View source for Malaria natural history, complications, and prognosis

__NOTOC__
{{Malaria}}

{{CMG}}; {{AE}} {{Rim}}, {{USAMA}}

==Overview==
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.<ref name=Trampuz>{{cite journal | author = Trampuz A, Jereb M, Muzlovic I, Prabhu R | title = Clinical review: Severe malaria. | url=http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12930555 | journal = Crit Care | volume = 7 | issue = 4 | pages = 315-23 | year = 2003 | id = PMID 12930555}}</ref>  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.<ref>{{cite journal | author = Kain K, Harrington M, Tennyson S, Keystone J | title = Imported malaria: prospective analysis of problems in diagnosis and management. | journal = Clin Infect Dis | volume = 27 | issue = 1 | pages = 142-9 | year = 1998 | id = PMID 9675468}}</ref><ref name="pmid25881316">{{cite journal| author=Unger HW, Ome-Kaius M, Karl S, Singirok D, Siba P, Walker J et al.| title=Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea. | journal=BMC Pregnancy Childbirth | year= 2015 | volume= 15 | issue=  | pages= 83 | pmid=25881316 | doi=10.1186/s12884-015-0511-6 | pmc=4404558 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25881316  }} </ref>

==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]].<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

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.<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

===Uncomplicated Malaria===
The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of:<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>
* A cold stage (sensation of cold, shivering)
* A hot stage ([[fever]], [[headache]]s, [[vomiting]]; [[seizures]] in young children)
* A sweating stage ([[sweat]]s, 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]]).<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

More commonly, the patient presents with a combination of any the following symptoms: [[fever]], [[chills]], [[sweats]], [[headache]]s, [[nausea]] and [[vomiting]], body aches, and general [[malaise]].<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

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").<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

===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.<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

===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 ("[[hypnozoite]]s") that may reactivate. Treatment to reduce the chance of such relapses is available and should follow treatment of the first attack.<ref name=CDC> Malaria, Disease. CDC. Accessed on 07/24/2014 </ref>

==Complications==
* Severe malaria and its complications are associated with ''[[P. falciparum]]'' infection.  Consequences of severe malaria include [[coma]] and death if untreated&mdash;young children and pregnant women are especially vulnerable. [[Splenomegaly]] ([[enlarged spleen]]), severe [[headache]], cerebral [[ischemia]], [[hepatomegaly]] ([[enlarged liver]]), [[hypotension]], [[ARDS]], and hemoglobinuria with [[renal failure]] may occur.

===Fetal Complications===
*[[Fetal growth retardation|Decreased fetal growth]]<ref name="pmid25881316">{{cite journal| author=Unger HW, Ome-Kaius M, Karl S, Singirok D, Siba P, Walker J et al.| title=Factors associated with ultrasound-aided detection of suboptimal fetal growth in a malaria-endemic area in Papua New Guinea. | journal=BMC Pregnancy Childbirth | year= 2015 | volume= 15 | issue=  | pages= 83 | pmid=25881316 | doi=10.1186/s12884-015-0511-6 | pmc=4404558 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25881316  }} </ref>
===Laboratory Complications===
* [[Thrombocytopenia]]<ref name="pmid23777019">{{cite journal| author=Limaye CS, Londhey VA, Nabar ST| title=The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai. | journal=J Assoc Physicians India | year= 2012 | volume= 60 | issue=  | pages= 15-8 | pmid=23777019 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777019  }} </ref>
* [[Leukopenia]]<ref name="pmid23777019">{{cite journal| author=Limaye CS, Londhey VA, Nabar ST| title=The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai. | journal=J Assoc Physicians India | year= 2012 | volume= 60 | issue=  | pages= 15-8 | pmid=23777019 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777019  }} </ref>
* High [[bilirubin]]<ref name="pmid23777019">{{cite journal| author=Limaye CS, Londhey VA, Nabar ST| title=The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai. | journal=J Assoc Physicians India | year= 2012 | volume= 60 | issue=  | pages= 15-8 | pmid=23777019 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777019  }} </ref>
* Elevated [[creatinine]]<ref name="pmid23777019">{{cite journal| author=Limaye CS, Londhey VA, Nabar ST| title=The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai. | journal=J Assoc Physicians India | year= 2012 | volume= 60 | issue=  | pages= 15-8 | pmid=23777019 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777019  }} </ref>
* [[Anemia]]<ref name="pmid23777019">{{cite journal| author=Limaye CS, Londhey VA, Nabar ST| title=The study of complications of vivax malaria in comparison with falciparum malaria in Mumbai. | journal=J Assoc Physicians India | year= 2012 | volume= 60 | issue=  | pages= 15-8 | pmid=23777019 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23777019  }} </ref>

===Metabolic Complications===
* [[Hypoglycemia]]<ref name="pmid16265889">{{cite journal| author=Planche T, Dzeing A, Ngou-Milama E, Kombila M, Stacpoole PW| title=Metabolic complications of severe malaria. | journal=Curr Top Microbiol Immunol | year= 2005 | volume= 295 | issue=  | pages= 105-36 | pmid=16265889 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16265889  }} </ref>
** Increased turnover of [[glucose]]
** [[Hyperinsulinemia]] secondary to treatment with [[quinine]]
* [[Lactic acidosis]]<ref name="pmid16265889">{{cite journal| author=Planche T, Dzeing A, Ngou-Milama E, Kombila M, Stacpoole PW| title=Metabolic complications of severe malaria. | journal=Curr Top Microbiol Immunol | year= 2005 | volume= 295 | issue=  | pages= 105-36 | pmid=16265889 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16265889  }} </ref>

===Spleen Related Complications===
* Spontaneous rupture of the spleen<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>
* [[Hematoma]]<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>
* Hyperreactive malarial syndrome<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>
* Enlarged spleen<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>
* [[Torsion]]<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>
* Splenic [[cyst]]s<ref name="pmid8443301">{{cite journal| author=Zingman BS, Viner BL| title=Splenic complications in malaria: case report and review. | journal=Clin Infect Dis | year= 1993 | volume= 16 | issue= 2 | pages= 223-32 | pmid=8443301 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8443301  }} </ref>

===Neurological Complications===
* [[Cerebral malaria]]<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
** Acute encephalopathy caused by infection with ''[[P. falciparum]]''
** Associated with 50% rate of mortality
** Symptoms might be further exacerbated in case of [[hypoglycemia]] secondary to treatment with [[quinine]]
* [[Intracranial hemorrhage]]<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
* [[Cerebral artery]] occlusion<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
* Self limiting cerebral [[ataxia]]<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
* [[Epilepsy]]<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
* Transient psychiatric symptoms<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>
* Transient extrapyramidal symptoms<ref name="pmid1298073">{{cite journal| author=Senanayake N, Román GC| title=Neurological complications of malaria. | journal=Southeast Asian J Trop Med Public Health | year= 1992 | volume= 23 | issue= 4 | pages= 672-80 | pmid=1298073 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1298073  }} </ref>

===Pulmonary Complications===
* [[Pulmonary edema]]<ref name="pmid12930555">{{cite journal| author=Trampuz A, Jereb M, Muzlovic I, Prabhu RM| title=Clinical review: Severe malaria. | journal=Crit Care | year= 2003 | volume= 7 | issue= 4 | pages= 315-23 | pmid=12930555 | doi=10.1186/cc2183 | pmc=PMC270697 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12930555  }} </ref>
** [[Tachypnea]]
** [[Dyspnea]]
* [[Hypoxemia]]<ref name="pmid12930555">{{cite journal| author=Trampuz A, Jereb M, Muzlovic I, Prabhu RM| title=Clinical review: Severe malaria. | journal=Crit Care | year= 2003 | volume= 7 | issue= 4 | pages= 315-23 | pmid=12930555 | doi=10.1186/cc2183 | pmc=PMC270697 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12930555  }} </ref>
* Respiratory failure and [[intubation]]<ref name="pmid12930555">{{cite journal| author=Trampuz A, Jereb M, Muzlovic I, Prabhu RM| title=Clinical review: Severe malaria. | journal=Crit Care | year= 2003 | volume= 7 | issue= 4 | pages= 315-23 | pmid=12930555 | doi=10.1186/cc2183 | pmc=PMC270697 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12930555  }} </ref>
* [[Acute respiratory distress syndrome]] ([[ARDS]])<ref name="pmid12930555">{{cite journal| author=Trampuz A, Jereb M, Muzlovic I, Prabhu RM| title=Clinical review: Severe malaria. | journal=Crit Care | year= 2003 | volume= 7 | issue= 4 | pages= 315-23 | pmid=12930555 | doi=10.1186/cc2183 | pmc=PMC270697 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12930555  }} </ref>

===Renal Complications===
* [[Acute renal failure]]
* [[Blackwater fever]] (hemoglobin from lysed [[red blood cell]]s leaks into the [[urine]].)

==Prognosis==
* In [[endemic]] areas, the overall [[fatality rate]] for all cases of malaria can be as high as one in ten.<ref>{{cite journal | author = Mockenhaupt F, Ehrhardt S, Burkhardt J, Bosomtwe S, Laryea S, Anemana S, Otchwemah R, Cramer J, Dietz E, Gellert S, Bienzle U | title = Manifestation and outcome of severe malaria in children in northern Ghana. | journal = Am J Trop Med Hyg | volume = 71 | issue = 2 | pages = 167-72 | year = 2004 | id = PMID 15306705}}</ref> Over the longer term, developmental impairments have been documented in children who have suffered episodes of severe malaria.<ref name="carter2005">{{cite journal | author=Carter JA, Ross AJ, Neville BG, Obiero E, Katana K, Mung'ala-Odera V, Lees JA, Newton CR | title=Developmental impairments following severe falciparum malaria in children | journal=Trop Med Int Health | year=2005 | volume=10 | pages=3-10  | id=PMID 15655008}}</ref>

* 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.<ref name=SCD and malaria>Protective Effect of Sickle Cell Trait Against Malaria-Associated Mortality And Morbidity. CDC.gov accessed on 7/24/2014 [http://www.cdc.gov/malaria/about/biology/sickle_cell.html] </ref>

==References==
{{Reflist|2}}
[[Category:Apicomplexa]]
[[Category:Insect-borne diseases]]
[[Category:Malaria]]
[[Category:Emergency medicine]]
[[Category:Parasitic diseases]]
[[Category:Tropical disease]]
[[Category:Deaths from malaria]]
[[Category:Infectious disease]]
[[Category:Disease]]

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