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Malaria is a communicable parasitic disorder spread through the bite of the Anopheles mosquito. Major symptoms may vary depending on which species of parasite causes the infection and the stage of development of the parasite. Chills and fever commonly occur, although not every case follows the same pattern. Although the disorder was once thought to be under control throughout the world, malaria is a widespread infection especially in the tropics where certain types of mosquitos are becoming resistant to pesticides. The annual number of cases reported in the United States has increased in recent years.
Symptoms of malaria vary depending on which of the four parasite species is the cause. Severity of symptoms may differ as the parasite goes through three different stages of development in humans. It is possible to contract more than one kind of malaria at a time. Symptoms may begin a week after exposure to the mosquito or may show up months later, even with preventive treatment.
An incubation period ranging of up to forty days is usually followed by a feeling of listlessness, loss of appetite, headaches, muscle aches, low fever, and other flu-like symptoms. Then onset of rigidity or spasms usually lasting twenty to thirty minutes may occur. Following this, teeth rattling chills and fever (possibly reaching 107 degrees F.) may last from three to eight hours. Profuse sweating and a feeling of exhaustion mark the end of the feverish stage. Cold sores may appear on the lips or nose, skin may be pale, slightly bluish, or dry and flushed in appearance. An increased heart rate may be associated with heavy breathing. The spleen may become enlarged. Bloody diarrhea rarely may occur. If the brain is involved, headaches or depression may develop. Anemia, marked weight loss, mild yellowish discoloration of the skin (jaundice), swelling of the ankles, digestive difficulties, and muscle weakness can occur.
Until drugs are administered, symptoms such as diarrhea, vomiting or nausea may recur. Between episodes of these symptoms, patients may feel well except for tiredness. Without treatment, symptoms often redevelop months or even years later. Although subsequent attacks may be milder due to built-up immunity, the infection can last from one to twenty years. With treatment, patients usually recover and live a normal life span. Cerebral malaria is a form of malaria that occurs when the immune system produces a certain protein called “tumor necrosis factor” (TNF) or “cachectin.” This complication develops in less than one percent of cases. In third world countries, malaria frequently presents life threatening complications.
Malaria is most commonly transmitted through the bite of the female Anopheles mosquito which is infected by a malaria parasite (Plasmodium). Plasmodium Falciparum, Plasmodium Ovale, Plasmodium Malariae and Plasmodium Vivax are the four species of the parasite which can affect humans. Additionally, transfusion of blood from an infected donor, or sharing contaminated needles may transmit the infection from one person to another. In very rare cases, the disorder has been transmitted from an infected mother to a fetus.
According to the Centers for Disease Control and Prevention (CDC) in Atlanta, malaria is uncommon in the United States where approximately 1,200 cases are diagnosed each year, usually having been contracted abroad. In the United States, malaria results in two to five deaths, on the average, each year. Most cases in the U.S. occur among travelers, immigrants, and refugees.
Treatment
The Centers for Disease Control and Prevention (CDC) in Atlanta provide extensive information on standard therapies for malaria. Treatment should begin as soon as possible, but not until the diagnosis has been confirmed by laboratory investigations.
Once the diagnosis has been confirmed, treatment with an antimalarial drug should begin right away. Antimalarial drugs that combat the parasite forms in the blood include Aralen (chloroquine), Fansidar (sulfadoxine-pyrimethamine), Lariam (mefloquine), Malarone (atovaquone-proguanil), and Doxy-100 (doxycycline).
In 2020, the U.S. Food and Drug Administration (FDA) approved artesunate for injection as the only drug to treat severe malaria in adult and pediatric patients. Prior to this approval, there had been no FDA-approved drug for treatment of severe malaria in the U.S. since the marketing of quinine was discontinued by the manufacturer in 2019.
Another drug, Primaquine (primaquine phosphate), is active against the dormant parasite liver forms and prevents relapses. However, Primaquine should not be taken by pregnant women or by people who are deficient in glucose-6 phosphate dehydrogenase (G6PD).
Patients who have severe P. falciparum malaria or who cannot take oral medications should be given the treatment by continuous intravenous infusion. Several antimalarial drugs are available that can be administered in this way.
Determining how to treat a patient with malaria depends on the species of the infecting parasite, the area where infection took place, the clinical status of the patient, and whether the patient is pregnant, has drug allergies, or is taking other medications.
Prevention is the most effective means of controlling malaria. In areas where malaria is known to be present, this is done through taking steps to avoid exposure to mosquitoes, especially at night, and wearing insect repellent and clothing that covers the arms and legs when outside.
Rural areas carry a higher risk for malaria than do cities. Travelers should remain in well-screened areas, especially at night when mosquitos usually feed. Clothes should cover most of the body and mosquito netting should be used around the bed. An insect repellent containing DEET should be used on any exposed area of the skin.
For travel information related to malaria and the degree of risk in an intended travel destination, call the CDC toll-free number (877) FYI-TRIP or (877) 394-8747 or visit CDC’s Travelers’ Health Web site, which has country-specific information, including where malaria is found, which antimalarial drugs to take, steps to protect children, and how to avoid mosquito bites.
Also, the CDC recommends that travelers going to a country with malaria risk should purchase antimalarial drug before leaving the United States.
In recent years, the number of cases of malaria in the United States caused by the P. falciparum parasite has increased. This is believed to be due to travel to areas where malaria is endemic.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website: https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact: www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Holtz T. Malaria in NORD Guide to Rare Disorders. Philadelphia, PA; Lippincott, Williams & Wilkins; 2003:291.
Bennett JC, Plum F, eds. Cecil Textbook of Medicine. 20th ed. Philadelphia, PA: W.B. Saunders Co; 1996:1893-96.
Fauci AS, et al., eds. Harrison’s Principles of Internal Medicine, 14th Ed. New York, NY: McGraw-Hill, Inc; 1998:1180.
Mandell GL, et al., eds. Mandell, Douglas and Bennett’s Principles and Practice of Infectious Diseases. 4th ed. New York, NY: Churchill Livingstone Inc; 1995:2415-27.
Gorbach SL, et al., eds. Infectious Diseases. Philadelphia, PA: W. B. Saunders Company; 1992:1967-75.
REVIEW ARTICLES
Mackinnon MJ, Read AF. Virulence in malaria: an evolutionary viewpoint. Philos Trans R Soc Lond B Biol Sci. 2004;359:965-86.
Blair JE. Evaluation of fever in the international traveler. Unwanted “souvenirs” can have many causes. Postgrad Med. 2004;116:13-20, 29.
Kent DM, Mwamburi DM, Bennish ML, et al. Clinical trials in sub-Saharan Africa and established standards of care: a systematic review of HIV, tuberculosis, and malaria trials. JAMA. 2004;292:237-42.
Maitland K, Marsh K. Pathophysiology of severe malaria in children. Acta Trop. 2004;90:131-40.
Ehiri JE, Anyanwu EC, Scarlett H. Mass use of insecticide-treated bednets in malaria endemic poor countries: public health concerns and remedies. J Public Health Policy. 2004;25:9-22.
Jacobs-Lorena M. Interrupting malaria transmission by genetic manipulation of anopheline mosquitoes. J Vector Borne Dis. 2003;40:73-77.
Verma P, Sharma YD. Malaria genome project and its impact on the disease. J Vector Borne Dis. 2003;40:9-15.
White NJ. Antimalarial drug resistance. J Clin Invest. 2004;113:1084-92.
Le Mire J, Arnulf L, Guibert P. Malaria: control strategies, chemoprophylaxis, diagnosis, and treatment. Clin occup Environ Med. 2004;4:143-65.
FROM THE INTERNET
Frequently Asked Questions about Malaria. Centers for Disease Control and Prevention. Date: August 13, 2004. 6pp.
www.cdc.gov/malaria/faq.htm
Malaria: Diagnosis. Centers for Disease Control and Prevention. Date: April 23, 2004. 3pp.
www.cdc.gov/malaria/dianosis_treatment/diagnosis.htm
Malaria: Treatment: Information for the General Public. Centers for Disease Control and Prevention. Date: April 23, 2004. 3pp.
www.cdc.gov/malaria/dianosis_treatment/treatment.htm
Treatment of Malaria (Guidelines For Clinicians.) Centers for Disease Control and Prevention. Date: June 28, 2004. 9pp.
www.cdc.gov/malaria/pdf/clinicalguidelines.pdf
Guidelines for the Treatment of Malaria in the United States. Centers for Disease Control and Prevention. nd. 3pp.
www.cdc.gov/malaria/pdf/treatmenttable/pdf
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