Malaria

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Malaria

Malaria is a disease that is caused by a type of single-celled germ that can live inside a person’s body (parasite). The malaria parasite is from the Plasmodium family of parasites. This parasite can get into a person’s blood when he or she is bitten by a certain type of mosquito (Anopheles mosquito). These mosquitoes are most common in tropical areas of the world. Usually, they are not found in the United States.

If you are bitten by an infected mosquito, the parasites can travel through your blood to your liver. The parasites mature in your liver, then they are released into your blood. They can then invade red blood cells. The parasites multiply inside red blood cells and cause the cells to break open (rupture). This infects more red blood cells. Losing red blood cells may cause you to have a low red blood cell count (anemia).

8 Interesting Facts of Malaria

  1. Malaria is systemic febrile illness caused by infection with 1 of 5 Plasmodium species transmitted by the bite of certain Anopheles mosquitoes
  2. In the United States, malaria is almost always diagnosed only in travelers who have returned from endemic areas
  3. Travelers to endemic areas are prescribed prophylactic antimalarial drugs to begin before the trip to prevent infection
  4. Suspect malaria in any patient presenting with a febrile illness who has traveled to an endemic country—however briefly—or who has recently been in an international airport
  5. Malaria is diagnosed by suggestive history and physical examination that includes testing with either microscopy (thick and/or thin smear) or rapid diagnostic test 
  6. After confirmation of a Plasmodium infection, it is essential to identify species and quantify degree of parasitemia to select appropriate antimalarial treatment and to monitor therapeutic success 
  7. Treat patients who have nonsevere (uncomplicated) malaria with oral antimalarials. Aggressively treat patients who have severe (complicated) malaria in an ICU with parenteral antimalarial therapy
  8. If diagnosis of malaria is suspected and cannot be confirmed, or if diagnosis of malaria is confirmed but species determination is not possible, immediately initiate antimalarial treatment effective against chloroquine-resistant Plasmodium falciparum 

Pitfalls

  • All positive results from rapid diagnostic tests must be followed by microscopy to confirm species and estimate degree of parasitemia
  • In severe falciparum malaria, parasites often are not seen on a peripheral blood slide owing to sequestration in capillaries and venules
  • Parasitemia on a blood smear in a long-term resident of an area of high malarial transmission may not be indicative of an acute malarial illness because these patients often have substantial immunity. Thus, symptoms may be caused by another illness 
  • More than 1 Plasmodium species may be present (coinfection)
  • In endemic areas, coexisting bacterial sepsis in the context of malaria is not uncommon
  • Artesunate for injection was approved by the FDA in 2020 for treatment of severe malaria; IV quinidine has been discontinued and is no longer available 

What are the causes?

This condition is caused by a Plasmodium parasite. Four different types of the parasite can cause disease in humans.

Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, or Plasmodium knowlesi transmitted through the bite of the female anopheline mosquito

Most cases of malaria come from a mosquito bite, but the disease can also be passed from person to person through blood.

What increases the risk?

This condition is more likely to develop in:

  • People who live or travel in an area of the world where malaria is common.
  • People who receive donated blood (transfusion) or an organ transplant that is contaminated with infected blood cells.
  • People who share needles with a person who is infected with malaria.
  • Children.
  • Pregnant women.
  • People who have never been exposed to malaria parasites before. These people have not built up protection (immunity) against the parasites.

Risk factors and/or associations

Age
  • In travelers, occurs in all ages
  • In endemic areas, long-term residents develop partial immunity as they age, thus most clinical disease is in children
  • Children are more susceptible to severe malaria
Genetics
  • Certain genetic conditions are protective (increased survival advantage)
    • Sickle cell trait (heterozygous hemoglobin S)
    • G6PD deficiency
    • Thalassemia
    • HLA-Bw53
    • Southeast Asian ovalocytosis 
    • Absence of Duffy factor (glycophorin A)
Other risk factors/associations
  • Geographic exposure (travel or residence)
    • Haiti or Dominican Republic
    • Mexico
    • Central and South America (except Chile and Uruguay)
    • North Africa, except Egypt, Libya, Algeria, and Morocco
    • Sub-Saharan, Central, and West Africa
    • Indian subcontinent
    • Middle, Central, and Southeast Asia (including China)
    • Oceania and Papua New Guinea
  • United States
    • Malaria in the United States is almost always diagnosed only in travelers who have returned from endemic areas
    • Suspect malaria in any patient presenting with a febrile illness who has traveled to an endemic country—however briefly—or who has recently been in an international airport
  • Other exposures
    • Blood transfusion
    • Organ transplant
    • Contaminated needles

What are the symptoms of Malaria?

Symptoms can vary depending on which parasite caused the infection. Symptoms usually come and go or occur in cycles. The first symptoms of this condition usually start 10 days to 4 weeks after the mosquito bite. Symptoms for all types of malaria usually happen in this order:

  • Chills, along with headache, muscle aches, fatigue, and nausea.
  • Fever, along with hot and dry skin.
  • Drenching sweats, along with weakness and exhaustion.

Other symptoms include:

  • Diarrhea or bloody stools (feces).
  • Yellowing of the skin and the whites of the eyes (jaundice).
  • Enlarged spleen or liver.

Severe symptoms include:

  • Trouble breathing.
  • Seizures.
  • Loss of consciousness (coma).
  • Bleeding.

History

  • Determine geographic area of exposure and history of previous antimalarial treatment or prophylaxis
  • Symptoms are usually milder in long-term residents of an endemic area owing to partial immunity
  • Symptoms usually appear within 30 days of a visit to an endemic country, but they may occur months to (rarely) years later
  • Plasmodium vivax and Plasmodium ovale can cause late relapse symptoms (up to 4 years after initial infection) 
  • With acute infection, symptoms may be indistinguishable from other febrile illnesses. Once infection is established, symptoms may occur episodically, coinciding with the synchronous rupture of blood schizonts (infected hepatocytes)
  • Most common initial symptoms 
    • Plasmodium life cycle occurs every 24 hours (Plasmodium knowlesi); every 48 hours (Plasmodium vivax, Plasmodium ovale, and Plasmodium falciparum); or every 72 hours (Plasmodium malariae), causing symptoms that may be erratic or cyclic:
      • Fever 
      • Diaphoresis
      • Chills
      • Fatigue
      • Nausea
      • Vomiting
  • Other symptoms
    • Headache
    • Myalgias (especially backache)
    • Arthralgias
    • Abdominal pain
    • Diarrhea
  • Additional symptoms associated with severe (complicated) malaria
    • Systemic symptoms
      • Prostration
      • Respiratory distress
      • Red or black urine
      • Bloody diarrhea
    • Cerebral symptoms (cerebral malaria)
      • Confusion
      • Drowsiness
      • Seizures
    • Symptoms suggestive of pulmonary edema and cardiogenic shock
      • Dyspnea
      • Lightheadedness
      • Chest pain
  • Symptoms may progress rapidly from mild to severe in disease caused by Plasmodium falciparum or Plasmodium knowlesi

Physical examination

  • Fever, chills, and diaphoresis may be present; absence of fever on a given day does not rule out malaria
  • Blood pressure may be within reference range with nonsevere malaria; hypotension and shock are common with severe disease
  • Deep, rapid respirations may indicate metabolic acidosis with severe malaria
  • Lungs may be clear, or there may be rales and signs of pleural effusion from pulmonary edema with severe malaria
  • Tender hepatomegaly is common in severe malaria
  • Spleen may be enlarged and palpable in both acute and chronic infection
  • Jaundice is more common in adults than in children
  • Seizures, confusion, somnolence, obtundation, and coma, with or without focal neurologic deficits, can occur with cerebral malaria
    • Children 
      • Coma usually resolves within 1 or 2 days in treated patients
      • Seizures are common (30% of patients)
      • Decorticate/decerebrate posturing with opisthotonic rigidity is common
    • Adults 
      • Coma may last 2 to 4 days despite treatment
      • Seizures are less common (12% of patients)
      • Posturing is rare
      • Increasing blood pressure with dropping heart rate and/or papilledema suggests increased intracranial pressure
  • Stool may be guaiac-positive or grossly bloody with severe malaria

Clinical Clarification

  • Malaria is systemic febrile illness caused by infection with any 1 of 5 Plasmodium species transmitted by the bite of certain Anopheles mosquitoes

Classification

  • By causative species (each species name can also serve as an adjective; for example, vivax malaria is Plasmodium vivax malaria)
    • Plasmodium falciparum malaria 
      • Affected geographic areas: Haiti, Dominican Republic, parts of the Middle East, sub-Saharan Africa, Afghanistan and the Indian subcontinent, South America, Southeast Asia, Oceania, and Papua New Guinea
      • Includes both nonsevere and severe malaria
      • Nonrelapsing course
    • Plasmodium vivax malaria 
      • Affected geographic areas: Mexico, Central America, the Middle East, North Africa, Afghanistan and the Indian subcontinent, South America, Southeast Asia, Oceania, and Papua New Guinea
      • Usually nonsevere malaria
      • Relapsing course
    • Plasmodium malariae malaria 
      • Affected geographic areas: rare, but exists in most malarious areas, especially Central and West Africa
      • Usually nonsevere malaria
      • Nonrelapsing course, but may become low-grade chronic infection
    • Plasmodium ovale malaria 
      • Affected geographic areas: primarily Africa, where it causes a small percentage of cases; occasionally seen in some parts of Asia
      • Usually nonsevere malaria
      • Relapsing course
    • Plasmodium knowlesi malaria 
      • Affected geographic areas: where humans live in close contact with macaque monkeys, especially in Borneo and peninsular Malaysia; some cases have been reported elsewhere in Southeast Asia
      • Species primarily infects nonhuman primates, but human infections are now being reported
      • May be severe malaria
  • By severity: severe or nonsevere (ie, complicated or uncomplicated)
    • Severe (complicated) malaria
      • Defined as symptoms or signs of vital organ dysfunction in a patient with documented Plasmodium falciparum parasitemia. Patient must have 1 of the following criteria to constitute designation as severe according to WHO: 
        • Hypotension
          • Adults: systolic blood pressure less than 80 mm Hg
          • Children: systolic blood pressure less than 50 mm Hg
        • Generalized weakness or prostration
        • Impaired consciousness or coma
        • Repeated generalized seizures
        • Acute respiratory distress syndrome with pulmonary edema
        • Jaundice plus evidence of other organ dysfunction
        • Abnormal bleeding
        • Hemoglobinuria
        • Acute kidney injury (creatinine level higher than 3 mg/dL)
        • Metabolic acidosis (plasma bicarbonate level less than 15 mmol/L)
        • Serum lactate level higher than 5 mmol/L
        • Hypoglycemia (glucose level less than 40 mg/dL)
        • Severe normocytic anemia
          • Adults: hemoglobin less than 7 g/dL
          • Children: hemoglobin less than 5 g/dL
      • CDC criteria includes parasite density of 5% or greater 
    • Nonsevere (uncomplicated) malaria
      • Malaria without vital organ dysfunction

How is this diagnosed?

This condition may be diagnosed based on:

  • Your symptoms and medical history. Your health care provider may suspect malaria if you have been living or traveling in an area where the disease is common.
  • A physical exam.
  • Blood tests to confirm the diagnosis. These may include:
    • Examining a blood sample under a microscope. This is the most common way to diagnose malaria. Each type of parasite looks different under the microscope. Identifying which parasite is causing your infection will help your health care provider to determine which medicines will work best.
    • Complete blood count (CBC) to check for anemia.

Primary Diagnostic Tools

  • High index of suspicion based on travel history, symptoms, and physical examination
  • Attempt preliminary diagnosis immediately through microscopy of Giemsa-stained peripheral blood smear or rapid diagnostic test 
  • Immediately after preliminary diagnosis, seek laboratory confirmation of species by experienced microscopist or molecular testing and quantification of parasite density 
  • If malaria is suspected to be imported from Southeast Asia, Plasmodium knowlesi infection is possible; polymerase chain reaction is needed to confirm infection because this species cannot be otherwise differentiated 
    • Testing is obtained through a state health laboratory that will forward the specimen to the CDC
    • Instructions and more information are available through the malaria section of the CDC website 
  • If needed, health care providers can contact CDC for diagnostic assistance: 
    • CDC Malaria Hotline: 770-488-7788 or 855-856-4713 (Monday-Friday, 9 am-5 pm EST) 
    • Outside Malaria Hotline hours: 770-488-7100 (ask for a Malaria Branch clinician)
  • Parasitemia on a blood smear in a long-term resident of an area of high malarial transmission may not be indicative of an acute malarial illness because these patients often have substantial immunity. Thus, symptoms may be caused by another illness
  • Microscopy
    • Gold standard test 
    • If result is negative for malarial parasites, repeat test every 12 to 24 hours for a total of 3 sets of smears before determining the result as definitively negative 
    • Obtaining both a thick film and a thin film is ideal
      • Thick blood film (more sensitive than a thin film for detecting presence of malarial parasites)
        • 1 or 2 drops of blood are stirred in a circle on a glass slide, allowed to air dry, then stained with Giemsa stain
        • Parasites can be identified by recognizing their eosinophilic nucleus and basophilic cytoplasm
      • Thin blood film (better for species identification and quantification of parasitemia)
        • A small drop of blood is spread across a slide using the edge of a second slide, then fixed with methanol and stained with Giemsa stain
        • Erythrocytes remain intact; species and quantity of parasites can be determined
        • On a thin smear, the percentage of parasitemia is estimated by examining the erythrocyte monolayer under oil immersion at ×100 magnification
          • Slide is examined where the erythrocytes are approximately touching (about 400 erythrocytes per field). Estimate parasite density from the percentage of infected erythrocytes 
        • Size and shape of and Schüffner dots in erythrocyte cytoplasm help determine parasite species 
          • Plasmodium falciparum
            • Ring trophozoites characterized by fine, thin rings with little cytoplasm opposite the nucleus
            • Often greater than 5% infestation with parasitized erythrocytes of all ages
            • Double-chromatin dots present in rings, and rings adhere peripherally to inside of erythrocyte membrane
            • Multiple parasitized erythrocytes (more than 1 parasite in a single erythrocyte) may be seen
            • Schizonts and trophozoites are usually absent
            • Banana-shaped gametocytes may be present; presence of these and multiple ring forms within a single red cell are unique identifying features
          • Plasmodium vivax
            • Rings are thicker opposite the nucleus (signet-shaped)
            • Fewer erythrocytes are affected
            • Large ameboid trophozoites that deform the morphology of the erythrocyte are seen
            • Macrocytes (a reticulocyte equivalent) are more often affected, and all phases of parasite life cycle are present in the circulating erythrocytes
            • Schüffner dots (pink dots in cytoplasm of erythrocytes) are seen
          • Plasmodium malariae
            • Band forms present in older erythrocytes, and are a distinguishing feature
            • Low-grade parasitemia (rarely 1% of erythrocytes parasitized)
            • Rosette-shaped schizonts are present
          • Plasmodium ovale
            • Affects early erythrocytes (reticulocyte equivalents) with fringed edges
            • Schüffner dots may be seen
    • Rapid diagnostic tests 
      • 1 antigen-detection rapid diagnostic test is FDA-approved in the United States (BinaxNOW) for hospital, commercial, and reference laboratories
        • Requires a blood sample to be applied to a test card and left for 15 minutes
        • Pattern of banding in the test window indicates the presence of a Plasmodium species; Plasmodium falciparum can be identified, but other malarial species are not reliably speciated
        • Reliability is unclear for detection of Plasmodium malariae and Plasmodium ovale
        • Test may not be sensitive enough to detect low levels of parasitemia
        • Confirm all results with microscopy
    • Nonroutine, reference laboratory diagnostic testing by polymerase chain reaction is available for confirmation of species and for drug resistance testing. Contact the state health department or CDC 
    • Obtain CBC and coagulation studies initially with falciparum malaria or any severe malaria, and repeat them at intervals for severe disease. Hemoglobin level may decrease to less than 5 mg/dL; platelet count may decrease to fewer than 20,000 cells/µL 
    • Obtain electrolyte, phosphate, calcium, BUN, creatinine, and glucose levels at baseline with falciparum malaria or any severe malaria, and repeat the tests at intervals for severe disease 
    • Obtain hepatic transaminase levels at baseline with falciparum malaria or any severe malaria, and repeat them at intervals for severe disease 
    • Obtain urinalysis early with severe malaria and repeat it if color darkens, which is suggestive of hemoglobinuria
    • Obtain a blood type and screen (or crossmatch) for patients with severe malaria if there is any indication of bleeding (genitourinary or gastrointestinal)
    • Coexisting bacterial sepsis is not uncommon; culture blood and other relevant clinical specimens 
    • In the setting of possible cerebral malaria, if the diagnosis is uncertain, perform a lumbar puncture to obtain cerebrospinal fluid for analysis to rule out other central nervous system infections

Procedures

Lumbar puncture
General explanation
  • Insertion of a hollow-bore needle between the vertebral bodies into the subarachnoid space to obtain a specimen of cerebrospinal fluid or to measure opening pressure
Indication
  • Signs/symptoms of central nervous system disease (eg, fever, stiff neck, altered mental status) when bacterial meningitis may be part of the differential diagnosis
Contraindications
  • Uncontrolled coagulopathy
  • Skin infection at site of needle insertion
  • Patient at risk of brain herniation 
    • Best predictors of precipitating herniation (even with normal CT scan result) include:
      • Deteriorating level of consciousness (particularly to a Glasgow Coma Scale score of 11 or less)
      • Brainstem signs (eg, pupillary changes, abnormal posturing, irregular respirations)
      • Very recent seizure
Complications
  • Post–dural puncture headache
  • Back pain
  • Radicular injury
  • Infection
    • Epidural abscess
    • Meningitis
    • Diskitis
    • Vertebral osteomyelitis
  • Epidural hematoma
  • Cerebral herniation
  • Epidermoid tumor formation
Interpretation of results
  • Elevated WBC count, decreased glucose level, elevated protein level, and/or a positive Gram stain suggest bacterial meningitis

How is this treated?

This condition may be treated with many different medicines and combinations of medicines, often requiring treatment in the hospital. The best treatment for you will depend on:

  • Which type of parasite is causing your infection.
  • Whether various medicines are effective against it.
  • How you got the infection.
  • How severe your infection is.
  • Your age and your general health.

Treatment in Detail

Goals

  • Relieve symptoms
  • Eliminate parasitemia and prevent recurrent disease

Disposition

Admission criteria

All patients who have 1 or more of the following criteria are assumed to have severe (complicated) malaria and should be hospitalized 

  • Hypotension
    • Adults: systolic blood pressure lower than 80 mm Hg
    • Children: systolic blood pressure lower than 50 mm Hg
  • Generalized weakness or prostration
  • Impaired consciousness or coma
  • Repeated generalized seizures
  • Acute respiratory distress syndrome with pulmonary edema
  • Jaundice plus evidence of other organ dysfunction
  • Abnormal bleeding
  • Hemoglobinuria
  • Acute kidney injury (creatinine level higher than 3 mg/dL)
  • Metabolic acidosis (plasma bicarbonate level less than 15 mmol/L)
  • Serum lactate level higher than 5 mmol/L
  • Hypoglycemia (serum glucose level less than 40 mg/dL)
  • Severe normocytic anemia (hemoglobin level less than 7 g/dL in adults or less than 5 g/dL in children)
  • Parasite density of 5% or more 
Criteria for ICU admission
  • Patients with severe malaria, especially malaria caused by Plasmodium falciparum infection, should be admitted to ICU

Recommendations for specialist referral

  • In the United States, consult an infectious disease and/or tropical medicine specialist to assist in diagnosis and management of all malaria cases
  • Consult with an obstetrician/gynecologist when treating a pregnant patient who has malaria (but do not delay treatment)
  • Telephone consultation is available from the CDC malaria hotline 

Treatment Options

Select treatment according to Plasmodium species, geographic likelihood of medication resistance, previous use of antimalarial medication (eg, prophylaxis), and severity of infection 

If cannot identify species promptly, treat with regimen for Plasmodium falciparum, based on geographic likelihood of resistance to antimalarial agents 

Available antimalarial agents in United States include chloroquine, primaquine, mefloquine, doxycycline, quinine sulfate, atovaquone-proguanil, and the artemisinin derivatives, artemether (available as artemether-lumefantrine) and artesunate

  • Artesunate for injection was approved by the FDA in 2020 for treatment of severe malaria 

Drug selection

  • Determine Plasmodium species by examining a thin Giemsa-stained blood smear
  • Determine likely antimalarial drug resistance patterns, given the geographic area of transmission
    • Chloroquine
      • Areas with chloroquine-sensitive malaria include many Latin American countries where there is predominantly Plasmodium vivax malaria; Chloroquine-sensitive Plasmodium falciparum is present in the Caribbean and Central American countries west of the Panama Canal 
      • Chloroquine-resistant Plasmodium falciparum is found throughout the world except in the Caribbean and countries west of the Panama Canal 
      • Chloroquine-resistant Plasmodium falciparum is the most common type found in Africa, and it is found in combination with chloroquine-sensitive Plasmodium vivax malaria in South America and Asia 
      • Chloroquine resistance has been confirmed in Plasmodium vivax in Papua New Guinea and Indonesia 
    • Mefloquine
      • Plasmodium falciparum resistance has been reported in Southeast Asia, as follows: 
        • Along the borders of Thailand with Myanmar (Burma) and Cambodia
        • In western provinces of Cambodia
        • In eastern states of Myanmar on the border with China
        • Along the borders of Laos and Burma
        • In the adjacent parts of the Thailand-Cambodia border area
        • In southern Vietnam
    • Artemisinins
      • Suspected resistance of Plasmodium falciparum to artemisinins has now been identified in 4 countries in the greater Mekong subregion: Cambodia, Myanmar, Thailand, and Vietnam
    • Determine illness severity category (nonsevere/uncomplicated or severe/complicated)
      • Infection is classified as severe when 1 or more of the following clinical factors are present: 
        • Hypotension (systolic blood pressure less than 80 mm Hg in adults or less than 50 mm Hg in children)
        • Generalized weakness or prostration
        • Impaired consciousness or coma
        • Repeated generalized seizures
        • Acute respiratory distress syndrome with pulmonary edema
        • Jaundice plus evidence of other organ dysfunction
        • Abnormal bleeding
        • Hemoglobinuria
        • Acute kidney injury (creatinine level higher than 3 mg/dL)
        • Metabolic acidosis (plasma bicarbonate level less than 15 mmol/L)
        • Serum lactate level higher than 5 mmol/L
        • Hypoglycemia (glucose level less than 40 mg/dL)
        • Severe normocytic anemia (hemoglobin level less than 7 g/dL in adults or less than 5 g/dL in children)
        • Parasitemia of more than 5% 
  • Treat nonsevere (uncomplicated) malaria with oral antimalarials 
    • Nonsevere (uncomplicated) malaria caused by Plasmodium falciparum or an unidentified species
      • Acquired in areas without chloroquine resistance (ie, Central America west of the Panama Canal, Haiti, Dominican Republic, most of the Middle East)
        • First line treatment is oral chloroquine
        • Alternative treatment is hydroxychloroquine
        • If neither chloroquine nor hydroxychloroquine is readily available, treatment regimens used for chloroquine-resistant malaria may be used
      • Acquired in areas with chloroquine resistance
        • First line treatment of nonpregnant adult and pediatric patients involves either atovaquone-proguanil (fixed-dose combination) or artemether-lumefantrine (fixed-dose combination)
        • Alternative treatments for nonpregnant adults and children aged 8 years or older include the following:
          • Quinine sulfate plus either doxycycline or tetracycline
          • Quinine sulfate plus clindamycin
          • Mefloquine may be used as an alternative, but the adverse effect profile (psychiatric disturbances seen at treatment doses) limits its use
        • Alternative treatments for children younger than 8 years include the following:
          • Quinine given alone for a 7-day regimen
          • Quinine plus clindamycin
    • Nonsevere (uncomplicated) malaria caused by Plasmodium malariae or Plasmodium knowlesi is presumed to be chloroquine-sensitive (no widespread chloroquine resistance has been identified)
      • Chloroquine or hydroxychloroquine are first line treatments
      • Alternatives include treatment regimens used for chloroquine-resistant infections
        • Atovaquone-proguanil
        • Artemether-lumefantrine
        • Quinine sulfate plus doxycycline or tetracycline
        • Quinine sulfate plus clindamycin
        • Mefloquine, but adverse effect profile (psychiatric disturbances seen at treatment doses) limits its use
    • Nonsevere (uncomplicated) malaria caused by Plasmodium vivax and Plasmodium ovale, acquired in areas without chloroquine resistance
      • Chloroquine and hydroxychloroquine are first line therapies
      • Alternative therapies include:
        • Atovaquone-proguanil
        • Artemether-lumefantrine
        • Quinine sulfate plus doxycycline or tetracycline
        • Quinine sulfate plus clindamycin
        • Mefloquine, but adverse effect profile (psychiatric disturbances seen at treatment doses) limits its use
      • Nonsevere (uncomplicated) malaria caused by Plasmodium vivax, acquired in an area of possible chloroquine resistance (eg, Papua New Guinea, Indonesia)
        • Quinine sulfate plus 1 of the following: doxycycline (or tetracycline), atovaquone-proguanil, artemether-lumefantrine, or mefloquine
          • For children younger than 8 years, in whom doxycycline and tetracycline are relatively contraindicated owing to teeth staining, mefloquine is the recommended treatment
          • If mefloquine is not available or not tolerated and if the treatment benefits outweigh the risks, atovaquone-proguanil or artemether-lumefantrine is used instead
      • To prevent relapse caused by hypnozoites that remain dormant in the liver, combine either Plasmodium vivax or Plasmodium ovale treatment with either a single 300-mg oral dose of tafenoquine (in those aged 16 years and older) or a 14-day course of daily primaquine (30-mg base, oral dose) for all nonpregnant patients who have no contraindication
        • Screen for G6PD deficiency before starting treatment, which can cause hemolytic anemia in people with G6PD deficiency
        • For people with borderline G6PD deficiency or as an alternative regimen, may give primaquine at a 45-mg base dose orally 1 time per week for 8 weeks
        • Consult with an expert in infectious diseases and/or tropical medicine if this alternative regimen is considered in G6PD-deficient patients
        • Do not use tafenoquine for children younger than 16 years or for those with a history of a psychotic disorder
  • Treat severe Plasmodium falciparum malaria (or any severe malaria) by using supportive therapy, correcting metabolic disturbances, and promptly administering IV antimalarial drugs
    • Admit patient to ICU
    • Administer oxygen by nasal cannula or Venturi mask if patient is hypoxemic; use endotracheal intubation and mechanical ventilation if respiratory failure occurs as a complication of pulmonary edema or acute respiratory distress syndrome
    • Obtain IV access 
      • If patient is hemodynamically unstable, infuse IV fluids (5% dextrose/0.9% saline)
      • WHO guidelines advise against rapid fluid infusion, recommending 1 to 2 mL/kg for adults and 3 to 4 mL/kg for children
    • Correct hypoglycemia, if present
    • If seizures are present, treat with IV benzodiazepines; if condition is unresponsive to 2 doses, treat as status epilepticus with phenytoin 
    • Begin treatment of presumed falciparum malaria if suspected, even if parasitologic confirmation is not available (after making a blood smear for later diagnostic use) 
      • Artesunate for injection was approved by the FDA in 2020 to treatment severe malaria; IV quinidine has been discontinued and is no longer available 
      • Treat all patients who have severe malaria, regardless of infecting species, with IV artesunate 
        • Clinicians caring for patients with suspected severe malaria should call CDC to obtain IV artesunate:
          • CDC Malaria Hotline: 770-488-7788 or 855-856-4713 (Monday-Friday, 9 am-5 pm EST) 
          • Outside Malaria Hotline hours: 770-488-7100 (ask for a Malaria Branch clinician)
        • Consider treating the patient with an oral antimalarial while waiting for IV artesunate to arrive, or determine the most feasible route for patients unable to tolerate oral antimalarial administration. One of the following antimalarials can be administered:
          • Artemether-lumefantrine
          • Atovaquone-proguanil
          • Quinine
          • Mefloquine: owing to risk for severe neuropsychiatric adverse events at treatment doses, only use mefloquine if atovaquone-proguanil or quinine is not available and if treatment is judged to be needed before IV artesunate arrives
        • When IV artesunate arrives, discontinue the oral medication
        • After course of IV artesunate is completed, a follow-on drug must be administered. Options include:
          • Artemether-lumefantrine
          • Atovaquone-proguanil
          • Doxycycline
          • Mefloquine: owing to risk for severe neuropsychiatric adverse events at treatment doses, only use mefloquine if other options are not available
        • For those patients who still cannot tolerate oral medications after completing artesunate treatment, potential options (in consultation with CDC) include:
          • Continue IV artesunate, 1 dose daily not to exceed a total course of 7 days
          • Switch to IV doxycycline (7 days) or IV clindamycin (7 days)
    • Parasitemia percentage is monitored at 12-hour intervals to document response to the antimalarial therapy. Results of rapid tests remain positive for up to 4 weeks after clearance of the parasites, thus cannot be used for monitoring 
    • In severely ill patients, consider empiric antibiotic coverage until coexisting bacterial infection has been ruled out 

Drug therapy

  • Treatment
    • Chloroquine
      • Chloroquine Phosphate Oral tablet; Infants, Children, and Adolescents: 16.6 mg (10 mg base)/kg/dose [Max: 1,000 mg/dose (600 mg base/dose)] PO once, then 8.3 mg (5 mg base)/kg/dose [Max: 500 mg/dose (300 mg base/dose)] PO in 6 to 8 hours, then 8.3 mg (5 mg base)/kg/dose [Max: 500 mg/dose (300 mg base/dose)] PO once daily for 2 days.
      • Chloroquine Phosphate Oral tablet; Adults: 16.6 mg (10 mg base)/kg/dose [Max: 1,000 mg/dose (600 mg base/dose)] PO once, then 8.3 mg (5 mg base)/kg/dose [Max: 500 mg/dose (300 mg base/dose)] PO in 6 to 8 hours, then 8.3 mg (5 mg base)/kg/dose [Max: 500 mg/dose (300 mg base/dose)] PO once daily for 2 days.
    • Hydroxychloroquine
      • Hydroxychloroquine Sulfate Oral tablet; Infants, Children, and Adolescents: 13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after initial dose.
      • Hydroxychloroquine Sulfate Oral tablet; Adults: 13 mg (10 mg base)/kg/dose [Max: 800 mg (620 mg base)/dose] PO, then 6.5 mg (5 mg base)/kg/dose [Max: 400 mg (310 mg base)/dose] PO at 6, 24, and 48 hours after initial dose.
    • Quinine sulfate
      • For treatment of uncomplicated malaria due to Plasmodium falciparum or Plasmodium vivax
        • Quinine Sulfate Oral capsule; Children and Adolescents 1 to 15 years†: 10 mg/kg/dose (Max: 650 mg/dose) PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia.
        • Quinine Sulfate Oral capsule; Adolesents 16 to 17 years: 648 or 650 mg PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia.
        • Quinine Sulfate Oral capsule; Adults: 648 or 650 mg PO every 8 hours for 3 days, in general, or 7 days for Southeast Asia.
      • For treatment of severe malaria before availability of IV artesunate
        • Quinine Sulfate Oral capsule; Children and Adolescents: 10 mg/kg/dose (Max: 650 mg/dose) PO every 8 hours. Discontinue when IV artesunate therapy started.
        • Quinine Sulfate Oral capsule; Adults: 650 mg PO every 8 hours. Discontinue when IV artesunate therapy started.
    • Tetracycline
      • Tetracycline Hydrochloride Oral capsule; Children younger 1 to 7 years: 25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days.
      • Tetracycline Hydrochloride Oral capsule; Children and Adolescents 8 to 17 years: 25 mg/kg/day PO divided 4 times daily (Max: 250 mg/dose) for 7 days.
      • Tetracycline Hydrochloride Oral capsule; Adults: 250 mg PO 4 times daily for 7 days.
    • Doxycycline
      • Oral
        • For treatment of uncomplicated malaria due to Plasmodium falciparum or Plasmodium vivax
          • Doxycycline Calcium Oral suspension; Children 1 to 7 years: 2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days.
          • Doxycycline Monohydrate Oral capsule; Children and Adolescents 8 to 17 years: 2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days.
          • Doxycycline Monohydrate Oral capsule; Adults: 100 mg PO twice daily for 7 days.
        • For treatment of severe malaria after IV artesunate therapy is completed
          • Doxycycline Monohydrate Oral capsule; Children and Adolescents 8 to 17 years: 2.2 mg/kg/dose (Max: 100 mg/dose) PO twice daily for 7 days.
          • Doxycycline Monohydrate Oral capsule; Adults: 100 mg PO twice daily for 7 days.
      • IV
        • For treatment of severe malaria after IV artesunate therapy is completed
          • Doxycycline Hyclate Solution for injection; Children and Adolescents 8 to 17 years: 2.2 mg/kg/dose (Max: 100 mg/dose) IV every 12 hours. Switch to oral therapy as soon as possible for total treatment duration of 7 days.
          • Doxycycline Hyclate Solution for injection; Adults: 100 mg IV every 12 hours. Switch to oral therapy as soon as possible for total treatment duration of 7 days.
    • Clindamycin
      • Oral
        • For treatment of uncomplicated malaria due to Plasmodium falciparum
          • Clindamycin Palmitate Hydrochloride Oral solution; Infants, Children, and Adolescents: 20 mg/kg/day PO divided 3 times daily for 7 days.
          • Clindamycin Hydrochloride Oral capsule; Adults: 20 mg/kg/day PO divided 3 times daily for 7 days.
        • For treatment of severe malaria after IV artesunate therapy is completed
          • Clindamycin Hydrochloride Oral capsule; Infants and Children younger than 8 years: 20 mg/kg/day PO divided 3 times daily for 7 days.
          • Clindamycin Hydrochloride Oral capsule; Pregnant Female Adolescents: 20 mg/kg/day PO divided 3 times daily for 7 days.
          • Clindamycin Hydrochloride Oral capsule; Pregnant Female Adults: 20 mg/kg/day PO divided 3 times daily for 7 days.
      • IV
        • For treatment of severe malaria after IV artesunate therapy is completed
          • Clindamycin Solution for injection; Infants and Children younger than 8 years: 10 mg/kg IV loading dose, then 5 mg/kg/dose IV every 8 hours. Switch to oral therapy as soon as possible for total treatment duration of 7 days.
          • Clindamycin Solution for injection; Pregnant Female Adolescents: 10 mg/kg IV loading dose, then 5 mg/kg/dose IV every 8 hours. Switch to oral therapy as soon as possible for total treatment duration of 7 days.
          • Clindamycin Solution for injection; Pregnant Female Adults: 10 mg/kg IV loading dose, then 5 mg/kg/dose IV every 8 hours. Switch to oral therapy as soon as possible for total treatment duration of 7 days.
    • Primaquine
      • Must check for G6PD deficiency before prescribing
      • Not prescribed for pregnant patients
      • Primaquine Phosphate Oral tablet; Infants†, Children†, and Adolescents†: 0.5 mg base/kg/dose (Max: 30 mg base/dose) PO once daily for 14 days.
      • Primaquine Phosphate Oral tablet; Adults: 52.6 mg (30 mg base) PO once daily for 14 days.
      • Primaquine Phosphate Oral tablet; Adults with borderline G6PD deficiency†: 78.9 mg (45 mg base) PO once weekly for 8 weeks.
    • Tafenoquine 
      • Must check for G6PD deficiency before prescribing. Tafenoquine is contraindicated in patients with G6PD deficiency or unknown G6PD status owing to risk of hemolytic anemia
      • Must not be used in children younger than 16 years or in those with a history of a psychotic disorder
      • Not recommended during breastfeeding or pregnancy
      • Tafenoquine Oral tablet; Adolescents 16 years and older: 300 mg PO as single dose on first or second day of appropriate antimalarial therapy.
      • Tafenoquine Oral tablet; Adults: 300 mg PO as single dose on first or second day of appropriate antimalarial therapy.
    • Mefloquine (use is recommended only if other options are not available owing to risk of severe neuropsychiatric adverse events at treatment doses)
      • For treatment of uncomplicated malaria due to Plasmodium vivax
        • Mefloquine Hydrochloride Oral tablet; Infants†, Children†, and Adolescents†: 15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose.
        • Mefloquine Hydrochloride Oral tablet; Adults: 1,250 mg PO as single dose, or alternately, 750 mg PO as initial dose then 500 mg PO at 6 to 12 hours after initial dose.
      • For treatment of uncomplicated malaria due to mefloquine-susceptible strains of Plasmodium falciparum
        • Mefloquine Hydrochloride Oral tablet; Infants 1 to 5 months†: 15 mg/kg/dose PO as initial dose then 10 mg/kg/dose PO at 6 to 12 hours after initial dose.
        • Mefloquine Hydrochloride Oral tablet; Infants, Children, and Adolescents 6 months to 17 years: 20 to 25 mg/kg/dose (Max: 1,250 mg) PO as a single dose, or alternately, 15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose.
        • Mefloquine Hydrochloride Oral tablet; Adults: 1,250 mg PO as single dose, or alternately, 750 mg PO as initial dose then 500 mg PO at 6 to 12 hours after initial dose.
      • For treatment of severe malaria† before IV artesunate is available
        • Mefloquine Hydrochloride Oral tablet; Infants, Children, and Adolescents: 15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose. Discontinue after IV artesunate therapy started.
        • Mefloquine Hydrochloride Oral tablet; Adults: 750 mg PO as initial dose then 500 mg PO at 6 to 12 hours after initial dose. Discontinue after IV artesunate therapy started.
      • For treatment of severe malaria† after IV artesunate is completed
        • Mefloquine Hydrochloride Oral tablet; Infants, Children, and Adolescents: 15 mg/kg/dose (Max: 750 mg/dose) PO as initial dose then 10 mg/kg/dose (Max: 500 mg/dose) PO at 6 to 12 hours after initial dose.
        • Mefloquine Hydrochloride Oral tablet; Adults: 750 mg PO as initial dose then 500 mg PO at 6 to 12 hours after initial dose.
    • Atovaquone-proguanil
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 5 to 8 kg: 2 pediatric strength tablets (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 9 to 10 kg: 3 pediatric strength tablets (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 11 to 20 kg: 1 adult strength tablet (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children weighing 21 to 30 kg: 2 adult strength tablets (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children and Adolescents weighing 31 to 40 kg: 3 adult strength tablets (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children and Adolescents weighing more than 40 kg: 4 adult strength tablets (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily for 3 consecutive days.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Adults: 4 adult strength tablets (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily for 3 consecutive days.
    • Artemether-lumefantrine
      • Usage contraindicated with concomitant use of strong CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin, St. John’s wort). Concurrent use of strong CYP3A4 inducers can lead to a marked decrease in artemether; lumefantrine concentrations and loss of anti-malarial efficacy.
      • Artemether, Lumefantrine Oral tablet; Infants and Children 2 months or older and weighing 5 to 14 kg: 1 tablet (20 mg artemether; 120 mg lumefantrine per tablet) PO as initial dose and 1 tablet PO at 8 hours after initial dose, then 1 tablet PO twice daily (morning and evening) for 2 days.
      • Artemether, Lumefantrine Oral tablet; Infants and Children 2 months or older weighing 15 to 24 kg: 2 tablets (20 mg artemether; 120 mg lumefantrine per tablet) PO as initial dose and 2 tablets PO at 8 hours after initial dose, then 2 tablets PO twice daily (morning and evening) for 2 days.
      • Artemether, Lumefantrine Oral tablet; Children and Adolescents weighing 25 to 34 kg: 3 tablets (20 mg artemether; 120 mg lumefantrine per tablet) PO as initial dose and 3 tablets PO at 8 hours after initial dose, then 3 tablets PO twice daily (morning and evening) for 2 days.
      • Artemether, Lumefantrine Oral tablet; Children and Adolescents weighing 35 kg or more: 4 tablets (20 mg artemether; 120 mg lumefantrine per tablet) PO as initial dose and 4 tablets PO at 8 hours after initial dose, then 4 tablets PO twice daily (morning and evening) for 2 days.
      • Artemether, Lumefantrine Oral tablet; Adults: 4 tablets (20 mg artemether; 120 mg lumefantrine per tablet) PO as initial dose and 4 tablets PO at 8 hours after initial dose, then 4 tablets PO twice daily (morning and evening) for 2 days.
    • Artesunate 
      • Treat all patients who have severe malaria, regardless of infecting species, with IV artesunate
      • Artesunate for injection was approved by the FDA in 2020 for treatment of severe malaria; IV quinidine has been discontinued and is no longer available 
      • Artesunate Solution for injection; Infants and Children weighing less than 20 kg: 2.4 or 3 mg/kg/dose IV administered at 0, 12, and 24 hours, and thereafter, once daily until able to switch to oral therapy. If cannot tolerate oral therapy, continue for a total of 7 days or switch to IV doxycycline (8 years or older) or clindamycin for 7 days.
      • Artesunate Solution for injection; Children and Adolescents weighing 20 kg or more: 2.4 mg/kg/dose IV administered at 0, 12, and 24 hours, and thereafter, once daily until able to switch to oral therapy. If cannot tolerate oral therapy, continue for a total of 7 days or switch to IV doxycycline (8 years or older) or clindamycin for 7 days.
      • Artesunate Solution for injection; Adults: 2.4 mg/kg/dose IV administered at 0, 12, and 24 hours, and thereafter, once daily until able to switch to oral therapy. If cannot tolerate oral therapy, continue for a total of 7 days or switch to IV doxycycline or clindamycin for 7 days.
      • CDC recommends checking parasite density after 24 hours of therapy. If, after the third IV artesunate dose, patient’s parasite density is greater than 1% (assessed on a blood smear collected 4 hours after the last artesunate dose), continue IV treatment with artesunate using the recommended daily dose for a maximum of 7 days. Doses given at 0, 12, and 24 hours count as 1 day, which means up to 6 additional days. If parasite density is 1% or less and patient can tolerate oral treatment, a full treatment course with a follow-on regimen must be administered.
  • Chemoprophylaxis
    • Chloroquine
      • Chloroquine Phosphate Oral tablet; Infants, Children, and Adolescents: 8.3 mg (5 mg base)/kg/dose [Max: 500 mg/dose (300 mg base/dose)] PO weekly (same day each week); start 2 weeks before entering endemic area and continue for 8 weeks after leaving area. If not feasible to begin therapy before entering area, use 16.6 mg (10 mg base)/kg/dose [Max: 1,000 mg/dose (600 mg base/dose)] as loading dose given in 2 divided doses 6 hours apart. Alternatively, guidelines suggest starting 1 to 2 weeks prior to entry and continuing for 4 weeks after leaving area.
      • Chloroquine Phosphate Oral tablet; Adults: 500 mg (300 mg base) PO weekly (same day each week); start 2 weeks before entering endemic area and continue for 8 weeks after leaving area. If not feasible to begin therapy before entering endemic area, use 1,000 mg (600 mg base) as loading dose given in 2 divided doses 6 hours apart. Alternatively, guidelines suggest starting 1 to 2 weeks prior to entry and continuing for 4 weeks after leaving area.
    • Atovaquone-proguanil
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 5 to 8 kg†: One-half pediatric tablet (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 9 to 10 kg†: Three-quarters pediatric tablet (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Infants and Children weighing 11 to 20 kg: 1 pediatric tablet (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children weighing 21 to 30 kg: 2 pediatric tablets (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children and Adolescents weighing 31 to 40 kg: 3 pediatric tablets (62.5 mg atovaquone; 25 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Children and Adolescents weighing more than 40 kg: 1 adult strength tablet (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • Atovaquone, Proguanil Hydrochloride Oral tablet; Adults: 1 adult strength tablet (250 mg atovaquone; 100 mg proguanil per tablet) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
    • Mefloquine
      • Mefloquine Hydrochloride Oral tablet; Infants and Children weighing 9 kg or less†: 5 mg/kg/dose PO weekly (same day each week); start 2 weeks or more before entering endemic area and continue for 4 weeks after leaving area.
      • Mefloquine Hydrochloride Oral tablet; Infants and Children weighing 10 to 19 kg†: One-quarter tablet (62.5 mg) PO weekly (same day each week); start 2 weeks or more before entering endemic area and continue for 4 weeks after leaving area.
      • Mefloquine Hydrochloride Oral tablet; Children weighing 20 to 29 kg: One-half tablet (125 mg) PO weekly (same day each week); start 1 to 2 weeks before entering endemic area and continue for 4 weeks after leaving area.
      • Mefloquine Hydrochloride Oral tablet; Children and Adolescents weighing 31 to 45 kg: Three-quarters tablet (187.5 mg) PO weekly (same day each week); start 1 to 2 weeks before entering endemic area and continue for 4 weeks after leaving area.
      • Mefloquine Hydrochloride Oral tablet; Children and Adolescents weighing more than 45 kg: 250 mg PO weekly (same day each week); start 1 to 2 weeks before entering endemic area and continue for 4 weeks after leaving area.
      • Mefloquine Hydrochloride Oral tablet; Adults: 250 mg PO weekly (same day each week); start 1 to 2 weeks before entering endemic area and continue for 4 weeks after leaving area.
    • Doxycycline
      • Doxycycline Monohydrate Oral capsule; Children and Adolescents 8 to 17 years: 2 mg/kg/dose (Max: 100 mg/dose) PO once daily. Begin 1 to 2 days prior to travel to malarious area and continue during stay and for 4 weeks after returning home.
      • Doxycycline Monohydrate Oral capsule; Adults: 100 mg PO once daily. Begin 1 to 2 days prior to travel to malarious area and continue during stay and for 4 weeks after returning home.
    • Primaquine
      • Must check for G6PD deficiency before prescribing (Related: Glucose-6-phosphate dehydrogenase deficiency)
      • For primary malaria prophylaxis†
        • Primaquine Phosphate Oral tablet; Infants, Children, and Adolescents: 0.8 mg/kg/dose (0.5 mg base/kg/dose) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
        • Primaquine Phosphate Oral tablet; Adults: 52.6 mg (30 mg base) PO once daily. Begin 1 to 2 days before entering endemic area; continue daily during stay and for 7 days after leaving area.
      • For presumptive antirelapse malaria prophylaxis† of either Plasmodium falciparum or Plasmodium vivax malaria
        • Primaquine Phosphate Oral tablet; Infants, Children, and Adolescents: 0.8 mg/kg/dose (0.5 mg base/kg/dose) PO once daily for 14 days after leaving endemic area. When chloroquine, doxycycline, or mefloquine used for primary prophylaxis, take primaquine during last 2 weeks of postexposure prophylaxis. When atovaquone; proguanil is used for primary prophylaxis, take primaquine during last 7 days of atovaquone; proguanil prophylaxis plus 7 more days.
        • Primaquine Phosphate Oral tablet; Adults: 52.6 mg (30 mg base) PO once daily for 14 days after leaving endemic area. When chloroquine, doxycycline, or mefloquine used for primary prophylaxis, take primaquine during last 2 weeks of postexposure prophylaxis. When atovaquone; proguanil is used for primary prophylaxis, take primaquine during last 7 days of atovaquone; proguanil prophylaxis plus 7 more days.

Nondrug and supportive care

Procedures
IV fluid infusion

General explanation

  • Volume per hour is calculated according to body weight (kg)
  • Children with severe malaria: if patient is unable to tolerate oral fluids, infuse 5% dextrose in isotonic saline (0.9%) maintenance fluids at 3 to 4 mL/kg/hour 
  • Adults with severe malaria: if patient is unable to tolerate oral fluids, infuse 5% dextrose in isotonic saline (0.9%) at 1 to 2 mL/kg/hour 

Indication

  • Severe malaria

Contraindications

  • Rapid fluid boluses are contraindicated in severe malaria 
  • Use caution and observe for adequate urine output and development of pulmonary edema

Comorbidities

  • HIV infection increases risk of severe disease 
    • Patients with significant immunosuppression (low CD4 counts) are advised to avoid travel to areas with high malarial transmission

Special populations

  • Pregnant women
    • Malaria during pregnancy increases risk of severe malaria, death from severe malaria, and pregnancy complications, including the following:
      • Anemia caused by placental and splenic sequestration of infected erythrocytes
      • Miscarriage
      • Premature birth
      • Low birth weight
      • Congenital infection
      • Perinatal death
    • WHO recommends that pregnant women living in areas of high transmission receive intermittent preventive treatment with sulfadoxine-pyrimethamine: 2 doses after 20th week of pregnancy 
    • Treatment of pregnant women with nonsevere (uncomplicated) malaria caused by Plasmodium malariae, Plasmodium vivax, Plasmodium ovale, or chloroquine-sensitive Plasmodium falciparum 
      • First line therapy is chloroquine
      • Alternative is hydroxychloroquine
      • For women in their second or third trimesters, artemether-lumefantrine is an additional option 
      • Primaquine and tafenoquine are not given during pregnancy; instead, pregnant women with infection caused by Plasmodium vivax or Plasmodium ovale receive weekly chloroquine until after pregnancy, when they receive a standard course of primaquine or tafenoquine (if not G6PD deficient and not breastfeeding). If breastfeeding, tafenoquine is not recommended
    • Treatment of pregnant women who are diagnosed with nonsevere (uncomplicated) malaria caused by chloroquine-resistant Plasmodium falciparum
      • In all trimesters, use mefloquine or quinine plus clindamycin
      • Can treat women in their second or third trimesters with artemether-lumefantrine 
      • Doxycycline and tetracycline are not indicated for use in pregnant women. Can consider using these medications in combination with quinine if other treatment options are unavailable or not tolerated and if potential benefit of adding doxycycline or tetracycline outweighs risks
      • Atovaquone-proguanil may be used if other treatment options are not available or are not tolerated and if potential benefit is judged to outweigh potential risks
    • Treatment of pregnant patients who have severe (complicated) malaria is the same as that of nonpregnant patients 
      • Doxycycline and tetracycline are generally not indicated for use in pregnant women; rarely, doxycycline or tetracycline can be combined with quinine if other treatment options are not available or not tolerated 
      • Atovaquone-proguanil is not indicated for use in pregnant women  
    • For prophylaxis in pregnant women, only chloroquine and mefloquine are currently recommended; travel to areas of mefloquine-resistant malaria is best avoided 

Monitoring

  • Monitor levels of parasitemia at 12-hour intervals to assess response to therapy

Follow these instructions at home:

  • Take over-the-counter and prescription medicines only as told by your health care provider.
  • Rest at home until your symptoms are under control.
  • Drink enough fluid to keep your urine clear or pale yellow.
  • Keep all follow-up visits as told by your health care provider. This is important.

Complications

  • Malaria caused by Plasmodium falciparum and Plasmodium knowlesi is frequently severe (complicated), causing the following:
    • Cerebral malaria
    • Pulmonary edema
    • Acute respiratory distress syndrome
    • Cardiogenic shock
    • Renal failure
    • Splenic rupture
    • Disseminated intravascular coagulation
    • Hemolysis
    • Pregnancy complications
    • Death due to multiorgan failure

Prognosis

  • In 2017, there were an estimated 405,000 deaths from malaria globally 
    • Children younger than 5 years accounted for 67% (272,000) of all malaria deaths worldwide in 2018 
    • Pregnant women with malaria have increased mortality risk
    • Parasitemia greater than 20% is associated with a high risk of death 
  • Pregnancy, asplenia (including surgical), and HIV infection increase risk of severe disease and complications

Can Malaria be prevented?

  • If you will be traveling to an area where malaria is common:
    • Visit the website of the Centers for Disease Control and Prevention (CDC) to check your risk: www.cdc.gov/malaria/travelers/index.html
    • Make an appointment with your health care provider at least 2 weeks before you leave. You may be given a medicine to help prevent malaria.
  • You can also prevent malaria by:
    • Using insect repellent.
    • Staying indoors after daytime starts to turn to night or dusk.
    • Wearing protective clothing that covers your arms and legs.
    • Hanging a mosquito net over your bed.

Screening and Prevention

Prevention

  • Apply insect repellents containing DEET (diethyltoluamide)
    • Higher concentrations of DEET give longer duration of protection
  • Wear protective clothing (eg, long sleeves, long pants); permethrin treatment may add further protection
  • Use screens to exclude mosquitoes (tight-fitting window screens and/or permethrin-treated bed nets)
  • Avoid outdoor activities during times of greatest Anopheles mosquito activity (dusk through dawn)
  • Antimalarial chemoprophylaxis
    • Chloroquine phosphate 
      • For travelers to areas without chloroquine-resistant malaria
      • Safe for pregnant women and children
    • Mefloquine 
      • For travelers to Southeast Asia, Amazon region of South America, and sub-Saharan Africa, or any area where chloroquine-resistant malaria exists
    • Atovaquone plus proguanil 
      • For travelers to Southeast Asia, Amazon region of South America, and sub-Saharan Africa, or any area where chloroquine-resistant malaria exists
    • Doxycycline 
      • Alternative to mefloquine or atovaquone plus proguanil
      • Alternative for travelers to areas of mefloquine-resistant malaria
    • Primaquine phosphate 
      • Given as terminal prophylaxis in people returning from travel to areas where Plasmodium vivax and Plasmodium ovale are common
      • May be used as primary prophylaxis in areas where Plasmodium vivax predominates
      • Must test for G6PD deficiency before prescribing

Contact a health care provider if:

  • You have an attack of malaria symptoms.
  • You develop jaundice.

Get help right away if:

  • You have a seizure.
  • You have bleeding.
  • You have trouble breathing.

Differential Diagnosis

Most common

  • Typhoid fever (Related: )Bacterial meningitis in children
    • Life-threatening systemic infection caused by Salmonella typhi
    • Systemic symptoms similar to those of malaria include fever, myalgias, and malaise
    • Physical signs and laboratory results of typhoid fever that overlap with those of malaria include splenomegaly and leukopenia
    • Some patients with typhoid fever also have a rash characterized by rose spots on chest and abdomen; these spots wax and wane thus are not always seen
    • Diagnosis is confirmed by positive culture (eg, blood, stool, urine) results, or retrospectively with serology for Salmonella typhi
  • Bacterial meningitis (Related: )Bacterial meningitis in children
    • Symptoms and signs may resemble those of cerebral involvement in severe malaria (cerebral malaria), including fever, lethargy, altered mental status, and seizures (Related: Bacterial meningitis in children)
    • Lumbar puncture is indicated for cerebrospinal fluid analysis to differentiate
  • Influenza
    • Some symptoms and signs are similar to those of malaria (eg, fever, chills, myalgias of acute onset), but respiratory symptoms predominate in influenza
    • Influenza is typically seasonal in temperate climates but not in tropical climates
    • Laboratory testing (eg, rapid influenza test, malaria rapid diagnostic test, microscopy) may assist in differential diagnosis in a traveler returning to the United States from areas in which influenza may be circulating
  • Gastroenteritis (Related: )Traveler’s diarrhea
    • Fever is variable with viral and bacterial gastroenteritis
    • Most prominent symptoms are explosive vomiting and diarrhea, both of which are short-lived
    • Although patients with malaria may have gastrointestinal symptoms, they are usually not the overriding manifestation
    • Laboratory testing (eg, CBC, presence of WBCs in stool, stool culture) may aid in differential diagnosis
  • Hepatitis (Related: )Hepatitis A
    • Fever is variable with viral hepatitis and does not occur in episodic fashion (Related: Hepatitis B)
    • Hepatomegaly, jaundice, and elevated hepatic transaminase levels may be present in both malaria and hepatitis (Related: Hepatitis C)
    • Laboratory testing (hepatitis panel) will aid in differential diagnosis (Related: Hepatitis D)
  • Babesiosis
    • Babesia are protozoa that, like plasmodial protozoa, parasitize erythrocytes
    • Cases of babesiosis have been reported in the United States as follows:
      • Eastern states (from southern New England to Virginia), especially the northeastern islands, including those of New York, Massachusetts, and Rhode Island
      • Other states have included California, Wisconsin, Georgia, Minnesota, and Washington
    • Mostly a mild systemic illness in healthy people, presenting with fatigue, chills, fever, headache, arthralgia, nausea, and vomiting
    • Fulminant disease may occur in asplenic or immunocompromised people
    • Diagnosis is by demonstration of intraerythrocytic parasites in thick or thin blood smears that usually resemble the ring forms of Plasmodium falciparum malaria; molecular testing can be used to differentiate

Sources

CDC: Malaria: Malaria Diagnostic Tests: Malaria Diagnosis (U.S.) – Microscopy. CDC website. Last Reviewed February 19, 2020. Accessed July 29, 2020. https://www.cdc.gov/malaria/diagnosis_treatment/diagnostic_tools.html#tabs-2-1 Reference

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