Malaria is known for its fever paroxysm, starting with chills, rigors, high grade fever, followed by sweating as the fever declines. However, this classical pattern may not be seen in many patients, particularly during the initial days of clinical malaria. In the initial 48 hours of the erythrocytic phase of the infection, patients may not experience any fever despite the parasitemia, but there may be prodromal symptoms such as headache and body ache.
The classical malarial paroxysm, when established, consists of chills, rigors, fever, followed by sweating, termed as cold stage, hot stage and sweating stage. The first cold stage lasts 15-60 minutes and is characterized by a feeling of cold and shivering. This is followed by the hot stage, with fever from 39-41.5°C, lasting 2-6 hours, also associated with flushed, dry skin, and often headache, nausea, and vomiting. At the end of it, the fever drops rapidly and the patient sweats profusely over a period of 2-4 hours.
The malarial paroxysms can occur intermittently, or in some cases, every day. During the initial period of the erythrocytic phase, most parasite populations are heterogeneous and schizogonic cycles are not synchronized, resulting in irregular or continuous fever. As the broods of the merozoites get synchronized, the typical paroxysms of fever occur with clock’s precision, corresponding with the release of fresh merozoites.[2-4] The synchronization of broods is more complete in non-falciparum infections, while in P. falciparum, a minor brood or subpopulation of parasites may remain asynchronous with the major brood. In P. falciparum infection, therefore, the fever may be continuous during the initial days, followed by poorly delineated paroxysms that may extend irregularly over 24 hours or more. In P. vivax infection, the paroxysms are short and sharply delineated within a period of usually <8 hours. Due to better synchronization of schizont rupture, rigors are more common in P. vivax and P. ovale than P. falciparum and P. malariare.[5,7] As the infection progresses, in cases of either parasites, the paroxysms get better established and are characterized by a sharp rise in temperature at the onset of a paroxysm, reaching peak values of up to about 39-41.5ºC within the first 1-2 hours from onset.[5,6] Due to the lower pyrogenic threshold, infections with P. vivax evoke greater proinflammatory cytokine response and serum cytokine levels are significantly higher in patients of vivax malaria compared with P. falciparum infections with similar parasitemia.[6-8] Patients of P. vivax malaria with hyperpyrexia have higher levels of serum cytokines than those without hyperpyrexia. As high temperatures are maintained for much longer periods (>24 hour) in P. falciparum infections, it is possible that high levels of cytokines may be sustained for longer duration in P. falciparum infection compared with P. vivax infection.
P. malariae with a 72 hours cycle, manifests with fever every fourth day (previous paroxysm being day 1) with two days of afebrile interval and is called quartan malaria. P. vivax and P. ovale with 48 hours cycles have the paroxysms every third day, termed as tertian malaria. P. knowlesi, with a 24 hour cycle, manifests with fever every day (Quotidian). In. P. falciparum infection, fever can occur every third day, or more frequently, even in a daily paroxysmal pattern, depending on the synchronization and size of the broods(tertian or subtertian or quotidian). Mixed infections of P. malariae with the other parasites can result in double quartan fever, with paroxysms for 2 consecutive days followed by one day of remission.
In areas with stable endemic malaria, older children and adults are immune to clinical illness and hence may not have fever despite parasitemia. However, loss of immunity due to pregnancy or immunosuppression as seen in HIV/AIDS can result in fever and more severe disease.[9,10] Rarely, fever may not be found in non-immune patients from areas with unstable transmission and some of these cases may indeed be having peripheral circulatory failure as a complication of malaria. Returning travelers who received suppression chemotherapy also may not have fever.
- Baron S. (editor). Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston; 1996. Available at https://www.ncbi.nlm.nih.gov/books/NBK8584/
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- McKenzie FE, Jeffery GM, Collins WE. Plasmodium malariae blood-stage dynamics. J Parasitol 2001;87(3):626–637. Available at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483342/pdf/nihms58079.pdf
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- White NJ. Malaria. In: Cook GC, Zumla AI, eds. Manson’s Tropical Diseases. 22nd edn. Saunders Elsevier(London). 2009. pp 1201–1300.
- Karunaweera ND, Graut GE, Gamage P, Kamini N. Mendiset al. Dynamics of fever and serum levels of tumor necrosis factor are closely associated during clinical paroxysms in Plasmodium vivax malaria. Proc Natl Acad Sci 1992;89(8):3200–3203. Available at http://www.pnas.org/content/89/8/3200.full.pdf+html
- Price RN, Tjitra E, Guerra CA, Nicholas J. WhiteNicholas M. Ansteyet al. Vivax malaria: Neglected and not benign. In: Breman JG, Alilio MS, White NJ, eds. Defining and Defeating the Intolerable Burden of Malaria: III. Progress and Perspectives. In: Breman JG, Alilio MS, Mills A, White NJ, eds. The Intolerable Burden of Malaria: A Collection from the American Journal of Tropical Medicine and Hygiene. CRC Press, Taylor & Francis Group, Boca Raton (FL), c2001–2007. Available at http://www.ncbi.nlm.nih.gov/bookshelf/picrender.fcgi?book=mal3&part=pg79&blobtype=pdf
- Seoh JY, Khan M, Park SH. Serum cytokine profiles in patients with Plasmodium vivax Malaria: A comparison between those who presented with and without hyperpyrexia. Am J Trop Med Hyg 2003;68(1):102–106. Available at http://www.ajtmh.org/cgi/reprint/68/1/102
- Desai M, ter Kuile FO, Nosten F, et al. Epidemiology and burden of malaria in pregnancy. Lancet Infect Dis 2007;7(2):93–104. Available at http://www.thelancet.com/journals/laninf/article/PIIS1473-3099%2807%2970021-X/fulltext
- Hewitt K, Steketee R, Mwapasa V, et al. Interactions between HIV and malaria in non-pregnant adults: Evidence and implications. AIDS 2006;20(16):1993–2004. Available at http://pdfs.journals.lww.com/aidsonline/2006/10240/Interactions_between_HIV_and_malaria_in.1.pdf
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- Mühlberger N, Jelinek T, Gascon J, et al. Epidemiology and clinical features of vivax malaria imported to Europe: Sentinel surveillance data from TropNetEurop. Malaria J 2004;3:5. Available at http://www.malariajournal.com/content/pdf/1475-2875-3-5.pdf
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