Jennifer* came down with malaria while touring Africa after college graduation. “We stayed in a beautiful coastal village in Sierra Leone. Most of my friends slept indoors under mosquito nets, but I wanted to sleep on the beach. The next morning, I was covered in dozens of mosquito bites. I didn’t worry because I was taking my preventive medicines. A few days later in the Ivory Coast, I broke out with a raging fever. A French doctor gave me quinine, and the fever was gone in 24 hours. When I got home the next month, I just kept getting skinnier. When I got down to 105 pounds, my mom took me to the University of Virginia. Tests showed the malaria parasite hiding out in my liver. They gave me a bunch of medicines to boot it out.”

Each year an estimated half billion people develop malaria, and over 1 million people die of it, most of them in sub-Saharan Africa.¹ Even though malaria is both preventable and treatable, a child dies of it every 30 seconds.¹ Malaria is caused by a parasite so tiny that 50,000 could fit inside the period following this sentence. Malaria is a re-emerging disease, one that once could easily be cured but now is resistant to many of the medications available.

Malaria is an ancient disease that has ravaged mankind for millennia. Hippocrates noted the symptoms of malaria as it decimated Greek city-states.² Historians believe malaria was a factor in the downfall of the Roman Empire.²

Scientists have probed the mystery of malaria for more than 100 years. Ronald Ross of Great Britain receive the Nobel Prize for Medicine in 1902 for discovering that the parasite was passed not by air or contaminated food, but by infected mosquitoes, and Alphonse Laveran of France received the prize, in 1907, for identifying the malaria parasite in human blood.² Italian neurophysiologist Camillo Golgi is credited with recognizing that there were at least two forms of malaria differentiated by the periodicity of the fever cycles that coincide with a particular stage of the parasite.²

Man is just a meal

The mosquitoes: Malaria is transmitted by several species of Anopheles mosquitoes.³ Male Anopheles mosquitoes feed on nectar to survive, but females require blood for their eggs to mature. Because only females bite humans, only females carry the malaria parasite. Mosquitoes are drawn to humans by exhaled carbon dioxide, body heat, and chemicals in sweat. A mosquito eats two times her body weight in blood each time she feeds. In a few days, she lays her eggs in water. It takes 10 to 14 days for eggs to hatch.³

The parasites: The parasite that causes malaria is the single-celled protozoan Plasmodium. There are many Plasmodium species that infect animals and birds, but only four cause human malaria:^3,4

• Plasmodium falciparum, found worldwide in tropical and subtropical areas, is the only species that causes severe, potentially fatal malaria. P. falciparum infection may cause profound anemia, and damaged red blood cells can block capillaries in the brain, placenta, and kidneys.
• P. vivax, found in Asia, Latin America, and parts of Africa, is the most widespread malaria parasite. It rarely causes death but may incapacitate its victims. One stage of the P. vivax parasite — the hypnozoites — can lie dormant in the human liver only to reactive years later and cause malaria. 
• P. ovale, found mostly in Africa and western Pacific islands, also has a dormant liver stage. The immune system of a healthy person may clear ovale from the body in about one year.
• P. malariae, found worldwide, is the only human parasite with a three-day cycle. (The others have a two-day cycle, described below.) It causes long-lasting chronic infection that may persist a lifetime if left untreated.

The cycle of infection: The malaria parasite has a complex life cycle that requires human and mosquito hosts. A mosquito’s salivary gland is packed with sporozoites (one stage of the parasite). During feeding, the mosquito injects dozens of sporozoites into the human bloodstream. In under an hour, the sporozoites reach the liver, where each enters a hepatocyte and forms a schizont (the stage within the liver that produces merozoites, which invade red blood cells). A week later, the schizont ruptures, releasing hoards of merozoites and their waste products into the bloodstream, causing the first round of chills and fever. Within moments, the merozoites find and enter erythrocytes, which renders the merozoites invisible to the immune system. After undergoing several changes, the merozoites burst a few days later from the ruined erythrocytes in search of new ones. The habitation and destruction of erythrocytes causes the cycles of chills and fever and the anemia seen with malaria.

After several cycles of asexual reproduction, some merozoites turn into the sexual stage, gametocytes. A mosquito ingests gametocytes while feeding on people. Sexual reproduction occurs within the mosquito, where gametocytes turn into male and female gametes. Fertilization results in zygotes, which dig deep into the mosquito’s gut to form oocysts, a sturdy stage that resists the insect’s digestive juices. Soon, the oocysts rupture, releasing the next generation of infectious sporozoites. These travel to the mosquito’s salivary gland, ready to be delivered into the bloodstream of the mosquito’s next victim.

Hot and humid

Malaria is dependent on environmental factors, such as humidity, rainfall, and a temperature above 68 F, making vast parts of Africa, Southeast Asia, Central and South America, and certain Pacific islands ideal settings for the parasitic disease.⁴ Malaria threatens people in 107 countries although about 60% of the world’s cases and 80% to 90% of malaria deaths occur in Africa.⁵ The remainder of the cases occur primarily in Southeast Asia and Brazil.

North America is not immune. An outbreak in Jamaica of P. falciparum malaria triggered the CDC to recommend antimalaria medications for American travelers to the region in 2007.⁶ In the United States, the right kind of mosquitoes abound; all that’s lacking is the parasite’s presence. Most cases of malaria in the United States are imported, i.e., brought into the country by immigrants or tourists. The CDC reports that U.S. malaria increased more than 15% from 2004 to 2005, probably because of increased tourism to areas where malaria is endemic (constantly present).⁶ While it’s possible that local mosquitoes could bite these infected tourists and spread malaria to other people in the United States, such transmission fortunately has been extremely limited.

Malaria is worse now than 30 years ago because the mosquitoes that carry the parasite have become increasingly resistant to the pesticides that used to promptly kill them. The parasites themselves are growing ever more resistant to the medications, as well. Global factors, such as climate change and deforestation, are aiding its spread, as are the vast numbers of people on the move because of war, famine, and poverty.

People in areas where malaria is endemic are repeatedly infected throughout their lives. With each infection, people gain additional immunity and can better tolerate subsequent infections. However, pregnant women and children under 5 years are especially vulnerable to malaria. Pregnant women may not have gained the full immunity of adulthood, and the pregnancy itself depresses immunity while young children have little or no immunity.

Younger mothers and primigravidas are especially at risk. P. falciparum can damage the fetus in several ways:^4,7

• The mother may transmit malaria to the fetus via placental blood. In one study, more than 10% of children born of infected Kenyan women carried P. falciparum parasites.⁸
• Maternal anemia resulting from extensive destruction of red blood cells may lead to fetal hypoxia.
• Sequestration of large number of parasites in placental capillaries may lead to fetal malnutrition and hypoxia.
• Spontaneous abortion, fetal death, and low birth weight may result from maternal malaria.
• Infant survivors may experience cerebral palsy and overall physical and mental impairment.

About 80% of the deaths attributed to malaria each year occur in children under 5.7 Babies are susceptible starting at about 4 months old, when any immunity they gained by breastfeeding has worn off.⁷ Most children who get malaria are infected by the time they reach 2 years of age. In areas of endemic malaria, seven out of 10 babies have parasites by their first birthday; in some locations, more than one-third of young children are ill with malaria at any one time.⁹

At its worse, P. falciparum malaria can kill children within hours as parasites occlude tiny cerebral arteries.^4,7,9 These children are critically ill, often remaining comatose and having seizures for days; their pulmonary and renal functions are impaired, and profound hypoglycemia may occur.⁷ One study showed that 18.6% of children with cerebral malaria die of it.¹⁰ Other children die of severe anemia, with hemoglobin measurements under 5 grams per deciliter, less than half of normal.¹¹ Children who survive malaria may be left with permanent physical and neurological damage, including motor disorders (ataxia, dyskinesia, and hemiplegia); cortical blindness; speech disorders; and deficits in learning and cognition.¹⁰ One expert believes that nearly every child in Africa may be neurologically scarred in some way.⁹

Humans Against Mosquitoes

The complexity of Plasmodium’s life cycle makes it a challenge to develop vaccines and medications, yet that very complexity means that prevention can target the mosquito or parasite.

Personal protection: Personal protection includes such measures as remaining indoors at dawn and dusk, when mosquitoes are most active; installing screening doors and windows; wearing long-sleeved shirts and long pants; and using insect repellants that contain DEET. These products come in varying strengths; some are safe to use on babies as young as 2 months.

In Africa, where homes may lack protective screens, insecticide-treated bed nets are proven lifesavers. ITNs work in three ways: The insecticide kills some of the malaria-carrying mosquitoes, repels many others, and serves as a barrier between mosquito and sleeper. But although ITNs cost $10 or less each, many families cannot afford them. Governments and aid organizations distribute free ITNs when possible, often when mothers take their children to clinics for vaccinations. Millions of ITNs are now in use, but millions more are needed. One study in Malawi showed that ITNs reduced malaria by 52% among children under 5, the most vulnerable group.¹²

Environmental controls: The drainage of standing water and the insecticide DDT wiped out malaria in the United States by 1951.² In the 1960s, DDT was banned in the United States and many parts of the world as scientific evidence suggested that it was harmful to the environment. The EPA approves several products to kill mosquitoes and their larvae: Malathion is sprayed over residential areas (with a goal of controlling mosquitoes carrying West Nile virus), methoprene is sprayed over large bodies of water, and temephos and low-toxicity pesticides called monomolecular films may be applied directly to water.^13,14

The resurgence of mosquitoes and malaria over the past 30 years has forced countries to take a second look at DDT because it’s six times cheaper than alternatives and lasts longer. In 2005, the World Health Organization (WHO) approved DDT for indoor residual spraying (IRS).¹⁵ Anopheles gambiae, the most efficient malaria vector in Africa, prefers to be indoors. Females rest on walls for several hours after feeding. The spraying of interior walls and ceilings can be extremely effective. In one mosquito-control program, the incidence of malaria was reduced by 90% by using IRS.¹⁶

Preventive medications: The CDC recommends that people planning trips to areas of endemic malaria consult healthcare providers knowledgeable about antimalaria medications. Several medications are used, depending on a person’s destination:¹⁷

• Atovaquone/proguanil (Malarone): a combination of two medications started two days before travel and continuing for seven days after leaving a malaria area
• Chloroquine (Nivaquine, Aralen, and others): started one to two weeks before travel and continuing four weeks after travel; P. falciparum is resistant to chloroquine in many countries.
• Doxycycline (Vibramycin and others): started two days before, taken for four weeks after
• Hydroxychloroquine (Plaquenil): one to two weeks before, four weeks after
• Mefloquine (Lariam): one to two weeks before, four weeks after

The WHO promotes intermittent preventive treatment (IPT) for pregnant women and infants living in areas of endemic malaria. Pregnant women should take at least two doses of an antimalaria drug during the second and third trimesters.⁷ This greatly reduces maternal anemia and placental infection among infected mothers, resulting in healthier babies. A combination of sulfadoxine-pyrimethamine (SP), given during routine prenatal visits, is often used for this purpose.⁷ A study in Malawi showed a decline in placental infection of 23% to 32% and a decrease in low-birthweight babies of 23% when pregnant women took IPT.¹⁸

The same concept works well for infants. Infants can be given SP, which is well tolerated by children, at 2, 3, and 9 months of age along with routine immunizations.^20,21 Studies in Tanzania and Mozambique show that infant IPT reduced episodes of malaria by 60%, cases of severe malaria by 50%, and hospital admissions for malaria by 19%.^20,21

The incubation period for malaria depends on the parasite: P. falciparum has the shortest incubation period, seven to 10 days, while P. malariae has the longest, 18 to 40 days — or longer.

The classic attack

The classic malaria attack occurs every second or third day and lasts six to 10 hours. It consists of 1) the cold stage — a feeling of intense cold and shivering as the body attempts to generate heat with muscle contractions; 2) the hot stage — high fever and headaches as the body attempts to kill the parasites with elevated body temperature; 3) the wet stage — profuse sweating as the body tries to cool off and return to a normal temperature.²²

In reality, the classic attack is seldom seen. Instead, patients with uncomplicated malaria present with fever, chills, sweats, headaches, nausea, vomiting, diarrhea, body aches, fatigue, and an enlarged spleen and liver.²² Laboratory findings may include mild anemia and thrombocytopenia, elevated bilirubin, and albuminuria.²²

Severe malaria occurs with P. falciparum. Symptoms include cerebral malaria (with impaired level of consciousness, seizures, coma); profound anemia due to hemolysis; pulmonary edema or acute respiratory distress syndrome; abnormalities in blood coagulation; thrombocytopenia; renal failure; metabolic acidosis; hypoglycemia; and cardiovascular collapse and shock.²² Severe malaria occurs most often in young children, pregnant women, and people with little or no immunity.²²

Malaria is usually diagnosed with a blood smear, in which peripheral blood is smeared on a slide, stained, and microscopically examined to visualize the parasite.²³ In nations with endemic malaria, laboratory staff may be insufficiently trained, reagents become ineffective in the heat, and electrical power is inconsistent. A number of rapid diagnostic tests are also available. In these tests, blood is smeared on a card or dipstick to determine whether malaria antigens are present.²³ Newer tests use the polymerase chain reaction method to look for Plasmodium’s DNA.²³ Cerebral malaria can be diagnosed by ophthalmoscope to visualize malarial retinopathy, consisting of retinal whitening, vessel changes, hemorrhages, and papilledema; the first two findings are seen only with malaria.²⁴

The choice of treatment for malaria depends on the parasite. Malaria caused by a parasite other than P. falciparum is likely to respond to chloroquine and similar medications (amodiaquine, lariam, and mefloquine, among others). In some countries, antibiotics in the macrolide, tetracycline, and sulfonamide classes are used to treat malaria. SP may be used alone or may be given with amodiaquine in a regimen called SP + AQ. Using drugs in combination reduces the risk of the parasite’s becoming resistant.

Malaria caused by P. falciparum is highly resistant to chloroquine and similar medications. Instead, artemisinin-based medications (i.e., sulfadoxine-pyrimethamine artemether, dihydroartemisinin) are required. The Chinese used drugs made from the herb artemisinin to treat malaria for 2,000 years. Today, natural and synthetic formulations of artemisinin are very effective against P. falciparum infections. To prevent resistance, these medications are commonly given in combination with one or two others, a process called artemisinin combination therapy.²⁵ The WHO has approved the following ACTs for selected countries in Africa, Southeast Asia, and South America:²⁵

1. Artemether plus lumefantrine (brand name Coartem)
2. Artesunate plus amodiaquine
3. Artesunate (another artemisinin drug) plus mefloquine
4. Artesunate plus SP

ACT may cure malaria in as little as three days.²⁵ However, ACT costs 10 times more than older drugs, making it inaccessible to much of the world’s population.²⁵ Governments and health organizations are moving toward providing ACT free. For example, Zambia provides Coartem, which has succeeded in reducing the childhood malaria death rate by one-third.⁹ The FDA has not approved artemisinin medications for use in the United States, but the CDC received permission in 2007 to use IV artesunate for severe malaria in this country, comprising about 10% of U.S. malaria cases.²⁶

Abroad and at home

While many nurses will never encounter patients with malaria, certainly some will, for example, nurses working in developing nations and military nurses. American military forces currently serve in several countries where malaria is present, including Afghanistan, Iraq, and South Korea.

Over the past decade, about 1,400 cases of imported malaria were reported each year in the United States, so ED nurses may see patients with fevers of uncertain etiology.⁵ Nurses should question such patients about their recent and past travel because malaria can manifest as either acute infection or through reactivation of a dormant liver stage. Nurses caring for patients with malaria need to use only standard infection control precautions.

Nurses can advise patients, family members, friends, and members of the community about the importance of seeing a travel medicine specialist before traveling to areas with endemic malaria. Travelers to such regions should be encouraged to take preventive medications before departure.

Where malaria is endemic, it contributes to the cycle of poverty, civil unrest, and political instability. Families may spend 25% of their income to prevent and treat malaria.²⁷ Malaria accounts for up to 40% of public health spending, 30% to 50% of hospital admissions, and 60% of outpatient visits in impoverished nations.¹ Wealthier nations are now accepting responsibility for helping to bring malaria under control. However, malaria is not a problem just for developing tropical nations. As global warming progresses, the possibility exists that malaria could recur in the United States, providing a impetus for nurses to understand this dangerous and deadly disease.

*Patient’s name has been changed.