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Malaria

Traveler's information 

Contents of this page:
Overview
    Causal Agents   
    Life Cycle   
    Geographic Distribution    
    Laboratory Diagnosis

Prevention 
Prescription Drugs for Preventing Malaria 
Preventing Malaria in the Pregnant Woman  
     Antimalarial Drug Warnings and Instructions for Use   
Preventing Malaria in Infants and Children   
 
Diagnosis
   Clinical features
    Laboratory Diagnosis    
    Microscopic Findings

Treatment
    Treatment    

Information for Health Care Providers:
Preventing Malaria in the Pregnant Woman

Determine Your Patient’s Risk

CDC has two sources of information for health care providers about malaria risk and prevention:

• CDC’s toll-free Fax Information Service. To request fax information, call 1-888-232-3299; listen to the instructions. For the directory of all travel faxes, request document number 000005.
• the CDC Travelers’ Health website.

  Identical malaria prevention information is provided at the CDC website and the toll-free fax information service.

Caution Against Travel During Pregnancy

It is best if travel to a malaria-risk area be postponed until after parturition. If travel cannot be postponed, taking an antimalarial drug and preventing mosquito bites is recommended to reduce, but not eliminate, the risk of developing malaria. Experience with the antimalarial chloroquine and limited experience with the antimalarial mefloquine indicate that they are safe to take during pregnancy, including the first trimester. Pregnant women should take their antimalarial exactly on schedule without missing doses. The antimalarial prescribed will depend on where the patient is traveling.

Provide Antimalarial Drug Warnings and Instructions for Use

Advise patients:

• Overdosage of antimalarials can be fatal. Keep drugs in childproof containers out of the reach of children.
• Take antimalarials exactly on schedule without missing doses.
• Buy antimalarials in the United States before travel overseas. The quality of antimalarials sold outside of the United States may not be reliable.

  Pregnant women traveling to malaria-risk areas in South America, Africa, the Indian subcontinent, Asia, and the South Pacific should take mefloquine as their antimalarial drug.

Mefloquine/ brand name Lariam^®*

Directions for use

• The adult dosage is 250 mg salt (one tablet) once a week.
• Take the first dose of mefloquine 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Mefloquine should be taken on a full stomach, for example, after dinner.

Mefloquine side effects:
Most travelers who take mefloquine have few, if any, side effects. The most commonly reported minor side effects include nausea, dizziness, difficulty sleeping, and vivid dreams. Mefloquine has very rarely been reported to cause serious side effects such as seizures, hallucinations, and severe anxiety. Minor side effects usually do not require stopping the drug. Travelers who experience serious side effects should be advised to see a health care provider.

Mefloquine is contraindicated for persons with a known allergy to mefloquine.
Mefloquine is NOT recommended for travelers with a history of

• Epilepsy or other seizure disorders;
• Severe psychiatric disorders;
• Cardiac conduction abnormalities.

Pregnant women traveling to malaria-risk areas in Mexico, Haiti, the Dominican Republic, and certain countries in Central America, the Middle East, and Eastern Europe should take either chloroquine or hydroxychloroquine sulfate as their antimalarial drug.

Chloroquine/ brand name Aralen^®*

Directions for use

• The adult dose is 500 mg (salt) chloroquine phosphate once a week.
• Take the first dose of chloroquine 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Chloroquine should be taken on a full stomach, for example, after dinner, to lessen nausea.

Chloroquine side effects
Although side effects are rare, nausea and vomiting, headache, dizziness, blurred vision, and itching have been reported. Chloroquine may worsen the symptoms of psoriasis.

Hydroxychloroquine sulfate/ brand name Plaquenil^®*

Directions for use

• The adult dosage is 400 mg (salt) once a week.
• Take the first dose of hydroxychloroquine sulfate 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Hydroxychloroquine sulfate should be taken on a full stomach, for example, after dinner, to minimize nausea.
• Hydroxychloroquine sulfate may be better tolerated than chloroquine.

Hydroxychloroquine sulfate side effects
Although side effects are rare, nausea and vomiting, headache, dizziness, blurred vision, and itching have been reported. Hydroxychloroquine sulfate may worsen the symptoms of psoriasis.

• Doxycycline is contraindicated during pregnancy. Malarone™ should NOT be used by pregnant women to prevent malaria.
• For advice on prophylaxis for pregnant women who cannot take the recommended antimalarial drug for their malaria-risk area, contact the CDC Malaria Hotline at 770-488-7788

Prescribe Antimalarial Drugs If Traveling While Breast-Feeding

Breast-feeding mothers will pass a very small amount of antimalarial in their breast milk. This small amount of drug will neither harm the infant nor be enough to protect him or her against malaria. Infants need to be given their own antimalarial. See Preventing Malaria in Infants and Children (Information for Health Care Providers) for additional information.

Describe Prevention of Insect Bites

Patients should be advised to prevent mosquito bites. Advise wearing long-sleeved shirts and long pants and applying insect repellent to exposed skin. Explain that the mosquitoes that transmit malaria bite between dusk and dawn. Use insect repellents that contain the active ingredient DEET.

When using repellent with DEET, follow these precautions

• Always use according to label directions.
• Use repellent only when outdoors and wash skin after coming indoors.
• Do not breathe in, swallow, or get repellent into the eyes.
• Do not put repellent on wounds or broken skin.
• Adults should use DEET at a concentration of 30% to 35%.

Travelers who will not be staying in well-screened or air-conditioned rooms should use a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours. In addition, travelers should take additional precautions, including sleeping under mosquito netting (bed nets). Bed nets sprayed with the insecticide permethrin are more effective. In the United States, permethrin is available as a spray or liquid to treat clothes and bed nets. Bed nets may be purchased that have already been treated with permethrin. Permethrin or another insecticide, deltamethrin, may be purchased overseas to treat nets and clothes.

Explain the Signs and Symptoms of Malaria

Travelers should be made aware that they can still contract malaria despite taking antimalarials. Malaria causes a flu-like illness; symptoms include fever, shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria symptoms will occur at least seven to nine days after being bitten by an infected mosquito. Fever in the first week of travel is unlikely to be malaria; however, travelers should be advised to have any fever promptly evaluated. Advise parents to seek immediate medical care if their child becomes sick with a fever or flu-like illness while traveling in a malaria-risk area and up to 1 year after returning home. They should tell their health care provider where they have been traveling.

For additional information about malaria risk and prevention, please see the following:

• Malaria: General Information
• Prescription Drugs for Preventing Malaria (Information for Health Care Providers)
• Preventing Malaria in Infants and Children (Information for Health Care Providers)

*Use of trade names is for identification purposes only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

Information for Health Care Providers:
Prescription Drugs for Preventing Malaria

Determine your Patient’s Risk

CDC has two sources of information for health care providers about malaria risk and prevention:

• CDC’s toll-free Fax Information Service. To request fax information, call 1-888-232-3299; listen to the instructions. For the directory of all travel faxes, request document number 000005.
• the CDC Travelers’ Health website.

  Identical malaria risk and prevention information is provided at the CDC website and the toll-free fax information service.

Prescription Drugs for Malaria

Provide Antimalarial Drug Warnings and Instructions for Use

Advise Patients:

• Overdosage of antimalarials can be fatal. Keep drugs in childproof containers out of the reach of children.
• Take antimalarials exactly on schedule without missing doses.
• Purchase antimalarials in the United States before travel overseas. The quality of antimalarials sold outside of the United States may not be reliable.

Mefloquine/ brand name Lariam^®*

Directions for use

• The adult dosage is 250 mg salt (one tablet) once a week.
• Take the first dose of mefloquine 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Mefloquine should be taken on a full stomach, for example, after dinner.

Mefloquine side effects
Most travelers who take mefloquine have few, if any, side effects. The most commonly reported minor side effects include nausea, dizziness, difficulty sleeping, and vivid dreams. Mefloquine has very rarely been reported to cause serious side effects, such as seizures, hallucinations, and severe anxiety. Minor side effects usually do not require stopping the drug. Advise travelers who have serious side effects to see a health care provider.

Mefloquine is contraindicated in persons with a known allergy to mefloquine.
Mefloquine is NOT recommended for travelers with a history of

• Epilepsy or other seizure disorders;
• Severe psychiatric disorders;
• Cardiac conduction abnormalities.

Doxycycline

Directions for use

• The adult dosage is 100 mg once a day.
• Take the first dose of doxycycline 1 or 2 days before arrival in the malaria-risk area, once a day, at the same time each day, in the malaria-risk area, and once a day for 4 weeks after leaving the malaria-risk area.

Doxycycline side effects and contraindications

• Doxycycline may cause photosensitivity. Travelers should be advised to avoid midday sun, use a sunscreen with SPF of at least 15, wear long-sleeved shirts, long pants, and a hat.
• Advise patients to take doxycycline on a full stomach to minimize nausea and to not lie down for 1 hour after taking the drug to prevent reflux of the drug into the esophagus.
• Doxycycline can predispose women to vaginal yeast infections. Women should be advised to bring an over-the-counter vaginal yeast infection medication for use if vaginal itching or discharge develops.
• Doxycycline is contraindicated in children under the age of 8; teeth may become permanently stained.
• Doxycycline should NOT be used during pregnancy.

Malarone™
Malarone™ is a new antimalarial drug in the United States. Malarone is a combination of two drugs (atovaquone and proguanil) and is an effective alternative for travelers who cannot or choose not to take mefloquine or doxycycline.

Directions for use

• The adult dosage is one adult tablet (250 mg atovaquone/100 mg proguanil) once a day.
• Take the first dose of Malarone 1 to 2 days before travel in the malaria-risk area.
• Take Malarone once a day in the malaria-risk area.
• Take Malarone once a day for 7 days after leaving the malaria-risk area.
• Take the dose at the same time each day with food or milk.

Malarone Side Effects and Warnings
Although side effects are rare, abdominal pain, nausea, vomiting, and headache can occur.
Malarone should not be taken by patients with severe renal impairment (creatinine clearance <30 ml/min).
Pregnant women or women breast-feeding infants weighing less than 11 kg should not take Malarone to prevent malaria. Infants weighing less than 11 kg should not be given Malarone.

Chloroquine/ brand name Aralen^®*

Directions for use

• The adult dosage is 500 mg (salt) chloroquine phosphate once a week.
• Take the first dose of chloroquine 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Chloroquine should be taken on a full stomach, for example, after dinner, to minimize nausea.

Chloroquine side effects
Although side effects are rare, nausea and vomiting, headache, dizziness, blurred vision, and itching have been reported. Chloroquine may worsen the symptoms of psoriasis.

Hydroxychloroquine sulfate/ brand name Plaquenil^®*

Directions for use

• The adult dosage is 400 mg (salt) once a week.
• Take the first dose of hydroxychloroquine sulfate 1 week before arrival in the malaria-risk area, once a week, on the same day of the week, in the malaria-risk area, and once a week for 4 weeks after leaving the malaria-risk area.
• Hydroxychloroquine sulfate should be taken on a full stomach, for example, after dinner, to minimize nausea.
• Hydroxychloroquine sulfate may be better tolerated than chloroquine.

Hydroxychloroquine sulfate side effects
Although side effects are rare, nausea and vomiting, headache, dizziness, blurred vision, and itching have been reported. Hydroxychloroquine sulfate may worsen the symptoms of psoriasis.

Describe Self-Treatment Medication

Travelers should be reminded that malaria can be fatal. If a traveler develops a fever or other flu-like symptoms, and professional medical care is not available within 24 hours, a self-treatment dose of either Fansidar^® or Malarone™ is recommended. Advise the traveler to seek professional medical care as soon as possible after self-treatment. Malaria symptoms will occur at least seven to nine days after being bitten by an infected mosquito. Fever in the first week of travel is unlikely to be malaria; however, travelers should be advised to have any fever promptly evaluated.

Fansidar^® may be used for presumptive self-treatment for travelers if:

• they are NOT allergic to sulfa drugs and
• their travel itinerary does NOT include the Amazon basin of South America, Southeast Asia, and certain countries in eastern and southern Africa (Kenya, Malawi, Mozambique, South Africa, Tanzania, and Uganda). These countries have documented Fansidar^®-resistant Plasmodium falciparum malaria.

Malarone™ may be used for presumptive self-treatment for travelers not taking Malarone for prophylaxis. Travelers on Malarone prophylaxis who take presumptive self-treatment should use Fansidar^® if they are traveling to an area without Fansidar^® resistance.

Consult the CDC Malaria Hotline (770-488-7788) for advice for travelers who cannot take Fansidar or Malarone for presumptive self-treatment.

For additional information about malaria prophylaxis, please see the following:

• Preventing Malaria in the Pregnant Woman (Information for Health Care Providers)
• Preventing Malaria in Infants and Children (Information for Health Care Providers)

*Use of trade names is for identification purposes only and does not imply endorsement by the Public Health Service or by the U.S. Department of Health and Human Services.

Diagnostic findings

• Microscopic identification is the method most frequently used to demonstrate an active infection.
• Microscopy
• Comparison of Plasmodium species
• Molecular diagnosis techniques can complement microscopy, especially in species identification.
• Antibody Detection can detect past (not necessarily active) infections.
• Immunologic/Biochemical detection of malaria parasite products are available and under evaluation.
• Bench aids for Malaria

Other Parasite Stages Seen Rarely in Blood: There are some other malaria stages that can be seen, but are rare and/or do not assist in diagnosis.  They are the merozoites, which are released when the schizont ruptures, and which will re-invade new erythrocytes to continue the asexual erythrocytic cycle; and on exceptional occasions, when blood samples are left at room temperature, the gametocytes can exflagellate and the blood smears can have exflagellating gametocytes, microgametes, or even ookinetes (the product of the fusion of a male and female gametes, usually found only in the mosquito).

 

Plasmodium species	Stages found in blood	Appearance of Erythrocyte (RBC)	Appearance of Parasite
P. falciparum Images	Ring Images	normal; multiple infection of RBC more common than in other species	delicate cytoplasm; 1 to 2 small chromatin dots; occasional appliqué (accollé) forms
	Trophozoite Images	normal; rarely, Maurer's clefts (under certain staining conditions)	seldom seen in peripheral blood; compact cytoplasm; dark pigment
	Schizont Images	normal; rarely, Maurer's clefts (under certain staining conditions)	seldom seen in peripheral blood; mature = 8 to 24 small merozoites; dark pigment, clumped in one mass
	Gametocyte Images	distorted by parasite	crescent or sausage shape; chromatin in a single mass (macrogametocyte) or diffuse (microgametocyte); dark pigment mass
P. vivax Images	Ring Images	normal to 11/4 ×, round; occasionally fine Schüffner's dots; multiple infection of RBC not uncommon	large cytoplasm with occasional pseudopods; large chromatin dot
	Trophozoite Images	enlarged 11/2 to 2 ×; may be distorted; fine Schüffner's dots	large ameboid cytoplasm; large chromatin; fine, yellowish-brown pigment
	Schizont Images	enlarged 11/2 to 2 ×; may be distorted; fine Schüffner's dots	large, may almost fill RBC; mature = 12 to 24 merozoites; yellowish-brown, coalesced pigment
	Gametocyte Images	enlarged 11/2 to 2 ×; may be distorted; fine Schüffner's dots	round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or diffuse (microgametocyte); scattered brown pigment
P. ovale Images	Ring Images	normal to 11/4 ×, round to oval; occasionally Schüffner's dots; occasionally fimbriated; multiple infection of RBC not uncommon	sturdy cytoplasm; large chromatin
	Trophozoite Images	normal to 11/4 ×; round to oval; some fimbriated; Schüffner's dots	compact with large chromatin; dark-brown pigment
	Schizont Images	normal to 11/4 ×, round to oval, some fimbriated, Schüffner's dots	mature = 6 to 14 merozoites with large nuclei, clustered around mass of dark-brown pigment
	Gametocyte Images	normal to 11/4 ×; round to oval, some fimbriated; Schüffner's dots	round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or more diffuse (microgametocyte); scattered brown pigment
P. malariae Images	Ring Images	normal to 3/4 ×	sturdy cytoplasm; large chromatin
	Trophozoite Images	normal to 3/4 ×; rarely, Ziemann's stippling (under certain staining conditions)	compact cytoplasm; large chromatin; occasional band forms; coarse, dark-brown pigment
	Schizont Images	normal to 3/4 ×; rarely, Ziemann's stippling (under certain staining conditions)	mature = 6 to 12 merozoites with large nuclei, clustered around mass of coarse, dark-brown pigment; occasional rosettes
	Gametocyte Images	normal to 3/4 ×; rarely, Ziemann's stippling (under certain staining conditions)	round to oval; compact; may almost fill RBC; chromatin compact, eccentric (macrogametocyte) or more diffuse (microgametocyte); scattered brown pigment

While morphologic characteristics provide valuable criteria for determination of malaria parasite species, they occasionally fail to differentiate between species that share morphologic characteristics (especially Plasmodium vivax and P. ovale) or in cases where parasite morphology has been altered by drug treatment or improper storage of the sample.  In such cases, molecular diagnostic tests can provide useful complementary information.  In addition, molecular tests can be more sensitive and their interpretation is less open to subjectivity than microscopy.  The method currently used at CDC is described below. Species-specific PCR diagnosis of malaria Plasmodium genomic DNA is extracted from 200 µl whole blood using the QIAamp Blood Kit (Cat. No. 29106; Qiagen Inc., Chatsworth, CA.) or a similar product that can yield the comparable concentration of genomic DNA from the same volume of blood. Detection and speciation of Plasmodium is done with a two step nested PCR using the primers of Snounou et al.  In the first step (PCR1), 1 µl of extracted DNA is amplified using genus specific primers; in the second step (PCR2), 1 µl of PCR1 amplification product is further amplified using species specific primers.  Ten µl of each PCR2 amplified DNA product is separated by 2% agarose gel electrophoresis, stained for 15 min with ethidium bromide and visualized by UV illumination. A A: Agarose gel (2%) analysis of a PCR diagnostic test for species-specific detection of Plasmodium DNA.  PCR was performed using nested primers of Snounou et al.1. Lane S: Molecular base pair standard (50-bp ladder).  Black arrows show the size of standard bands. Lane 1: The red arrow shows the diagnostic band for P. vivax (size: 120 bp) Lane 2: The red arrow shows the diagnostic band for P. malariae (size: 144 bp) Lane 3: The red arrow shows the diagnostic band for P. falciparum (size: 205 bp) Lane 4: The red arrow shows the diagnostic band for P. ovale (size: 800 bp) Reference: Snounou G, Viriyakosol S, Zhu XP, et al. High sensitivity detection of human malaria parasites by the use of nested polymerase chain reaction. Mol Biochem Parasitol 1993;61:315-320.

Malaria antibody detection can be performed using various techniques.  For the clinical laboratory, the most practical approach is the indirect fluorescent antibody (IFA) test.  This test, with malaria parasites as antigens, detects most sensitively antibody responses to a wide range of plasmodial antigens. The IFA procedure can be used to determine if a patient has been infected with Plasmodium.  Because of the time required for development of antibody and also the persistence of antibodies, serologic testing is not practical for routine diagnosis of malaria.  However, serology may be useful for: screening blood donors involved in cases of transfusion-induced malaria when the donor's parasitemia may be below the detectable level of blood film examination testing a patient with a febrile illness who is suspected of having malaria and from whom repeated blood smears are negative Species-specific testing is available for the four human species: P. falciparum, P. vivax, P. malariae, and P. ovale.  Cross reactions often occur between Plasmodium species and Babesia species.  Blood stage Plasmodium species schizonts (meronts) are used as antigen.  The patient's serum is exposed to the organisms; homologous antibody, if present, attaches to the antigen, forming an antigen-antibody (Ag-Ab) complex.  Fluorescein-labeled anti-human antibody is then added, which attaches to the patient's malaria-specific antibody.  When examined with a fluorescence microscope, a positive reaction is when the parasites appear fluorescent yellow. A A: Positive malaria IFA showing a fluorescent schizont. Reference: Sulzer AJ,Wilson M. The fluorescent antibody test for malaria. Crit Rev Clin Lab Sci 1971;2:601-609.

In addition to microscopy and molecular methods, there are methods for detecting malaria parasites on the basis of antigens or enzymatic activities associated with the parasites.

These methods include, among others:

• detection of an antigen (histidine rich protein-2, HRP-2) associated with malaria parasites (especially P. falciparum and P. vivax)
• detection of a Plasmodium associated lactate dehydrogenase (pLDH) either through its enzymatic activity or by immunoassay

The detection of HRP-2 and of pLDH  forms the basis for diagnostic kits that have been, and continue to be evaluated.  Consensus information, when available, will be reviewed.

Bench Aids

The bench aids are in PDF format, and in order to access these files you must have Adobe Acrobat Reader.  If you do not have Acrobat Reader, please click here for more information.  If you experience problems downloading these files due to file size, email us at dpdx@cdc.gov.

• Comparison of the Plasmodium Species Which Cause Human Malaria (PDF file: 28 kb)
• Plasmodium spp. Blood Stage Parasites, Thick Blood Smears (PDF file: 938 kb)
• Plasmodium spp. Blood Stage Parasites, Thin Blood Smears (PDF file: 512 kb)

The following bench aid was developed for the Democratic Republic of Congo by the National Malaria Control Program of that country, with assistance from the Centers for Disease Control and Prevention and United States Agency for International Development.

• Planches pour le Diagnostic microscopique du paludisme (PDF file: 885 kb)

Treatment:
Treatment varies according to the infecting species, the geographic area where the infection was acquired, and the severity of the disease.  A complete guide for treatment of malaria can be found in The Medical Letter (Drugs for Parasitic Infections), as well as on the Division of Parasitic Diseases Web site.