Incubation Period

All the clinical symptoms and manifestations of malaria, involving the different organs, are due to the asexual, erythrocytic phase of infection.[1] The pre-erythrocytic phase that affects only a very few hepatocytes passes off as a ‘silent’ phase[2] without any symptoms. The sexual forms of the parasite (gametocytes), also do not cause any illness. The symptoms and signs of malarial illness start after the completion of the first erythrocytic cycle, coinciding with release of the fresh merozoites and have been attributed to the proinflammatory cascade activated by the parasite DNA and proteins, particularly glycosylphosphatidylinositol (GPI).[3-6] [Also See Pathophysiology]

Source: Oakley MS, Gerald N, McCutchan TF, Aravind L, Kumar S. Clinical and molecular aspects of malaria fever. Trends in Parasitology. October 2011;27(10):442–449.

Pre-Patent Period Interval between inoculation of sporozoites into the skin and appearance of merozoites in the blood; corresponds to the length of hepatic or pre-erythrocytic schizogony, which is usually fixed for the different parasite species.[5,7]
Incubation Period Interval between inoculation of the sporozoites and appearance of the symptoms; reported to be inversely related to the dose of the sporozoite inoculum, higher loads manifesting with a shorter incubation period.[5,6] Depending on the species, it takes about 7-40 days for the symptoms to appear following inoculation by the mosquito.[5,7] Higher dose of the inoculum and a shorter incubation period are likely to be associated with a more severe disease, however, this remains unproven.[5,6] Antimalarial chemoprophylaxis taken by travelers can also prolong the incubation period by many weeks, particularly for the non-falciparum species; malarial illness in such travelers can occur several weeks to months after returning from the endemic area.[8]

The appearance of the parasites in the blood and development of clinical symptoms may not correlate. The first few cycles of the parasite’s development in the blood may not initiate much response and the host may remain symptom free despite there being detectable, early, parasitemia (incubation period longer than pre-patent period). Some non-immune hosts, however, may develop fever even before detectable parasitemia (incubation period shorter than pre-patent period).[7,9] A significant number of patients may also have vague prodromal illness for up to 2 days preceding the fever, characterized by malaise, headache, myalgia, arthralgia, abdominal discomfort, lethargy, lassitude, dysphoria or anorexia.

The primary attack (onset of first symptoms) of malaria presents as a non-specific febrile illness, with worsening of the prodrome, such as increasing head ache, followed by sudden shaking chills, rigors and high fever. As the typical malarial paroxysm gets established, the symptoms occur in a sequence of chills, fever followed by sweating, often described as cold, hot and wet stages, respectively. Some patients may also experience cough, chest pain, nausea, vomiting or diarrhea, delirium, anxiety and restlessness.

The level of parasitemia that induces fever, termed the pyrogenic density, tends to be lower for non-falciparum infections, being <100 parasites/µL for P. vivax (and P. ovale), 500/µL for P. malariae and higher, 10000/µL, for P. falciparum.[7,10] True rigors are more common in P. vivax and P. ovale than in P. falciparum and P. malariae.[7]

The malarial paroxysms generally occur during mid-day. This probably allows the short lived gametocytes to mature in the blood over a few hours so that the infection can be successfully transmitted in the limited time at night when the vector mosquitoes prefer to suck the blood from the victim.[11]

Sources:

  1. Omer FM, de Souza JB, Riley EM. Differential induction of TGF-{beta} regulates proinflammatory cytokine production and determines the outcome of lethal and nonlethal Plasmodium yoelii J Immunol 2003;171;5430–5436. http://www.jimmunol.org/cgi/reprint/171/10/5430.pdf
  2. Vaughan AM, Aly ASI, Kappe SHI. Malaria parasite pre-erythrocytic stage infection: Gliding and Hiding. Cell Host Microbe 2008;4(3):209–218. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2610487/pdf/nihms69860.pdf
  3. Mackintosh CL, Beeson JG, Marsh K. Clinical features and pathogenesis of severe malaria. Trends Parasitol 2004;20(12):597–603.
  4. Chakravorty SJ, Hughes KR, Craig AG. Host response to cytoadherence in Plasmodium Falciparum. Biochem Soc Trans 2008;36:221–228. DOI: 10.1042/BST0360221. http://www.biochemsoctrans.org/bst/036/0221/0360221.pdf
  5. Matteelli A, Castelli F, Caligaris S. Life cycle of malaria parasites. In: Carosi G, Castelli F, eds. Handbook of Malaria Infection in the Tropics. Associazione Italiana ‘Amici di R Follereau’ Organizzazione per la Cooperazione Sanitaria Internazionale. Bologna, 1997, pp. 17–23.
  6. Glynn JR. Infecting dose and severity of malaria: A literature review of induced malaria. J Trop Med Hyg 1994;97(5):300–316.
  7. White NJ. Malaria. In: Cook GC, Zumla AI, eds. Manson’s Tropical Diseases. 22nd edn. Saunders Elsevier(London). 2009, pp 1201–1300.
  8. Schwartz E, Parise M, Kozarsky P, et al. Delayed onset of malaria — Implications for chemoprophylaxis in travelers. N Engl J Med 2003;349:1510–1516. http://content.nejm.org/cgi/reprint/349/16/1510.pdf
  9. Mert A, Ozaras R, Tabak F, et al. Malaria in Turkey: A review of 33 cases. Eur J Epidemiol 2003;18(6):579–582.
  10. Anstey NM, Russell B, Yeo TW, Price RN. The pathophysiology of vivax malaria. Trends Parasitol 2009;25(5):220–227. http://www.naramed-u.ac.jp/~para/18.pdf
  11. Hawking F, Worms MJ, Gammage K. 24- and 48-hour cycles of malaria parasites in the blood; their purpose, production and control. Trans Royal Soc Trop Med Hyg 1968;62(6):731–760.

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