomal subunit, causing bacterial growth inhibition.
Adult Dose	20 mg base/kg/d PO divided tid for 7 d
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis by allowing overgrowth of Clostridium difficile

Drug Name	Doxycycline (Vibramycin, Vibra-Tabs, Doryx)
Description	Inhibits protein synthesis and thus bacterial growth by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	100 mg PO bid for 7d
Pediatric Dose	<8 years: Not recommended unless treatment benefit outweighs risks (consult CDC) >8 years: 4 mg/kg/d PO divided bid for 7d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Name	Primaquine
Description	If uncomplicated infection is caused by P vivax or P ovale, important to treat patient with primaquine to prevent relapse. If species is initially unknown, then identified as P vivax or P ovale, primaquinephosphate treatment should be initiated. Binds to DNA and may disrupt parasite's mitochondria, causing major disruption in metabolic process of the parasite. Exoerythrocytic forms of the parasite are inhibited.
Adult Dose	30 mg base PO qd for 14 d
Pediatric Dose	0.5 mg base/kg PO qd for 14 d or 0.8 mg base/kg PO once/wk for 14 d
Contraindications	Documented hypersensitivity; drugs that suppress bone marrow
Interactions	Coadministration with quinacrine or other quinidinelike drugs may increase toxicity (see chloroquine)
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Caution in G-6-PD deficiency and those with tendency to develop granulocytopenia

Drug Name	Quinine sulfate (Formula Q)
Description	Used in chloroquine-resistant or unknown resistant infections. By increasing pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.
Adult Dose	542 mg base (=650 mg salt) PO tid for 3-7 d
Pediatric Dose	8.3 mg base/kg (=10 mg salt/kg) PO tid for 3-7 d
Contraindications	Documented hypersensitivity; those with optic neuritis, tinnitus, G-6-PD deficiency, or history of black water fever
Interactions	Aluminum-containing antacids may delay or decrease quinine bioavailability when administered concurrently; cimetidine increases quinine blood levels and creates potential for toxicity; rifamycins decrease quinine concentrations by increasing hepatic clearance of quinine (effect can persist for several days after discontinuing rifamycins); concurrent administration of acetazolamide or sodium bicarbonate may increase toxicity by increasing quinine blood levels; quinine may enhance action of warfarin and other oral anticoagulants by decreasing synthesis of vitamin K-dependent clotting factors; digoxin serum concentrations may increase when digoxin administered concurrently with quinine; important to monitor digoxin levels periodically; quinidine may decrease plasma cholinesterase activity, causing decrease in metabolism of succinylcholine
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in G-6-PD deficiency and tendency to develop granulocytopenia; prolonged treatment or overdosing with quinine may cause cinchonism; quinine has quinidinelike activity and thus can cause cardiac dysrhythmias due to sodium channel blocking activity

Drug Name	Quinidine gluconate
Description	Indicated for severe or complicated malaria and used in conjunction with one of the following: doxycycline, tetracycline, or clindamycin. Increases pH within intracellular organelles and possibly by intercalating into DNA of parasites, may inhibit growth of parasite.
Adult Dose	6.25 mg base/kg (=10 mg salt/kg) loading dose IV over 1-2 h, then 0.0125 mg base/kg/min (=0.02 mg salt/kg/min) continuous infusion for at least 24 h Length of treatment varies by geographic origin of infection (consult CDC)
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity; those with optic neuritis, tinnitus, G-6-PD deficiency, or history of cardiac dysrhythmias
Interactions	Delays absorption of digoxin; antagonizes effects of antimyasthenics; mefloquine increases risk of seizures
Pregnancy	X - Contraindicated in pregnancy
Precautions	Caution in G-6-PD deficiency and in patients with a tendency to develop granulocytopenia; prolonged treatment or overdosing with quinine may cause cinchonism; quinine has quinidinelike activity and can cause cardiac dysrhythmias via sodium channel blocking activity

Drug Name	Tetracycline (Achromycin V, Sumycin)
Description	Treats susceptible bacterial infections of both gram-positive and gram-negative organisms as well as infections caused by Mycoplasma, Chlamydia, and Rickettsia species. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunits of susceptible bacteria.
Adult Dose	250 mg PO qid for 7 d
Pediatric Dose	<8 years: Not recommended unless benefits outweigh risks (consult with CDC) >8 years: 25 mg/kg/d PO divided qid for 7 d
Contraindications	Documented hypersensitivity; severe hepatic dysfunction
Interactions	Bioavailability decreases with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy; tetracyclines can increase hypoprothrombinemic effects of anticoagulants
Pregnancy	D - Unsafe in pregnancy
Precautions	Photosensitivity may occur with prolonged exposure to sunlight or tanning equipment; reduce dose in renal impairment; consider drug serum level determinations in prolonged therapy; tetracycline use during tooth development (last one half of pregnancy through age 8 y) can cause permanent discoloration of teeth; Fanconilike syndrome may occur with outdated tetracyclines

Drug Category: Antimalarials

These agents inhibit growth of malarial pathogens by interfering with their stages of growth.

Drug Name	Artemether (Artenam)
Description	Used only for severe or complicated malaria. Not FDA approved.
Adult Dose	3.2 mg/kg IM (anterior thigh), then 1.6 mg/kg IM q24h until PO therapy is possible (never IV)
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Brainstem neurotoxicity and death in nonhuman primates have been reported; drug fever may occur

Drug Name	Artesunate
Description	Experimental drug.
Adult Dose	4 mg/kg PO qd for 3 d (total dose 12 mg/kg; 1 tab = 50 mg); for severe or complicated malaria, use 2.4 mg/kg IV load, then 1.2 mg/kg IV at 12 h and 24 h, then 1.2 mg/kg IV q24h until PO therapy is possible
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Brainstem neurotoxicity and death in nonhuman primates have been reported; drug fever may occur

FOLLOW-UP

Section 8 of 11  

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• Follow-up
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Further Inpatient Care

• Perform thick and thin blood smears every 12 hours until parasitemia falls below 1% to ensure that the therapy instituted is clearing the infection.
• If parasitemia does not fall by 75% within 48 hours or if the blood is not cleared of parasites after 7 days, immediately initiate a different therapeutic regimen.
• Consult CDC in all cases.

Deterrence/Prevention

• Avoid endemic regions.
• Take the proper prophylactic drugs at proper intervals if traveling to endemic regions.
• Use topical insect repellent (30-35% diethyltoluamide [DEET]), especially from dusk to dawn.
• Wear long-sleeved permethrin-coated clothing if not allergic to permethrin; spray under beds, chairs, tables, and along walls.
• Sleep under fine-nylon netting impregnated with permethrin.
• Avoid wearing perfumes and colognes.
• Seek out medical attention immediately upon contracting any tropical fever or flulike illness.
• Chemoprophylaxis is available in many different forms.
• • The drug of choice is determined by the destination of the traveler and any medical conditions the traveler may have that contraindicate the use of a specific drug.
  • Before traveling, people should consult their physician and consult the CDC's Malaria and Traveler's Web site to determine the most appropriate chemoprophylaxis.

Complications

• Most complications are caused by P falciparum, and they may include the following:
• • Coma (cerebral malaria)
    • Defined as coma, altered mental status, or multiple seizures with P falciparum in the blood, cerebral malaria is the most common cause of death in malaria patients. If untreated, this complication is lethal.
    • Even with treatment, 15% of children and 20% of adults who develop cerebral malaria die.
    • The symptoms of cerebral malaria are similar to those of toxic encephalopathy.
  • Seizures
  • Renal failure: As many as 30% of nonimmune adults infected with P falciparum suffer acute renal failure.
  • Hemoglobinuria (blackwater fever)
    • Blackwater fever is the passage of dark, Madeira-colored urine.
    • Hemolysis, hemoglobinemia, and the subsequent hemoglobinuria and hemozoinuria cause this condition.
  • Noncardiogenic pulmonary edema: This affliction is most common in pregnant women and results in death in 80% of patients.
  • Profound hypoglycemia: Hypoglycemia often occurs in young children and pregnant women. It often is difficult to diagnose since adrenergic signs are not always present and since stupor already may have occurred in the patient.
  • Lactic acidosis: This occurs when the microvasculature becomes clogged with P falciparum. If the venous lactate level reaches 45 mg/dL, a poor prognosis is very likely.
  • Hemolysis resulting in severe anemia and jaundice
  • Bleeding (coagulopathy)

Prognosis

• Most patients with uncomplicated malaria exhibit marked improvement within 48 hours after the initiation of treatment and are fever free after 96 hours.
• Only P falciparum infection carries a poor prognosis with a high mortality rate if untreated. However, if diagnosed early and treated appropriately, the prognosis is excellent.

Patient Education

• For excellent patient education resources, visit eMedicine's Blood and Lymphatic System Center. Also, see eMedicine's patient education article Malaria.

MISCELLANEOUS

Section 9 of 11  

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Medical/Legal Pitfalls

• The emergency physician should have a high index of suspicion if a history of fever is accompanied by suggestive symptoms in a patient with a history of travel to an endemic region.
• Failure to consider malaria in the differential of a febrile illness following such travel, even if seemingly temporally remote, can result in significant morbidity or mortality, especially in children and pregnant or immunocompromised patients.

Special Concerns

• Pregnancy
• • Pregnant women, especially primigravid women, are up to 10 times more likely to contract malaria than nongravid women. Gravid women who contract malaria also have a greater tendency to develop severe malaria.
  • Unlike malarial infection in nongravid individuals, pregnant women with P vivax are at high risk for severe malaria, and those with P falciparum have a greatly increased predisposition for severe malaria as well.
  • For these reasons, it is important that nonimmune pregnant women in endemic areas use the proper prophylaxis.
  • If a pregnant woman becomes infected, she should know that many of the antimalarial and antiprotozoal drugs used to treat malaria are safe for use during pregnancy for both the mother and the fetus. Therefore, they should be used, since the benefits of these drugs much outweigh the risks associated with leaving the infection untreated.
  • To obtain the latest CDC recommendations for malaria prophylaxis and treatment, call the CDC Malaria Hotline at (770) 488-7788 (M-F, 8 am-4:30 pm, eastern time). For emergency consultation after hours, call (770) 488-7100 and request to speak with a CDC Malaria Branch clinician.
• Pediatrics
• • In children, malaria has a shorter course, often rapidly progressing to severe malaria.
  • Children are more likely to present with hypoglycemia, seizures, severe anemia, and sudden death, but they are much less likely to develop renal failure, pulmonary edema, or jaundice.
  • Cerebral malaria results in neurologic sequelae in 9-26% of children, but of these sequelae, approximately one half completely resolve with time.
  • Most antimalarial drugs are very effective and safe in children, provided that the proper dosage is administered. Children commonly recover from malaria, even severe malaria, much faster than adults.

MULTIMEDIA

Section 10 of 11  

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• Multimedia
• References

Media file 1:  Malarial merozoites in the peripheral blood. Note that several of the merozoites have penetrated the erythrocyte membrane and entered the cell.
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Media type:  Photo

Media file 2:  This micrograph illustrates the trophozoite form, or immature-ring form, of the malarial parasite within peripheral erythrocytes. RBCs infected with trophozoites do not produce sequestrins and, therefore, are able to pass through the spleen.
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Media type:  Photo

Media file 3:  An erythrocyte filled with merozoites, which soon will rupture the cell and attempt to infect other RBCs. Notice the darkened central portion of the cell; this is hemozoin, or malaria pigment, which is a paracrystalline precipitate formed when heme polymerase reacts with the potentially toxic heme stored within the erythrocyte. When treated with chloroquine, the enzyme heme polymerase is inhibited, leading to the heme-induced demise of non–chloroquine-resistant merozoites.
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Media type:  Photo

Media file 4:  A mature schizont within an erythrocyte. These RBCs are sequestered in the spleen when malaria proteins, called sequestrins, on the RBC surface bind to endothelial cells within that organ. Sequestrins are only on the surfaces of erythrocytes that contain the schizont form of the parasite.
	View Full Size Image
Media type:  Photo

REFERENCES

Section 11 of 11

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Article Last Updated: May 2, 2006