Reproduction of the malaria parasite in humans allows the parasite to progress through a complicated life cycle that requires both the mosquito and human hosts. The Plasmodium male (microgametocytes) and female (macrogametophytes) parasites are ingested by the female Anopheles mosquito during a blood meal from an infected animal. Inside of the mosquito, the parasites go through a sporogonic cycle. The sporogonic cycle begins in the mosquito’s stomach, where the male microgametocyte penetrates the female macrogametophyte resulting in a fertilized zygote. The zygote changes shape becoming elongated and is able to move to the midgut of the mosquito where it grows and continues to change shape to form an enclosed sac called the oocyst. The parasites multiply inside the oocyst sacs until they rupture and release cells called sporozoites. It is the sporozoites that move to the mosquito’s salivary glands and are introduced into the human hosts when the mosquito feeds. Once inside of the human host, the sporozoites migrate to the liver and infect cells where they develop into schizonts. The schizonts grow and eventually rupture to release merozoites. Some forms of malaria can lay dormant in the liver for months or years. While in the liver, the merozoites can infect erythrocytes (red blood cells) where the parasites multiply as the erythrocytes circulate out of the liver and into the human blood system. While in human red blood cells, the merozoites develop into yet another stage of the parasitic life cycle called trophozoite. The trophozoite-infected red blood cells can also form schizonts, which will eventually rupture and release more merozoites. It is during this rupturing stage that the host develops the characteristic malaria fever symptoms. Alternatively, the trophozoite can develop into a gametocyte (with male and female reproductive cells). These gametophytes can be ingested by the mosquito as she takes a blood meal from the infected individual, continuing the life cycle of the Plasmodium parasite. If not treated, the infection can progress in a growing population of blood parasites and cause death. When a person is infected, uninfected mosquitos can acquire Plasmodium and expand the population of malaria vectors.

When a person is infected with the malaria parasite, the first onset of symptoms can be observed in 7 and 30 days after the bite, depending in part on the causative species of the Plasmodium infection. The symptoms of malaria include flu-like symptoms, such as fever, chills, fatigue, headaches, sweats, body aches, and nausea. These symptoms can occur in waves of alternating fever and chills, with the frequency varying depending on the Plasmodium species since these waves of symptoms reflect waves of Plasmodium reproduction in the patient. Additional symptoms that might occur during a malaria infection include increased breathing rate, perspiration, enlarged spleen, mild jaundice, and enlarged liver. Given the similarity of malaria symptoms to other diseases, malaria symptoms can be misdiagnosed, particularly in countries where malarial infections are less common. In more serious cases, organ failure can occur such as acute respiratory distress syndrome or acute kidney failure. Serious impairment of the blood system can occur where the destruction of red blood cells results in severe anemia or hyperparasitemia (more than 5 percent infected red blood cells). A patient’s metabolism might also be severely affected to the point where metabolic acidosis or hypoglycemia (low blood sugar) occurs. When people suffer from repeated infections, they may experience an immune response to the Plasmodium, resulting in hyperactive malarial splenomegaly, which can be characterized by an enlarged spleen, enlarged liver, anemia, with susceptibility to other infections. There are some geographical areas where individuals carry the parasite, but do not experience symptoms. These malaria parasite carriers appear to have the ability to fight off the aspects of infection that give rise to symptoms, but are not able to clear the parasite from their bodies. These individuals provide an undiagnosed reservoir that amplifies the spread of malaria in unpredictable ways. Malaria carriers might also present symptoms that are consistent with malaria, carry Plasmodium, but experience the symptoms due to some other pathogen, which complicates diagnosis of other diseases.

Confirming that a patient has malaria is essential for treatment and controlling the spread of disease to the broader population. Diagnosis begins with the recognition that characteristic symptoms might be due to malaria because the patient has been in regions where the Anopheles mosquito is known to carry malaria. In countries where malaria is very common, a person might treat the malaria with no confirmation of diagnosis. In the United States, where malaria is uncommon, diagnosis employs laboratory tests designed to detect the parasite in patient samples, or detect the patient’s immune response to the presence of the parasite. Visualization of patient blood through a microscope can detect the presence of Plasmodium and is considered a reliable diagnostic tool for malaria. In these cases, the blood is stained so that the parasite can be more easily observed and trained personnel are able to identify structures consistent with Plasmodium infection inside red blood cells of the patient. Collection and handling of patient blood samples can be problematic in some areas of the world, and research to develop more robust methods of diagnosis is underway. A negative visual result would lead to new blood samples being tested every 12 to 24 hours at least three times before concluding an absence of parasite in the patient’s blood. If parasite is found in the blood sample, then the amount or density of parasite infection is estimated by determining how many cells contain a parasite after observing 500 to 2,000 red blood cells. The higher the parasite density, the more advanced the infection.

In addition to microscopic identification of the parasite, antigen detection kits are available to quantify parasite abundance. An antigen is any protein or other molecule that can be bound by an antibody. Antibodies are produced by human immune cells and can direct destructive immune cells to destroy antigen that they bind. In this way, if a parasite is present in the patient, small components of the parasite (antigens) will be bound by antibodies and targeted for destruction by the immune system. In antigen detection kits, commercially available antibodies are used to determine if the Plasmodium antigens are present in the patient’s blood. Commercially available antibodies to Plasmodium have been developed and the U.S. Food and Drug Administration (FDA)–approved antibody-based tests have been used in hospitals and commercial laboratories since 2007. Antibody-based tests are quick but continue to be developed to ensure accuracy, and are usually used if microscopic analysis is not available. An alternative test detects the presence of the patient’s own antibodies to Plasmodium. In this case, the test does not indicate the presence of the Plasmodium antigens, but rather indicates that the patient’s immune system reacted to the Plasmodium antigens at some point. Since the patient’s immune response will continue to function even after the infection has been cleared, the serological approach cannot distinguish between past and current infections of Plasmodium. In addition to tests that use the patient’s immune response, Plasmodium can also be detected directly in patient samples by the presence of the parasite’s genetic material, or DNA. Molecular diagnostic tests that detect Plasmodium DNA are restricted to high-tech labs and are used to confirm the specific species of Plasmodium present in the patient after initial diagnosis. In the United States, the CDC also recommends that the infecting Plasmodium be tested for drug resistance. The presence of drug-resistant strains of Plasmodium in patients presents serious health care concerns for the individual patient as well as the entire population, since these strains would be resistant to (not respond to) standard treatments for the disease.

An individual who contracts WNV from a mosquito bite will have a 20 to 30 percent chance of showing symptoms associated with the WNV infection. In an otherwise healthy person, symptoms will occur within 2 to 6 days after the mosquito bite. Immunocompromised individuals manifest symptoms within 2 to 14 days after exposure. Symptoms can include fever, headache, body a...