Malaria natural history, complications, and prognosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Severe malaria is almost exclusively caused by P. falciparum infection and usually arises 6-14 days after infection.[1] Severe malaria can progress extremely rapidly and cause death within hours or days.[1] In the most severe cases of the disease fatality rates can exceed 20%, even with intensive care and treatment.[2]

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.

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 infective mosquito bite.)

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.

Uncomplicated Malaria

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

  • a cold stage (sensation of cold, shivering)
  • a hot stage (fever, headaches, vomiting; seizures in young children)
  • and finally a sweating stage (sweats, return to normal temperature, tiredness).

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).

More commonly, the patient presents with a combination of the following symptoms:

  • Fever
  • Chills
  • Sweats
  • Headaches
  • Nausea and vomiting
  • Body aches
  • General malaise

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").

Physical findings may include:

  • Elevated temperatures
  • Perspiration
  • Weakness
  • Enlarged spleen
  • Mild jaundice
  • Enlargement of the liver

Severe Malaria

Severe malaria occurs when infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism. The manifestations of severe malaria include

  • Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities
  • Severe anemia due to hemolysis (destruction of the red blood cells)
  • Hemoglobinuria (hemoglobin in the urine) due to hemolysis
  • Acute respiratory distress syndrome (ARDS), an inflammatory reaction in the lungs that inhibits oxygen exchange, which may occur even after the parasite counts have decreased in response to treatment
  • Abnormalities in blood coagulation
  • Low blood pressure caused by cardiovascular collapse
  • Acute kidney failure
  • Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
  • Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia
  • Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

Severe malaria is a medical emergency and should be treated urgently and aggressively.

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.

Complications

Prognosis

  • In endemic areas, the overall fatality rate for all cases of malaria can be as high as one in ten.[3] Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.[4]

References

  1. 1.0 1.1 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. 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.
  4. 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.

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