Malaria

Malaria is a parasitic infection of red blood cells and the liver caused by any of four related species: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae. Malaria is transmitted by female Anopheline mosquitoes, which typically bite between dusk and dawn. The chief symptoms are fever, sweats, chills, headache, body aches, and malaise, typically accompanied by anemia and enlargement of the spleen. Complications may include jaundice, low blood sugar, kidney failure, fluid in the lungs (pulmonary edema or ARDS), and circulatory collapse. Infections caused by P. falciparum are particularly dangerous because of a propensity for infected red blood cells to obstruct blood flow to the brain, causing seizures, impaired consciousness, and sometimes coma. (There is recent evidence that a fifth species, P. knowlesi, previous thought to cause malaria only in monkeys, may also cause malaria in humans, especially in southeast Asia. In March 2009, a case was reported in a U.S. traveler to the Philippines. See MMWR for further information.)

It is essential for all travelers to take medication to prevent malaria when visiting any area where malaria occurs, especially sub-Saharan Africa, which accounts for a majority of cases of travel-related malaria. In the United States, most cases of malaria occur in travelers who did not take appropriate malaria prophylaxis. Malaria pills should be purchased before departure, since medications obtained in developing nations may be fake. For countries where chloroquine-resistant malaria occurs, which includes most countries with malaria, there is a choice of three medications: mefloquine (Lariam), atovaquone/proguanil (Malarone)(PDF), or doxycycline. Mefloquine is given once weekly in a dosage of 250 mg, starting one-to-two weeks before arrival and continuing through the trip and for four weeks after departure. Mefloquine may cause mild neuropsychiatric symptoms, including nausea, vomiting, dizziness, insomnia, and nightmares. Rarely, severe reactions occur, including depression, anxiety, psychosis, hallucinations, and seizures. Mefloquine should not be given to anyone with a history of seizures, psychiatric illness, cardiac conduction disorders, or allergy to quinine or quinidine, which are related medications. Mefloquine should be avoided in scuba divers, because of the potential for lowering the seizure threshold, which might complicate decompression illness. For further information, see the Lariam Medication Guide (PDF). For children, the dosage is 5 mg/kg weekly for those weighing less than 15 kg but more than 5 kg, 1/4 pill (62.5 mg) weekly for those weighing 15-19 kg, 1/2 pill (125 mg) weekly for those weighing 20-30 kg, and 3/4 pill (187.5 mg) weekly for those weighing 31-45 kg. Children weighing more than 45 kg should be given the adult dosage. A review of mefloquine use in pregnancy, from clinical trials and reports of inadvertent use of mefloquine during pregnancy, suggests that its use at prophylactic doses is not associated with adverse fetal or pregnancy outcomes.

Malarone is a combination pill consisting of 250 mg of atovaquone and 100 mg of proguanil, taken once daily with food starting two days before arrival and continuing through the trip and for seven days after departure. Side-effects, which are typically mild, may include abdominal pain, nausea, vomiting, headache, diarrhea, or dizziness. Serious adverse reactions are rare. For children, the dosage is one-half pediatric Malarone pill (containing 62.5 mg of atovaquone and 25 mg of proguanil) each day for those weighing 5-8 kg, 3/4 pediatric pill each day for those weighing 8-10 kg, one pediatric pill daily for those weighing 10-20 kg, two pediatric pills daily for those weighing 20-30 kg, and three pediatric pills daily for those weighing 30-40 kg. Children weighing more than 40 kg (88 pounds) should be given the adult dosage. Malarone is not recommended for use in pregnant or lactating women, in children weighing less than 5 kg (11 pounds), or in those with renal insufficiency. Proguanil may enhance the anticoagulant effect of warfarin (Coumadin).

Limited data indicate that the efficacy of the two drugs is about the same and that Malarone may be somewhat better tolerated than Lariam. Malarone is only given for seven days after leaving a malarious area, compared to four weeks for Lariam. However, since Lariam is only given once weekly, the total number of pills that must be taken is greater for Malarone. Some authorities recommend Malarone for shorter trips and reserve Lariam for longer journeys abroad. Others prefer Lariam because of its longer track record and reserve Malarone for those unable to tolerate Lariam. The chief point is that, with the exception of travel to certain areas in Thailand, either drug is entirely appropriate for any trip to any area where chloroquine-resistant malaria occurs, i.e. what's important is to take one of the approved drugs, not which drug is taken.

Doxycycline is also effective, but may cause an exaggerated sunburn reaction, which limits its usefulness in the tropics. Sunscreen is essential. Doxycycline may cause inflammation of the esophagus when taken on an empty stomach, especially at bedtime, so it should always be taken with food and never before lying down. In women, doxycycline is a frequent cause of vaginal yeast infections; an antifungal medication should be included in the medical kit. The usual dosage of doxycycline is 100 mg daily starting one or two days before arrival in the malarious area and continuing through the trip and for four weeks after departure. For children greater than 12 years of age, the dosage is 2 mg/kg daily up to the adult dosage of 100 mg. Doxycycline should not be given to children less than 12 years old, pregnant or lactating women, or anyone with a history of tetracycline allergy. It should also be avoided in anyone taking hepatotoxic medications and anyone with a history of liver disease, lupus, or myasthenia gravis. Doxycycline may increase the plasma levels of cyclosporine and may enhance the anticoagulant effect of warfarin (Coumadin).

Though not approved for this usage in the United States, several studies have shown that primaquine is highly effective in preventing malaria. It is available in tablets containing 5, 7.5, and 15 mg of primaquine base (15 mg base is equivalent to 26.3 mg primaquine phosphate). The usual adult dosage is two 15 mg pills starting one day before arrival in the malarious area and continuing through the trip and for seven days after departure. For children 4 years or older, the dosage is 0.5 mg base/kg body weight. Adverse reactions may include nausea, vomiting, and abdominal pain. Primaquine may cause hemolytic anemia in those with G6PD deficiency, so a blood test documenting normal G6PD levels must be obtained before starting primaquine. In those with normal G6PD levels, the main side-effect of primaquine is gastrointestinal disturbance, which can be minimized by taking the medication with food.

The combination of chloroquine and proguanil is no longer recommended by the CDC for the prevention of chloroquine-resistant malaria, because it appears less effective than either Lariam, Malarone, or doxycycline.

There are a small number of countries where chloroquine, which for many years was the first-line drug against malaria, is still reliably effective. The list includes the Dominican Republic, Haiti, Central America west of the Panama Canal Zone, Egypt, and most countries in the Middle East. For these countries, the recommended prophylaxis is chloroquine 500 mg weekly, starting one week before arrival in the malarious area and continuing through the trip and for four weeks after departure. For children, the dosage is 8.3 mg/kg weekly, up to the adult dosage of 500 mg. The side-effects of chloroquine, which are generally minor, may include gastrointestinal disturbances, headache, dizziness, blurred vision, and itching. Those who have trouble tolerating chloroquine may take it with food or may divide the dose in half and take it twice weekly. Chloroquine may cause exacerbations of psoriasis or myasthenia gravis. Chloroquine should be avoided in travelers with a history of seizures, retinal disease, liver disease, or known hypersensitivity to the drug. There is no evidence of harmful effects during pregnancy. Because of possible drug interactions, chloroquine should be avoided in those taking moxifloxacin (Avelox) (increased risk of ventricular arrhythmias), amiodarone (increased risk of ventricular arrhythmias), cyclosporine (increased risk of toxicity), digoxin (possibly increases digoxin levels), and mefloquine (increased risk of seizures). Those taking chloroquine for more than 6 years should undergo periodic eye examinations because of a small risk of retinal toxicity.

None of the above regimens gives complete protection. Both during and after the trip, travelers should be alert to the symptoms of malaria, which may include fever, chills, headaches, muscle aches, weakness, vomiting, or diarrhea. Travelers who may not have access to medical care should bring along medications for emergency self-treatment should they develop symptoms suggestive of malaria and cannot obtain medical care within 24 hours.

One option for emergency self-treatment is to take a combination of artemether and lumefantrine, marketed as Coartem in the United States and as Riamet in Europe. Each pill contains 20 mg of artemether and 120 mg of lumefantrine. A 3-day course is recommended: one pill twice daily for those weighing 5-14 kg, 2 pills twice daily for those weighing 15-24 kg, 3 pills twice daily for those weighing 25-34 kg, and 4 pills twice daily for those weighing 35 kg or greater. The second dose should be given 8 hours after the first. Riamet/Coartem should be taken with milk or a fat-containing food. In adults, the most common adverse reactions are headache, loss of appetite, dizziness, weakness, joint pain, and muscle pain. In children, the most common adverse reactions are fever, cough, vomiting, loss of appetite, and headache. Riamet/Coartem should not be given during the first trimester of pregnancy, to nursing mothers, or to children weighing less than 5 kg. (A related drug called artesunate recently became available in the United States for treatment of severe malaria in-hospital, but only through the CDC's Drug Service and Quarantine Stations. To obtain the medication, physicians should call 770-488-7788 M-F, 8am-4:30pm eastern time, or 770-488-7100 after hours).

Increasing resistance to artemisinin and artemisinin-derivatives, including artemether, has been reported from parts of southeast Asia, including western Cambodia, the border regions of Thailand and Cambodia, border regions of Thailand and Myanmar, eastern Myanmar, and the Binh Phuc Province of Viet Nam (see the World Health Organization.

Another option is to take Malarone in a dosage of four pills daily for three consecutive days, but Malarone should not be used for self-treatment if the traveler has been on Malarone prophylaxis. For children weighing 25-45 pounds, the dosage is one adult pill taken daily for three days. For those weighing 46-67 or 68-88 pounds, the dosage is 2 or 3 adult pills daily, respectively, for three days.

A final option for self-treatment is to take quinine 650 mg three times daily and doxycycline 100 mg twice daily for one week.

For pregnant women, the recommendation for emergency self-treatment is quinine 650 mg mg three times daily with clindamycin 450 mg three times daily for 5-7 days, though pregnant women should make all possible efforts to obtain medical care rather than self-medicating.

Malaria prophylaxis should be resumed one week after the first treatment dose, unless quinine has been used for self-treatment and mefloquine for prophylaxis, in which case mefloquine should be resumed one week after the last dose of quinine.

Every effort should be made to consult with a physician rather than relying upon self-medication. Travelers who will have access to medical care do not need to bring along medication for emergency self-treatment.

The importance of insect protection measures cannot be overstated. These are reviewed elsewhere.

From the World Health Organization

Roll back malaria department

What is malaria?

Malaria in pregnancy

Children and malaria

Insecticide-treated mosquito nets

Guidelines for the treatment of malaria

Roll Back Malaria Partnership

Malaria (from "International Travel and Health")

From the Centers for Disease Control

Malaria home page

Malaria

Information for the Public: Prescription Drugs for Malaria

Malaria: Prescription Drugs, Provider Info

Diseases: Malaria: Prevention, Pregnant Women, Public Info

Malaria Deaths Following Inappropriate Malaria Chemoprophylaxis ---United States, 2001 (MMWR)

Availability and Use of Parenteral Quinidine Gluconate for Severe or Complicated Malaria (MMWR)

From the U.K. Health Protection Agency

Malaria

Malaria treatment guidelines

Malaria Imported into the UK, 2003: implications for those advising travellers

An internet-based tool-kit for the initial investigation of cases of cryptic malaria

Guidelines for malaria prevention in travellers from the United Kingdom in 2003 (PDF)

Malaria prophylaxis for long-term travellers (PDF)

Cryptic malaria cases in England - 2002

From the Pan American Health Organization

Malaria