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DAN Discusses Malaria and Antimalarial Drugs

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Travelers Beware

DAN Discusses Malaria and Antimalarial Drugs

By Dan Leigh, Managing Editor

The July and August issues of Alert Diver hosted stories about dengue fever. Within the series we also mentioned dengue's better-know sister ailment. Malaria, a serious and sometimes fatal disease is caused, like dengue, by the bite of an infected mosquito.

According to the Centers for Disease Control, four kinds of malaria can infect humans: Plasmodium falciparum (plaz-MO-dee-um fal-SIP-a-rum), P. vivax (VIGH-vacks), P. ovale (o-VAHL-ley), and P. malariae (muh-LAIR-ee-uh).

Where Does Malaria Happen?

Malaria occurs in more 100 countries and territories worldwide. More than 40 percent of the people in the world are at risk of contracting the disease. Large areas of Central and South America, Hispaniola (Haiti and the Dominican Republic), Africa, the Indian subcontinent, Southeast Asia, the Middle East and Oceania are considered malaria-risk areas.

How Common Is It?

The World Health Organization estimates that yearly 300-500 million cases of malaria occur; more than 1 million people die of malaria each year. About 1,200 cases of malaria are diagnosed in the United States annually. Most U.S. cases are in immigrants and travelers returning from malaria-risk areas - mostly from sub-Saharan Africa and the Indian subcontinent.

Which Drug To Take?

Prescription Only. Antimalarials are available only by prescription through a healthcare provider, who typically prescribes such medication based on your travel itinerary and medical history. Some antimalarials are more effective in some parts of the world than others. In fact, certain areas of the world have developed strains of malaria (e.g., in P. falciparum or P. vivax; the "P" in both stands for "Plasmodium") that are resistant to conventional suppression with chloroquine phosphate. Additionally, a medical condition may prevent someone from taking certain drugs. Later in this article, you'll read about some available alternative drugs.

Specific to Diving:

There is no clinical data that establishes any interactions with antimalarial drugs and diving. Most dive medicine professionals do not expect any complications with the antimalaria drugs and diving. However, the use of Mefloquine (Lariam) by divers is not universally accepted by all dive medicine professionals. Please consult the dive operator at your destination for the local opinon regarding Mefloquine (Lariam).

Watch Your Dosage.

Overdosage of antimalarials can be fatal. Keep drugs in childproof containers out of the reach of children. Follow dosage schedule exactly, without missing doses. Buy antimalarials in the United States before traveling overseas. The quality of antimalarials sold outside the United States may not be reliable, and they may be difficult to obtain.

Your healthcare provider will prescribe the antimalarial best suited to you and your destination. If you have any questions about the drug recommended, call your healthcare provider or pharmacist.

Prevention

Protect yourself from mosquito bites. Wear long-sleeved shirts and long pants, and apply insect repellent to exposed skin. Mosquitoes that transmit malaria bite between dusk and dawn.

Use insect repellents that contain DEET (chemical name N,N-diethyl-meta-toluamide), a colorless oily liquid insect repellent developed in the early 1960s. The concentration of DEET varies among repellents. Those with concentrations of 30-35 percent are quite effective, generally lasting about four hours. Follow label directions and take these precautions:

  • Use only when outdoors and wash skin after coming indoors.
  • Do not inhale, swallow, or get into the eyes
  • Do not put on wounds or broken skin.
  • Travelers who will not be staying in well-screened or air-conditioned rooms should spray a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours. Sleep under mosquito netting, or bed nets sprayed with the insecticide permethrin or a similarly used insecticide, deltamethrin. In the United States, permethrin is available as a spray or liquid to treat clothes and bed nets. Bed nets already treated with permethrin may also be purchased. Adequate prophylaxis against malaria should also include an antimalarial drug, tailored to the sensitivity of the organism according to the geographic location. THIS IS NOT OPTIONAL: IT IS ESSENTIAL. Tourists traveling to places where malaria is endemic without taking appropriate prophylaxis have died of the disease.

    Antimalarials & Regions

    In this section we'll discuss drugs that are commonly used for malaria prophylaxis. These guidelines and schedules are ones commonly recommended at the time of writing (July, 2002). However, antimalarial drug prophylaxis recommendations frequently change. For updated recommendations check the CDC website (listed below) or with your doctor. Your doctor can recommend dosage schedules and amounts, for both adults and children. The schedules listed in this article apply only for malaria PROPHYLAXIS (PREVENTION). If you contract malaria, treatment of the disease will likely require different dosages, schedules or drugs. If you require malaria prophylaxis and are allergic to any antimalarial drugs, report this to your doctor so that a different drug can be selected.

    Travelers to malaria-risk areas in South America, Africa, the Indian subcontinent, Asia and the South Pacific should take one of the following drugs:

  • Mefloquine;
  • Doxycycline; or
  • Atovaquone/proguanil Malarone(tm).
  • Travelers to the borders of Thailand with Burma (Myanmar) and Cambodia, the western provinces of Cambodia, and in the eastern states of Burma should read "Malaria Information for Travelers to Southeast Asia" at www.cdc.gov/travel/malariadrugs.htm. Mefloquine resistance has been reported in these areas and either doxycycline or Malarone are the recommended antimalarial drug.

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

    Mefloquine (brand name Lariam ®)

    Directions for mefloquine use:

  • Take on a full stomach: e.g., after dinner.
  • Take first dose a week before arrival.
  • Take weekly, on the same day each week, while in risk area.
  • Take once a week for four weeks after leaving the risk area.
  • Mefloquine side effects and warnings:

    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 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 have serious side effects should see a healthcare provider.

    Mefloquine should not be taken by people who are allergic to it. A doctor will usually prescribe the drug for people with the following conditions only after careful consideration:

  • Epilepsy or other seizure disorders;
  • A history of severe mental illness or other psychiatric disorders;
  • An irregular heartbeat, whether diagnosed or treated.
  • Alternatives for travelers who cannot or choose not to take mefloquine include doxycycline or Malarone™.

    Doxycycline

    Directions for doxycycline use:

  • Take the first dose one or two days before arriving in risk area.
  • Take daily, at the same time each day, in risk area.
  • After leaving risk area, take drug once a day for four weeks.
  • Doxycycline side effects and warnings:

  • The drug may cause travelers to sunburn faster than normal. To prevent sunburn, wear protective clothing (optimally dark-colored, tightly woven and highly opaque), a hat, and glasses coated with UVL-absorbing chemicals; avoid the sun between 10 a.m. and 4 p.m., when its rays are at its peak; and use sunscreens with a Sun Protection Factor (SPF) of 15 or higher.
  • Take on a full stomach; for people who experience 'stomach upset' after taking it can often avoid this symptom by avoidance of lying down for an hour after taking the drug.
  • Women who use doxycycline may sometimes develop a vaginal yeast infection. Take an over-the-counter yeast medication on your trip for use if vaginal itching or discharge develops.
  • Doxycycline is not for children under the age of 8 because it can cause staining of the permanent teeth. Additionally, doxycycline is not to be taken by pregnant women because it can cause staining of the teeth of the unborn child.

    Malarone™

    A relatively new antimalarial drug in the United States, Malarone combines two drugs (atovaquone and proguanil) and is an effective alternative for travelers who cannot or choose not to take mefloquine or doxycycline.

    Directions for Malarone use:

  • Take the first dose one to two days before travel to risk area;
  • Take once a day while in risk area;
  • Take once a day for seven days after leaving risk area; and
  • Take the dose at the same time each day with food or milk.
  • Malarone side effects and warnings:

  • Side effects are rare, but abdominal pain, nausea, vomiting and headache can occur;
  • Should not be used for malaria prevention by patients with severe renal impairment;
  • Because the effects of Malarone on small infants is not fully known, the drug is not recommended for children who weigh less than 11 kg; and
  • Data on the safety of Malarone in pregnant women are limited. Thus, it is not currently recommended for use in women who are pregnant or attempting to become pregnant.
  • hloroquine (brand name Aralen®)

    Directions for chloroquine use:

  • Take first dose a week before arrival in risk area;
  • Take chloroquine once a week, on the same day, while in risk area;
  • Take chloroquine once a week for four weeks after leaving risk area; and
  • Take on a full stomach to minimize nausea.
  • Chloroquine is considered by many experts to be safe for use during pregnancy.
  • Chloroquine side effects and warnings:

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

    Hydroxychloroquine sulfate (brand name Plaquenil®)

    Directions for hydroxychloroquine use:

  • Take first dose a week before arriving in risk area;
  • Take once a week, on the same day, while in risk area;
  • Take weekly for four weeks after leaving risk area;
  • Take on a full stomach to minimize nausea; and
  • 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; and hydroxychloroquine sulfate may worsen the symptoms of psoriasis.

    Pyrimethamine (brand name Daraprim)

    Direction for pyrimethamine use:

    Adults and adolescents take pyrimethamine as a single dose. For children, dosage is based on body weight.

    Pyrimethamine side effects:

    When you are taking pyrimethamine, it is especially important that your health care professional know if you are taking any of the following:

    Amphotericin B by injection (e.g., Fungizone);
    Antineoplastics (cancer medicine);
    Antithyroid agents (medicine for overactive thyroid);
    Azathioprine (e.g., Imuran);
    Chloramphenicol (e.g., Chloromycetin);
    Colchicine;
    Flucytosine (e.g., Ancobon);
    Ganciclovir (e.g., Cytovene);
    Interferon (e.g., Intron A, Roferon-A);
    Mercaptopurine (e.g., Purinethol);
    Methotrexate (e.g., Mexate);
    Plicamycin (e.g., Mithracin); or
    Zidovudine (e.g., AZT, Retrovir).

    Use of these medicines together with pyrimethamine may increase the chance of side effects affecting the blood. Make sure you tell your doctor if you have any other medical problems, especially:

  • Anemia or other blood problems - high doses of pyrimethamine may make these conditions worse;
  • Liver disease - Individuals with liver disease may have an increased chance of side effects; and
  • Seizure disorders, such as epilepsy - high doses of pyrimethamine may increase the chance of convulsions and seizures.
  • Fansidar (sulfadoxine and pyrimethamine)

    Direction for fansidar use:

    The first dose of Fansidar should be taken one or two days before departure to an endemic area; administration should be continued during the stay and for four to six weeks after return.

    Fansidar side effects / adverse reactions:

    Adverse effects of Fansidar include: nausea, vomiting, headache, photosensitivity (increased sensitivity to the sun's rays), dizziness. Rare side effects include convulsions and blood disorders like anemia and low white blood cell or platelet counts. Fansidar should not be taken by people who are allergic to sulfa drugs.

    A Final Word

    Succinctly: Avoidance is your best bet, but travel is an exhilarating and educational experience as well. Worth the risks? It's up to you, but if you plan your travels with your health in mind, you'll reduce your chances of encountering a life-threatening disease.

    Sources:

    www.cdc.gov/travel/malariadrugs.htm

    www.rocheusa.com/products/fansidar/pi.html

    www.nlm.nih.gov/medlineplus/druginformation.html

    © 2002 DAN - Alert Diver, September 2002