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Are you prepared for malaria?

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By: Barbara Chamberlain

You’ve probably never encountered a patient with malaria in the United States. But this potentially fatal parasitic disease, though officially eradicated here in 1951, is making a comeback of sorts. It strikes 350 million to 500 million people worldwide, and kills more than 1 million.
Why should you learn about malaria? Global travel has become so common that malaria and other diseases endemic to foreign countries are likely to show up here eventually. Between 1995 and 2004, approximately 8,000 cases of malaria were reported in the United States. Most entered this country by way of Americans who’d traveled to malaria-endemic regions or immigrants who came here to escape disasters, poverty, and the ravages of war.
Would you know when to suspect malaria, or what to do if your patient had it? To help you prepare for these possibilities, this article describes the pathophysiology, assessment, treatment, and prevention of the disease.

Incidence
Malaria is endemic in developing countries, primarily in sub-Saharan Africa, South America, India, and Southeast Asia. About 40% of the world’s population (an estimated 3 billion people) live in these high-risk areas; more than 1 million (most of them young children) die annually from malaria. Most high-risk areas are poverty stricken and lack medical care and preventive measures. What’s more, such factors as local weather conditions, mosquito vector density, and infection prevalence can quickly increase the potential for malarial transmission in these regions.
Children in high-risk areas are particularly prone to malaria; the parasites hide in the small arteries of the brain, causing cerebral malaria and increased intracranial pressure. These children haven’t yet developed the immunity to survive repeated exposure to the infectious agent.

Pathophysiology
Malaria is transmitted from the bite of a female Anopheles mosquito that has been infected by any of four different Plasmodium species—P. falciparum, P. vivax, P. malariae, or P. ovale.
To become infected, a mosquito must take a blood meal on a person who is already infected. Once in the mosquito’s body, the parasites reside in the gut as an oocyst, where they grow and rupture. After rupture, the new parasites migrate to the salivary glands. When the female mosquito takes her next blood meal on a human, her saliva—along with the malarial parasites—is injected into the victim.
Once in the person’s body, the parasites migrate to the liver. When they rupture from host hepatic cells and enter the bloodstream as mature organisms, they number in the thousands. Then they enter red blood cells (RBCs), causing waves of fever that arise each time the parasites break out and invade new RBCs. (Being “clothed” inside the various cells protects the parasites from the immune system.) This process takes 48 hours for all forms of malaria except P. malariae, which takes 72 hours to mature.
Infection with P. falciparum results in severe anemia and has the highest mortality. However, P. vivax, the most common malarial organism, also can have severe debilitating and life-threatening consequences. P. vivax and P. ovale can produce relapses, as some parasites stay dormant in the liver from several weeks to 5 years. P. malariae also may cause relapse after lying dormant in splenic RBCs.

Blood-borne transmission
Malaria also can spread by transfusion of blood from an infected person or from use of needles
or syringes contaminated with blood from an infected person.
Between 1963 and 1999, the United States saw 93 cases of transfusion-transmitted malaria.
To help prevent blood-borne transmission, individuals wishing to donate blood are asked if they’ve traveled outside the United States. Those who’ve been to high-risk countries on short-term visits must wait 1 year before they can donate blood; those who’ve lived in such countries for more than 1 year are barred from donating for 3 years.

Signs and symptoms
All Plasmodium species cause similar clinical features. Signs and symptoms are most severe in P. falciparum and mildest in P. malariae.
At onset, the victim experiences flulike symptoms—chills, fever, and sweating over a 10-hour period. Chills may be accompanied by headache, nausea, and vomiting. Soon fever develops, along with hot, dry skin and a bounding pulse. If body temperature rises high enough, confusion and then delirium may set in. When the fever falls, sweating begins. Other common signs and symptoms include nosebleed, muscle weakness, diarrhea, anemia, pallor, and spleen and liver enlargement.
P. falciparum infection also may cause respiratory distress, acidosis, disseminated intravascular coagulation, fluid imbalance, anemia, hypo­glycemia, renal failure, and cerebral malaria (possibly resulting in delirium, disorientation, seizures, and
coma). Victims need to be hospitalized in an intensive care unit, because their condition can worsen almost instantly.

When to suspect malaria
To play it safe, healthcare providers should suspect malaria in patients with unexplained fever who have immigrated to the United States or have lived or traveled abroad for as little as 7 days. The hospital admission process should include a thorough history, including recent travel to a foreign country. During physical assessment, be sure to assess the size of the patient’s liver and spleen, which enlarge in response to the infection.

Diagnosis
To differentiate malaria from other disorders and ensure proper treatment, expect to obtain peripheral blood samples for a thick and thin blood smear. This test confirms the diagnosis and identifies the parasite.
The Food and Drug Administration recently approved a rapid laboratory antigen test that requires only a fingerstick of blood to identify P. falciparum parasites. About 95% accurate, this test is used for patients who live in areas where malaria is endemic or who’ve returned from such regions. However, results still need to be confirmed microscopically. Malaria also can be diagnosed by stool culture for ova and parasites. Be aware that malaria is reportable in most states.

Treatment
For uncomplicated, nonresistant P. falciparum, the patient typically takes quinine every 8 hours for 7 days and doxycycline daily for 7 days. However, less expensive alternatives to doxycycline exist. Severe malaria calls for I.V. quinine therapy.
Resistance has arisen to all classes of antimalarials except artemis­inin derivatives. An ancient Chinese treatment derived from the sweet wormwood plant, artemisinin may be given I.V. or I.M. to treat multidrug-resistant malaria. It’s unrelated to other antimalarial drugs, and parasites require multiple genetic mutations to gain resistance to it. Because of its short half-life, it’s usually given in combination with other agents. Although artemisinin-based combination therapy is expensive, the World Health Organization is considering recommending it as a first-line treatment for uncomplicated P. falciparum disease. Artemisinin-based drugs aren’t available in the United States.
One of the newest antimalarial drugs is a tablet called ASAQ, which combines artesunate (an artemisinin derivative) with the anti-inflammatory agent amodiaquine. Soon this inexpensive agent will be available to treat uncomplicated malaria in Africa; it isn’t available in the United States.

Supportive therapy
Besides drug therapy, patients with malaria need frequent physical assessment and vital sign monitoring. As indicated and ordered, provide fluid replacement, appropriate therapy for diarrhea and fever, and a nutritious diet. Draw samples and specimens for laboratory studies as needed.

Prevention
No malaria vaccine exists, although one is currently under development. In the meantime, people who travel to or live in endemic areas can use various approaches to prevent becoming the Anopheles mosquito’s nighttime blood meal.
Molecular biologists are researching malaria control by trying to create a genetically engineered malaria-resistant mosquito. But even if they ultimately succeed, this mosquito would need to mate with a wild mosquito to carry on malaria resistance.

Chemoprophylaxis
In malaria chemoprophylaxis, a person receives drug therapy before, during, and after traveling to a malaria-endemic area, with the goal of suppressing the parasites. To select the appropriate prophylactic drug, the healthcare provider and patient review the travel destination and discuss adverse effects of the various prophylactic drugs available. When the traveler returns to this country, the healthcare pro­vider determines if the patient took the recommended medication at the proper dosage for the prescribed time.
For P. falciparum, chloroquine is the drug of choice for chemoprophylaxis. However, in African countries, parasites have become chloroquine-resistant. For resistant malaria, the drug of choice is sulfadoxine/pyrimethamine; however, resistance to this drug is prevalent in Southeast Asia and the Amazon river basin of South America. Thus, the Centers for Disease Control and Prevention no longer recommends sulfadoxine/pyrimethamine for ma­laria treatment.
Other drugs may be used for chemoprophylaxis in areas with resistant malaria strains. All of these drugs have serious adverse effects, and none prevents relapse infections of P. vivax or P. ovale. Primaquine is the preferred drug for treating these infections.

Swatting away malaria
As more Americans travel to malaria-endemic areas and people from those areas travel here, U.S. healthcare workers can expect to see more malaria cases. When patients present with a high fever, be sure to ask whether they’ve traveled or lived abroad recently. With a high index of suspicion for malaria, we can help keep the disease at bay in this country.

Selected references
Baer S, Hunter A, Mayo R, Meehan N. A quick reference guide to malaria treatment. Am J Nurs Practitioners. 2004;8:51-59.
Centers for Disease Control and Prevention. Malaria. www.cdc.gov/malaria/. Accessed April 8, 2009.
Fredrich M. Malaria researchers target mosquitoes. JAMA. 2007;297:2187.
Jurgen M, Evans J, Timmann C, et al. Hemoglobin variants and disease manifestations in severe falciparum malaria. JAMA. 2007;297:
2220-2226.
Leder K, Black J, O’Brien D, et al. Malaria in travelers: a review of the GeoSentinel Surveillance Network. Clin Infect Dis. 2004;39:
1104-1112.
World Health Organization. Malaria. www
.who.int/topics/malaria. Accessed April 8, 2008.
Zuccotti G, DeAngelis CD. Malaria 2007—Progressing research, persisting challenges. JAMA. 2007;297:2285-2286.

Barbara Chamberlain is a Critical Care Clinical Nurse Specialist and the Corporate Director of Clinical Education and Research at the Kennedy Health System in Cherry Hill, N.J.

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