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Malaria

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Posted by  Simba Saturday, 06 May 2006 20:13

Malaria

Malaria

Description

Malaria in humans is caused by one of four protozoan species of the genus Plasmodium: P. falciparum , P. vivax , P. ovale , or P. malariae . All species are transmitted by the bite of an infected female Anopheles mosquito. Occasionally, transmission occurs by blood transfusion, organ transplantation, needle-sharing, or congenitally from mother to fetus. Although malaria can be a fatal disease, illness and death from malaria are largely preventable.

Occurrence

Malaria is a major international public health problem, causing 300-500 million infections worldwide and approximately 1 million deaths annually. Information about malaria risk in specific countries (Yellow Fever Vaccine Requirements and Information on Malaria Risk and Prophylaxis, by Country) is derived from various sources, including WHO. The information presented herein was accurate at the time of publication; however, factors that can change rapidly and from year to year, such as local weather conditions, mosquito vector density, and prevalence of infection, can markedly affect local malaria transmission patterns. Updated information may be found on the CDC Travelers' Health website: http://www.cdc.gov/travel .

Malaria transmission occurs in large areas of Central and South America, the island of Hispaniola (the Dominican Republic and Haiti), Africa, Asia (including the Indian Subcontinent, Southeast Asia, and the Middle East), Eastern Europe, and the South Pacific.

The estimated risk for a traveler's acquiring malaria differs substantially from area to area. This variability is a function of the intensity of transmission within the various regions and of the itinerary and time and type of travel. From 1985 through 2002, 11,896 cases of malaria among U.S. civilians were reported to CDC. Of these, 6,961 (59%) were acquired in sub-Saharan Africa; 2,237 (19%) in Asia; 1,672 (14%) in the Caribbean and Central and South America; and 822 (7%) in other parts of the world. During this period, 76 fatal malaria infections occurred among U.S. civilians; 71 (93%) were caused by P. falciparum , of which 52 (73%) were acquired in sub-Saharan Africa.

Thus, most imported P. falciparum malaria among U.S. travelers was acquired in Africa, even though only 467,940 U.S. residents traveled to countries in that region in 2002. In contrast, that year 21 million U.S. residents traveled from the United States to other countries where malaria is endemic (including 19 million travelers to Mexico). This disparity in the risk for acquiring malaria reflects the fact that the predominant species of malaria transmitted in sub-Saharan Africa is P. falciparum , that malaria transmission is generally higher in Africa than in other parts of the world, and that malaria is often transmitted in urban areas as well as rural areas in sub-Saharan Africa. In contrast, malaria transmission is generally lower in Asia and South America, a larger proportion of the malaria is P. vivax , and most urban areas do not have malaria transmission.

Risk to Travelers

Estimating the risk for infection for various types of travelers is difficult. Risk can differ substantially even for persons who travel or reside temporarily in the same general areas within a country. For example, travelers staying in air-conditioned hotels may be at lower risk than backpackers or adventure travelers. Similarly, long-term residents living in screened and air-conditioned housing are less likely to be exposed than are persons living without such amenities, such as Peace Corps volunteers. Travelers should also be reminded that even if one has had malaria before, one can get it again and so preventive measures are still necessary.

Persons who have been in a malaria risk area, either during daytime or nighttime hours, are not allowed to donate blood in the United States for a period of time after returning from the malarious area. Persons who are residents of nonmalarious countries are not allowed to donate blood for 1 year after they have returned from a malarious area. Persons who are residents of malarious countries are not allowed to donate blood for 3 years after leaving a malarious area. Persons who have had malaria are not allowed to donate blood for 3 years after treatment for malaria.

Clinical Presentation

Malaria is characterized by fever and influenza-like symptoms, including chills, headache, myalgias, and malaise; these symptoms can occur at intervals. Malaria may be associated with anemia and jaundice, and P. falciparum infections can cause seizures, mental confusion, kidney failure, coma, and death. Malaria symptoms can develop as early as 7 days after initial exposure in a malaria-endemic area and as late as several months after departure from a malarious area, after chemoprophylaxis has been terminated.

Prevention

No vaccine is currently available. Taking an appropriate drug regimen and using anti-mosquito measures will help prevent malaria. Travelers should be informed that no method can protect completely against the risk for contracting malaria.

Personal Protection Measures

Because of the nocturnal feeding habits of Anopheles mosquitoes, malaria transmission occurs primarily between dusk and dawn. Travelers should be advised to take protective measures to reduce contact with mosquitoes, especially during these hours. Such measures include remaining in well-screened areas, using mosquito bed nets (preferably insecticide-treated nets), and wearing clothes that cover most of the body. Additionally, travelers should be advised to purchase insect repellent for use on exposed skin. The most effective repellent against a wide range of vectors is DEET (N, N-diethylmetatoluamide), an ingredient in many commercially available insect repellents. The actual concentration of DEET varies widely among repellents. DEET formulations as high as 50% are recommended for both adults and children >2 months of age (See Protection against Mosquitoes and Other Arthropod Vectors).

Travelers not staying in well-screened or air-conditioned rooms should be advised to use a pyrethroid-containing flying-insect spray in living and sleeping areas during evening and nighttime hours. They should take additional precautions, including sleeping under bed nets (preferably insecticide-treated bed nets). In the United States, permethrin (Permanone) is available as a liquid or spray. Overseas, either permethrin or another insecticide, deltamethrin, is available and may be sprayed on bed nets and clothing for additional protection against mosquitoes. Bed nets are more effective if they are treated with permethrin or deltamethrin insecticide; bed nets may be purchased that have already been treated with insecticide. Information about ordering insecticide-treated bed nets is available at http://www.travmed.com , telephone 1-800- 872 8633, fax: 413-584-6656; or http://www.travelhealthhelp.com , telephone 1-888-621-3952.


Chemoprophylaxis

Chemoprophylaxis is the strategy that uses medications before, during, and after the exposure period to prevent the disease caused by malaria parasites. The aim of prophylaxis is to prevent or suppress symptoms caused by blood-stage parasites. In addition, presumptive anti-relapse therapy (also known as terminal prophylaxis) uses medications towards the end of the exposure period (or immediately thereafter) to prevent relapses or delayed-onset clinical presentations of malaria caused by hypnozoites (dormant liver stages) of P. vivax or P. ovale .

In choosing an appropriate chemoprophylactic regimen before travel, the traveler and the health-care provider should consider several factors. The travel itinerary should be reviewed in detail and compared with the information on areas of risk in a given country to determine whether the traveler will actually be at risk for acquiring malaria. Whether the traveler will be at risk for acquiring drug-resistant P. falciparum malaria should also be determined. Resistance to antimalarial drugs has developed in many regions of the world. Health-care providers should consult the latest information on resistance patterns before prescribing prophylaxis for their patients. (See section "Malaria Hotline" below for details about accessing this information from CDC.)

The resistance of P. falciparum to chloroquine has been confirmed in all areas with P. falciparum malaria except the Dominican Republic, Haiti, Central America west of the Panama Canal, Egypt, and some countries in the Middle East. In addition, resistance to sulfadoxine-pyrimethamine (e.g., Fansidar) is widespread in the Amazon River Basin area of South America, much of Southeast Asia, other parts of Asia, and, increasingly, in large parts of Africa. Resistance to mefloquine has been confirmed on the borders of Thailand with Burma (Myanmar) and Cambodia, in the western provinces of Cambodia, and in the eastern states of Burma (Myanmar).

Tolerability

Malaria chemoprophylaxis with mefloquine or chloroquine should begin 1-2 weeks before travel to malarious areas; prophylaxis with doxycycline, atovaquone/proguanil, or primaquine can begin 1-2 days before travel. Beginning the drug before travel allows the antimalarial agent to be in the blood before the traveler is exposed to malaria parasites. Chemoprophylaxis can be started earlier if there are particular concerns about tolerating one of the medications. Starting the medication 3-4 weeks in advance allows potential adverse events to occur before travel. If unacceptable side effects develop, there would be time to change the medication before the traveler's departure.

The drugs used for antimalarial chemoprophylaxis are generally well tolerated. However, side effects can occur. Minor side effects usually do not require stopping the drug. Travelers who have serious side effects should see a health-care provider. See the section below on "Adverse Reactions and Contraindications" for more detail on safety and tolerability of the drugs used for malaria prevention. The health-care provider should establish whether the traveler has previously experienced an allergic or other reaction to one of the antimalarial drugs of choice. In addition, the health-care provider should determine whether medical care will be readily accessible during travel should the traveler develop intolerance to the drug being used and need to change to a different agent.

General Recommendations for Prophylaxis

Chemoprophylaxis should continue during travel in the malarious areas and after leaving the malarious areas (4 weeks after travel for chloroquine, mefloquine, and doxycycline, and 7 days after travel for atovaquone/proguanil and primaquine). In comparison with drugs with short half-lives, which are taken daily, drugs with longer half-lives, which are taken weekly, offer the advantage of a wider margin of error if the traveler is late with a dose. For example, if a traveler is 1-2 days late with a weekly drug, prophylactic blood levels can remain adequate; if the traveler is 1-2 days late with a daily drug, protective blood levels are less likely to be maintained.

 

Transmission and Symptoms

 

Malaria is a serious disease that is transmitted to humans by the bite of an infected female Anopheles mosquito. Symptoms may include fever and flu-like illness, including chills, headache, muscle aches, and fatigue. Malaria may cause anemia and jaundice. Plasmodium falciparum infections, if not immediately treated, may cause kidney failure, coma, and death.
Malaria can often be prevented by using antimalarial drugs and by using personal protection measures to prevent mosquito bites. However, in spite of all protective measures, travelers may still develop malaria.

Malaria symptoms will occur at least 7 to 9 days after being bitten by an infected mosquito. Fever in the first week of travel in a malaria-risk area is unlikely to be malaria; however, any fever should be promptly evaluated.

Malaria is always a serious disease and may be a deadly illness. If you become ill with a fever or flu-like illness either while traveling in a malaria-risk area or after you return home (for up to 1 year), you should seek immediate medical attention and should tell the physician your travel history.

 
Malaria Risk by Country
 

Burundi: All areas. Comoros: All areas. Djibouti: All areas. Eritrea: All areas at altitudes lower than 2,200 meters (7,218 feet). No risk in Asmara. Ethiopia: All areas at altitudes lower than 2,000 meters (6,561 feet). No risk in Addis Ababa. Kenya: All areas (including game parks) at altitudes lower than 2,500 meters (8,202 feet). No risk in Nairobi. Madagascar: All areas. Malawi: All areas. Mauritius: Rural areas only. No risk on Rodrigues Island. Mayotte (French territorial collectivity): All areas. Mozambique: All areas. Réunion (France): No risk. Rwanda: All areas. Seychelles: No risk. Somalia: All areas. Tanzania: All areas at altitudes lower than 1,800 meters (5,906 feet). Uganda: All areas.

 
Prevention
 

All travelers to malaria-risk areas in East Africa , except travelers to Mauritius* , including infants, children, and former residents of East Africa should take one of the following antimalarial drugs (listed alphabetically):

  • atovaquone/proguanil,
  • doxycycline,
  • mefloquine,
  • primaquine (in special circumstances).

*Travelers to the malaria risk areas of Mauritius should take chloroquine to prevent malaria ( see below ). All travelers to malaria-risk areas in Mauritius, including infants, children, and former residents of Mauritius, should take chloroquine as their antimalarial drug.

NOTE: Chloroquine is NOT an effective antimalarial drug for the other countries in East Africa and should not be taken to prevent malaria in these countries.

Most antimalarial drugs are well-tolerated; most travelers do not need to stop taking their drug because of side effects. However, if you are particularly concerned about side effects, discuss the possibility of starting your drug early (3-4 weeks in advance of your trip) with your health care provider. If you cannot tolerate the drug, ask your doctor to change your medication.

Atovaquone/proguanil (brand name: Malarone™)

Atovaquone/proguanil is a fixed combination of two drugs, atovaquone and proguanil. In the United States, it is available as the brand name, Malarone.

Directions for Use
The adult dosage is 1 adult tablet (250mg atovaquone/100mg proguanil) once a day.

  • Take the first dose of atovaquone/proguanil 1 to 2 days before travel to the malaria-risk area.
  • Take atovaquone/proguanil once a day during travel in the malaria-risk area.
  • Take atovaquone/proguanil 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.

Atovaquone/proguanil Side Effects and Warnings
The most common side effects reported by travelers taking atovaquone/proguanil are abdominal pain, nausea, vomiting, and headache. Most travelers taking atovaquone/proguanil do not have side effects serious enough to stop taking the drug. Other antimalarial drugs are available if you cannot tolerate atovaquone/proguanil; see your health care provider.

Contraindications
The following travelers should NOT take atovaquone/proguanil for prophylaxis (other antimalarial drugs are available; see your health care provider):

  • children weighing less than 11 kilograms (25 pounds);
  • pregnant women;
  • women breast-feeding infants weighing less than 11 kilograms (25 pounds);
  • patients with severe renal impairment;
  • patients allergic to atovaquone or proguanil.
Doxycycline (many brand names and generics are available)

Doxycycline is related to the antibiotic tetracycline.

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.
  • Take doxycycline once a day, at the same time each day, while in the malaria-risk area.
  • Take doxycycline once a day for 4 weeks after leaving the malaria-risk area.

Doxycycline Side Effects and Warnings
The most common side effects reported by travelers taking doxycycline include sun sensitivity (sunburning faster than normal). To prevent sunburn, avoid midday sun, wear a high SPF sunblock, wear long-sleeved shirts, long pants, and a hat. Doxycycline may cause nausea and stomach pain. Always take the drug on a full stomach with a full glass of liquid. Do not lie down for 1 hour after taking the drug to prevent reflux of the drug (backing up into the esophagus). Women who use doxycycline may develop a vaginal yeast infection. You may either take an over-the-counter yeast medication or have a prescription pill from your health care provider for use if vaginal itching or discharge develops. Most travelers taking doxycycline do not have side effects serious enough to stop taking the drug. (Other antimalarial drugs are available if you cannot tolerate doxycycline; see your health care provider.)

Contraindications
The following travelers should NOT take doxycycline (other antimalarial drugs are available; see your health care provider):

  • pregnant women;
  • children under the age of 8 years;
  • persons allergic to doxycycline or other tetracyclines.
Mefloquine (brand name: Lariam ™ and generic)

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.
  • Take mefloquine once a week, on the same day each week, while in the malaria-risk area.
  • Take mefloquine once a week for 4 weeks after leaving the malaria-risk area.
  • Mefloquine should be taken on a full stomach, for example, after a meal.

Personal Lariam Warning
I have had the malaria falciparum and, due to a lack of alternatives, used Lariam for treatment. Of course the dosage for treatment is much higher and therefore the side effects are much more likely to appear. I must say, I suffered nearly every side effect mentioned on the leaflet and some it took me three months to recover completely from those. Dizziness, visual disturbance, headache and psychological effects were so strong, that I had lost orientation, balance and sense of relativity for many weeks. I was barely able to walk and generally felt more like a "vegetable" rather than a human being. Therefore, I can only advice everybody to reconsider the use of Lariam.

Mefloquine Side Effects and Warnings
The most common side effects reported by travelers taking mefloquine include headache, nausea, dizziness, difficulty sleeping, anxiety, vivid dreams, and visual disturbances.
Mefloquine has rarely been reported to cause serious side effects, such as seizures, depression, and psychosis. These serious side effects are more frequent with the higher doses used to treat malaria; fewer occurred at the weekly doses used to prevent malaria. Most travelers taking mefloquine do not have side effects serious enough to stop taking the drug. (Other antimalarial drugs are available if you cannot tolerate mefloquine; see your health care provider.)

Contraindications
Some travelers should NOT take mefloquine (other antimalarial drugs are available; see your health care provider):

  • persons with active depression or a recent history of depression;
  • persons with a history of psychosis, generalized anxiety disorder, schizophrenia, or other major psychiatric disorder;
  • persons with a history of seizures (does not include the typical seizure caused by high fever in childhood);
  • persons allergic to mefloquine.
Primaquine (primary prophylaxis)

In certain circumstances, when other antimalarial drugs cannot be used and in consultation with malaria experts , primaquine may be used to prevent malaria while the traveler is in the malaria-risk area (primary prophylaxis).

Directions for Use
Note :Travelers must be tested for G6PD deficiency (glucose-6-phosphate dehydrogenase) and have a documented G6PD level in the normal range before primaquine use. Primaquine can cause a fatal hemolysis (bursting of the red blood cells) in G6PD deficient persons.

The adult dosage is 52.6mg salt (30mg base primaquine)/once a day.

  • Take the first dose of primaquine 1-2 days before travel to the malaria-risk
    area.
  • Take primaquine once a day, at the same time each day, while in the malaria-risk area.
  • Take primaquine once a day for 7 days after leaving the malaria-risk area.

Primaquine Side Effects
The most common side effects reported by travelers taking primaquine include abdominal cramps, nausea, and vomiting.

Contraindications
Some travelers should not take primaquine (other antimalarial drugs are available; see your health care provider):

  • persons with G6PD deficiency;
  • pregnant women (the fetus may be G6PD deficient, even if the mother is in the normal range);
  • women breast-feeding infants unless the infant has a documented normal G6PD level;
  • persons allergic to primaquine.
Chloroquine (brand name Aralen™ and generics)

Directions for Use

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

Chloroquine Side Effects
The most common side effects reported by travelers taking chloroquine include nausea and vomiting, headache, dizziness, blurred vision, and itching. Chloroquine may worsen the symptoms of psoriasis. Most travelers taking chloroquine do not have side effects serious enough to stop taking the drug. Other antimalarial drugs are available if you cannot tolerate chloroquine; see your health care provider.

 
Antimalarial Drugs Purchased Overseas
 

You should purchase your antimalarial drugs before travel. Drugs purchased overseas may not be manufactured according to United States standards and may not be effective.

They also may be dangerous, contain counterfeit medications or contaminants, or be combinations of drugs that are not safe to use. Halofantrine (marketed as Halfan) is widely used overseas to treat malaria. CDC recommends that you do NOT use halofantrine because of serious heart-related side effects, including deaths. You should avoid using antimalarial drugs that are not recommended unless you have been diagnosed with life-threatening malaria and no other options are immediately available.

 
Protect Yourself from Mosquito Bites
 

Malaria is transmitted by the bite of an infected mosquito; these mosquitoes usually bite between dusk and dawn. To avoid being bitten, remain indoors in a screened or air-conditioned area during the peak biting period. If out-of-doors, wear long-sleeved shirts, long pants, and hats. Apply insect repellent (bug spray) to exposed skin.

Choosing an Insect Repellent

For the prevention of malaria, CDC recommends an insect repellent with DEET (N, N-diethyl-m-toluamide) as the repellent of choice. Many DEET products give long-lasting protection against the mosquitoes that transmit malaria (the anopheline mosquitoes).

A new repellent is now available in the United States that contains 7% picaridin (KBR 3023). Picaridin may be used if a DEET-containing repellent is not acceptable to the user. However, there is much less information available on how effective picaridin is at protecting against all of the types of mosquitoes that transmit malaria. Also, since the percent of picaridin is low, this repellent may only protect against bites for 1-4 hours.

At this time, use of other repellents is not recommended for the prevention of malaria because there is insufficient data on how well they protect against the mosquitoes that transmit malaria.

Precautions When Using Any Repellent
  • Read and follow the directions and precautions on the product label.
  • Use only when outdoors and thoroughly wash off the repellent from the skin with soap and water after coming indoors.
  • Do not breathe in, swallow, or get repellent into the eyes or mouth. If using a spray product, apply to your face by spraying your hands and rubbing the product carefully over the face, avoiding eyes and mouth.
  • Never use repellents on wounds or broken skin.
  • Pregnant women should use insect repellent as recommended for other adults. Wash off with soap and water after coming indoors.
  • Repellents may be used on infants older than 2 months of age.
  • Children under 10 years old should not apply insect repellent themselves. Do not apply to young children's hands or around their eyes and mouth.
Using Repellents With DEET
  • Do not get repellent containing DEET into the mouth. DEET is toxic if swallowed.
  • Higher concentrations of DEET may have a longer repellent effect; however, concentrations over 50% provide no added protection.
  • Timed-release DEET products, which are micro-encapsulated, may have a longer repellent effect than liquid DEET products. Re-apply as necessary, following the label directions.
Using Repellents With Picaridin
  • Spray enough picaridin repellent to slightly moisten skin.
  • Reapply repellents with picaridin (7% picaridin is the only product currently available in the United States) every 3 to 4 hours. Do not apply more than 3 times a day.
  • Picaridin repellent causes moderate eye irritation. Avoid contact with eyes. If in eyes, wash with water for 15 to 20 minutes.
Other Recommended Anti-mosquito Measures
  • Travelers should take a flying insect spray on their trip to help clear rooms of mosquitoes. The product should contain a pyrethroid insecticide; these insecticides quickly kill flying insects, including mosquitoes.
  • Travelers not staying in well-screened or air-conditioned rooms should sleep under bed nets (mosquito nets), preferably nets treated with the insecticide permethrin. Permethrin both repels and kills mosquitoes as well as other biting insects and ticks. In the United States, permethrin is available as a spray or a liquid (e.g. Permanone™). Pre-treated nets, permethrin or another insecticide deltamethrin, are available overseas.

    For information on ordering insecticide-treated bed nets: www.travmed.com , phone 1-800-872-8633, fax: 413-584-6656; or www.travelhealthhelp.com , phone 1-866-621-6260.
  • Protect infants (especially infants under 2 months of age not wearing insect repellent) by using a carrier draped with mosquito netting with an elastic edge for a tight fit.
  • Clothing, shoes, and camping gear, can also be treated with permethrin. Treated clothing can be repeatedly washed and still repel insects. Some commercial products (clothing) are now available in the United States that have been pretreated with permethrin.

Bibliography

  • Connor BA. Expert recommendations for antimalarial prophylaxis. J Travel Med . 2001;8 Suppl 3: S57-64.
  • Magill AJ. The prevention of malaria. Prim Care . 2002;29:815-42.
  • Newman RD, Parise ME, Barber AM, et al. Malaria-related deaths among U.S. travelers, 1963-2001. Ann Intern Med . 2004;141:547-55.
  • Parise ME, Lewis LS. Severe malaria: North American perspective. In: Feldman C, Sarosi GA, editors. Tropical and parasitic infections in the ICU . Springer Science+Business Media, Inc, 2005.
  • Powell VI, Grima K. Exchange transfusion for malaria and Babesia infection. Transfus Med Rev . 2002;16:239-50.
  • Re VL 3rd, Gluckman SJ. Prevention of malaria in travelers. Am Fam Physician . 2003;68:509-14.
  • Schlagenhauf-Lawlor P. Travelers' malaria . Hamilton, Ontario: BC Decker; 2001.
  • Schwartz E, Parise M, Kozarsky P, et al. Delayed onset of malaria—implications for chemoprophylaxis in travelers. N Engl J Med . 2003;349:1510-6.
  • Shah S, Filler S, Causer LM, et al. Malaria surveillance—United States, 2002. MMWR Surveill Summ . 2004;53:21-34.

- Monica Parise, Ann Barber, and Sonja Mali

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