Malaria

What is Malaria?

About 1,300 cases of malaria are diagnosed in the United States each year. The vast majority of cases in the United States are in travelers and immigrants returning from malaria-risk areas, many from sub-Saharan Africa and South Aisa.

The World Health Organization estimates that each year 300-500 million cases of malaria occur and more than 1 million people die of malaria, especially in developing countries. Most deaths occur in young children. For example, in Africa, a child dies from malaria every 30 seconds. Because malaria causes so much illness and death, the disease is a great drain on many national economies. Since many countries with malaria are already among the poorer nations, the disease maintains a vicious cycle of disease and poverty.

This sometimes fatal disease can be prevented and cured. Bednets, insecticides, and antimalarial drugs are effective tools to fight malaria in areas where it is transmitted. Travelers to a malaria-risk area should avoid mosquito bites and take a preventive antimalarial drug.

Where does malaria occur? Malaria typically is found in warmer regions of the world -- in tropical and subtropical countries. Higher temperatures allow the Anopheles mosquito to thrive. Malaria parasites, which grow and develop inside the mosquito, need warmth to complete their growth before they are mature enough to be transmitted to humans. Malaria occurs in over 100 countries and territories. More than 40% of the world's population is at risk. Large areas of Central and South America, Hispaniola (the Caribbean island that is divided between Haiti and the Dominican Republic), Africa, South Asia, Southeast Asia, the Middle East, and Oceania are considered malaria-risk areas. Yet malaria does not occur in all warm climates. For example, malaria has been eliminated in some countries with warm climates, while a few other countries have no malaria because Anopheles mosquitoes are not found there. Malaria has been eradicated from many developed countries with temperate climates. However, the disease remains a major health problem in many developing countries, in tropical and subtropical parts of the world. An eradication campaign was started in the 1950s, but it failed globally because of problems including the resistance of mosquitoes to insecticides used to kill them, the resistance of malaria parasites to drugs used to treat them, and administrative issues. In addition, the eradication campaign never involved most of Africa, where malaria is the most common.

How is malaria transmitted?

Because the malaria parasite is found in red blood cells of an infected person, malaria can also be transmitted through blood transfusion, organ transplant, or the shared use of needles or syringes contaminated with blood. Malaria may also be transmitted from a mother to her unborn infant before or during delivery ("congenital" malaria).

Is malaria a contagious disease?

Who is at risk for malaria?

Who are the people most at risk of getting very sick and dying from malaria?

What are the signs and symptoms of malaria?

Uncomplicated Malaria

The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:

• a cold stage (sensation of cold, shivering)
• a hot stage (fever, headaches, vomiting; seizures in young children)
• and finally a sweating stage (sweats, return to normal temperature, tiredness)

Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).

More commonly, the patient presents with a combination of the following symptoms:

• Fever
• Chills
• Sweats
• Headaches
• Nausea and vomiting
• Body aches
• General malaise.

In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria and treat themselves without seeking diagnostic confirmation ("presumptive treatment").

Physical findings may include:

• Elevated temperature
• Perspiration
• Weakness
• Enlarged spleen.

In P. falciparum malaria, additional findings may include:

• Mild jaundice
• Enlargement of the liver
• Increased respiratory rate.

Diagnosis of malaria depends on the demonstration of parasites on a blood smear examined under a microscope. In P. falciparum malaria, additional laboratory findings may include mild anemia, mild decrease in blood platelets (thrombocytopenia), elevation of bilirubin, elevation of aminotransferases, albuminuria, and the presence of abnormal bodies in the urine (urinary "casts").

Severe Malaria

Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The manifestations of severe malaria include:

• Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
• Severe anemia due to hemolysis (destruction of the red blood cells)
• Hemoglobinuria (hemoglobin in the urine) due to hemolysis
• Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment
• Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets)
• Cardiovascular collapse and shock

Other manifestations that should raise concern are:

• Acute kidney failure
• Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
• Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
• Hypoglycemia (low blood glucose). Hypoglycaemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

Severe malaria occurs most often in persons who have no immunity to malaria or whose immunity has decreased. These include all residents of areas with low or no malaria transmission, and young children and pregnant women in areas with high transmission.

In all areas, severe malaria is a medical emergency and should be treated urgently and aggressively.

Malaria Relapses

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.

Other Manifestations of Malaria

• Neurologic defects may occasionally persist following cerebral malaria, especially in children. Such defects include troubles with movements (ataxia), palsies, speech difficulties, deafness, and blindness.
• Recurrent infections with P. falciparum may result in severe anemia. This occurs especially in young children in tropical Africa with frequent infections that are inadequately treated.
• Malaria during pregnancy (especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.
• On rare occasions, P. vivax malaria can cause rupture of the spleen or acute respiratory distress syndrome (ARDS).
• Nephrotic syndrome (a chronic, severe kidney disease) can result from chronic or repeated infections with P. malariae.
• Hyperreactive malarial splenomegaly (also called "tropical splenomegaly syndrome") occurs infrequently and is attributed to an abnormal immune response to repeated malarial infections. The disease is marked by a very enlarged spleen and liver, abnormal immunologic findings, anemia, and a susceptibility to other infections (such as skin or respiratory infections).

How soon will a person feel sick after being bitten by an infected mosquito?

Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. (This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the infective mosquito bite.)

Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in malaria-risk areas during the past 12 months.

How do I know if I have malaria for sure?

Diagnosis of malaria can be difficult:

• Where malaria is not endemic any more (such as the United States), health care providers are not familiar with the disease. Clinicians seeing a malaria patient may forget to consider malaria among the potential diagnoses and not order the needed diagnostic tests. Laboratorians may lack experience with malaria and fail to detect parasites when examining blood smears under the microscope.
• In some areas, malaria transmission is so intense that a large proportion of the population is infected but not made ill by the parasites. Such carriers have developed just enough immunity to protect them from malarial illness but not from malarial infection. In that situation, finding malaria parasites in an ill person does not necessarily mean that the illness is caused by the parasites.
• In many malaria-endemic countries, lack of resources is a major barrier to reliable and timely diagnosis. Health personnel are undertrained, underequipped and underpaid. They often face excessive patient loads, and must divide their attention between malaria and other equally severe infectious diseases such as pneumonia, diarrhea, tuberculosis and HIV/AIDS.

Malaria parasites can be identified by examining under the microscope a drop of the patient's blood, spread out as a "blood smear" on a microscope slide. Prior to examination, the specimen is stained (most often with the Giemsa stain) to give to the parasites a distinctive appearance. This technique remains the gold standard for laboratory confirmation of malaria. However, it depends on the quality of the reagents, of the microscope, and on the experience of the laboratorian.

Blood smear stained with Giemsa, showing a white blood cell (on left side) and several red blood cells, two of which are infected with Plasmodium falciparum (on right side).

Another diagnostic approach: Parasite nucleic acids are detected using polymerase chain reaction (PCR). This technique is more accurate than microscopy. However, it is expensive, and requires a specialized laboratory (even though technical advances will likely result in field-operated PCR machines).

Serology detects antibodies against malaria parasites, using either indirect immunofluorescence (IFA) or enzyme-linked immunosorbent assay (ELISA). Serology does not detect current infection but rather measures past experience.

What is the best drug to take against malaria?

Many effective antimalarial drugs are available. Your health care provider and you will decide on the best drug for you based on your travel plans, medical history, age, drug allergies, pregnancy status, and other health factors.

To allow enough time for the drugs to become effective and for a pharmacy to prepare any special doses of medicine (especially doses for children and infants), visit your health care provider 4-6 weeks before travel.

In general, most drugs used to prevent and treat malaria have been shown to be well tolerated for at least 1 year or more.

Is it safe to buy my malaria drugs in the malaria-risk country where I will be traveling?

It would be best to purchase all the medications that you need before you leave the United States. As a precaution, note the name of the medication(s) and the name of the manufacturer(s). That way, in case of accidental loss, you can replace the drug(s) abroad at a reliable vendor.

Isn't there a malaria vaccine? And if not, why?

Should infants and children be given antimalarial drugs?

Pregnancy and Malaria

Because there is no evidence that chloroquine and mefloquine are associated with congenital defects when used for preventing malaria (prophylaxis), CDC does not recommend that women planning pregnancy need to wait a specific period of time after their use before becoming pregnant. However, if women or their health-care providers wish to decrease the amount of antimalarial drug in the body before conception, this table provides information on the half-lives of selected antimalarial drugs. After two, four, and six half-lives, approximately 25%, 6%, and 2% of the drug remain in the body.

Is it considered safe for me to breastfeed while taking an antimalarial drug?

No information is available on the amount of primaquine that enters human breast milk; the mother and infant should be tested for G6PD deficiency before primaquine is given to a woman who is breastfeeding.

It is not known whether atovaquone, which is a component of the antimalarial drug Malarone, is excreted in human milk. Proguanil, the other component of Malarone, is excreted in human milk in small quantities.

Note: Because there is little information available on the safety of atovaquone/proguanil to prevent malaria in infants weighing less than 5 kg (11 lbs), CDC does not currently recommend it for the prevention of malaria in women breastfeeding infants weighing less than 5 kg.

Based on experience with other antimalarial drugs, the quantity of drug transferred in breast milk is not likely to be enough to provide protection against malaria for the infant.

In an area where malaria is a problem, you can prevent malaria by:

• Keeping mosquitoes from biting you, especially at night
• Taking antimalarial drugs to kill the parasites
• Spraying insecticides on your home's walls to kill adult mosquitoes that come inside
• Sleeping under bed nets - especially effective if they have been treated with insecticide, and
• Using insect repellent and wearing long-sleeved clothing if out of doors at night

How long after returning from an area with malaria could you develop malaria?

When and how should malaria be treated?

Malaria can be cured with prescription drugs. The type of drugs and length of treatment depend on the type of malaria, where the person was infected, their age, whether they are pregnant, and how sick they are at the start of treatment.

Travelers who are taking effective malaria preventive drugs but who will be in very remote areas may decide, in consultation with their healthcare provider, to take along antimalarial mediation for self-treatment. Malaria self-treatment should begin right away if fever, chills, or other influenza-like illness occurs and if professional medical care is not available within 24 hours. Self-treatment of a possible malarial infection is only a temporary measure and immediate medical care is important.

The CDC Malaria Branch (Malaria Hotline 770-488-7788) can provide consultation to health-care providers on other potential options for self-treatment if atovaquone/proguanil cannot be used.

If I get malaria, will I have it for the rest of my life?

Two types (species) of parasites, Plasmodium vivax and P. ovale, have liver stages and can remain in the body for years without causing sickness. If not treated, these liver stages may re-activate and cause malaria attacks ("relapses") after months or years without symptoms. People diagnosed with P. vivax or P. ovale are often given a second drug to help prevent these relapses. Another type of malaria, P. malariae, if not treated, has been known to stay in the blood of some people for several decades.

However, in general, if you are correctly treated for malaria, the parasites are eliminated and you are no longer infected with malaria.

Malaria Facts

Malaria in the United States

• 1,337 cases of malaria, including 8 deaths, were reported for 2002 in the United States, even though malaria has been eradicated in this country since the early 1950's
• Of the 1,337 malaria cases reported for 2002 in the United States, all but five were imported, i.e., acquired in malaria-endemic countries.
• Between 1957 and 2003, in the United States, 63 outbreaks of locally transmitted mosquito-borne malaria have occurred; in such outbreaks, local mosquitoes become infected by biting persons carrying malaria parasites (acquired in endemic areas) and then transmit malaria to local residents.
• Of the ten species of Anopheles mosquitoes found in the United States, the two species that were responsible for malaria transmission prior to eradication (Anopheles quadrimaculatus in the east and An. freeborni in the west) are still widely prevalent; thus there is a constant risk that malaria could be reintroduced in the United States.
• During 1963-1999, 93 cases of transfusion-transmitted malaria were reported in the United States; approximately two thirds of these cases could have been prevented if the implicated donors had been deferred according to established guidelines.

Malaria Worldwide

• Forty-one percent of the world's population live in areas where malaria is transmitted (e.g., parts of Africa, Asia, the Middle East, Central and South America, Hispaniola, and Oceania).
• Each year 350–500 million cases of malaria occur worldwide, and over one million people die, most of them young children in sub-Saharan Africa.
• In areas of Africa with high malaria transmission, an estimated 990,000 people died of malaria in 1995 – over 2700 deaths per day, or 2 deaths per minute.
• In 2002, malaria was the fourth cause of death in children in developing countries, after perinatal conditions (conditions occurring around the time of birth), lower respiratory infections (pneumonias), and diarrheal diseases. Malaria caused 10.7% of all children's deaths in developing countries.
• In Malawi in 2001, malaria accounted for 22% of all hospital admissions, 26% of all outpatient visits, and 28% of all hospital deaths. Not all people go to hospitals when sick or having a baby, and many die at home. Thus the true numbers of death and disease caused by malaria are likely much higher.

Biology, Pathology, Epidemiology

• Residents of Asembo Bay (Western Kenya) were bitten 60-300 times a year by a malaria-carrying mosquito in the 1990's, before control measures (including the use of insecticide-treated bed nets) were put in place.
• Among the four malaria species that infect humans, Plasmodium vivax and P. ovale can develop dormant liver stages that can reactivate after symptomless intervals of up to 2 (P. vivax) to 4 years (P. ovale).
• 84% of the blood transfusions given in March-June 2000 in a major hospital in Kinshasa (Democratic Republic of Congo) were for anemia caused by malaria.
• Pregnant women have increased susceptibility to Plasmodium falciparum malaria; in malaria-endemic countries, P. falciparum contributes to 8-14% of low birth weight, which in turn decreases the chance of a baby’s survival
• After a single sporozoite (the parasite form inoculated by the female mosquito) of Plasmodium falciparum invades a liver cell, the parasite grows in 6 days and produces 30,000-40,000 daughter cells (merozoites) which are released into the blood when the liver cell ruptures. In the blood, after a single merozoite invades a red blood cell, the parasite grows in 48 hours and produces 8-24 daughter cells, which are released into the blood when the red blood cell ruptures.

Prevention and Treatment

• Four Nobel prizes have been awarded for work associated with malaria, to Sir Ronald Ross (1902), Charles Louis Alphonse Laveran (1907), Julius Wagner-Jauregg (1927) and Paul Hermann Muller (1948).
• Two important currently used antimalarial drugs are derived from plants whose medicinal values had been noted for centuries: artemisinin from the Qinghao plant (Artemisia annua L, China, 4th century) and quinine from the cinchona tree (South America, 17th century).
• Insecticide-treated bed nets decreased the mortality of children aged 1-11 months in a trial in western Kenya in 1997-1999.
• A survey in Southeast Asia in 1999-2000 showed that of 104 shop-bought samples purportedly containing the antimalarial drug artesunate, 38% contained no artesunate.
• The average cost for potentially life-saving treatments of malaria are estimated to be US$0.13 for chloroquine, US$0.14 for sulfadoxine-pyrimethamine, and US$2.68 for a 7-day course of quinine.