Plasmodium malariae

''Plasmodium malariae'' is a parasitic protozoan that causes malaria in humans. It is one of several species of ''Plasmodium'' parasites that infect other organisms as pathogens, also including ''Plasmodium falciparum'' and ''Plasmodium vivax'', responsible for most malarial infection. Found worldwide, it causes a so-called "benign malaria", not nearly as dangerous as that produced by ''P. falciparum'' or ''P. vivax''. The signs include fevers that recur at approximately three-day intervals – a '' quartan fever'' or ''quartan malaria'' – longer than the two-day (tertian) intervals of the other malarial parasites.

History

Malaria has been recognized since the Greek and Roman civilizations over 2,000 years ago, with different patterns of fever described by the early Greeks. In 1880, Alphonse Laveran discovered that the causative agent of malaria is a parasite. Detailed work of Golgi in 1886 demonstrated that in some patients there was a relationship between the 72-hour life cycle of the parasite and the chill and fever patterns in the patient. The same observation was found for parasites with 48-hour cycles. Golgi concluded that there must be more than one species of malaria parasite responsible for these different patterns of infection.

Epidemiology

Each year, approximately 500 million people will be infected with malaria worldwide Of those infected, roughly two million will die from the disease. Malaria is caused by six ''Plasmodium'' species: ''Plasmodium falciparum'', ''Plasmodium vivax,'' '' Plasmodium ovale curtisi'', '' Plasmodium ovale wallikeri'', ''Plasmodium malariae'' and ''Plasmodium knowlesi''. At any one time, an estimated 300 million people are said to be infected with at least one of these ''Plasmodium'' species and so there is a great need for the development of effective treatments for decreasing the yearly mortality and morbidity rates.

''P. malariae'' is the one of the least studied of the six species that infect humans, in part because of its low prevalence and milder clinical manifestations compared to the other species. It is widespread throughout sub-Saharan Africa, much of southeast Asia, Indonesia, on many of the islands of the western Pacific and in areas of the Amazon Basin of South America. In endemic regions, prevalence ranges from less than 4% to more than 20%, but there is evidence that ''P. malariae'' infections are vastly underreported.

The Centers for Disease Control (CDC) has an application that allows people to view specific parts of the world and how they are affected by ''Plasmodium vivax'', and other types of the ''Plasmodium'' parasite. It can be found at the following link: http://cdc.gov/malaria/map/index.html.

Role in disease

''P. malariae'' can infect several species of mosquito and can cause malaria in humans. ''P. malariae'' can be maintained at very low infection rates among a sparse and mobile population because unlike the other ''Plasmodium'' parasites, it can remain in a human host for an extended period of time and still remain infectious to mosquitoes.

Vector

The vector of transmission of the parasite is the female Anopheles mosquito, but many different species have been shown to transmit the parasite at least experimentally. Collins and Jeffrey report over thirty different species, which vary by geographic region.

Incubation period

Information about the prepatent period, or the period of time between the infection of the parasite and demonstration of that parasite within the body, of ''P. malariae'' associated malaria is limited, but the data suggests that there is great variation, often the length of time depending on the strain of ''P. malariae'' parasite. Usually, the prepatent period ranges from 16 to 59 days.

Infection in humans

''Plasmodium malariae'' causes a chronic infection that in some cases can last a lifetime. The ''P. malariae'' parasite has several differences between it and the other ''Plasmodium'' parasites, one being that maximum parasite counts are usually low compared to those in patients infected with ''P. falciparum'' or ''P. vivax.'' The reason for this can possibly be accounted for by the lower number of merozoites produced per erythrocytic cycle, the longer 72-hour developmental cycle (compared to the 48-hour cycle of ''P. vivax'' and ''P. falciparum''), the preference for development in older erythrocytes and the resulting earlier development of immunity by the human host.
Another defining feature of ''P. malariae'' is that the fever manifestations of the parasite are more moderate relative to those of ''P. falciparum'' and ''P. vivax'' and fevers show quartan periodicity. Along with bouts of fever and more general clinical symptoms such as chills and nausea, the presence of edema and the nephrotic syndrome has been documented with some ''P. malariae'' infections. It has been suggested that immune complexes may cause structural glomerular damage and that renal disease may also occur. Although ''P. malariae'' alone has a low morbidity rate, it does contribute to the total morbidity caused by all ''Plasmodium'' species, as manifested in the incidences of anemia, low birth rate and reduced resistance to other infections.

Due to a similarity in the appearances of the pathogens, ''P. knowlesi'' infections are often misdiagnosed as ''P. malariae'' infections. Molecular analysis is usually required for an accurate diagnosis.

Diagnostics

The preferable method for diagnosis of ''P. malariae'' is through the examination of peripheral blood films stained with Giemsa stain. PCR techniques are also commonly used for diagnoses confirmation as well as to separate mixed ''Plasmodium'' infections. Even with these techniques, however, it may still be impossible to differentiate infections, as is the case in areas of South America where humans and monkeys coexist and ''P. malariae'' and ''P. brasilianum'' are not easily distinguishable.

Biology

Life cycle

''P. malariae'' is the only human malaria parasite that causes fevers which recur at approximately three-day intervals (therefore occurring every fourth day, a ''quartan fever''), longer than the two-day (''tertian'') intervals of the other malarial parasites.

Human infection

Liver Stage and Blood Stage

In the liver stage, many thousands of merozoites are produced in each schizont. As the merozoites are released, they invade erythrocytes and initiate the erythrocytic cycle, where the parasite digests hemoglobin to obtain amino acids for protein synthesis.

The total length of the intraerythrocytic development is roughly 72 hours for ''P. malariae''.

At the schizont stage, after schizogonic division, there are roughly 6–8 parasite cells in the erythrocyte.

Following the erythrocytic cycle, which lasts for seventy two hours on average, six to fourteen merozoites are released to reinvade other erythrocytes. Finally, some of the merozoites develop into either micro- or macrogametocytes. The two types of gametocytes are taken into the mosquito during feeding and the cycle is repeated. There are no animal reservoirs for ''P. malariae.''

Mosquito stage

Similar to the other human-infecting ''Plasmodium'' parasites, ''Plasmodium malariae'' has distinct developmental cycles in the ''Anopheles'' mosquito and in the human host. The mosquito serves as the definitive host and the human host is the intermediate. When the ''Anopheles'' mosquito takes a blood meal from an infected individual, gametocytes are ingested from the infected person. A process known as exflagellation of the microgametocyte soon ensues and up to eight mobile microgamete