Developments in Malaria
Johanna Daily, MD
Johanna P. Daily, MD
Associate Professor, Departments of Medicine (Infectious Diseases) and Microbiology & Immunology
Malaria, an infectious disease transmitted through infected mosquitoes, can rapidly advance and become life-threatening within days or even hours if left untreated. Promising advances in diagnostic testing and antimalarial medicines may improve outcomes for malaria, which currently affects nearly 2400 people in the United States and Canada and 300-500 million people in Africa each year.
The Need to Feed
Malaria’s life cycle begins with the female anopheles mosquito who, in need of blood to feed her eggs, injects a few sporozoites (infectious cells) through her salivary gland into the human liver. Over the next couple of weeks the sporozoites multiply exponentially and eventually burst, releasing merozoites (invasive cells) into the bloodstream. These cells continue to increase rapidly, and a small percentage of them develop into sexual forms, which are picked up by the next female anopheles, continuing the transmission cycle.
Five species of malaria infect humans, ranging from the benign (Plasmodium [P.] vivax, the most common in the world, and the rarer P. malariae and P. ovale) to the potentially lethal (the very common P. falciparum and the recently identified P. knowelsi).
A patient isolate of P. falciparum
, at zero hours.
Short-term development of malaria in vitro (at 24 hours)
A true host-pathogen moment as the human white cell takes up the parasite.
If malaria is treated immediately, mortality ranges from 15 to 20%; left untreated, it approaches 100%. Death from severe malaria often occurs within hours of admission to a hospital or clinic, so it is essential that the right antimalarial treatment is given as quickly as possible.
Malaria is a difficult disease to detect. It can easily be mistaken as the flu, with symptoms such as fever, chills, headache, shaking, cough, and vomiting. A person with severe malaria may show some of the same symptoms as a burn or trauma patient.
When diagnosing an infectious disease, nearly every detail of a patient’s travel experience is important. As physicians, we discern clues from asking patients about the specific countries they passed through or stayed in, when they arrived and departed from the endemic area, their accommodations (a 4-star hotel, for example, would place them in a different risk category than camping in the woods, for example), their activity (whether they hiked, swam in fresh or salt water, or engaged in sex), how their food was prepared and what they ate, and whether they took prophylactic vaccines prior to their trip.
Knowing where a patient traveled is particularly important, as location can help identify which species of malaria is present. P. falciparum frequently occurs in Africa, Haiti, and southeast Asia; P. vivax is more commonly seen in south and southeast Asia, and South America; and P. knowelsi is restricted to Malaysia, Philippines, Singapore, and Thailand, native regions of its original host, the long-tailed Macaque monkey.
When and how long a patient traveled can also provide clues to the species. Different types of malaria have unique periods of latency (delay). Cases of P. falciparum, for example, generally occur within 30 days, while other species may appear up to a year later.
Malarial parasites can detect the age of the red blood cells they attack, and some types are selective about the cells’ age. P. vivax and P. ovale choose only reticulocytes (very young red blood cells), of which the human body has a limited number. Conversely, P. malariae selects only old red blood cells. The promiscuous P. falciparum, however, will invade a cell of any age, generating high parasitemia in a short time period—this feature likely contributes to its higher virulence.
Racing the Clock
Malaria is usually identified by using a microscope to obtain a count of the parasitic organisms present on a thick film (for low parasitemia) or thin film blood smear (for high parasitemia). However, hospital microscopy services are often limited, particularly on evenings or weekends and in areas where diseases like malaria are uncommon.
A non-immune patient can deteriorate quickly, so physicians need an effective, easily accessible diagnostic method. Rapid Diagnostic Tests (RDTs) work similarly to a pregnancy or HIV test, with antigen-sensitive paper that changes color upon detection of parasites in the blood smear. While not foolproof (certain types of malaria, particular P. ovale, are not detected), the RDT is an excellent, low-cost alternative to microscopy, particularly for physicians in resource-limited settings and for laboratories without rapid microscopic diagnostic capacity.
Treatment and Future Direction
Determining the right course of treatment depends on which type of malaria is causing the infection, and where that malaria originated. Malaria that occurs in Africa, for example, is most often P. falciparum, which is typically resistant to chloroquine, a commonly prescribed antimalarial medication. (In a few regions such as Haiti, P. falciparum is still responsive to chloroquine.) Alternatives to chloroquine, including Malarone, Coartem, quinine, and mefloquine, may provide options, but these medications vary considerably in how well they are tolerated. Artemisinin, an herbal treatment manufactured as artesunate, has been shown to be particularly effective in treating P. falciparum, and is emerging as the drug of choice for severe malaria. Artesunate was recently approved by the Food and Drug Administration.
Resistance to antimalarial drugs is a widespread public health problem, and new vaccines and therapies are urgently needed in order to control this disease. The long-term goal of our research at Einstein is to identify specific targets within the P. falciparum parasite-host interaction for development of new vaccines or chemotherapeutic drugs. Through studies of people infected with malaria in Africa, we have developed a new model of parasite-host interaction. Our research has identified novel parasite biology when it resides in the human host, which may play a role in enhanced virulence and/or transmission capacity. We will continue to study the parasite’s behavior in the host blood stream, and examine the host’s response to malarial infection in order to identify host factors associated with severe disease outcomes.