Plasmodium malariae
| Plasmodium malariae | |
|---|---|
| |
| Giemsa-stained micrograph of a maturePlasmodium malariaeschizont | |
Scientific classification
| |
| Domain: | Eukaryota |
| Clade: | Diaphoretickes |
| Clade: | SAR |
| Clade: | Alveolata |
| Phylum: | Apicomplexa |
| Class: | Aconoidasida |
| Order: | Haemospororida |
| Family: | Plasmodiidae |
| Genus: | Plasmodium |
| Species: | P. malariae
|
| Binomial name | |
| Plasmodium malariae | |
| Synonyms[1] | |
| |
Plasmodium malariaeis a parasiticprotozoanthat causes malaria in humans. It is one of several species ofPlasmodiumparasitesthat infect other organisms as pathogens, also includingPlasmodium falciparumandPlasmodium vivax,responsible for mostmalarialinfection. Found worldwide, it causes a so-called "benign malaria", not nearly as dangerous as that produced byP. falciparumorP. vivax.The signs includefeversthat recur at approximately three-day intervals – aquartan feverorquartan malaria– longer than the two-day (tertian) intervals of the other malarial parasite.
History
[edit]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.[2]In 1880,Alphonse Laverandiscovered that the causative agent of malaria is a parasite.[2]Detailed work ofGolgiin 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.[2]The same observation was found for parasites with 48-hour cycles.[2]Golgi concluded that there must be more than one species of malaria parasite responsible for these different patterns of infection.[2]
Epidemiology
[edit]
Each year, approximately 500 million people will be infected with malaria worldwide.[4]Of those infected, roughly two million will die from the disease.[5]Malaria is caused by sixPlasmodiumspecies:Plasmodium falciparum,Plasmodium vivax,Plasmodium ovale curtisi,Plasmodium ovale wallikeri,Plasmodium malariaeandPlasmodium knowlesi.[2]At any one time, an estimated 300 million people are said to be infected with at least one of thesePlasmodiumspecies and so there is a great need for the development of effective treatments for decreasing the yearly mortality and morbidity rates.[6]
P. malariaeis 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 throughoutsub-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.[5]In endemic regions, prevalence ranges from less than 4% to more than 20%,[7]but there is evidence thatP. malariaeinfections are vastly underreported.[8]
The Centers for Disease Control (CDC) has an application that allows people to view specific parts of the world and how they are affected byPlasmodium vivax,and other types of thePlasmodiumparasite. It can be found at the following link:http://cdc.gov/malaria/map/index.html.
Role in disease
[edit]P. malariaecan infect several species of mosquito and can cause malaria in humans.[2]P. malariaecan be maintained at very low infection rates among a sparse and mobile population because unlike the otherPlasmodiumparasites, it can remain in a human host for an extended period of time and still remain infectious to mosquitoes.[8]
Vector
[edit]The vector of transmission of the parasite is the femaleAnophelesmosquito, but many different species have been shown to transmit the parasite at least experimentally.[2]Collins and Jeffrey report over thirty different species, which vary by geographic region.[2]
Incubation period
[edit]Information about theprepatent period,or the period of time between the infection of the parasite and demonstration of that parasite within the body, ofP. malariaeassociated malaria is limited, but the data suggests that there is great variation, often the length of time depending on the strain ofP. malariaeparasite.[2]Usually, the prepatent period ranges from 16 to 59 days.[2]
Infection in humans
[edit]Plasmodium malariaecauses a chronic infection that in some cases can last a lifetime. TheP. malariaeparasite has several differences between it and the otherPlasmodiumparasites, one being that maximum parasite counts are usually low compared to those in patients infected withP. falciparumorP. vivax.[2]The reason for this can possibly be accounted for by the lower number of merozoites produced pererythrocytic cycle,the longer 72-hour developmental cycle (compared to the 48-hour cycle ofP. vivaxandP. falciparum), the preference for development in older erythrocytes and the resulting earlier development of immunity by the human host.[2] Another defining feature ofP. malariaeis that the fever manifestations of the parasite are more moderate relative to those ofP. falciparumandP. vivaxand fevers show quartan periodicity.[7]Along with bouts of fever and more general clinical symptoms such as chills and nausea,the presence of edema and the nephrotic syndromehas been documented with someP. malariaeinfections.[2]It has been suggested that immune complexes may cause structural glomerular damage and that renal disease may also occur.[2]AlthoughP. malariaealone has a low morbidity rate, it does contribute to the total morbidity caused by allPlasmodiumspecies, as manifested in the incidences of anemia, low birth rate and reduced resistance to other infections.[7]
Due to a similarity in the appearances of the pathogens,P. knowlesiinfections are often misdiagnosed asP. malariaeinfections. Molecular analysis is usually required for an accurate diagnosis.[9]
Diagnostics
[edit]The preferable method for diagnosis ofP. malariaeis through the examination of peripheral blood films stained with Giemsa stain.[2]PCR techniques are also commonly used for diagnoses confirmation as well as to separate mixedPlasmodiuminfections.[2]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 andP. malariaeandP. brasilianumare not easily distinguishable.[2]
Biology
[edit]
Life cycle
[edit]
P. malariaeis the only human malaria parasite that causesfeverswhich recur at approximately three-day intervals (therefore occurring every fourth day, aquartan fever), longer than the two-day (tertian) intervals of the other malarial parasites.[10]
Human infection
[edit]Liver stage and blood stage
[edit]In the liver stage, many thousands of merozoites are produced in each schizont.[2]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.[5]
The total length of the intraerythrocytic development is roughly 72 hours forP. malariae.[11]
At the schizont stage, afterschizogonic division,there are roughly 6–8 parasite cells in the erythrocyte.[11]
Following the erythrocytic cycle, which lasts for seventy two hours on average, six to fourteen merozoites are released to reinvade other erythrocytes.[2]Finally, some of the merozoites develop into either micro- or macrogametocytes.[2]The two types of gametocytes are taken into the mosquito during feeding and the cycle is repeated.[2]There are no animal reservoirs forP. malariae.
Mosquito stage
[edit]Similar to the other human-infectingPlasmodiumparasites,Plasmodium malariaehas distinct developmental cycles in theAnophelesmosquito and in the human host.[2]The mosquito serves as the definitive host and the human host is the intermediate.[2]When theAnophelesmosquito takes a blood meal from an infected individual, gametocytes are ingested from the infected person.[2]A process known asexflagellationof themicrogametocytesoon ensues and up to eight mobilemicrogametesare formed.[2]
Sexual stage
[edit]Following fertilization of themacrogamete,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.[2]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.[2]The number of sporozoites that are produced varies with temperature and can range from anywhere between many hundreds to a few thousand.[2] 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.[2]A small number of sporozoites are introduced into the salivary duct and injected into the skin of the bitten human.[12]This subsequently leads to the cycle in the human liver.[2]
Morphology
[edit]The ring stages that are formed by the invasion ofmerozoitesreleased by rupturing liver stageschizontsare the first stages that appear in the blood.[2]The ring stages grow slowly but soon fill one-fourth to one-third of the parasitized cell.[2]Pigment increases rapidly and the half-grown parasite may have from 30 to 50 jet-black granules.[2]The parasite changes various shapes as it grows and stretches across the host cell to form the band form.[2]
Laboratory considerations
[edit]P. vivaxandP. ovalesitting inEDTAfor more than 30 minutes before the blood film is made will look very similar in appearance toP. 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 parasitisedred blood cell(erythrocyte) is never enlarged and may even appear smaller than that of normal red blood cells. Thecytoplasmis 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 ofmalarial pigmentare often seen in these parasites: more so than any otherPlasmodiumspecies, 8 merozoites.
Management and therapy
[edit]Failure to detect someP. malariaeinfections has led to modifications of thespecies-specificprimers and to efforts towards the development of real-timePCR assays.[2]The development of such an assay has included the use of generic primers that target a highly conserved region of the 18S rRNA genes of the four human-infecting species ofPlasmodium.[2]This assay was found to be highly specific and sensitive. Although serologic tests are not specific enough for diagnostic purposes, they can be used as basic epidemiologic tools.[2]The immunofluorescent-antibody (IFA) technique can be used to measure the presence of antibodies toP. malariae..[2]A pattern has emerged in which an infection of short duration causes a rapidly declining immune response, but upon re-infection or recrudescence, the IFA level rises significantly and remains present for many months or years.[5]
The increasing need to correctly identifyP. malariaeinfection is underscored by its possible anti-malarial resistance. In a study by Müller-Stöveret al.,the researchers presented three patients who were found to be infected with the parasite after taking anti-malarial medications.[13]Given the slower pre-erythrocytic development and longer incubation period compared to the other malaria causingPlasmodiumspecies, the researchers hypothesized that the anti-malarials may not be effective enough against the pre-erythrocytic stages ofP. malariae.[13]They thought that further development ofP. malariaecan occur when plasma concentrations of the anti-malarials gradually decrease after the anti-malarial medications are taken. According to Dr. William E. Collins from the Center of Disease Control (CDC),chloroquineis most commonly used for treatment and no evidence of resistance to this drug has been found.[14]In that event, it is possible that the results from Müller-Stöveret al.provided isolated incidences.
Public health, prevention strategies and vaccines
[edit]The food vacuole is the specialized compartment that degrades hemoglobin during the asexual erythrocytic stage of the parasite.[6]It is implied that effective drug treatments can be developed by targeting the proteolytic enzymes of the food vacuole. In a paper published in 1997, Westlinget al.[5]focused their attention on the aspartic endopeptidase class of enzymes, simply called plasmepsins. They sought to characterize the specificity for the enzymes cloned fromP. vivaxandP. malariae.Using substrate specificity studies and inhibitor analysis, it was found that the plasmepsins forP. malariaeandP. vivaxshowed less specificity than that forP. falciparum.Unfortunately, this means that the development of a selective inhibitor forP. malariaemay prove more challenging than the development of one forP. falciparum.[5] Another study by Bruceet al.[7]presented evidence that there may be regular genetic exchange withinP. malariaepopulations. Six polymorphic genetic markers fromP. malariaewere isolated and analyzed in 70 samples of naturally acquiredP. malariaeinfections from different parts of the world. The data showed a high level of multi-genotypic carriage in humans.[7]
Both of these experiments illustrate that development of vaccine options will prove challenging, if not impossible. Dr. William Collins doubts that anyone is currently looking for possible vaccines forP. malariae[14]and given the complexity of the parasite it can be inferred why. He states that very few studies are conducted with this parasite,[14]perhaps as a result of its perceived low morbidity and prevalence. Collins cites the great restrictions of studies with chimpanzees and monkeys as a sizeable barrier.[14]Since thePlasmodium brasilianiumparasite that infects South American monkeys is thought to be an adapted form ofP. malariae,more research withP. brasilianiummay hold valuable insight intoP. malariae.
A recent study shows that quartan malaria parasites are easily exchanged between humans and monkeys in Latin America. Thus, a lack of host specificity in mammalian hosts can be hypothesized and quartan malaria can be considered to be a true anthropozoonosis.[15]
The continuing work with the plasmepsin associated withP. malariae,plasmepsin 4, by Professor Ben Dunn and his research team from the University of Florida may provide hope for long term malaria control in the near future.[16]
Genome
[edit]In 2017 the full genome was published.[17]The sequences can be accessed ongeneDB.organdplasmoDB.org.
See also
[edit]References
[edit]
- ^Coatney GR, Collins WE, Warren M, Contacos PG (1971)."18Plasmodium malariae(Grassi and Feletti, 1890) ".The primate malarias.Division of Parasitic Disease, CDC. p. 209.
- ^abcdefghijklmnopqrstuvwxyzaaabacadaeafagahaiajakalamCollins WE, Jeffery GM (October 2007)."Plasmodium malariae: parasite and disease".Clinical Microbiology Reviews.20(4): 579–92.doi:10.1128/CMR.00027-07.PMC2176047.PMID17934075.
- ^Tatem AJ, Jia P, Ordanovich D, Falkner M, Huang Z, Howes R; et al. (2017)."The geography of imported malaria to non-endemic countries: a meta-analysis of nationally reported statistics".Lancet Infect Dis.17(1): 98–107.doi:10.1016/S1473-3099(16)30326-7.PMC5392593.PMID27777030.
{{cite journal}}:CS1 maint: multiple names: authors list (link) - ^Madabushi A, Chakraborty S, Fisher SZ, Clemente JC, Yowell C, Agbandje-McKenna M, Dame JB, Dunn BM, McKenna R (February 2005)."Crystallization and preliminary X-ray analysis of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae".Acta Crystallographica Section F.61(Pt 2): 228–31.doi:10.1107/S1744309105001405.PMC1952262.PMID16511002.
- ^abcdefWestling J, Yowell CA, Majer P, Erickson JW, Dame JB, Dunn BM (November 1997). "Plasmodium falciparum, P. vivax, and P. malariae: a comparison of the active site properties of plasmepsins cloned and expressed from three different species of the malaria parasite".Experimental Parasitology.87(3): 185–93.doi:10.1006/expr.1997.4225.PMID9371083.
- ^abClemente JC, Govindasamy L, Madabushi A, Fisher SZ, Moose RE, Yowell CA, Hidaka K, Kimura T, Hayashi Y, Kiso Y, Agbandje-McKenna M, Dame JB, Dunn BM, McKenna R (March 2006). "Structure of the aspartic protease plasmepsin 4 from the malarial parasite Plasmodium malariae bound to an allophenylnorstatine-based inhibitor".Acta Crystallographica Section D.62(Pt 3): 246–52.Bibcode:2006AcCrD..62..246C.doi:10.1107/S0907444905041260.PMID16510971.
- ^abcdeBruce MC, Macheso A, Galinski MR, Barnwell JW (May 2007)."Characterization and application of multiple genetic markers for Plasmodium malariae".Parasitology.134(Pt 5): 637–50.doi:10.1017/S0031182006001958.PMC1868962.PMID17140466.
- ^abMohapatra PK, Prakash A, Bhattacharyya DR, Goswami BK, Ahmed A, Sarmah B, Mahanta J (July 2008). "Detection & molecular confirmation of a focus of Plasmodium malariae in Arunachal Pradesh, India".The Indian Journal of Medical Research.128(1): 52–6.PMID18820359.
- ^Singh B, Kim Sung L, Matusop A, Radhakrishnan A, Shamsul SS, Cox-Singh J, Thomas A, Conway DJ (March 2004)."A large focus of naturally acquired Plasmodium knowlesi infections in human beings"(PDF).Lancet.363(9414): 1017–24.doi:10.1016/S0140-6736(04)15836-4.PMID15051281.S2CID7776536.
- ^"Biology: Malaria (CDC malaria)".Archived fromthe originalon 13 October 2008.
- ^ab"Malaria eModule - ASEXUAL ERYTHROCYTIC STAGES".Archived fromthe originalon 22 December 2007.Retrieved11 December2007.
- ^Ménard, R; Tavares, J; Cockburn, I; Markus, M; Zavala, F; Amino, R (2013)."Looking under the skin: the first steps in malarial infection and immunity".Nature Reviews Microbiology.11(10): 701–712.doi:10.1038/nrmicro3111.PMID24037451.S2CID21437365.
- ^abMüller-Stöver I, Verweij JJ, Hoppenheit B, Göbels K, Häussinger D, Richter J (February 2008). "Plasmodium malariae infection in spite of previous anti-malarial medication".Parasitology Research.102(3): 547–50.doi:10.1007/s00436-007-0804-4.PMID18060428.S2CID12491253.
- ^abcdCollins, William. "RE: Current research onPlasmodium malariae."Email to Chibuzo Eke. 18 February 2009.
- ^Albert Lalremruata, Magda Magris, Sarai Vivas-Martínez, Maike Koehler, Meral Esen (September 2015), "Natural infection of Plasmodium brasilianum in humans: Man and monkey share quartan malaria parasites in the Venezuelan Amazon",eBioMedicine,vol. 2, no. 9, pp. 1186–1192,doi:10.1016/j.ebiom.2015.07.033,PMC4588399,PMID26501116
{{citation}}:CS1 maint: multiple names: authors list (link) - ^Dunn, Ben. "RE:Current research onPlasmodium malariae."Email to Chibuzo Eke. 18 February 2009.
- ^Rutledge GG, Böhme U, Sanders M, Reid AJ, Cotton JA, Maiga-Ascofare O, Djimdé AA, Apinjoh TO, Amenga-Etego L, Manske M, Barnwell JW, Renaud F, Ollomo B, Prugnolle F, Anstey NM, Auburn S, Price RN, McCarthy JS, Kwiatkowski DP, Newbold CI, Berriman M, Otto TD (February 2017)."Plasmodium malariae and P. ovale genomes provide insights into malaria parasite evolution".Nature.542(7639): 101–104.Bibcode:2017Natur.542..101R.doi:10.1038/nature21038.PMC5326575.PMID28117441.
