Malaria

Introduction

Infectious agent

Malaria in humans is caused by protozoan parasites of the genus Plasmodium, including Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax. Zoonotic forms, especially Plasmodium knowlesi, a parasite of Old World (Eastern Hemisphere) monkeys in Southeast Asia, have been documented as causes of human infections and some deaths.

Transmission

Plasmodium species are transmitted by the bite of an infective female Anopheles mosquito. Malaria transmission occurs in large areas of Africa, Latin America, and parts of the Caribbean, the South Pacific, and in Asia, including South Asia, Southeast Asia, and the Middle East. Occasionally, transmission occurs by blood transfusion, needle sharing, organ transplantation, or vertically from mother to fetus. Spread through contamination of shared medical equipment or medication has been reported.

Epidemiology

Malaria is a major international public health problem. According to the World Health Organization (WHO) World malaria report 2024, 83 countries reported approximately 263 million infections and 597,000 deaths in 2023. Travelers going to malaria-endemic destinations are at risk of contracting the disease, and almost all the approximately 2,000 cases of malaria that occur each year in the United States are imported. After 2 decades of no reported locally acquired mosquito-transmitted malaria in the United States, 10 cases were reported from 4 states (FL, TX, MD, AR) in 2023.

The risk of acquiring malaria differs substantially from traveler to traveler and from region to region, even within a single country. This variability is a function of the intensity of transmission within the various regions and the itinerary, duration, season, and type of travel. Risk also varies by travelers' adherence to mosquito precautions and chemoprophylaxis recommendations. In 2019 and 2020, the number of cases of malaria diagnosed in the United States and its territories and reported to the Centers for Disease Control and Prevention (CDC) were 2,048 and 602, respectively. Of cases in 2019 for which country of acquisition was known, 93% were acquired in Africa, 4% in Asia, 2% in the Caribbean and the Americas, and <1% in Oceania and the Middle East. Of U.S. civilians with malaria who reported a reason for travel, 76% were visiting friends and relatives.

Information about malaria transmission in specific countries is derived from various sources, including WHO (see Yellow Fever Vaccine and Malaria Prevention Information, by Country chapter). The information presented here was accurate at the time of publication; readers are encouraged to see updated information on the CDC website because malaria transmission can change rapidly and from year to year due to changes in local weather conditions, mosquito vector density, and prevalence of infection.

Clinical presentation

Malaria is characterized by fever and influenza-like symptoms, including chills, headache, myalgias, and malaise; symptoms can occur intermittently. In severe disease, acute kidney injury, acute respiratory distress syndrome, mental confusion, severe anemia, seizures, coma, and death can occur. Malaria symptoms can develop as early as 7 days after being bitten by an infectious mosquito and as late as several months or more after exposure. Suspected or confirmed malaria, especially P. falciparum, is a medical emergency requiring urgent intervention because clinical deterioration, including death, can occur rapidly and unpredictably. Travelers who decline to take chemoprophylaxis, who receive a suboptimal drug regimen (e.g., chloroquine in an area with chloroquine-resistant P. falciparum), or who require a less-than-optimal drug regimen for medical reasons are at increased risk for acquiring malaria. Travelers with symptoms of malaria should seek the best available medical services as soon as possible, even if still traveling, and should continue their chemoprophylaxis regimen until they have a definitive diagnosis. See Box 4.10.1 for frequently asked clinical questions.

Box: 4.10.1

Diagnosis

Consider malaria in any patient with a febrile illness who has recently returned from a malaria endemic country. All patients in which malaria is considered should receive diagnostic testing immediately; blood smear microscopy is recommended for all of these patients and, if available, additional diagnostic testing such as a malaria RDT should be conducted concurrently if the results can be available more quickly (e.g., within hours) to guide initial antimalarial treatment.

Diagnostic assistance is available from state public health laboratories or CDC. CDC can also assist laboratories conducting blood smear microscopy through a telediagnosis service; in some cases, confirmation of the species causing malaria is conducted using PCR testing. CDC conducts surveillance for mutations in malaria parasites that confer resistance to medications. For further information on submission of specimens for antimalarial resistance surveillance testing, contact malarialab@cdc.gov.

In the United States, malaria is a notifiable disease. Positive malaria tests are reported electronically to public health departments by laboratories, but healthcare professionals are encouraged to report atypical presentations of malaria (e.g., no travel history, non-response to treatment) to local or state health departments or the CDC Malaria Hotline. See more information on reporting malaria.

Blood smear microscopy

Blood smear microscopy remains the most important method for malaria diagnosis. Microscopy can provide immediate information about the presence of parasites, allow quantification of the density of the infection, and allow determination of the species of the malaria parasite, all of which are necessary for providing the most appropriate treatment. Tests should be performed immediately, and microscopy results should be available as soon as possible, within 24 hours of the patient's presentation. Assistance with speciation of malaria on smears is available from state health departments or CDC.

Rapid diagnostic testing

RDTs for malaria detect antigens derived from malaria parasites. Malaria RDTs are immunochromatographic tests that most often use a dipstick or cassette format and provide results in 2–15 minutes. RDTs offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not immediately available. The U.S. Food and Drug Administration (FDA) has approved an RDT (the BinaxNOW Malaria test) for hospital and commercial laboratory use; the test is not approved for use by clinicians or patients. Although RDTs can detect malaria antigens within minutes, they have several limitations. RDTs cannot distinguish between all Plasmodium species that affect humans; they might be less sensitive than expert microscopy or PCR for diagnosis; they cannot quantify parasitemia; and an RDT-positive test result might persist for days or weeks after an infection has been treated and cleared. RDTs are not useful for assessing response to therapy. In some areas, mutations are increasingly identified in malaria parasites, resulting in an absence of the malaria antigen usually detected by many RDTs, including the only RDT used in the United States. The absence of this parasite antigen in peripheral blood can lead to false-negative RDT results.

In the United States, positive and negative RDT results must always be confirmed by microscopy. Microscopy confirmation of the RDT result should occur as soon as possible because information on the presence, density, and parasite species is critical for optimal management of malaria. Laboratories that do not provide in-house, on-the-spot microscopy services should maintain a stock of malaria RDTs to perform immediate malaria diagnostic testing when needed.

PCR testing

PCR tests are more sensitive than routine microscopy, but results are not usually available as quickly as microscopy results, thus limiting the utility of PCR for rapid diagnosis and initial clinical management. Use of PCR testing is encouraged to confirm the species of malaria parasite and detect mixed infections.

Treatment

Malaria can be treated effectively if treatment begins early in the disease; delaying therapy can have serious or even fatal consequences. Specific treatment options depend on the species of malaria, severity of infection, likelihood of drug resistance (based on where the infection was acquired), the patient's age, and whether the patient is pregnant or breastfeeding.

See detailed CDC recommendations for malaria treatment. Consultation with a clinician experienced with management and treatment of malaria is recommended. For assistance with diagnosis or treatment of malaria, call the CDC Malaria Hotline (770-488-7788 or toll-free at 855-856-4713) from 9 a.m. to 5 p.m. Eastern Time. After hours, on weekends, or on holidays, call the CDC Emergency Operations Center at 770-488-7100 and ask the operator to contact the subject matter expert on call for the Malaria Branch.

If a traveler becomes ill and is diagnosed with malaria while abroad, be aware that medications not used in the United States to treat malaria are widely available in other countries. However, the treatment prescribed should be based on the malaria treatment guidelines of the country. Halofantrine is not recommended for treatment because of documented adverse cardiac events, including deaths. These adverse events have occurred in people with and without preexisting cardiac problems, and both in the presence and absence of other antimalarial drugs. Sulfadoxine-pyrimethamine alone is not recommended because of widespread drug-resistant Plasmodium falciparum.

Reliable supply of malaria treatment

Some travelers who take effective chemoprophylaxis but who will be in remote areas might decide, in consultation with their travel health professional, to carry a reliable supply of a full course of an approved malaria treatment regimen. This reliable supply does not obviate the need for malaria chemoprophylaxis. In the event a traveler carrying a reliable supply is diagnosed with malaria, they will have immediate access to an approved treatment.

The reliable supply should be acquired in the United States, so clinicians can consider the traveler's other medical conditions or medications when selecting an antimalarial drug and to avoid the possibilities of travelers obtaining counterfeit drugs in the local pharmacy or market or depleting local resources. In rare instances when access to medical care is not available and the traveler develops a febrile illness consistent with malaria, the reliable supply medication can be self-administered presumptively. Self-treatment of a possible malarial infection is only a temporary measure, and prompt medical evaluation is imperative.

Two malaria treatment regimens available in the United States can be prescribed as a reliable supply for self-treatment: atovaquone-proguanil and artemether-lumefantrine. The chosen medication should not be the same (or related) drug that has been taken for chemoprophylaxis. For example, atovaquone-proguanil can be used as a reliable supply medication by travelers who are not taking atovaquone-proguanil for chemoprophylaxis. See Table 4.10.1 for dosing recommendations.

Table 4.10.1: Reliable supply regimens for malaria treatment¹

Prevention

Malaria prevention consists of a combination of mosquito-avoidance measures and chemoprophylaxis. Prevention measures must address all malaria species in the travel area. Although highly efficacious, interventions are not 100% effective, so all febrile persons returning from malaria-endemic areas should be tested for malaria even if they took chemoprophylaxis.

Preventing malaria involves striking a balance between effectiveness and safety: ensuring that all people at risk for infection use the recommended prevention measures and preventing rare occurrences of adverse effects. A risk assessment for every traveler includes collecting detailed information about travel itinerary, including countries, specific areas to be visited in those countries (e.g., cities, rural areas, both), types of accommodation, season, and style of travel. As part of the risk assessment, consider traveler characteristics (e.g., pregnancy, underlying health conditions, medications) and epidemiological features of malaria at the destination (e.g., intensity of transmission, local parasite resistance to drugs). Depending on the level of risk, it might be appropriate to recommend no specific interventions, mosquito avoidance measures only, or mosquito avoidance measures plus chemoprophylaxis.

Several factors increase a traveler's risk for malaria. Travel, even for short periods of time, to areas with intense malaria transmission can result in infection. Malaria transmission is not distributed homogeneously throughout a country, so review the exact itinerary to determine if travel will occur in highly endemic areas. In countries where malaria is seasonal, travel during peak transmission season increases risk. Travelers going to rural areas or staying in accommodations without screens or air conditioning also will be at greater risk. Most cases of malaria seen in the United States are in first- and second-generation immigrants living in non-endemic countries who return to their countries of origin to visit friends and relatives (VFRs). VFR travelers may erroneously consider themselves immune to malaria because they grew up in a malaria-endemic country. The partial immunity acquired through continuous exposure to malaria is lost quickly, and VFR travelers should be considered to have the same risk of malaria as other nonimmune travelers (see Visiting Friends and Relatives: VFR Travel chapter). Even if a traveler has had malaria in the past, they still need to take preventive measures.

Mosquito avoidance measures

Malaria transmission occurs primarily between dusk and dawn because of the nocturnal feeding habits of Anopheles mosquitoes. Travelers can reduce contact with mosquitoes by remaining in enclosed air-conditioned rooms or well-screened areas, sleeping under mosquito nets (preferably insecticide-treated), using an effective insecticide spray or mosquito coils in living and sleeping areas during evening and nighttime hours, and wearing clothes that cover most of the body.

All travelers should use an effective mosquito repellent, such as those that contain DEET (see Mosquitoes, Ticks, and Other Arthropods chapter). Repellents should be applied to exposed parts of the skin. If travelers are also wearing sunscreen, they should apply sunscreen first and insect repellent second (see Sun Exposure in Travelers chapter). A permethrin-containing product can be applied to mosquito nets and clothing for additional protection against mosquitoes. Mosquito repellant-impregnated clothing also is available.

Chemoprophylaxis

Choosing a drug to prevent malaria

All recommended malaria chemoprophylaxis regimens involve taking a medicine before, during, and after travel to an area with malaria. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites. In choosing a chemoprophylaxis regimen before travel, the traveler and the travel medicine specialist should consider several factors, including the presence of antimalarial drug resistance in the area of travel, length of travel, the patient's other medical conditions, allergy history, other medications prescribed or already being taken (to assess possible drug interactions), potential side effects, and the cost of the antimalarial (see Medication and Vaccine Interactions in Travel Medicine chapter). Long-term travelers, defined as people who travel for ≥6 months, have additional considerations (Box 4.10.2; see Long-Term Travelers and Expatriates chapter). Table 4.10.2 lists some of the benefits and limitations of medicines used for malaria chemoprophylaxis; see additional information about choosing a malaria chemoprophylaxis regimen. Because both tafenoquine and primaquine can cause hemolytic anemia in persons with glucose-6-phosphate-dehydrogenase (G6PD) deficiency, quantitative G6PD testing must be done before prescribing primaquine or tafenoquine. No antimalarial drug is 100% protective, so travelers must combine chemoprophylaxis with mosquito avoidance and personal protective measures (e.g., insect repellent, long-sleeved shirts, long pants, sleeping in a mosquito-free setting, using an insecticide-treated mosquito net).

It is helpful to provide travelers with approaches to managing any adverse events they may experience from malaria chemoprophylaxis medication (e.g., remember to take with food; change time of day; identify other causes of symptoms; manage symptoms without stopping antimalarial if possible) and know what to do if they miss a dose (take the next dose with food as soon as possible; do not double the dose the day after the missed dose).

Recommended options for malaria chemoprophylaxis by country of travel can be found in the Yellow Fever Vaccine and Malaria Prevention Information, by Country chapter. Table 4.10.2 provides additional information to help determine which of the recommended malaria chemoprophylaxis drugs might be best for a traveler.

Table 4.10.2: Malaria chemoprophylaxis, prescribing considerations

Obtaining medications overseas

Travelers should be discouraged from obtaining chemoprophylaxis medications while abroad. Malaria chemoprophylaxis medications might be available at overseas destinations, including drugs not recommended in the United States; however, the quality of these products is often not known. Products might be produced under substandard manufacturing practices, be counterfeit, contain contaminants, not be protective, or be dangerous. See additional information on medications obtained while traveling.

Travel to areas with chloroquine-resistant malaria

Chloroquine-resistant P. falciparum is found in all parts of the world (Africa, Asia, South America) except the Caribbean and Central American countries west of the Panama Canal. Chloroquine-resistant P. vivax has been confirmed only in Papua New Guinea and Indonesia. For destinations with known chloroquine-resistant Plasmodium spp., effective malaria chemoprophylaxis options include atovaquone-proguanil, doxycycline, mefloquine, or tafenoquine.

Travel to areas with chloroquine-sensitive malaria

Areas with chloroquine-sensitive Plasmodium spp. include several Latin American countries where malaria predominantly is caused by P. vivax. Chloroquine-sensitive P. falciparum is present in the Caribbean and Central American countries west of the Panama Canal. For destinations in which all Plasmodium spp. are known to be chloroquine-sensitive, effective malaria chemoprophylaxis options include chloroquine, atovaquone-proguanil, doxycycline, mefloquine, and tafenoquine. In countries where P. vivax predominates, primaquine is also an option. Because both tafenoquine and primaquine can cause hemolytic anemia in persons with G6PD deficiency, quantitative G6PD testing must be done before prescribing primaquine or tafenoquine.

Travel to areas with mefloquine-resistant malaria

Mefloquine-resistant P. falciparum has been confirmed in Southeast Asia on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, in the eastern states of Burma on the border between Burma and China, along the borders of Burma and Laos, and in southern Vietnam. For destinations with known mefloquine-resistant Plasmodium spp., effective malaria chemoprophylaxis options are atovaquone-proguanil, doxycycline, and tafenoquine.

Medications used for chemoprophylaxis

Atovaquone-proguanil

Atovaquone-proguanil (Malarone) is a fixed combination of the drugs atovaquone and proguanil. Chemoprophylaxis should begin 1–2 days before travel to malaria-endemic areas; the medication should then be taken daily, with food, ideally at the same time each day, while in malaria-endemic areas, and daily for 7 days after leaving the endemic areas (see Table 4.10.3 for recommended dosages). Atovaquone-proguanil is well-tolerated, and side effects are rare. The most common adverse effects reported in people using atovaquone-proguanil for chemoprophylaxis or treatment are abdominal pain, nausea, vomiting, and headache.

Atovaquone-proguanil is not recommended for chemoprophylaxis in children weighing <5 kg (<11 lb), pregnant women, women breastfeeding infants <5 kg, or patients with severe renal impairment (creatinine clearance <30 mL/min). Proguanil can increase the effect of warfarin, so travelers might need international normalized ratio monitoring or adjustment of warfarin dosage. No data are available regarding the clinical impact of taking atovaquone-proguanil and warfarin at the same time.

Table 4.10.3: Malaria chemoprophylaxis, dosing information

Chloroquine and hydroxychloroquine

Chloroquine phosphate or hydroxychloroquine sulfate (Plaquenil) can be used to prevent malaria only in destinations where chloroquine-resistant Plasmodium spp. are not prevalent (see Yellow Fever Vaccine and Malaria Prevention Information, by Country chapter). Chemoprophylaxis should begin 1–2 weeks before travel to malaria-endemic areas. Travelers should continue taking the drug once a week, on the same day of the week, during travel in malaria-endemic areas, and for 4 weeks after they leave endemic areas (see Table 4.10.3 for recommended dosages).

Reported side effects of chloroquine and hydroxychloroquine include blurred vision, dizziness, gastrointestinal disturbance, headache, insomnia, and pruritus, but generally, these effects do not require travelers to discontinue the drug. An alternative drug might be preferred by travelers who experienced pruritus with previous use of the drug. High doses of chloroquine (e.g., those used to treat rheumatoid arthritis) have been associated with retinopathy; this serious side effect appears to be extremely unlikely when chloroquine is used for routine weekly malaria chemoprophylaxis. Chloroquine and related compounds reportedly can exacerbate psoriasis. People who experience uncomfortable side effects after taking chloroquine might tolerate the drug better by taking it with meals. As an alternative, a traveler experiencing side effects might better tolerate the related compound, hydroxychloroquine sulfate.

Doxycycline

Doxycycline chemoprophylaxis should begin 1–2 days before travel to malaria-endemic areas. Doxycycline should be taken once a day during travel in malaria-endemic areas and daily for 4 weeks after the traveler leaves endemic areas. Insufficient data exist on the antimalarial prophylactic efficacy of related compounds (e.g., minocycline, commonly prescribed for the treatment of acne). People on a long-term regimen of minocycline who need malaria chemoprophylaxis should stop taking minocycline 1–2 days before travel and start doxycycline instead. Minocycline can be restarted after the full course of doxycycline is completed (see Table 4.10.3 for recommended dosages).

Doxycycline can cause photosensitivity, usually manifested as an exaggerated sunburn reaction. The risk for such a reaction can be minimized by avoiding prolonged, direct exposure to the sun and by using sunscreen (see Sun Exposure in Travelers chapter). Doxycycline use is associated with an increased frequency of vaginal yeast infections.

Gastrointestinal side effects (e.g., nausea, vomiting) can be minimized by taking the drug with a meal or by specifically prescribing doxycycline monohydrate or the enteric-coated doxycycline hyclate, rather than the generic doxycycline hyclate, which is often less expensive. To reduce the risk for esophagitis, advise travelers to swallow the medicine with sufficient fluids and to avoid taking doxycycline before lying down or going to bed.

Doxycycline is contraindicated in people with an allergy to tetracyclines, in pregnant women, and in infants and children aged <8 years. Vaccination with the oral typhoid vaccine Ty21a should be completed ≥24 hours before taking a dose of doxycycline.

Mefloquine

Mefloquine chemoprophylaxis should begin ≥2 weeks before travel to malaria-endemic areas. Travelers should continue taking the drug weekly, on the same day each week, during travel in malaria-endemic areas and for 4 weeks after leaving endemic areas (see Table 4.10.3 for recommended dosages).

Mefloquine has been associated with rare but serious adverse reactions (e.g., psychosis, seizures) when taken at prophylactic doses; these reactions are more frequent with the higher doses used for treatment. Other side effects reported in chemoprophylaxis studies include abnormal dreams, anxiety disorder, depression, dizziness, gastrointestinal disturbance, headache, insomnia, and visual disturbances. Other neuropsychiatric disorders occasionally reported include aggressive behavior, agitation or restlessness, confusion, encephalopathy, forgetfulness, hallucinations, mood changes, panic attacks, paranoia, and sensory and motor neuropathies (e.g., ataxia, paresthesia, tremors).

FDA also includes a boxed warning that mefloquine may cause neuropsychiatric adverse reactions that can persist after mefloquine has been discontinued. Mefloquine is contraindicated in people with active depression, a recent history of depression, generalized anxiety disorder, psychosis, schizophrenia and other major psychiatric disorders, or seizures. Mefloquine should be avoided in people with a history of depression. Mefloquine is also contraindicated for travelers with a known hypersensitivity to the drug or related compounds (e.g., quinidine, quinine).

Mefloquine is not recommended for people with cardiac conduction abnormalities. A review of available data suggests that mefloquine can be used safely in people concurrently taking beta-blockers if they have no underlying arrhythmia.

Any traveler receiving a prescription for mefloquine must also receive a copy of the FDA medication guide.

Primaquine

Primaquine can cause potentially life-threatening hemolysis in people with glucose-6-phosphate-dehydrogenase (G6PD) deficiency. G6PD deficiency must be ruled out with a quantitative laboratory test before prescribing primaquine to patients.

Primaquine phosphate has 2 distinct uses for malaria prevention in people with normal G6PD levels: primary chemoprophylaxis in areas with primarily P. vivax and terminal chemoprophylaxis for travelers who have had prolonged exposure to P. vivax or P. ovale in malaria-endemic areas. Among people with normal G6PD levels taking primaquine, the most common adverse event is gastrointestinal upset, which can be minimized or eliminated if it is taken with food.

Primary chemoprophylaxis

When taken for primary chemoprophylaxis, primaquine should be taken 1–2 days before travel to malaria-endemic areas, daily, with food, ideally at the same time each day, while in the malaria-endemic area, and daily for 7 days after leaving the area (see Table 4.10.3 for recommended dosages).

Terminal chemoprophylaxis

Terminal chemoprophylaxis (also known as presumptive antirelapse therapy) is indicated for long-term travelers (e.g., military personnel, missionaries, Peace Corps volunteers) with prolonged exposure to P. ovale or P. vivax malaria. Terminal prophylaxis involves taking primaquine toward the end of the exposure period (or immediately thereafter) for the purpose of eliminating hypnozoites (dormant liver stages) of P. ovale or P. vivax and preventing relapses or delayed-onset clinical presentations of malaria. Most malaria-endemic areas of the world (except the Caribbean) have circulating P. vivax and/or P. ovale. Travelers to these areas have some risk of relapsing malaria, although the actual risk for an individual traveler is difficult to define.

When indicated, travelers should take primaquine for 14 days after leaving a malaria-endemic area, concurrently with their primary chemoprophylaxis medication. If chloroquine, doxycycline, or mefloquine is used for primary chemoprophylaxis, prescribe primaquine for travelers to take during the last 2 weeks of chemoprophylaxis. When atovaquone-proguanil is used, travelers can take primaquine during the final 7 days of atovaquone-proguanil, and then for an additional 7 days. If concurrent administration of primary and terminal chemoprophylaxis is not feasible, instruct travelers to take primaquine after completing their primary chemoprophylaxis medication. Primary chemoprophylaxis with primaquine or with tafenoquine (see the following section) obviates the need for terminal chemoprophylaxis.

Tafenoquine

Tafenoquine can cause potentially life-threatening hemolysis in people with G6PD deficiency. Rule out G6PD deficiency with a quantitative laboratory test before prescribing tafenoquine to patients.

Primary chemoprophylaxis

Tafenoquine (Arakoda 100 mg tablets) can be used to prevent malaria in adults (see Table 4.10.3 for recommended dosages). Travelers should take a daily loading dose of tafenoquine for 3 days before leaving for a malaria-endemic area; starting 7 days after the loading dose is complete, they should take a weekly maintenance dose while in the malaria-endemic area; then take a final dose in the week after leaving the malaria-endemic area. Doses should be taken on the same day each week.

Tafenoquine is contraindicated in pregnant women. It is contraindicated during breastfeeding if either the breastfeeding woman or the infant have intermediate or low G6PD activity or if their G6PD status is unknown. Avoid prescribing tafenoquine for people with a history of psychotic disorder; rare psychiatric adverse events have been observed in people with a history of psychotic disorder using higher doses of tafenoquine. The most common adverse events reported with use of tafenoquine are dizziness, gastrointestinal disturbances, headache, and clinically insignificant decreases in hemoglobin. Tafenoquine should be taken with food.

Terminal chemoprophylaxis

As of 2020, CDC no longer recommends tafenoquine for terminal chemoprophylaxis of P. ovale or P. vivax malaria.

Chemoprophylaxis for infants, children, and adolescents

All children traveling to malaria-endemic areas should use recommended prevention measures, which often include taking an antimalarial drug. Calculate pediatric doses carefully according to the patient's body weight, but never exceed the adult dose. In the United States, antimalarial drugs are not available in liquid formulation and can taste bitter. Pharmacists can pulverize tablets and prepare gelatin capsules for each measured dose. If a child is unable to swallow capsules or tablets, parents should prepare the child's medication dose by breaking open the gelatin capsule or crushing the pill and mixing the drug with a small amount of something sweet (e.g., condensed milk, chocolate syrup, chocolate spread) to ensure the entire dose is delivered to the child. Giving the dose on a full stomach can minimize stomach upset and vomiting.

Atovaquone-proguanil can be used as chemoprophylaxis for infants and children weighing ≥5 kg (≥11 lb); prophylactic dosing for children weighing <11 kg (<24 lb) constitutes off-label use in the United States. Chloroquine and mefloquine are options for infants and children of all ages and weights, depending on drug resistance at the destination. Doxycycline can be used for children aged ≥8 years. Primaquine can be used for children who are not G6PD-deficient and who are traveling to areas with principally P. vivax. Pediatric dosing regimens are included in Table 4.10.3.

Chemoprophylaxis during pregnancy

Malaria infection can be more severe in pregnant than in nonpregnant women. Malaria increases the risk for adverse pregnancy outcomes, including premature birth, spontaneous abortion, and stillbirth. Because no chemoprophylaxis regimen is completely effective, avoidance of travel to areas with malaria transmission during pregnancy is optimal (see Pregnant Travelers chapter). If travel to a malaria-endemic area cannot be deferred, an effective chemoprophylaxis regimen and mosquito avoidance measures are essential.

Pregnant women traveling to areas where chloroquine-resistant P. falciparum has not been reported can take chloroquine chemoprophylaxis. Chloroquine has not been found to have harmful effects on the fetus when used in the recommended doses for malaria chemoprophylaxis.

For travel to areas with chloroquine-resistant Plasmodium, mefloquine is the only medication recommended for malaria chemoprophylaxis during pregnancy. Studies of mefloquine use during pregnancy have found no indication of adverse effects on the fetus.

Atovaquone-proguanil is not recommended for use during pregnancy because of limited availability of data on its safety and because other options are available. If other antimalarial drug options are not feasible, clinicians and patients should weigh the options, risks, and benefits of using atovaquone-proguanil to make the best decision for the patient. Doxycycline is contraindicated for malaria chemoprophylaxis during pregnancy because of the risk for adverse effects seen with tetracycline, a related drug, on the fetus. These adverse effects include discoloration and dysplasia of the teeth and inhibition of bone growth. Neither primaquine nor tafenoquine should be used during pregnancy; both drugs can be passed transplacentally to a G6PD-deficient fetus and cause hemolytic anemia in utero.

Women planning to become pregnant can use the same medications recommended for use during pregnancy (chloroquine or mefloquine, depending on the area of travel). There are no data to guide specific recommendations about delaying pregnancy after the use of malaria chemoprophylaxis medicines. If the traveler or their healthcare professional wishes to decrease the amount of antimalarial drug in the body before conception, Table 4.10.4 provides information on half-lives of the recommended malaria chemoprophylaxis medicines. After 2 half-lives, approximately 25% of the drug remains in the body, 6% remains after 4 half-lives, and 2% remains after 6 half-lives.

Chemoprophylaxis during breastfeeding

Antimalarial drug concentrations in breast milk are too low to protect nursing infants from malaria (see Travel and Breastfeeding). Infants who require chemoprophylaxis should receive the recommended dosages of antimalarial drugs listed in Table 4.10.3. The small amounts of chloroquine and mefloquine excreted in breast milk do not pose a safety hazard to infants. Data about use of doxycycline in lactating women are very limited; the theoretical possibility of adverse events to the infant is considered to be remote.

Atovaquone-proguanil chemoprophylaxis is not recommended for lactating women when their infants weigh <5 kg (<11 lb) because of lack of safety data. Atovaquone-proguanil can be used to treat women with malaria who are breastfeeding infants of any weight when the potential benefit outweighs the potential risk to the infant (e.g., treating a breastfeeding woman who has acquired P. falciparum malaria in an area of multidrug-resistant strains and who cannot tolerate other treatment options).

Limited information is available on the amount of primaquine in human breast milk, and no data are available for tafenoquine. The woman breastfeeding and the infant must be tested for G6PD deficiency before initiating chemoprophylaxis with either of these drugs.

Changing medications as a result of side effects during chemoprophylaxis

Medications recommended for malaria chemoprophylaxis have different modes of action that affect the parasites at different stages of the life cycle. Thus, if the medication needs to be changed because of side effects before a full course has been completed, some special considerations exist (Table 4.10.5). Ideally, travelers would identify side effects before departing so medications switches can occur before arrival in endemic areas. Switching from a daily to a weekly chemoprophylaxis medication is not recommended because it takes time for the weekly medication to reach protective levels.

Table 4.10.4: Half-lives of medications used at doses recommended for malaria chemoprophylaxis

Table 4.10.5: Malaria chemoprophylaxis, changing medications due to side effects¹

Box: 4.10.2

Travel to areas with limited malaria transmission

For destinations where malaria cases occur sporadically and risk for infection to travelers is considered low, CDC recommends that travelers use mosquito avoidance measures only, and no chemoprophylaxis (see Yellow Fever Vaccine and Malaria Prevention Information, by Country chapter).

Blood donation after travel to malaria-endemic areas

People who have been in an area where malaria transmission occurs should defer donating blood after returning from the malaria-endemic area to prevent transmission of malaria through blood transfusion (Table 4.10.6).

Risk assessments can differ between travel medicine specialists and blood banks. A travel medicine specialist advising a traveler going to a country with relatively low malaria transmission for a short period of time and engaging in low-risk behaviors might suggest the traveler use only mosquito-bite precautions and no chemoprophylaxis. Upon the traveler's return, however, a blood bank might still choose to defer blood donations from that traveler because of travel to an area where transmission occurs.

Table 4.10.6: U.S. Food and Drug Administration recommendations for deferring blood donation in people returning from malaria-endemic areas

Acknowledgements

The following authors contributed to the previous version of this chapter: Francisca Abanyie and Kathrine R. Tan.