What is malaria?

Malaria is a disease caused by a parasite. Mosquitoes spread the parasite to people.

Malaria symptoms usually appear within in 7 to 30 days but can take up to one year to develop. Symptoms may include high fevers and shaking chills, flu-like illness. Without treatment, malaria can cause severe illness and death.

Who is at risk?

The mosquitoes that spread malaria are found in Africa, Central and South America, parts of the Caribbean, Asia, Eastern Europe, and the South Pacific (See maps: Eastern Hemisphere and Western Hemisphere). Travelers going to these countries may get bit by mosquitoes and get infected.

About 2,000 cases of malaria are diagnosed in the United States annually, mostly among returned travelers.

What can travelers do to prevent malaria?

Travelers can protect themselves from malaria by taking prescription medicine and preventing mosquito bites. There is no malaria vaccine.

Take Malaria Medicine

Check your destination to see if you should take prescription malaria medication. Depending on the medicine you take, you will need to start taking this medicine multiple days before your trip, as well as during and after your trip. Talk to your doctor about which medicine you should take.

Travelers should also take steps to prevent mosquito bites:

• Stay and sleep in screened or air-conditioned rooms.
  • Use a bed net if the area where you are sleeping is exposed to the outdoors.

• Cover exposed skin by wearing long-sleeved shirts, long pants, and hats.
• Use EPA-registered insect repellents with one of the following active ingredients: DEET, picaridin, IR3535, oil of lemon eucalyptus (OLE), para-menthane-diol (PMD), or 2-undecanone. Find an EPA-registered insect repellent that’s right for you.
  • Always follow product directions and reapply as directed.
  • If you are also using sunscreen, apply sunscreen first and insect repellent second.
• When using insect repellent on children:
  • Do not use products containing oil of lemon eucalyptus (OLE) or para-menthane-diol (PMD) on children under 3 years old.
  • Do not apply insect repellent to a child’s hands, eyes, mouth, cuts, or irritated skin.
  • Adults: Spray insect repellent onto your hands and then apply to a child’s face.
• Use permethrin-treated clothing and gear (such as boots, pants, socks, and tents). You can buy pre-treated clothing and gear or treat them yourself:
  • Treated clothing remains protective after multiple washings. See the product information to find out how long the protection will last.
  • If treating items yourself, follow the product instructions carefully.
  • Do not use permethrin directly on skin.

If you are bitten by mosquitoes, avoid scratching mosquito bites and apply hydrocortisone cream or calamine lotion to reduce itching.

If you traveled and feel sick, particularly if you have a fever, talk to a healthcare provider, and tell them about your travel. Avoid contact with other people while you are sick.

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 more than 100 countries and territories. About half of the world’s population is at risk. Large areas of Africa and South Asia and parts of Central and South America, the Caribbean, Southeast Asia, the Middle East, and Oceania are considered areas where malaria transmission occurs.

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.

Why is malaria so common in Africa?

In Africa south of the Sahara, the principal malaria mosquito, Anopheles gambiae, transmits malaria very efficiently. The type of malaria parasite most often found, Plasmodium falciparum, causes severe, potentially fatal disease. Lack of resources and political instability can prevent the building of solid malaria control programs. In addition, malaria parasites are increasingly resistant to antimalarial drugs, presenting one more barrier to malaria control on that continent.

In some countries, malaria is said to exist in “rural” areas. How would one know if an area is rural vs urban?

What constitutes a rural area can vary by country. In general, urbanization can be said to involve both population size and economic development of an area in which there is concentrated commercial activity, such as manufacturing, the sale of goods and services, and transportation. Rural areas tend to have less commercial activity, less population density, more green space, and agriculture may be a main feature.

I will be traveling outside the United States to an area with malaria. How do I find out what is the best drug to take to prevent malaria?

CDC has a list of all the places in the world where malaria transmission occurs and the malaria drugs that are recommended for prevention in each place.

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

To allow enough time for some of the drugs to become effective and for a pharmacy to prepare any special doses of medicine (especially doses for children and infants), you may need to visit your health-care provider 4-6 weeks before travel. Other malaria medicines only need to be started the day before travel and so last-minute travelers can still benefit from a visit to their health-care provider before traveling.

What is known about the long-term effects of drugs that are commonly used to prevent malaria?

The drugs used to prevent malaria have been shown to be safe and well-tolerated for long term use.

I was born in a country where malaria is present and had malaria as a child, and then moved to the United States many years ago. Do I need to worry about getting malaria when I return home to visit my friends and relatives?

Yes. Anyone who goes to a country where malaria transmission occurs should take precautions against contracting malaria. During the time that you have spent in the United States, you have lost any malaria immunity that you might have had while living in your native country. Without frequent exposure to malaria parasites, your immune system has lost its ability to fight malaria. You are now as much at risk as someone who was born in the United States (a “nonimmune” person). Please consult with your health-care provider or a travel clinic about precautions to take against malaria (preventive drugs and protection against mosquito bites) and against other diseases.

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

Buying medications abroad has its risks. The drugs could be of poor quality because of the way they are produced. The drugs could contain contaminants or they could be counterfeit drugs and therefore may not provide you the protection you need against malaria. In addition, some medications that are sold overseas are not used anymore in the United States or were never sold here. These drugs may not be safe or their safety has never been evaluated.

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?

Attempts at producing an effective malaria vaccine and vaccine clinical trials are ongoing. The malaria parasite is a complex organism with a complicated life cycle. The parasite has the ability to evade your immune system by constantly changing its surface, so developing a vaccine against these varying surfaces is very difficult. In addition, scientists do not yet totally understand the complex immune responses that protect humans against malaria. However, many scientists all over the world are working on developing an effective vaccine. Because other methods of fighting malaria, including drugs, insecticides, and insecticide-treated bed nets, have not succeeded in eliminating the disease, the search for a vaccine is considered to be one of the most important research projects in public health.

Considerations when choosing a drug for malaria prophylaxis:

• Recommendations for drugs to prevent malaria differ by country of travel and can be found in Malaria Information by Country. Recommended drugs for each country are listed in alphabetical order and have comparable efficacy in that country.
• No antimalarial drug is 100% protective and must be combined with the use of personal protective measures, (i.e., insect repellent, long sleeves, long pants, sleeping in a mosquito-free setting or using an insecticide-treated bednet).
• For all medicines, also consider the possibility of drug-drug interactions with other medicines that the person might be taking as well as other medical contraindications, such as drug allergies.
• When several different drugs are recommended for an area, the following table might help in the decision process.

Atovaquone/Proguanil (Malarone)

Chloroquine

Doxycycline

Mefloquine

Primaquine

Tafenoquine (Arakoda)

What Are They?

Counterfeit (fake) antimalarial or other drugs are deliberately made to look like brand name drugs. However, they may have no active ingredients, they may have less than the required amount of active ingredient, or they may contain ingredients which are not what is described on the package label. Counterfeiters tend to focus on the more expensive brands. Substandard drugs are found even among cheaper products, because some manufacturers try to avoid costly quality control and good manufacturing practices.

The quality of commercially available drugs varies greatly in malaria-endemic countries:

• The amount of the active ingredient can vary due to lack of regulations and poor quality control practices in many of these countries.
• Some pills may release very little if any drug due to poor formulation techniques.
• Chemical break-down of some drugs can occur due to poor storage conditions, especially in warm and humid tropical climates.
• Some drugs may be contaminated with other substances.
• Counterfeiters may also obtain expired drugs and repackage them with new expiration dates.

Where Do You Find Them?

Worldwide prevalence of counterfeit and substandard products is summarized in a Drug Quality Report matrix by the U.S. Pharmacopeia Drug Quality and Information (USP DQI) Program. Information on domestic (U.S.) issues regarding counterfeit and poor-quality drugs is provided by the U.S. Food and Drug Administration.

When Buying Drugs, Take the Following Precautions

• Travelers should buy in their home country all the medicines they will need before their trip.
• Travelers should write down the drug’s generic and brand names as well as the name of the manufacturer. In case they run out, they can look for the correct product.
• Make sure that the drug is in its original packaging.
• Inspect the packaging because many times poor quality printing indicates a counterfeited product.
• Be suspicious of tablets that have a peculiar odor, taste, or color, or that are extremely brittle.

The risk for a traveler contracting malaria differs substantially from region to region and from traveler to traveler, even within a single country, based upon travelers’ behaviors and circumstances.

There is no accepted method of quantifying the risk and no numerical value for a risk threshold beyond which chemoprophylaxis is or is not recommended. Thus experience and judgment are required in assessing the factors described below to arrive at the best prevention strategy for the individual traveler.

A travel or tropical medicine specialist can be an excellent source of guidance when making these decisions. Depending on level of risk, it may be appropriate to recommend no specific interventions, mosquito avoidance measures only, or mosquito avoidance measures plus chemoprophylaxis.

For the risk-averse traveler, remember that even in low risk situations, it only takes one bite from an infective female Anopheles mosquito to transmit malaria.

Questions to Ask When Assessing an Individual Traveler’s Risk

Where is the traveler going?

• For some areas with limited malaria transmission, where malaria cases occur sporadically and risk of infection to travelers is assessed as being very low, it is recommended that travelers use mosquito avoidance measures only, and no chemoprophylaxis should be prescribed.
• Regions associated with the highest estimated relative risk of infection for travelers are West Africa and Oceania. For these areas of intense transmission, exposure for even short amounts of time can result in transmission, and so chemoprophylaxis should always be used.
• Regions associated with moderate estimated relative risk of infection for travelers are the other parts of Africa, South Asia, and South America.
• Regions associated with lower estimated relative risk for travelers are Central America and other parts of Asia. There is considerable country-by-country variation, as well as variable transmission within countries. See the malaria information by country table for details.

Malaria transmission is not distributed homogeneously throughout all countries. Some destinations have malaria transmission occurring throughout the whole country, while in others it occurs in defined pockets. If travelers are going to the highly endemic pockets during peak transmission times, even though the country as a whole may be low transmission, this destination for this individual may be high risk.

When is the traveler going?

In some countries with significant seasonal shifts in temperature or rainfall, malaria transmission intensity may decrease during the colder or drier months of the year. Based on knowledge of the climactic conditions in some sub-tropical or temperate destinations, travelers may choose mosquito avoidance measures only, for example, during the winter months.

What is the style and duration of travel?

It is important to assess factors such as the types of accommodations and activities as well as the reason and duration of travel as a part of the risk assessment. For example, short-term business travelers staying in air-conditioned hotels may be at lower risk than backpackers or adventure travelers.

Because malaria-transmitting mosquitoes are most active at night, include an assessment of the likelihood that the travelers might be spending time outdoors in the evenings for dining or entertainment. Longer durations of stay in a malaria-endemic area may also increase the chance that an individual might become infected.

Who is the traveler?

Certain travelers have been shown to have greater risk of malaria infection. Particular care should be given to ensure an effective malaria prevention strategy for these travelers.

• The highest risk is associated with first- and second-generation immigrants living in nonendemic countries who return to their countries of origin to visit friends and relatives (VFRs). Ironically, VFR travelers often consider themselves to be at no risk because they grew up in a malaria-endemic country and consider themselves to be immune. However, acquired immunity is lost very quickly, and VFR travelers, especially those going to West Africa and India, should always use appropriate chemoprophylaxis.
• Malaria infection in pregnant women can be more severe than in nonpregnant women. Malaria can increase the risk for adverse pregnancy outcomes, including prematurity, abortion, and stillbirth.

For these reasons and because no chemoprophylactic regimen is completely effective, women who are pregnant or likely to become pregnant should be advised to avoid travel to areas with malaria transmission if possible. If travel to a malarious area cannot be deferred, use of an effective chemoprophylaxis regimen is essential. Depending on the destination, this is usually either chloroquine or mefloquine.

Every year approximately half of all of the cases of malaria in US travelers are among first- and second-generation immigrants (including their spouses) who traveled back to their country of origin to visit friends and relatives. For convenience, this group of travelers is referred to as VFR travelers.

Why are VFR travelers at greater risk?

There is no single reason why VFR travelers are at higher risk for malaria infection. Many factors contribute to this increased risk – not all of them may be true for all VFR travelers.

• The duration of travel tends to be longer than for other types of travel such as business trips or packaged tours.
• When visiting friends or relatives, travelers are more likely to stay at the houses of these friends and relatives rather than at hotels. Depending on the destination or socioeconomic status, private residences may be less likely to be air-conditioned or have screened windows.

• VFR travelers are less likely to use the recommended malaria prevention measures, which places them at greater risk of infection than the other types of travelers who are more likely to use insect repellent and take chemoprophylactic medicines.

  Again, reasons for this are complex, but may include some socioeconomic factors such as access to healthcare. Some recent immigrants may not have medical insurance or may not have established a relationship with a primary healthcare provider, which limits opportunities to receive appropriate preventive medical interventions including malaria prevention.

• Another significant factor is the incorrect risk perception by the VFR travelers. Some VFR travelers consider themselves to be at low or no risk for infection because they grew up in a malaria-endemic country and consider themselves to be immune. This includes a belief that even if they are infected, the infection will be mild and easily treatable with medicines acquired while abroad.

  However, VFR travelers should know that any partial immunity that they may have developed while growing up in a malaria-endemic country is lost very quickly after moving away making them as vulnerable to infection as people who grew up in non-endemic countries. Their children and spouses who may be accompanying them on the trip will also have no immunity against malaria. Also, depending on the destination, not all of the medicines that are available overseas to treat malaria may be appropriate or effective.

Do VFR travelers need to take special precautions to prevent malaria?

No. They simply need to use the same preventive measures that are recommended for all travelers. They should avoid mosquito bites by using a recommended insect repellent (especially if outside at night) and by sleeping under an insecticide-treated bed net if staying in an open-air accommodation. They should also start taking one of the chemoprophylaxis medicines recommended for their destination prior to, during, and for the complete amount of time after, travel.

Every year, millions of U.S. residents travel to countries where malaria and other diseases spread by mosquitoes (mosquito-borne) are found. These diseases can cause serious illness and death in some cases. Preventing mosquito-borne infections is very important to staying well when you travel.

Why do I need to use an insect repellent when I travel to an area with malaria?

An insect repellent will help protect you from mosquitoes that spread malaria and other diseases, such as dengue, chikungunya, and Yellow fever. You can use an insect repellent on your skin and clothes to keep away (repel) insects.

Your doctor may also prescribe you a medication to prevent malaria (antimalarial drug).

Although antimalarial drugs are very effective, they are not 100% effective in preventing malaria. This is why you need to also use an insect repellent and take other steps to keep mosquitoes from biting you (mosquito avoidance).

In some areas where only a few cases of malaria occur, CDC recommends mosquito avoidance as the only way to prevent malaria.

Are insect repellents safe?

Most insect repellents that can be put on the skin must be registered by the U.S. Environmental Protection Agency (EPA) before they can be sold in stores.

EPA registration means the insect repellent has been tested and approved for human safety and is effective when used according to directions on the label. Before you buy an insect repellent, be sure to look on the label for EPA approval.

Which insect repellents will give me long-lasting protection against mosquitoes?

For hours of long-lasting protection, look for insect repellents with the following active ingredients:

• DEET
• IR3535
• Oil of lemon eucalyptus (OLE)*
• Picaridin (KBR 3023)

Some brand names of repellents include:

• DEET products: Off!, Cutter, Sawyer, Ultrathon.
• IR3535 products: Skin So Soft Bug Guard Plus Expedition, SkinSmart.
• OLE products: Repel, Off! Botanicals.
• Picaridin products (Autan, Bayrepel and icaridinoutside U.S.): Cutter Advanced, Skin So Soft Bug Guard Plus.

*”Pure” oil of lemon eucalyptus (essential oil) is not recommended. It has not been tested by EPA for safety and effectiveness

See a doctor or other healthcare provider 4-6 weeks before your trip to get any prescriptions, shots, and information you may need to stay healthy while you travel. Even if your trip is sooner, see a doctor to be safe. For more information visit CDC Travelers’ Health website at www.cdc.gov/travel

How do I use an insect repellent?

• Always follow directions on the label.
• Spray or rub the insect repellent onto your skin that is NOT covered by your clothes. Do not use under clothing.
• Use just enough insect repellent to cover your skin not covered by clothing. Heavy use of insect repellent or pouring it all over your body is not necessary.
• Never use insect repellents over cuts, wounds, or irritated skin.
• Do not spray insect repellents directly on your face—spray it onto your hands first and then pat the insect repellent onto your face.
• Do not spray or put insect repellents on your eyes or mouth, and put only a little around your ears.
• Use separate sunscreen and insect repellent products. Put the sunscreen on first, then spray on the insect repellent.
• After returning indoors, wash the insect repellent off your skin with soap and water or take a bath. This is especially important when you use insect repellents daily.
• Wash any clothes you treated with insect repellent before wearing them again.

Can I use an insect repellent if I am pregnantor breastfeeding

Yes. Pregnant and breastfeeding women can use EPA-approved insect repellents. Always follow directions on the label.

Can I put insect repellent on my baby?

• Do not put insect repellent on babies younger than 2 months of age.
• Protect small babies under the age of 2 months by placing a fitted mosquito net around their infant seat or carrier.

How do I put insect repellent on a child?

• Follow directions on the label.
• See directions for how to use an insect repellent on this page.
• Use no more than 30% DEET on a child.
• Do not use insect repellent with lemon eucalyptus on children under the age of 3 years.

What other things can I do to prevent mosquito bites?

• Wear a long-sleeved shirt, long pants, and a hat when you are outdoors.
• Spray insect repellent on your clothes for extra protection or buy a product with permethrin to treat your clothes and bed net to repel insects.
• Sleep in a well-screened or air-conditioned room, or sleep under a permethrin-treated bed net. This is because malaria mosquitoes mostly bite at night (dusk until dawn).
• Stay indoors during the times biting mosquitoes are most active.

Always spray insect repellents in open areas and wash your hands after using

What should I do if I develop a rash or reaction to the insect repellent?

Stop using the insect repellent and wash the area with soap and water.

If you see a doctor about the reaction, take the repellent container with you. You can also call the Poison Help Hotline at 1-800-222-1222.

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

Any traveler who becomes ill with a fever or flu-like illness while traveling, and up to 1 year after returning home, should immediately seek professional medical care. You should tell your health-care provider that you have been traveling in an area where malaria transmission occurs and ask to be tested for malaria infection.

Can I give blood if I have been in a country where there is malaria?

It depends on what areas of that country you visited, how long ago you were there, and whether you ever had malaria. In general, most travelers to an area with malaria are deferred from donating blood for 1 year after their return. People who used to live in countries where malaria transmission occurs cannot donate blood for 3 years. People diagnosed with malaria cannot donate blood for 3 years after treatment, during which time they must have remained free of symptoms of malaria.

Blood banks follow strict guidelines for accepting or deferring donors who have been in malaria-endemic areas. They do this to avoid collecting blood for transfusions from an infected donor. In the United States during the period 1963-2012, there were 97 cases reported to CDC where people acquired malaria through a transfusion. Because of these control measures, transfusion-transmitted malaria is very rare in the United States and occurs at a rate of less than 1 per million units of blood transfused.

In 2020, an estimated 627,000 people died of malaria—most were young children in sub-Saharan Africa. Within the last decade, increasing numbers of partners and resources have rapidly increased malaria control efforts. This scale-up of interventions has saved millions of lives globally and cut malaria mortality by 36% from 2010 to 2020, leading to hopes and plans for elimination and ultimately eradication. CDC brings its technical expertise to support these efforts with its collaborative work in many malaria-endemic countries and regions.

Malaria’s Impact

Malaria occurs mostly in poor tropical and subtropical areas of the world. In many of the countries affected by malaria, it is a leading cause of illness and death. In areas with high transmission, the most vulnerable groups are young children, who have not developed immunity to malaria yet, and pregnant women, whose immunity has been decreased by pregnancy. The costs of malaria – to individuals, families, communities, nations – are enormous.

Geography

Malaria occurs mostly in poor, tropical and subtropical areas of the world. Africa is the most affected due to a combination of factors:

• A very efficient mosquito (Anopheles gambiae complex) is responsible for high transmission.
• The predominant parasite species is Plasmodium falciparum , which is the species that is most likely to cause severe malaria and death.
• Local weather conditions often allow transmission to occur year round.
• Scarce resources and socio-economic instability have hindered efficient malaria control activities.
• In other areas of the world, malaria is a less prominent cause of deaths, but can cause substantial disease and incapacitation, especially in some countries in South America and South Asia.

Statistics

Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries, where young children and pregnant women are the groups most affected. According to the 2021 World Malaria Report:

• Nearly half the world’s population lives in areas at risk of malaria transmission in 87 countries and territories.
• In 2020, malaria caused an estimated 241 million clinical episodes, and 627,000 deaths. An estimated 95% of deaths in 2020 were in the WHO African Region.

Who Is Most Vulnerable?

Pregnant woman having a blood smear taken at an antenatal clinic at the Maela Camp in Thailand near the Burmese Border. Pregnant women are at increased risk of malaria. Image contributed by the Shoklo Malaria Research Unit, Mae Sot, Thailand.

The most vulnerable are persons with no or little immunity against the disease. In areas with high transmission (such as Africa south of the Sahara), the most vulnerable groups are:

• Young children, who have not yet developed partial immunity to malaria
• Pregnant women, whose immunity is decreased by pregnancy, especially during the first and second pregnancies
• Travelers or migrants coming from areas with little or no malaria transmission, who lack immunity

In areas with lower transmission (such as Latin America and Asia), residents are less frequently infected. Many persons may reach adult age without having built protective immunity and are thus susceptible to the disease, including severe and fatal illness.

Social and Economic Toll

Malaria imposes substantial costs to both individuals and governments.

Costs to individuals and their families include purchase of drugs for treating malaria at home; expenses for travel to, and treatment at, dispensaries and clinics; lost days of work; absence from school; expenses for preventive measures; and expenses for burial in case of deaths.

Costs to governments include maintenance, supply and staffing of health facilities; purchase of drugs and supplies; public health interventions against malaria, such as insecticide spraying or distribution of insecticide-treated bed nets; lost days of work with resulting loss of income; and lost opportunities for joint economic ventures and tourism.

Direct costs (for example, illness, treatment, premature death) have been estimated to be at least US $12 billion per year. The cost in lost economic growth is many times more than that.

The goal of most current National Malaria Control Programs and most malaria activities is to reduce the number of malaria-related cases and deaths. To reduce malaria transmission to a level where it is no longer a public health problem is the goal of what is called malaria “control.”

“Control” of malaria differs from “elimination” or “eradication of malaria.” “Elimination” is local or regional in scope. Eradication is “global elimination.” Eradication is not achieved until malaria is gone from the natural world. These terms can be defined differently for different illnesses.

Recent increases in resources, political will, and commitment have led to discussion of the possibility of malaria elimination and, ultimately, eradication.

Where malaria exacts the largest burden, Africa, it has been extremely difficult to control. Many reasons account for this: an efficient mosquito that transmits the infection, a high prevalence of the most deadly species of the parasite, favorable climate, weak infrastructure to address the disease, and high intervention costs that are difficult to bear in poor countries.

However, the scale-up of effective, safe, and proven prevention and control interventions made possible by global support and national commitment has shown that the impact of malaria on residents of malaria-endemic countries can be dramatically reduced when these are used together.

Malaria Treatment and Prevention Interventions

Malaria control is carried out through the following recommended malaria treatment and prevention interventions. The choice of interventions depends on the malaria transmission level in the area (e.g., in areas of low transmission level, intermittent preventive treatment for pregnant women [IPTp] is usually not recommended).

• Case management (diagnosis and treatment) of patients with malaria
• Prevention
  • Insecticide-treated nets (ITNs)
  • Intermittent preventive treatment of malaria in pregnant women (IPTp)
  • Intermittent preventive treatment of malaria in infancy (IPTi)
  • Indoor residual spraying (IRS)

In most malaria-endemic countries, four interventions—case management (diagnosis and treatment), ITNs, IPTp, and IRS—make up the essential package of malaria interventions.

Occasionally, other interventions are used:

• Larval control and other vector control interventions
• Mass drug administration and Mass fever treatment

In addition, several companies and groups are at work on developing a malaria vaccine, but there is currently no effective malaria vaccine on the market.

Why Pregnant Women Are Especially at Risk

Adults who have survived repeated malaria infections throughout their lifetimes may become partially immune to severe or fatal malaria. However, because of the changes in women’s immune systems during pregnancy and the presence of a new organ (the placenta) with new places for parasites to bind, pregnant women lose some of their immunity to malaria infection.

Malaria infection during pregnancy can have adverse effects on both mother and fetus, including maternal anemia, fetal loss, premature delivery, intrauterine growth retardation, and delivery of low birth-weight infants (<2500 g or <5.5 pounds), a risk factor for death.

It is a particular problem for women in their first and second pregnancies and for women who are HIV-positive.

Adverse Effects Vary by Transmission Level

The problems that malaria infection causes differ somewhat by the type of malaria transmission area: stable (high) or unstable (low) transmission.

• In high transmission areas, women have developed immunity that generally prevents severe disease, however, parasite specifically target the placenta, leading in an increased risk during pregnancygained a level of immunity to malaria that wanes somewhat during pregnancy. Malaria infection is more likely to contribute to maternal anemia and delivery of low birth-weight infants (<2500 g or <5.5 pounds). It is a particular problem for women in their first and second pregnancies, for younger women, and for women who are HIV-positive.
• In low transmission areas, women generally have developed no immunity to malaria. Malaria infection is more likely to result in severe malaria disease, maternal anemia, premature delivery, or fetal loss.

Malaria-infected human placenta examined under the microscope. The intervillous spaces (central area of the picture) are filled with red blood cells, most of which are infected with Plasmodium falciparum malaria parasites. The parasites appear here as black dots. A malaria-infected placenta is unable to carry out normally its main function: to provide nutrients to the fetus.

Recommended Interventions

The currently recommended interventions for pregnant women are

• Use of insecticide-treated bed nets
• Intermittent preventive treatment (IPTp) (for HIV negative women in high transmission areas).
• Effective case management (diagnosis and treatment of illness)

Women should also receive iron/folate supplementation to protect them against anemia, a common occurrence among all pregnant women.

IPTp

IPTp entails administration of a curative dose of an effective antimalarial drug (currently sulfadoxine-pyrimethamine) to all pregnant women without testing whether or not they are infected with the malaria parasite . IPTp should be given at each routine antenatal care visit, starting as early as possible in the second trimester.

Pregnant women are routinely given folic acid supplementation to prevent neural tube defects in their infants. However, high doses of folic acid counteract the effect of sulfadoxine-pyrimethamine. Therefore, it is preferred that women take only the recommended 0.4 mg daily dose of folic acid. In some countries, 5 mg of folic acid are used, and in those countries, it is recommended to withhold folic acid supplementation for two weeks after taking IPTp with sulfadoxine-pyrimethamine to ensure optimal efficacy.

A pregnant woman during an antenatal consultation in Malawi receives sulfadoxine-pyrimethamine for intermittent preventive treatment of malaria (IPTp). The plastic bag on the table holds an insecticide-treated bed net, another method for protecting her against malaria.

Insecticide-treated bed nets (ITNs) are a form of personal protection that has been shown to reduce malaria illness, severe disease, and death due to malaria in endemic regions. In community-wide trials in several African settings, ITNs were shown to reduce the death of children under 5 years from all causes by about 20%.

How Do ITNs Work?

Bed nets form a protective barrier around people sleeping under them. However, bed nets treated with an insecticide are much more protective than untreated nets.

The insecticides that are used for treating bed nets kill mosquitoes, as well as other insects. The insecticides also repel mosquitoes, reducing the number that enter the house and attempt to feed on people inside. In addition, if high community coverage is achieved, the numbers of mosquitoes, as well as their length of life will be reduced. When this happens, all members of the community are protected, regardless of whether or not they are using a bed net. To achieve such effects, more than half of the people in a community must use an ITN.

Insecticide-treated bed nets (ITNs) are a major intervention for malaria control. Photo credit: Maggie Hallahan Photography

Net Materials and Insecticides

Nets may vary by size, shape, color, material, and/or insecticide treatment status. Most nets are made of polyester, polyethylene, or polypropylene.

Only two insecticides classes are approved for use on ITNs (pyrroles and pyrethroids). These insecticides have been shown to pose very low health risks to humans and other mammals, but are toxic to insects and kill them. Previously, nets had to be retreated every 6 to 12 months, or even more frequently if the nets were washed. Nets were retreated by simply dipping them in a mixture of water and insecticide and allowing them to dry in a shady place. The need for frequent retreatment was a major barrier to widespread use of ITNs in endemic countries. In addition, the additional cost of the insecticide and the lack of understanding its importance resulted in very low retreatment rates in most African countries.

Recent studies have suggested that the rise of pyrethroid resistance may undermine the effectiveness of nets. To help manage resistance, some net products incorporate piperonyl butoxide (PBO) along with a pyrethroid insecticide, but there is not yet evidence that this significantly improves ITN effectiveness in areas with high levels of pyrethroid resistance, and WHO currently does not consider nets that incorporate PBO to be tools for managing pyrethroid resistance.

Long-Lasting Insecticide-treated Nets (LLINs)

Several companies have developed long-lasting insecticide-treated nets (LLINs) that maintain effective levels of insecticide for at least 3 years, even after repeated washing. The WHO Pesticide Evaluation Scheme (WHOPES) has given either full or interim approval to more than 15 of these LLINs for use in the prevention of malaria. CDC is currently testing some of these and other LLINs to assess their performance and durability in the field.

LLINs have been associated with sharp decreases in malaria in countries where malaria programs have achieved high LLIN coverage. WHO now recommends that LLINs be distributed to and used by all people (“universal coverage”) in malarious areas, not just by the most vulnerable groups: pregnant women and children under 5 years. LLINs are most commonly distributed through mass campaigns approximately every 3 years.

Between 2008 and 2010, a total of 294 million nets were distributed in sub-Saharan Africa. Funding for LLINs gradually increased from 2004 when 5.6 million nets were delivered, to 2010, when 145 million nets were delivered. However, funding for nets, and other malaria prevention and control interventions, is likely to plateau or even decline in the next few years due to the current economic situation. One way to maintain net coverage is to increase the lifespan of LLINs. A recent study estimated that up to $3.8 billion could be saved over 10 years by increasing the lifespan of nets from 3 years to 5 years.

Mobilizing resources to procure these nets remains a major challenge. After much debate, WHO now recommends that LLINs be provided free. Multilateral and bilateral donors and programs such as the Global Fund against HIV/AIDs, Tuberculosis, and Malaria and the President’s Malaria Initiative support the purchase of LLINs for many countries. Individual donations of nets can be made through organizations such as CDC Foundation or Malaria No More.

Many malaria vectors are considered “endophilic”; that is, the mosquito vectors rest inside houses after taking a blood meal. These mosquitoes are particularly susceptible to control through indoor residual spraying (IRS).

What Is Indoor Residual Spraying?

As its name implies, IRS involves coating the walls and other surfaces of a house with a residual insecticide. For several months, the insecticide will kill mosquitoes and other insects that come in contact with these surfaces. IRS does not directly prevent people from being bitten by mosquitoes. Rather, it usually kills mosquitoes after they have fed if they come to rest on the sprayed surface. IRS thus prevents transmission of infection to other persons. To be effective, IRS must be applied to a very high proportion of households in an area (usually >80%).

History of IRS

IRS with DDT was the primary malaria control method used during the Global Malaria Eradication Campaign (1955-1969). The campaign did not achieve its stated objective but it did eliminate malaria from several areas and sharply reduced the burden of malaria disease in others.

Concern over the environmental impact of DDT led to the introduction of other, more expensive insecticides. As the eradication campaign wore on, the responsibility for maintaining it was shifted to endemic countries that were not able to shoulder the financial burden. The campaign collapsed and in many areas, malaria soon returned to pre-campaign levels.

As a result of the cost of IRS, the negative publicity due to the failure of the Malaria Eradication Campaign, and environmental concerns about residual insecticides, IRS programs were largely disbanded other than in a few countries with resources to continue them. However, the recent success of IRS in reducing malaria cases in South Africa by more than 80% has revived interest in this malaria prevention tool.

Indoor residual spraying

Larval Control

Interventions targeting the larval stages of the mosquito have been used effectively for decades, but their effectiveness varies widely from species to species. In general, if habitats are large and amenable to environmental modification, the intervention is effective, but if habitats are small, widely dispersed, and transient the intervention is less effective.

Anopheles gambiae, one of the primary vectors of malaria in Africa, breeds in numerous small pools of water that form due to rainfall. The larvae develop within a few days, escaping their aquatic environment before it dries out. It is difficult, if not impossible, to predict when and where the breeding sites will form, and to find and treat them before the adults emerge. Therefore, larval mosquito control for the prevention of malaria in Africa has not been attempted on a large scale. It may, however, be appropriate for specific settings such as urban environments or desert fringe areas where habitats are more stable and predictable. In contrast, in Southeast Asia, Europe and the Americas, larval control has proven extremely effective.

Larval control may be implemented through environmental modification – draining and filling – or through use of larvacides. Though biological control using fish is often used, evidence for its effectiveness is limited.

Source reduction: The burrow pit resulting from the activity of this brickmaker in Kisian (western Kenya) is a potential breeding site for Anopheles larvae. Filling the burrow pit would remove a source of Anopheles adults.

Source Reduction

Source reduction is removal or permanent destruction of mosquito breeding sites. The larval habitats may be destroyed by filling depressions that collect water, by draining swamps or by ditching marshy areas to remove standing water. Mosquitoes that breed in irrigation water can be controlled through careful water management.

Chemical Larviciding

For some mosquito species, habitat elimination is not possible. For these species, chemical insecticides can be applied directly to the larval habitats. Other methods, which are less disruptive to the environment, are usually preferred:

• Oils may be applied to the water surface, suffocating the larvae and pupae. Most oils in use today are rapidly biodegraded.
• Toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti) can be applied in the same way as chemical insecticides. They are very specific, affecting only mosquitoes, black flies, and midges.
• Insect growth regulators such as methroprene are specific to mosquitoes and can be applied in the same way as chemical insecticides.

Biological Control

Potential biological control agents, such as fungi (e.g., Laegenidium giganteum) or mermithid nematodes (e.g., Romanomermis culicivorax), parasitize and kill larval mosquitoes but they are not efficient for mosquito control and are not widely used. Likewise, mosquito fish (including Gambusia affinis) have largely been ineffective.

Other Vector Control Interventions

Fogging (area spraying) using a machine mounted on the back of a truck.

Fogging or Area Spraying

Fogging or ultra-low volume spraying or area spraying is primarily reserved for emergency situations such as epidemics. Fogging has not been shown to be effective in any malaria-endemic areas. Fogging and area sprays must be properly timed to coincide with the time of peak adult mosquito activity, because resting mosquitoes are often found in areas that are difficult for the insecticide to reach (e.g., under leaves, in small crevices). In addition, fogging and area spraying will have to be repeatedly applied to have an impact, and it can easily become too costly to maintain.

Personal Protection Measures

Personal protection measures include the use of window screens, ITNs, and repellents (such as DEET) and wearing of light-colored clothes, long pants, and long-sleeved shirts. Well-constructed houses with window screens are effective for preventing biting by mosquitoes that bite indoors and may have contributed to the elimination of malaria from the United States and Europe. Recent evidence suggests that repellents may be effective in reducing malaria transmission and may be appropriate for areas where mosquitoes bite outdoors or early in the evening when people are not using ITNs. However, while repellents are recommended for travelers to malaria-endemic areas, further work to develop repellent formulations that are easily deployed in endemic countries is needed.

Sterile Male Release

Introducing sterile male mosuitoes into an area has been successfully applied in several small-scale areas. However, the need for large numbers of mosquitoes for release makes this approach impractical for most areas.

Genetic Modification of Malaria Vectors

Genetic modification aims to develop mosquitoes that are not susceptible to the parasite. This approach is still years from application in field settings, though there have been remarkable advances in recent years in technology to allow direct modification of the mosquito genome.

Malaria must be diagnosed and treated promptly with a recommended antimalarial drug to keep the illness from progressing and to help prevent further spread of infection in the community.

In the malaria-endemic world, diagnosis of malaria can be difficult for several reasons:

• Malaria’s clinical symptoms are shared with other diseases and conditions, and many malaria-endemic countries lack resources, such as microscopes and rapid diagnostic tests (RDTs), to make a definitive diagnosis.
• Health personnel in these areas are often undertrained, underequipped and underpaid.
• Health personnel in the malaria-endemic world 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 may be “uncomplicated” or “severe.”

• Uncomplicated malaria: Symptoms may include fever, chills, sweats, headaches, muscle pains, nausea and vomiting.
• Severe malaria: Symptoms may include confusion, coma, focal neurologic signs, severe anemia, and respiratory difficulties. A patient with symptoms of severe malaria should be assessed quickly and treated immediately. Severe malaria is most often caused by the most dangerous parasite, Plasmodium falciparum.

Diagnosis of Malaria

When a patient with fever is brought to a health facility in the malaria-endemic world, a health worker may suspect that the patient has malaria based on the patient’s symptoms, although these symptoms are not specific to malaria. For many years, national malaria control programs recommended treating children under 5 years with fever for malaria, based on symptoms alone, because most health facilities did not have working microscopes, a trained microscopist, and necessary equipment (e.g., slides, stains) to perform a laboratory test. Malaria was extremely common and potentially fatal, and providing treatment based on clinical diagnosis alone could save the child’s life. However, if the child had an illness other than malaria, it would go untreated.

As malaria interventions have been scaled up in sub-Saharan Africa in the last decade, rapid diagnostic tests for malaria have become available in health facilities, microscopes have been provided, and microscopists have been trained.

In 2010, the World Health Organization recommended that all suspected cases of malaria be confirmed with a diagnostic test prior to treatment. The Roll Back Malaria Partnership has set new targets of universal access to malaria diagnostic testing in public and private sectors as well as at the community level. In many countries, community health workers (CHWs) have been trained on integrated community case management of common childhood illnesses, including malaria, pneumonia, and diarrhea. Many CHWs are being trained to use rapid diagnostic tests for febrile children and to treat them with recommended antimalarials if they are positive.

Diagnosis Based on Laboratory Methods

Microscopy and rapid diagnostic tests can be used to make a definitive diagnosis of malaria.

Microscopy

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

More on: Malaria Microscopy

Rapid Diagnostic Tests

Over the last fifteen years, test kits have become available that can detect antigens derived from malaria parasites in a person’s blood. These immunologic (“immunochromatographic”) tests are referred to as RDTs and provide results quickly—depending on the test, in about 20 minutes.

RDTs offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available. Malaria RDTs are currently used in many clinical settings and programs in countries where malaria is transmitted. CDC and others are conducting operational research to help optimize their use.

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).

The WHO Malaria RDT Product Testing Programme, coordinated by WHO/TDR and the Foundation for Innovative New Diagnostics (FIND) and executed in collaboration with CDC, provides comparative data on the performance of various RDTs available in the market to assist in procurement. Since 2008, more than 290 products have been evaluated over seven rounds of the WHO Malaria RDT Product Testing Programme.

More on: Rapid Diagnostic Tests

Treatment

The World Health Organization recommends that patients in malaria-endemic areas be treated within 24 hours after their first symptoms appear.

Treatment of a patient with malaria depends on the country’s national guidelines, which typically take the following into consideration:

• Type (species) of the infecting parasite
• Clinical status of the patient
• Any accompanying illness(es) or condition(s)
• Pregnancy
• Drug allergies, or other medications taken by the patient
• Where the infection was acquired and the presence of antimalarial drug resistance there.

Uncomplicated Malaria

Patients who have uncomplicated malaria can be treated on an outpatient basis; however, patients with severe malaria should be hospitalized.

Most drugs recommended for treatment of uncomplicated malaria cases in the malaria-endemic world are active against the parasite forms in the blood (the form that causes disease). Listed below are some of the drugs approved by the World Health Organization and those most commonly recommended by national malaria control programs in the malaria-endemic world:

• Artemesinin-based combination treatments, (e.g, artemether-lumefantrine, artesunate-amodiaquine)
• Chloroquine*
• Doxycycline
• Mefloquine*
• Quinine

*Two of these drugs, chloroquine and mefloquine, are no longer effective in some or many parts of the world.

More on: Treatment in the United States

Another drug, primaquine, is used as an adjunct for certain species of malaria (e.g., P. falciparum,P. vivax, and P. ovale). It is active against the dormant parasite liver forms (hypnozoites) and can prevent relapses of P. vivax and P. ovale. Primaquine should not be taken by pregnant women or by people who are deficient in G6PD (glucose-6-phosphate dehydrogenase). Patients should not take primaquine until a screening test has excluded G6PD deficiency or unless the risk of deficiency in the surrounding population is known to be low, because primaquine given to people with G6PD deficiency can cause hemolytic anemia. In some countries, primaquine is also used in a single dose to prevent secondary transmission of P. falciparum.

Counterfeit and substandard drugs are sold in some areas and should be avoided.

Severe Malaria

Severe malaria occurs when an infection is complicated by serious organ failure or abnormalities in the patient’s blood or metabolism.

More on: Malaria Symptoms – Severe Malaria

Patients who have severe P. falciparum malaria or who cannot take oral medications should be given treatment by continuous parenteral infusion in a hospital. The World Health Organization recommends parenteral artesunate for treatment of severe P. falciparum malaria in both adults and children. However, if artesunate is not available, parenteral artemether and quinine are acceptable alternatives for treatment of severe malaria. Some malaria-endemic countries recommend pre-referral drugs be given by suppository or injection before a severely ill patient is referred to a hospital for definitive care.

Intravenous treatment must be followed up with a complete course of oral antimalarial drugs, usually an artemisinin-based combination therapy or, when the preceding is not available, quinine plus doxycycline or quinine plus clindamycin.

In severe malaria (caused by Plasmodium falciparum) the drug quinine must be administered by intravenous perfusion. Emergency room of the St Marc Hospital in Kingasani, outskirts of Kinshasa, DR Congo.

A number of strategies use antimalarial drugs to reduce transmission by clearing the affected population of malaria parasites. The best known of these is mass drug administration (MDA). MDA has been implemented in the past as part of attempts to eliminate malaria from an area and to respond to malaria epidemics caused by P. falciparum, the most lethal of the malaria parasites, and P. vivax. MDA and related strategies that deploy antimalarials to reduce malaria transmission are described below.

Distribution of antimalarials in Italy in the 1930s. Attempts to control malaria through mass treatment with antimalarial drugs date back to at least the early 1930s. (Source: Archivio Casini, Sezione di storia della medicina, University of Rome 'La Sapienza')

Mass drug administration (MDA) is the administration of antimalarial treatment to every member of a defined population or every person living in a defined geographical area (except those for whom the medicine in contraindicated) at approximately the same time and often at repeated intervals.

The World Health Organization currently recommends MDA for malaria in the following settings:

1. Use of MDA to interrupt transmission of falciparum malaria can be considered in endemic island communities and in low-endemic non-island settings approaching elimination, where there is minimal risk of re-introduction of infection, good access to treatment, and implementation of vector control and surveillance.
2. In view of the growing threat of multidrug resistance and the need to use extreme measures, MDA can be considered as a component of malaria elimination efforts in the Greater Mekong subregion, in areas with good access to treatment, vector control and good surveillance.
3. Use of MDA to rapidly reduce malaria morbidity and mortality can be considered for epidemic control as part of the immediate response, while other interventions are put in place.
4. Use of MDA to reduce malaria morbidity and mortality can be considered during exceptional circumstances, where the health system is overwhelmed and unable to serve the affected communities.

WHO concluded in 2016 that there is insufficient evidence to provide guidance on use of MDA in settings with moderate or high transmission. Recent studies conducted in high and moderate transmission settings of Zambia and Myanmar, respectively, showed no difference in Zambia and only early impact in Myanmar.

Variations of MDA:

• Targeted mass drug administration (TMDA) is MDA implemented over a smaller high-risk area, such as a house, village, or hot spot.
• Intermittent preventive treatment (IPT), which is endorsed by WHO, is administration of a curative dose of an antimalarial drug to the entire population of asymptomatic individuals at discrete periods of time (frequently more than once). Various forms of IPT exist to address specific populations:
  • Pregnant women (IPTp)
  • Infants (IPTi)
  • Children (IPTc – also referred to as seasonal malaria chemoprevention [SMC])
  • Schoolchildren (IPTsc)

Mass screening and treatment (MSAT) refers to screening all people in a population with an appropriate malaria diagnostic test and providing treatment to those with a positive test result. This intervention is based on the assumption that most of the people who can serve to infect mosquitoes will have high enough levels of parasites or antigen in their blood to be detected at the time of screening. Focal screen and treat (FSaT) is a variation of an MSaT performed in a smaller geographic area, such as a household, village, or hot spot.

WHO does not currently recommend MSAT and FSAT as suitable interventions to reduce malaria transmission using current diagnostic tests.

Mass fever treatment (MFT), like MDA, refers to the treatment of malaria with a curative dose of an antimalarial drug within a well-defined population without testing, but unlike MDA, only persons with a fever are treated. MFT is a rapid measure that can be considered as part of an outbreak response. The criteria for choosing an antimalarial drug for MFT are the same as for the national policy for treating uncomplicated malaria (most likely an artemisinin-based combination therapy [ACT]). WHO states that mass treatment of fever cases with an ACT is appropriate as a strategy to reduce mortality once malaria has been established as the cause of the epidemic. This strategy aims to get treatment to people with probable malaria cases as quickly as possible to cure illness, avert death, and help contain the epidemic. After the outbreak response is more fully implemented in the community, laboratory confirmation of malaria parasites will precede treatment.

Malaria vaccines have been in development since the 1960’s, with substantial progress in the last decade. October 6, 2021, marks an historic day in the development of malaria vaccines, with release of the World Health Organization (WHO) recommendation for widespread use of the RTS,S/AS01 (RTS,S) malaria vaccine among children living in sub-Saharan Africa and other regions with moderate to high P. falciparum malaria transmission.

Barriers to Developing a Malaria Vaccine

The development of a malaria vaccine has faced several obstacles: the lack of a traditional market, few developers, and the technical complexity of developing any vaccine against a parasite.

Malaria parasites have a complex life cycle, and there is poor understanding of the complex immune response to malaria infection. Malaria parasites are also genetically complex, producing thousands of potential antigens. Unlike the diseases for which we currently have effective vaccines, exposure to malaria parasites does not confer lifelong protection. Acquired immunity only partially protects against future disease, and in many cases people still become infected with the parasite; malaria infection can persist for months without symptoms of disease.

RTS,S/AS01 Vaccine

More than a dozen vaccine candidates are now in clinical development, and one, GlaxoSmithKline Biologicals’ RTS,S/AS01, completed Phase III clinical testing, and on October 6, 2021, following a large scale pilot implementation, became the first malaria vaccine to receive a WHO recommendation for widespread use among children living in areas of moderate to high malaria transmission.

KEMRI Clinical Officer Paul Ogai reviews a prospective participant's vaccination card during trial enrollment at the KEMRI/CDC site in Kenya. (Courtesy Alan Rubin, KEMRI)

The vaccine has been in development since the mid-1980s and has advanced thanks to a unique public-private partnership of GSKBio, the PATH Malaria Vaccine Initiative, and African and other research organizations, with funding support from the Bill and Melinda Gates Foundation.

From 2009–2011, children ages 6–12 weeks and 5–17 months were enrolled in the trial at 11 sites in seven African countries. CDC, in collaboration with the Kenya Medical Research Institute, led the trial at one site in western Kenya.

The trial’s final results, made available in 2015, were a promising advance in development of a malaria vaccine for African children. The RTS,S vaccine reduced clinical and severe cases of malaria by about one-third in 5–17-month-old children over four years who received the three-dose vaccine series plus a booster dose. The vaccine was less effective in children in the young infant group. The vaccine was generally found to be safe, but there were a few safety signals that warranted further study, including febrile convulsions, meningitis, and cerebral malaria.

Notably, the vaccine provided this protection in settings with ongoing use of other effective malaria prevention and treatment interventions: bed nets, antimalarial drugs for disease treatment, indoor residual insecticide spraying to prevent mosquito-borne transmission, and drugs to protect pregnant women and their newborns from malaria’s adverse effects.

In July 2015, the European Medicines Agency (EMA) gave a positive regulatory assessment of the RTS,S/AS01 vaccine for 5–17-month-olds, but WHO recommended in October 2015 that the vaccine be further evaluated in large-scale pilot studies before recommending it. Large-scale pilots of the vaccine began in Ghana, Kenya, and Malawi in 2019, including several hundreds of thousands of infants. CDC, in collaboration with KEMRI and several other organizations, is leading the evaluation of the large-scale RTS,S/AS01 pilot in western Kenya. The goal of these pilot evaluations is to assess the feasibility of delivering the three-dose vaccine series plus booster through routine health systems, carefully examine the relationship of the vaccine to specific adverse events (febrile seizures, meningitis, cerebral malaria), and also evaluate its impact on all-cause mortality. CDC, in collaboration with KEMRI and several other organizations, will lead the evaluation of the large-scale RTS,S/AS01 pilot in western Kenya.

While the pilots are still on-going until 2023, sufficient data on safety and efficacy have been collected to allow for a broader recommendation for the use of the vaccine to take place.

Key findings from the malaria vaccine pilots include:

• Feasible to deliver: Vaccine introduction is feasible, improves health and saves lives, with good and equitable coverage of RTS,S seen through routine immunization systems. This occurred even in the context of the COVID-19 pandemic.
• Reaching the unreached: RTS,S increases equity in access to malaria prevention.
  • Data from the pilot programme showed that more than two-thirds of children in the 3 countries who are not sleeping under a bednet are benefitting from the RTS,S vaccine.
  • Layering the tools results in over 90% of children benefitting from at least one preventive intervention (insecticide treated bednets or the malaria vaccine).
• Strongsafety profile: To date, more than 2.3 million doses of the vaccine have been administered in 3 African countries – the vaccine has a favorable safety profile.
• Nonegative impact on uptake of bednets, other childhood vaccinations, or health seeking behavior for febrile illness. In areas where the vaccine has been introduced, there has been no decrease in the use of insecticide-treated nets, uptake of other childhood vaccinations or health seeking behavior for febrile illness.
• High impact in real-life childhood vaccination settings: Significant reduction (30%) in deadly severe malaria, even when introduced in areas where insecticide-treated nets are widely used and there is good access to diagnosis and treatment.
• Highly cost-effective: Modelling estimates that the vaccine is cost effective in areas of moderate to high malaria transmission.

Next steps include funding decisions from the global health community for broader rollout, and country decision-making on whether to adopt the vaccine as part of national malaria control strategies.Further research into ways to maximize efficacy of the RTS,S/AS01 vaccine, including assessing alternative dosing schedules such as a fractionated third dose, is underway. CDC is leading one of these studies, in collaboration with KEMRI, in infants in western Kenya.

Whole Sporozoite Vaccines

Another promising malaria vaccine candidate includes whole sporozoites, the sexual form of the parasite extracted from mosquito salivary glands, which have either been made non-infectious through irradiation or are administered along with chemoprophylaxis. Recent trials have shown that the irradiated whole sporozoite PfSPZ Vaccine made by Sanaria® is safe and well tolerated and had promising protection against malaria when administered intravenously. A collaborative CDC and KEMRI trial in western Kenya has shown that the PfSPZ Vaccine is safe and well tolerated in infants and young children. Unfortunately, the vaccine did not provide significant protection against P. falciparum infection at 6 months, precluding further evaluation in this age group, although other studies are currently evaluating the efficacy of the PfSPZ Vaccine in different populations in Mali, Gabon, Tanzania, and Equatorial Guinea. This study did, however, provide important information on the immune response to the vaccine; this information will aid researchers in developing a more effective vaccine for young children.

Nurse Dinah Mauti Maragwa gives malaria candidate vaccine to an infant at the Siaya KEMRI/CDC Malaria Vaccine Trial Site in Kenya. (Courtesy Alice Onsase and Kevin Shikanga, KEMRI/CDC)

Malaria Vaccines: The Way Forward

The RTS,S/AS01 vaccine and the PfSPZ vaccine products are two of the most promising malaria vaccine candidates to date. Another pre-erythrocytic vaccine candidate, R21, recently showed good efficacy in an early trial testing it among children 5 – 17 months of age in Burkina Faso. Other malaria vaccine candidates are in development or trial phases, including transmission-blocking vaccines that target the sexual stage of parasite development in the mosquito, and mRNA vaccines against malaria. The world’s leading global health organizations have developed the Malaria Vaccine Technology Roadmap for accelerating development of a highly effective malaria vaccine.

The roadmap includes the following strategic goals for malaria vaccines by 2030:

• Develop and license malaria vaccines with protective efficacy of at least 75% against clinical malaria for areas with ongoing malaria transmission.
• Develop malaria vaccines that reduce transmission and human malaria infection, enabling elimination in multiple settings through mass vaccination campaigns.

Microscopic examination remains the gold standard for laboratory confirmation of malaria in the malaria-endemic world, as well as in the United States.

Technique

A blood specimen collected from the patient is spread as a thick or thin blood smear, stained with a Romanovsky stain (most often Giemsa), and examined with a 100X oil immersion objective. Visual criteria are used to detect malaria parasites and to differentiate (when possible) the various species and life cycle stages. (See DPDx specimen preparation and DPDx Plasmodium species comparison chart.)

Advantages and Disadvantages

Advantages: Microscopy is an established, relatively simple technique that is familiar to most laboratorians in endemic countries. In such areas, microscopy is a standard technique used for diagnosing other diseases (such as tuberculosis), often by the same laboratorians using the same facilities and equipment. Blood slide microscopy makes it possible to count the number of parasites and is more useful than rapid diagnostic tests for monitoring the effectiveness of malaria treatment.

Migrant workers clinic at Mawker Tai camp in Thailand near the border with Burma. Microscopy plays a critical role in diagnosis of malaria, one of the major health problems in this area. Image contributed by the Shoklo Malaria Research Unit, Mae Sot, Thailand.

Disadvantages: Microscopy requires a level of skill often not available in many health facilities in several malaria-endemic countries, especially in remote rural areas, where most malaria transmission occurs. In addition, lack of functional microscopes or electricity to run them, lack of or sub-standard reagents such as stains, and high workloads may affect the quality of results.

Rapid diagnostic tests (RDTs) most often use a dipstick or cassette format, and provide results in about 20 minutes. A blood specimen collected from the patient is applied to the sample pad on the test card along with certain reagents. Currently approved RDTs for use in the malaria-endemic world can detect 2 types of malaria antigens; one is specific for P. falciparum and the other is found in all 4 human species of malaria. After 15 to 20 minutes (depending on the test), the presence of specific bands in the test card window indicates whether the patient is infected with P. falciparum or one of the other 3 species of human malaria.

RDTs’ Importance in Diagnosis and Treatment in the Malaria-Endemic World

Rapid diagnostic tests (RDTs) offer a useful alternative to microscopy in situations where reliable microscopic diagnosis is not available—or is not available right away. This is the case in most of the malaria-endemic world.

Health worker in Tanzania performing an RDT. (Courtesy S. Patrick Kachur, CDC)

Malaria RDTs are being widely used in malaria-endemic countries, but the use of an RDT does not completely eliminate the need for malaria microscopy.

Because RDTs may not be able to detect some infections with lower numbers of malaria parasites in the patient’s blood and the less common species of malaria, P. ovale and P. malariae, in the malaria-endemic world,

• Patients with negative RDT results can be followed up by microscopy where available to confirm the result.
• Patients with positive RDT results who are not responding to initial antimalarial treatment should be evaluated for other causes of their symptoms to determine whether the treatment was appropriate and to examine parasites in the blood by microscopy to determine the possibility of drug resistance.

Other Considerations

Test Performance and Cost: For RDTs to be optimally useful, the tests must perform well. At this time, product testing has shown that some tests on the market perform much better than others. In addition, care must be taken during transport and storage of RDTs. High temperatures and high humidity in particular can contribute to poor performance. The tests must also be affordable to national malaria programs. The costs of the tests have fallen in the last few years; even so, many malaria control programs find that procuring the large numbers of test kits needed to ensure universal diagnosis is a considerable expense.

Health-Worker Training: New methodologies require training. Health-care workers need training both in the new test methodology, as well as in using the results to treat patients. Available resources can limit the amount and quality of training available under real-world conditions.

The development of resistance to drugs poses one of the greatest threats to malaria control and results in increased malaria morbidity and mortality. Resistance to currently available antimalarial drugs has been confirmed in only two of the four human malaria parasite species, Plasmodium falciparum and P. vivax. It is unknown if P. malariae or P. ovale has developed resistance to any antimalarial drugs. P. knowlesi, a zoonotic monkey malaria that infects humans in forest fringe areas of Southeast Asia, is fully susceptible to chloroquine and other currently used drugs.

Drug-resistant P. falciparum

Chloroquine-resistant P. falciparum first developed independently in three to four areas in Southeast Asia, Oceania, and South America in the late 1950s and early 1960s. Since then, chloroquine resistance has spread to nearly all areas of the world where falciparum malaria is transmitted.

P. falciparum has also developed resistance to nearly all of the other currently available antimalarial drugs, such as sulfadoxine/pyrimethamine, mefloquine, halofantrine, and quinine. Although resistance to these drugs tends to be much less widespread geographically, in some areas of the world, the impact of multi-drug resistant malaria can be extensive. Most recently, resistance to the artemisinin and non-artemisinin components of artemisinin-based combination therapy has emerged in parts of Southeast Asia, impacting the efficacy of this vital antimalarial class.

Drug-resistant P. vivax

Chloroquine-resistant P. vivax malaria was first identified in 1989 among Australians living in or traveling to Papua New Guinea. P. vivax resistance to chloroquine has also now been identified in Southeast Asia, Ethiopia , and Madagascar.Isolated reports have suggested chloroquine-resistance P. vivax in other countries and regions, but further evaluation is needed. Vivax malaria parasites, particularly from Oceania, show greater resistance to chloroquine than P. vivax isolates from other regions of the world.

What are counterfeit and substandard antimalarial drugs, and why are they important to public health?

Counterfeit (fake) and substandard antimalarial drugs may contain no active ingredients, less than the required amount of active ingredients, or ingredients not described on the package label. Manufacturers of counterfeit drugs tend to copy more expensive brands of drugs and make them look like brand-name drugs. They may also repackage expired products and substitute a later expiration date, or they may package another drug or alternative substance as if it were an active product. Substandard drugs are made by manufacturers trying to avoid costly quality control and good manufacturing practices; these can result from deliberate or unintended lapses in the manufacturing process. These medicines may have too little or too much of the active ingredients and may not be absorbed properly by the body. If they are taken to treat an illness like malaria, they may be incompletely effective or altogether useless. A counterfeit or substandard treatment can prolong illness and increase the risk of severe disease or death. If substandard medicines are widely used, they can also select for drug-resistant parasites.

Where can they be found?

They can be found anywhere, but they are especially prevalent in developing countries lacking effective drug regulatory agencies as well as resources required to effectively evaluate drug quality or enforce drug quality regulations.

What types of antimalarial drug quality issues can be found?

• Drugs with too little, too much, or absolutely no active ingredient, due to intentional fraud or poor manufacturing and quality control practice.
• A tablet’s inability to release drug, due to poor formulation techniques.
• Chemical breakdown of drugs caused by storage conditions, especially in warm, humid climates.
• Contamination with other substances due to poor manufacturing procedures.
• Incomplete, inaccurate or misleading packaging and labeling.

How can I avoid buying counterfeit or substandard antimalarial drugs to prevent malaria when I travel to an area with malaria transmission?

• Buy the antimalarial drugs you need in your home country and keep the original packaging.
• Write down the drug’s generic and brand names as well as the name of the manufacturer so in case you run out, you can look for the correct product.
• If you need to purchase medicine in the country you are visiting, inspect and compare the packaging of the medicine available for sale in that country with the original. Many times poor quality printing or paper indicates a counterfeited product.
• Be suspicious of tablets that have a peculiar odor, taste, or color, or ones that are extremely brittle. Ill-defined imprints on the tablet may indicate a counterfeit.

The quality of commercially available drugs varies greatly in malaria-endemic countries:

• The amount of the active ingredient can vary due to lack of regulations and poor quality control practices.
• Some pills may release very little if any drug due to poor formulation techniques.
• Chemical break-down of some drugs can occur due to poor storage conditions, especially in warm and humid tropical climates.
• Some drugs may be contaminated with other substances.
• Counterfeiters may also obtain expired drugs and repackage them with false or missing expiration dates.

What are countries with malaria transmission doing about this problem?

With help from the Global Fund to Fight HIV/ AIDS, Tuberculosis and Malaria, the U.S. Agency for International Development, the U.S. Pharmacopeia (USP), and CDC, countries are improving their capacity to monitor the appearance of counterfeit drugs and to execute their regulatory functions.

A

Anemia: A reduction in the number of circulating red blood cells or in the quantity of hemoglobin.

Anopheles: A genus of mosquito, some species of which can transmit human malaria.

Anorexia: Lack of appetite, lack of desire or interest in food.

Anthropophilic: Describes mosquitoes that prefer to take blood meals from humans.

Antibiotic: A drug that kills or slows the growth of bacteria. Example: penicillin.

Antibody: A specialized serum protein (immunoglobulin or gamma globulin) produced by B lymphocytes in the blood in response to an exposure to foreign proteins (“antigens”). The antibodies specifically bind to the antigens that induced the immune response. Antibodies help defend the body against infectious agents such as bacteria, viruses or parasites.

Antigen: Any substance that stimulates the immune system to produce antibodies. Antigens are often foreign substances such as parts of invading bacteria, viruses or parasites.

Antimicrobial agents: The drugs, chemicals, or other substances that kill or slow the growth of microbes. They include antibacterial drugs (which kill bacteria), antiviral agents (which kill viruses), antifungal agents (which kill fungi), and antiparasitic drugs (which kill parasites).

Antimicrobial resistance: Antimicrobial resistance is the result of microbes changing in ways that reduce or eliminate the effectiveness of drugs, chemicals, or other agents to cure or prevent infections.

Aralen: A brand name for chloroquine phosphate.

Artemisinins: A class of drugs used for the treatment (not prevention) of malaria usually as a part of a combination therapy, derived from the sweet wormwood or Qinghao plant (Artemisia annua).

Atovaquone: A drug used against malaria. It is found in the combination atovaquone-proguanil which can be used for both prevention and treatment.

Autochthonous: Regarding malaria, it refers to local transmission by mosquitoes. This can either be indigenous (a geographic area where malaria occurs regularly) or introduced (in a geographic area where malaria does not occur regularly).

B

Bacteria: (singular: Bacterium) Single-celled organisms that are found throughout nature and can be beneficial or cause disease.

B-cell (B-lymphocyte): White blood cells of the immune system that are derived from the bone marrow and spleen. B cells develop into plasma cells, which produce antibodies.

C

Carbamate: A chemical product used as an insecticide.

Cerebral malaria: A severemalaria syndrome in which infected red blood cells obstruct blood circulation in the small blood vessels in the brain and/or release cytokines that disrupt normal brain function.

Chemoprophylaxis: The use of antimalarial drugs to prevent malaria disease.

Chloroquine: A drug used against malaria for both prevention and treatment. A very safe and inexpensive drug, its value has been compromised by the emergence of chloroquine-resistant malaria parasites.

Cinchonism: Side effects from quinine or quinidine. Includes tinnitus, headache, nausea, diarrhea, altered auditory acuity, and blurred vision. The term derives from cinchona bark, the natural source of quinine.

Clindamycin: An antibiotic that can be used for the treatment of malaria in combination with a second drug, usually quinine or quinidine.

Clinical cure: Elimination of malaria symptoms, sometimes without eliminating all parasites. See “radical cure” and “suppressive cure/treatment.”

Coma: A decreased state of consciousness from which a person cannot be roused.

Congenital malaria: Malaria in a newborn or infant, transmitted from the mother.

Cryptic malaria: A case of malaria where epidemiologic investigations fail to identify an apparent mode of acquisition (this term applies mainly to cases found in non-endemic countries).

D

DEET: N,N-diethylmetatoluamide, an ingredient of insect repellents.

Defervescence: The reduction of a patient’s abnormally elevated temperature into the normal range.

Deltamethrin: An insecticide.

Diurnal: During the daytime.

Doxycycline: An antibiotic drug that can be used against malaria; by itself for prevention or in combination with either quinine or quinidine when used for treatment.

Drug resistance: Drug resistance is the result of microbes changing in ways that reduce or eliminate the effectiveness of drugs, chemicals, or other agents to cure or prevent infections.

Dyspnea: Shallow, labored breathing.

E

Efficacy: The power or capacity to produce a desired effect.

Elimination: In the context of malaria, reducing all local transmission down to zero cases within a defined geographic location.

ELISA: Enzyme-linked immunosorbent assay. This laboratory test is now often used to determine whether mosquito salivary glands are positive for sporozoites.

Endemic: Where disease occurs on a consistent basis.

Endophagic: An endophagic mosquito is a mosquito that feeds indoors.

Endophilic: An endophilic mosquito is a mosquito that tends to inhabit/rest indoors. Endophilism facilitates the blocking of malaria transmission through application of residual insecticides to walls.

Epidemic: The occurrence of more cases of disease than expected in a given area or among a specific group of people over a particular period of time.

Epidemiology: The study of the distribution and determinants of health-related states or events in specified populations, and the application of this study to the control of health problems.

Eradication: In the context of malaria, reducing the number of malaria parasites that circulate in the natural world to zero.

Erythrocyte: A red blood cell.

Erythrocytic stage: A stage in the life cycle of the malaria parasite found in the red blood cells. Erythrocytic stage parasites cause the symptoms of malaria.

Etiology: The cause or origin of a disease or disorder; the study of the factors that cause disease and of the method of their introduction into the host.

Exoerythrocytic stage: A stage in the life cycle of the malaria parasite found in liver cells (hepatocytes). Exoerythrocytic stage parasites do not cause symptoms.

Exophagic: An exophagic mosquito is a mosquito that feeds outdoors.

Exophilic: An exophilic mosquito tends to inhabit/rest outdoors. Residual insecticides in buildings are less effective at controlling exophilic mosquitoes.

F

Falciparum: See Plasmodium.

Fansidar: Brand name of sulfadoxine-pyrimethamine, a drug used against malaria. Its value has been compromised by the emergence of drug-resistant malaria parasites.

G

G6PD deficiency: An inherited abnormality that causes the loss of a red blood cell enzyme. People who are G6PD deficient should not take the antimalarial drug primaquine.

Gametocyte: The sexual stage of malaria parasites. Male gametocytes (microgametocytes) and female gametocytes (macrogametocytes) are inside red blood cells in the circulation. If they are ingested by a female Anopheles mosquito, they undergo sexual reproduction which starts the extrinsic (sporogonic) cycle of the parasite in the mosquito. Gametocytes of Plasmodium falciparum are typically banana or crescent-shaped (from the latin falcis=sickle).

Gene: The basic unit of inheritance. A gene is a segment of DNA that specifies the structure of a protein or an RNA molecule.

Genetic diversity: The variety of different types of genes in a species or population.

H

Halofantrine: A drug used against malaria in some countries, but not recommended by CDC.

Hematocrit: The amount of blood consisting of red blood cells, measured as a percentage.

Hematologic: Having to do with the blood.

Hemoglobin: The red, oxygen-carrying protein found in red blood cells.

Hemolysis: Destruction of red blood cells. Malaria causes hemolysis when the parasites rupture the red blood cells in which they have grown.

Hepatocytes: Liver cells.

Hepatomegaly: Enlarged liver.

Hypnozoite: Dormant form of malaria parasites found in liver cells. Hypnozoites occur only with Plasmodium vivax and P. ovale. After sporozoites (inoculated by the mosquito) invade liver cells, some sporozoites develop into dormant forms (the hypnozoites), which do not cause any symptoms. Hypnozoites can become activated months or years after the initial infection, producing a relapse.

Hypoglycemia: Low blood glucose. Hypoglycemia can occur in malaria. In addition, treatment with quinine and quinidine stimulate insulin secretion, reducing blood glucose.

I

Icterus: See jaundice.

Immune system: The cells, tissues and organs that assist the body to resist infection and disease by producing antibodies and/or cells that inhibit the multiplication of the infectious agent.

Immunity: Protection generated by the body’s immune system, in response to previous malaria attacks, resulting in ability to control or lessen a malaria attack.

Immunization: The process or procedure by which a subject (person, animal, or plant) is rendered immune, or resistant to a specific disease. This term is often used interchangeably with vaccination or inoculation, although the act of inoculation does not always result in immunity.

Imported malaria: Malaria acquired outside a specific geographic area.

Incubation period: The interval of time between infection by a microorganism and the onset of the illness or the first symptoms of the illness. In malaria, the incubation is between the mosquito bite and the first symptoms. Incubation periods range from 7 to 40 days, depending on species.

Indoor residual spraying (IRS): Treatment of houses where people spend night-time hours, by spraying insecticides that have residual efficacy (i.e., that continue to affect mosquitoes for several months). Residual insecticide spraying aims to kills mosquitoes when they come to rest on the walls, usually after a blood meal. Â

Infection: The invasion of an organism by a pathogen such as bacteria, viruses, or parasites. Some, but not all, infections lead to disease.

Indigenous malaria: Mosquito-borne transmission of malaria in a geographic area where malaria occurs regularly.

Induced malaria: Malaria acquired through artificial means (e.g. blood transfusion, shared needles or syringes, or malariotherapy).

Introduced malaria: Mosquito-borne transmission of malaria from an imported case in a geographic area where malaria does not occur regularly.

J

Jaundice: Yellow discoloration of skin and eyes due to elevated blood levels of bilirubin.

K

Knowlesi: See Plasmodium

L

Lariam: Brand name of mefloquine, a drug used against malaria for both prevention and treatment.

Larvae: An immature stage of a developing mosquito. Mosquito larvae are wingless and develop in water.

Leukocyte: White blood cell.

Leukocytosis: Increase in total white blood cell count.

Leukopenia: Decrease in total white blood cell count.

Lymphocyte: Leukocyte with a large round nucleus and usually a small cytoplasm. Specialized types of lymphocytes have enlarged cytoplasms and produce antibodies. Other specialized lymphocytes are important in cellular immune responses.

M

Macrogametocyte: The female form of the gametocyte.

Malarone: Brand name of atovaquone-proguanil, a drug used against malaria for both prevention and treatment.

Malariae: See Plasmodium.

Merozoite: A daughter cell formed by asexual development in the life cycle of malaria parasites. Liver-stage and blood-stage malaria parasites develop into schizonts which contain many merozoites. When the schizonts are mature, they (and their host cells!) rupture; the merozoites are released and infect red blood cells.

Mefloquine: A drug used against malaria for both prevention and treatment.

Microgametocyte: The male form of the gametocyte.

Molecular methods: Laboratory techniques that are based on identification and characterization of certain molecules and gene sequences of a pathogen’s genetic makeup.

Monocyte: Leukocyte with a large, usually kidney-shaped nucleus. Within tissues, monocytes develop into macrophages which ingest bacteria, dead cells, and other debris.

O

Oocyst: A stage in the life cyle of malaria parasites, oocysts are rounded structures located in the outer wall of the stomach of mosquitoes. Sporozoites develop inside the oocysts. When mature, the oocysts rupture and release the sporozoites, which then migrate into the mosquito’s salivary glands, ready for injection into the human host.

Ovale: See Plasmodium.

P

Parasite: Any organism that lives in or on another organism without benefiting the host organism; commonly refers to pathogens, most commonly in reference to protozoans and helminths.

Parasitemia: The presence of parasites in the blood. The term can also be used to express the quantity of parasites in the blood (e.g., “a parasitemia of 2%”).

Paroxysm: A sudden attack or increase in intensity of a symptom, usually occurring in intervals.

Pathogen: Bacteria, viruses, parasites or fungi can cause disease.

Permethrin: A pyrethroid insecticide.

Phagocyte: A type of white blood cell that can engulf and destroy foreign organisms, cells and particles. Phagocytes are an important part of the immune system.

Plasmodium: The genus of the parasite that causes malaria. The genus includes many species. The four species that naturally infect humans are  Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. Plasmodium knowlesi is a zoonotic species that naturally infects macaques in Southeast Asia that can also infect humans. Â

Platelets: Small, irregularly-shaped bodies in the blood that contain granules. These cells are important components of the blood coagulation (clotting) system.

Polymorphic: Literally meaning having more than one form. In terms of genes it means that there are several variants (alleles) of a particular gene that occur simultaneously in a population.

Presumptive treatment: Treatment of clinically suspected cases without, or prior to, results from confirmatory laboratory tests.

Primaquine: A drug used against malaria for the prevention of P. vivax or for the eradication of the hypnozoites of P. vivax and P. ovale.

Proguanil: A drug used against malaria. It is found in the combination atovaquone-proguanil which can be used for both prevention and treatment.

Prophylaxis: See “chemoprophylaxis.”

Protozoan: Single-celled organism that can perform all necessary functions of metabolism and reproduction. Some protozoa are free-living, while others, including malaria parasites, parasitize other organisms for their nutrients and life cycle.

Pyrethroid: A class of insecticides derived from the natural pyrethrins.

Q

Quinine: A drug used against malaria, obtained from the bark of the cinchona tree. Quinine is used for treatment but not prevention of malaria.

R

Radical cure: (also: radical treatment) Complete elimination of malaria parasites from the body; the term applies specifically to elimination of dormant liver stage parasites (hypnozoites) found in Plasmodium vivax and P. ovale.

Recrudescence: A repeated attack of malaria due to the survival of malaria parasites in red blood cells.

Radical treatment: See radical cure.

Relapse: Recurrence of disease after it has been apparently cured. In malaria, true relapses are caused by reactivation of dormant liver stage parasites (hypnozoites) found in Plasmodium vivax and P. ovale.

Residual insecticide spraying: See indoor residual spraying.

Resistance: The ability of an organism to develop ways to be impervious to specific threats to their existence. The malaria parasite has developed strains that are resistant to drugs such as chloroquine. The Anopheles mosquito has developed strains that are resistant to DDT and other insecticides.

Rigor: Severe shaking chill.

S

Schizogony: Asexual reproductive stage of malaria parasites. In red blood cells, schizogony entails development of a single trophozoite into numerous merozoites. A similar process happens in infected liver cells.

Schizont: A developmental form of the malaria parasite that contains many merozoites. Schizonts are seen in the liver-stage and blood-stage parasites.

Sequelae: Morbid conditions following as a consequence of a disease.

Serology: The branch of science dealing with the measurement and characterization of antibodies and other immunological substances in body fluids, particularly serum.

Species: Organisms in the same genus that have similar characteristics.

Splenectomy: Removal of the spleen.

Splenomegaly: Enlargement of the spleen. Found in some malaria patients. Splenomegaly can be used to measure malaria endemicity during surveys (e.g., in communities or in schoolchildren).

Sporozoite: A stage in the life cycle of the malaria parasite. Sporozoites are produced in the mosquito and migrate to the mosquito’s salivary glands. They can be inoculated into a human host when the mosquito takes a blood meal on the human. In the human, the sporozoites enter liver cells where they develop into the next stage of the malaria parasite life cycle (the liver stage or exo-erythrocytic stage).

Sporozoite rate: The proportion of female anopheline mosquitoes of a particular species that have sporozoites in their salivary glands (as seen by dissection), or that are positive in immunologic tests to detect sporozoite antigens.

Strain: A genetic variant within a species.

Sulfadoxine-pyrimethamine: A drug used against malaria. Its value has been compromised by the emergence of drug-resistant malaria parasites

Suppressive treatment: Treatment intended to prevent clinical symptoms and parasitemia through destruction of parasites in red blood cells. It does not prevent infection because the parasite stages inoculated by the mosquito (sporozoites) will survive and invade the liver with the development of liver-stage parasites. It is when the parasites leave the liver cells to invade the blood that they are eliminated. Because the blood- stage parasites are the ones that cause disease, eliminating these stages will prevent symptoms.

T

Tachycardia: Increased heart rate.

Tachypnea: Increased rate of breathing.

Tafenoquine: A drug used against malaria for the prevention of malaria or the eradication of the hypnozoites of P. vivax and P. ovale.

Tetracycline: An antibiotic drug that can be used against malaria for treatment only, not prevention.

Thrombocytopenia: Low platelet count that can lead to impaired blood clotting and spontaneous bleeding.

Tinnitus: Ringing sound in the ears, a common side effect of quinine treatment.

Trophozoite: A developmental form during the blood stage of malaria parasites. After merozoites have invaded the red blood cell, they develop into trophozoites (sometimes, early trophozoites are called “rings” or “ring stage parasites”); trophozoites develop into schizonts.

V

Vaccine: A preparation that stimulates an immune response that can prevent an infection or create resistance to an infection.

Vector: An organism (e.g., Anopheles mosquitoes) that transmits an infectious agent (e.g. malaria parasites) from one host to the other (e.g., humans).

Vector competence: The ability of a vector (e.g., Anopheles mosquitoes) to transmit a disease (e.g., malaria).

Virus: A microorganism composed of a piece of genetic material – RNA or DNA – surrounded by a protein coat. To replicate, a virus must infect a cell and direct its cellular machinery to produce new viruses.

Vivax: See Plasmodium

Z

Zoonosis: A disease that naturally occurs in animals that can also occur in humans.

Zoophilic: Zoophilic mosquitoes are mosquitoes that prefer to take blood meals on animals.