CYCLE 48 SLIDE 3 Plasmodium Malariae

Home , Plasmodium malariae, Plasmodium ovale curtisi, Protozoa, Quartan fever

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DIFFERENTIAL SLIDES LEGEND CYCLE 48 SLIDE 3 Plasmodium malariae

Plasmodium malariae (Pl. malariae) is a parasitic protozoa that causes malaria in humans. It is one of several species of Plasmodium parasites that infect humans including Plasmodium falciparum and Plasmodium vivax which are responsible for most malarial infection. While found worldwide, it is a so-called "benign malaria" and is not nearly as dangerous as that produced by P. falciparum or P. vivax. It causes fevers that recur at approximately three-day intervals (a quartan fever), longer than the two-day (tertian) intervals of the other malarial parasites, hence its alternate names quartan fever and quartan malaria. 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.

Geographical areas of malaria transmission Giemsa-stained micrograph of a mature Pl. malariae schizont

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.

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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 types of 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 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.

Life cycle P. malariae is the only human malaria parasite that causes fevers that 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.

Liver stage In this 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.

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Erythrocytic cycle The total length of the intra-erythrocytic 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 microgametes are formed.

Sexual stage Following fertilization of the macrogamete, a mobile ookinete is formed, which penetrates the peritropic membrane surrounding the blood meal and travels to the outer wall of the mid-gut of the mosquito. The oocyst then develops under the basal membrane and after a period of two to three weeks a variable amount of sporozoites are produced within each oocyst. The number of sporozoites that are produced varies with temperature and can range from anywhere between many hundreds to a few thousand. Eventually, the oocyst ruptures and the sporozoites are released into the hemocoel of the mosquito. The sporozoites are then carried by the circulation of the hemolymph to the salivary glands, where they become concentrated in the acinal cells. A small number of sporozoites are introduced into the salivary duct and injected into the venules of the bitten human. This initiates the cycle in the human liver.

Morphology The ring stages that are formed by the invasion of merozoites released by rupturing liver stage schizonts are the first stages that appear in the blood. The ring stages grow slowly but soon fill one-fourth to one-third of the parasitized cell. Pigment increases rapidly and the half-grown parasite may have from 30 to 50 jet-black granules. The parasite changes various shapes as it grows and stretches across the host cell to form the band form.

Laboratory considerations P. vivax and P. ovale sitting in EDTA for more than 30 minutes before the blood film is made will look very similar in appearance to P. malariae, which is an important reason to warn the laboratory immediately when the blood sample is drawn so they can process the sample as soon as it arrives. Microscopically, the parasitised red blood cell (erythrocyte) is never enlarged and may even appear smaller than that of normal red blood cells. The cytoplasm is not decolorized and no dots are visible on the cell surface. The food vacuole is small and the parasite is compact. Cells seldom host more than one parasite. Band forms, where the parasite forms a thick band across the width of the infected cell, are characteristic of this species (and some would say is diagnostic). Large grains of malarial pigment are often seen in these parasites: more so than any other Plasmodium species, 8 merozoites.

References 1. https://en.wikipedia.org/wiki/Plasmodium_malariae

Questions 1. Discuss the role of Pl. malariae in disease. 2. Discuss the life cycle of Pl. malariae. 3. Discuss the lab findings in a patient diagnosed with Pl. malariae.

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