Malaria natural history, complications, and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [3], Usama Talib, BSc, MD [4]


Following the infective bite of the Anopheles mosquito, a period of time goes by before the first symptoms appear, with the incubation period varying between 7 to 30 days depending on the immune status of the patient, type and strain of the plasmodium, the dose of sporozoites injected on the bite, and the presence of prophylactic drugs. The classical but rarely observed malaria attack lasts 6-10 hours, and it consists of a cold stage, hot stage, and sweating stage. Severe malaria is almost exclusively caused by P. falciparum infections and usually arises 6-14 days following infection.[1] Complications of severe malaria include splenomegaly, severe headache, cerebral ischemia, hepatomegaly, hypotension, ARDS, and hemoglobinuria with renal failure. Severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases, fatality rates can exceed 20%, even with intensive care and treatment.[2][3]

Natural History

Incubation Period

  • Following the infective bite by the Anopheles mosquito, a period of time (the "incubation period") goes by before the first symptoms appear.
  • The incubation period in most cases varies from 7 to 30 days.
  • The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.[4]
  • Antimalarial drugs taken for prophylaxis by travelers can delay the appearance of malaria symptoms by weeks or months, long after the traveler has left the malaria-endemic area. This can happen particularly with P. vivax and P. ovale, both of which can produce dormant liver stage parasites; the liver stages may reactivate and cause disease months after the bite of the infective mosquito. Such long delays between exposure and development of symptoms can result in misdiagnosis or delayed diagnosis because of reduced clinical suspicion by the health-care provider. Returned travelers should always remind their health-care providers of any travel in areas where malaria occurs, during the past 12 months.[4]

Uncomplicated Malaria

The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:[4]

Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).[4]

More commonly, the patient presents with a combination of any the following symptoms: fever, chills, sweats, headaches, nausea and vomiting, body aches, and general malaise.[4]

In countries where cases of malaria are infrequent, these symptoms may be attributed to influenza, a cold, or other common infections, especially if malaria is not suspected. Conversely, in countries where malaria is frequent, residents often recognize the symptoms as malaria, and treat themselves without seeking diagnostic confirmation ("presumptive treatment").[4]

Severe Malaria

Severe malaria occurs when infections are complicated by serious organ failure or abnormalities in the patient's blood or metabolism. Severe malaria is a medical emergency and should be treated urgently and aggressively.[4]

Malaria Relapse

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites ("hypnozoites") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.[4]


Fetal Complications

Laboratory Complications

Metabolic Complications

Spleen Related Complications

Neurological Complications

Pulmonary Complications

Renal Complications


  • In endemic areas, the overall fatality rate for all cases of malaria can be as high as one in ten.[10] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.[11]
  • Only in some individuals do malaria episodes progress to severe life-threatening disease, while in the majority the episodes are self-limiting. This is partly because of host genetic factors such as the sickle cell gene.[12]


  1. Trampuz A, Jereb M, Muzlovic I, Prabhu R (2003). "Clinical review: Severe malaria". Crit Care. 7 (4): 315–23. PMID 12930555.
  2. Kain K, Harrington M, Tennyson S, Keystone J (1998). "Imported malaria: prospective analysis of problems in diagnosis and management". Clin Infect Dis. 27 (1): 142–9. PMID 9675468.
  3. 3.0 3.1 Unger HW, Ome-Kaius M, Karl S, Singirok D, Siba P, Walker J; et al. (2015). "Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea". BMC Pregnancy Childbirth. 15: 83. doi:10.1186/s12884-015-0511-6. PMC 4404558. PMID 25881316.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Malaria, Disease. CDC. Accessed on 07/24/2014
  5. 5.0 5.1 5.2 5.3 5.4 Limaye CS, Londhey VA, Nabar ST (2012). "The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai". J Assoc Physicians India. 60: 15–8. PMID 23777019.
  6. 6.0 6.1 Planche T, Dzeing A, Ngou-Milama E, Kombila M, Stacpoole PW (2005). "Metabolic complications of severe malaria". Curr Top Microbiol Immunol. 295: 105–36. PMID 16265889.
  7. 7.0 7.1 7.2 7.3 7.4 7.5 Zingman BS, Viner BL (1993). "Splenic complications in malaria: case report and review". Clin Infect Dis. 16 (2): 223–32. PMID 8443301.
  8. 8.0 8.1 8.2 8.3 8.4 8.5 8.6 Senanayake N, Román GC (1992). "Neurological complications of malaria". Southeast Asian J Trop Med Public Health. 23 (4): 672–80. PMID 1298073.
  9. 9.0 9.1 9.2 9.3 Trampuz A, Jereb M, Muzlovic I, Prabhu RM (2003). "Clinical review: Severe malaria". Crit Care. 7 (4): 315–23. doi:10.1186/cc2183. PMC 270697. PMID 12930555.
  10. Mockenhaupt F, Ehrhardt S, Burkhardt J, Bosomtwe S, Laryea S, Anemana S, Otchwemah R, Cramer J, Dietz E, Gellert S, Bienzle U (2004). "Manifestation and outcome of severe malaria in children in northern Ghana". Am J Trop Med Hyg. 71 (2): 167–72. PMID 15306705.
  11. Carter JA, Ross AJ, Neville BG, Obiero E, Katana K, Mung'ala-Odera V, Lees JA, Newton CR (2005). "Developmental impairments following severe falciparum malaria in children". Trop Med Int Health. 10: 3–10. PMID 15655008.
  12. Protective Effect of Sickle Cell Trait Against Malaria-Associated Mortality And Morbidity. accessed on 7/24/2014 [1]