The symptoms of malaria were first described around 2700 B.C.E. in ancient Chinese medical writings [1]. Thousands of years later, malaria continues to be one of the most significant infectious diseases. Approximately 3.2 billion people live in areas of malaria transmission, and an estimated 150 to 300 million cases of malaria are reported each year. Malaria is a leading cause of illness and death in the developing world, killing an average of 600,000 people each year [2,58]. Young children and pregnant women are the groups most affected [2,37,58]. Although the transmission of malaria was successfully interrupted in the United States during the late 1940s, it continues to pose a challenging health threat to individuals who travel to and emigrate from malarious areas [5,54].

Malaria is a mosquito-borne disease caused by a parasite from the genus Plasmodium. Although there are more than 100 species of Plasmodium, only five are known to infect humans. These include P. falciparum, P. vivax, P. malariae, P. ovale, and the more recently discovered P. knowlesi (a simian malaria parasite), which has previously been misdiagnosed in humans as P. malariae [6,7,8,9,26]. P. falciparum and P. vivax cause the most infections worldwide. P. falciparum is the agent of severe, potentially fatal malaria due to its unique ability to invade and multiply inside erythrocytes. If treated promptly and effectively, however, it is almost always curable. P. vivax is the most geographically widespread of the species. Although it produces symptoms that are less severe, relapses of infection caused by P. vivax may occur up to three years after the initial infection. P. malariae produces long-lasting infections that have the ability to persist asymptomatically for years. Occurrences of infection from P. ovale are rare and generally limited to West Africa [3,10,11]. Little is known about the morphology of P. knowlesi parasites, but they do appear to have unique characteristics that can be identified through the use of light microscopy [12]. P. knowlesi appears to cause less severe clinical disease than P. falciparum; however, it may cause more severe and potentially fatal infections than P. vivax o rP. malariae [6]. The severity of infection caused by P. knowlesi is the result of its rapid (i.e., 24-hour), targeted erythrocytic cycle. P. knowlesi is widespread throughout Malaysia, accounting for approximately 70% of human malaria infections in this area. Cases of infection with P. knowlesi have also been reported in Thailand, China, Singapore, and the Philippines [12,26].

Malaria is transmitted in areas that allow the Anopheles mosquito to survive and multiply. This occurs mainly in tropical and subtropical areas where the temperature, humidity, and rainfall create an environment that allows malaria parasites to complete their growth cycle in the mosquitoes. Temperature is particularly critical to completion of the life cycle. For example, even within the areas where transmission is most common (i.e., tropical and subtropical regions), it does not occur at high altitudes, during cooler seasons in some areas, and in most desert areas. Transmission is most common in sub-Saharan Africa (85% of cases in 2018), with the highest case rates (69.9%) occurring among travelers returning from West Africa [15]. Although malaria has been eliminated in western Europe and the United States, the presence of the Anopheles mosquito in these regions poses a constant risk of reintroduction of the disease, especially in regions with temperate climates [2,53].

Following the infective mosquito bite, an incubation period of between 7 and 30 days usually passes before the first symptoms of disease appear. Shorter incubation periods are associated with P. falciparum; longer periods are characteristic of P. malariae. A string of recurrent attacks is typical and generally includes chills, fever, and sweating. In addition to these symptoms, headache, general malaise, fatigue, muscular pains, nausea, vomiting, and diarrhea are also common [3,10,18].

Following the infective mosquito bite, an incubation period of between 7 and 30 days usually passes before the first symptoms of disease appear. Shorter incubation periods are associated with P. falciparum; longer periods are characteristic of P. malariae. A string of recurrent attacks is typical and generally includes chills, fever, and sweating. In addition to these symptoms, headache, general malaise, fatigue, muscular pains, nausea, vomiting, and diarrhea are also common [3,10,18].

Malaria infections with P. falciparum are categorized as severe when complicated by serious organ failure or abnormalities in the patient's blood or metabolism. Severe malaria occurs most frequently in persons either with no immunity or decreased immunity to the disease. The presence of one or more of the following clinical criteria indicates severe malaria [3,4]:

The criterion standard of microscopic diagnosis involves examination of thick and thin blood smears. (Thick smears are more sensitive but more difficult to read.) The smears are stained, usually with the Giemsa stain, which gives the parasites a distinctive appearance. A negative blood smear usually indicates no presence of infection. However, because nonimmune individuals may be symptomatic at very low parasite densities that are initially undetectable, the CDC has recommended that smears be repeated every 12 to 24 hours for 48 to 72 hours [4,19,20].

The CDC and the Infectious Diseases Society of America have recommended that individuals traveling outside the United States be aware of and employ the following personal protective measures [30,33]:

Malaria may be effectively treated early in the course of the disease; however, delay of appropriate treatment may have serious, even fatal, consequences. Travelers who choose not to take an antimalarial drug, who are on a less than effective regimen (e.g., chloroquine in a chloroquine-resistant risk area), whose medical history dictates a suboptimal drug, or who may be traveling to very remote areas may be prescribed a presumptive self-treatment course (Table 4). Travelers should be advised to take the treatment promptly if fever, chills, or other influenza-like illness occurs. This is particularly important if the traveler is unable to access professional medical care within 24 hours. Travelers should also be advised to seek medical care as soon as possible after self-treatment [15,35].