While the disease burden of malaria is devastating, there are effective antimalarial drugs available. The World Health Organization (WHO), among other public health organizations, emphasizes early diagnosis and prompt treatment of malaria. However, drug resistance is a major problem in treating this disease and traditional first-line treatments have lost much of their effectiveness in many countries. This has led to the need for new (and affordable) antimalarial drugs, including combination therapies to reduce the chance of drug resistance. Some of the most commonly-used treatments include¹:

• Artemisinin derivatives in combination: Artemisinin-based combination therapies (ACTs) are currently the most effective treatment for malaria, particularly because there is no clinical evidence of parasite resistance, and they are recommended as the treatment of choice by the WHO. However, the cost of ACTs makes them inaccessible to millions of people in the developing world.

• Chloroquine: Chloroquine is an inexpensive and safe antimalarial treatment. However, due to widely prevalent resistance throughout sub-Saharan Africa, it can no longer be considered an effective treatment option.

• Sulfadoxine-pyrimethamine: Sulfadoxine-pyrimethamine (SP) is a safe, effective, and inexpensive antimalarial, but resistance has been growing at an alarming rate throughout Asia, Latin America, and sub-Saharan Africa.

• Mefloquine: Mefloquine is very effective against chloroquine-resistant parasites, and is frequently used by travelers. However, it can be associated with negative side effects and is relatively expensive. Decreased sensitivity to mefloquine has been reported in some parts of Southeast Asia and in Brazil.

• Atovaquone-proguanil: This is a very effective antimalarial, particularly in areas of chloroquine resistance. It has fewer side effects than some other treatments, but is prohibitively expensive in most areas of the world.

• Quinine: Used as an antimalarial for almost 400 years², quinine is one of the oldest and most effective antimalarial drugs. However, quinine is quite poorly tolerated, and it is generally reserved for treatment after failure of other drugs or to treat severe malaria. Additionally, it is relatively expensive.

• Doxycycline: This antibiotic is very inexpensive and has no known resistance. It can cause some side effects, and its use should be reserved for treatment in combination with other, more rapidly acting drugs.

• Amodiaquine: This drug, which is closely related to chloroquine, remains active against many chloroquine-resistant infections. It recently has shown efficacy in many parts of Africa when used in combination with artesunate (a WHO-recommended ACT regimen) or SP.

• Chlorproguanil-dapsone: This new regimen, commonly referred to as "LapDap," has a mechanism of action similar to that of SP, but it is active against SP-resistant infections in Africa, and is under study combined with artesunate.

• Primaquine: This is used for the treatment of P. ovale and P. vivax chronic liver stages. It is usually given in conjunction with a second drug that targets the parasites' blood stage, such as chloroquine. Primaquine can cause hemolysis and severe adverse events in patients with G6PD deficiency.

In the last few decades, the resistance of P. falciparum to first-line therapies has grown to unprecedented levels, prompting several international health organizations to create a global partnership to "Roll Back Malaria." The intensive and unsupervised use of malaria drugs such as chloroquine led to the appearance in Southeast Asia and South America of chloroquine-resistant P. falciparum in the early 1960s, which rapidly spread around the world. Today there are reported cases of Plasmodium resistance to each of the currently available malaria first-line therapies.³ Even more alarming are the reported cases of parasites resistant to more than one of the available malaria drugs, which has increased the need for combination therapies. This strategy parallels methods used for the treatment of HIV and tuberculosis (see section on Artemisinins). The method of treatment consists of simultaneously administering two or three antimalarial drugs, each with a distinct mechanism of action against the parasite. This method is predicted to dramatically reduce the development of resistance. The now-documented emergence of multiple resistance increases the urgency of new antimalarial drug development, leading to new treatments.

There is much interest in the development of malaria vaccines. To date, field testing of candidate vaccines has shown only a limited degree of protection. An ideal vaccine would prevent infection by preparing the immune system to destroy malaria parasites before they enter the liver and blood stages. This degree of protection is extremely difficult to achieve, due to the complex life cycle of the parasite. Several malaria vaccine candidates are currently in human clinical trials in Africa, Asia, Europe, and the United States; however, it could be many years before a safe and effective vaccine is developed.

There are a number of drugs capable of preventing Plasmodium infection. Prophylaxis is appropriate for travelers to malaria-endemic regions, but is generally not practical for residents of these areas. Some standard prophylactic treatments are mefloquine, atovaquone-proguanil, doxycycline, and chloroquine (in areas without resistant parasites). For a full list of the available prophylactic drugs in the U.S., consult the Centers for Disease Control website.

The overwhelming health burden of malaria, combined with increasing drug resistance, has brought the need for effective preventive measures to the forefront of public health efforts. The goal of malaria prevention (vector, or mosquito, control) is to reduce the burden and impact of the disease in malaria-endemic areas.

The main vector control methods are the use of insecticide-treated bed nets (ITNs) and spraying homes' interior surfaces, walls, ceilings, and roofs with a residual insecticide.

The insecticide most widely used for house spraying has been DDT, which has been recommended because of its affordability and stability. It allows programs to be based on spraying twice a year, or only once in areas with a short annual malaria mosquito season.⁴ Due to concern regarding adverse effects of DDT and insect resistance, it has been replaced by organophosphate or carbamate insecticides such as malathion or bendiocarb in Sri Lanka, parts of India, Pakistan, Turkey, and Central America. However, these compounds are considerably more expensive than DDT, and malathion is unstable when used on mud walls.

Recent studies have demonstrated that insecticide-treated nets (ITNs) constitute a simple, low-cost method with enormous potential to prevent malaria, especially for young children. As a result, an increasing number of organizations, governments, and donors are seeking cost-effective and sustainable strategies for implementing ITN interventions.