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==Overview==
The natural history of Ebola hemorrhagic fever is highly dependent on the Ebola virus species and the host immunity. The symptoms of Ebola hemorrhagic fever usually develop 2 to 21 days following exposure to Ebola virus. The clinical course of Ebola hemorrhagic fever has 2 phases, which may possibly be separated by a phase of "pseudoremission". The majority of patients develop severe symptoms that gradually worsen with time. Patients with non-fatal disease typically develop isolated high-grade fever that resolves within 7 to 10 days of disease onset. In contrast, fatal disease is associated with early clinical signs and symptoms, and these patients typically experience rapid clinical deterioration, including hemorrhagic, infectious, and neurological complications, and die 6 to 16 days following the onset of symptoms. Recovery from Ebola depends on good supportive care and the patient’s immune response. People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola.  Patients who survive are susceptible to late complications that are not related to the acute illness. The most common long-term complication of Ebola virus among survivors is arthralgia of the large joints that is usually not accompanied by findings on physical examination.


==Overview==
==Natural History==
The natural history of Ebola hemorrhagic fever is highly dependent on the Ebola virus species and the host immunity. The symptoms of Ebola hemorrhagic fever usually develop 2 to 21 days following exposure to Ebola virus. The clinical course of Ebola hemorrhagic fever has 2 phases, which may possibly be separated by a phase of "pseudoremission".<ref name="pmid9988156">{{cite journal| author=Ndambi R, Akamituna P, Bonnet MJ, Tukadila AM, Muyembe-Tamfum JJ, Colebunders R| title=Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S8-10 | pmid=9988156 | doi=10.1086/514297 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988156  }} </ref> The clinical course of Ebola virus is a spectrum of manifestations. If left untreated, patients may remain asymptomatic or develop mild non-fatal disease, but the majority of patients develop severe symptoms that gradually worsen with time. Patients with non-fatal disease typically develop isolated high-grade fever that resolves within 7 to 10 days of disease onset. In contrast, fatal disease is associated with early clinical signs and symptoms, and these patients typically experience rapid clinical deterioration and die 6 to 16 days following the onset of symptoms.<ref name="pmid9988184">{{cite journal| author=Ksiazek TG, West CP, Rollin PE, Jahrling PB, Peters CJ| title=ELISA for the detection of antibodies to Ebola viruses. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S192-8 | pmid=9988184 | doi=10.1086/514313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988184  }} </ref><ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
 
===Phase 1: Early, Non-specific Signs and Symptoms===
*Early symptoms include high-grade fever, chills, myalgias, arthritis, and generalized fatigue that typically develop within 6 to 13 days of viral incubation (incubation period ranges from 2 to 21 days). Early symptoms typically persist for approximately one week.<ref name="pmid23327370">{{cite journal| author=Muyembe-Tamfum JJ, Mulangu S, Masumu J, Kayembe JM, Kemp A, Paweska JT| title=Ebola virus outbreaks in Africa: past and present. | journal=Onderstepoort J Vet Res | year= 2012 | volume= 79 | issue= 2 | pages= 451 | pmid=23327370 | doi=10.4102/ojvr.v79i2.451 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23327370  }} </ref>
*Without treatment, patients subsequently develop non-specific multisystem symptoms, including constitutional (asthenia and anorexia), respiratory (cough and nasal discharge), and gastrointestinal (abdominal pain, nausea, and vomiting) manifestations.
*During this phase, work-up is usually remarkable for leucopenia with lymphopenia.
*At day 5-7 following onset of symptoms, patients may develop cutaneous flushing or a characteristic desquematous, maculopapular, non-pruritic, erythematous rash with a centripetal distribution.
* Patients with non-fatal disease usually develop non-life-threatening symptoms that self-resolve approximately 7 to 10 days following onset of symptoms. When no improvement is observed within one week of phase 1 symptoms, patients are more likely to deteriorate into the potentially fatal phase 2 symptoms.<ref name="pmid12698919">{{cite journal| author=Casillas AM, Nyamathi AM, Sosa A, Wilder CL, Sands H| title=A current review of Ebola virus: pathogenesis, clinical presentation, and diagnostic assessment. | journal=Biol Res Nurs | year= 2003 | volume= 4 | issue= 4 | pages= 268-75 | pmid=12698919 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12698919  }} </ref>
 
===Pseudoremission Phase===
*A phase of pseudoremission, that typically occurs at day 7-8 of symptoms onset and lasts for 1 to 2 days, may be observed prior to the development of neurological and hemorrhagic manifestations.<ref name="pmid9988156">{{cite journal| author=Ndambi R, Akamituna P, Bonnet MJ, Tukadila AM, Muyembe-Tamfum JJ, Colebunders R| title=Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S8-10 | pmid=9988156 | doi=10.1086/514297 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988156  }} </ref><ref name="pmid23327370">{{cite journal| author=Muyembe-Tamfum JJ, Mulangu S, Masumu J, Kayembe JM, Kemp A, Paweska JT| title=Ebola virus outbreaks in Africa: past and present. | journal=Onderstepoort J Vet Res | year= 2012 | volume= 79 | issue= 2 | pages= 451 | pmid=23327370 | doi=10.4102/ojvr.v79i2.451 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23327370  }} </ref>
*Patients often report significant improvement in clinical symptoms with adequate food intake and mobility.<ref name="pmid23327370">{{cite journal| author=Muyembe-Tamfum JJ, Mulangu S, Masumu J, Kayembe JM, Kemp A, Paweska JT| title=Ebola virus outbreaks in Africa: past and present. | journal=Onderstepoort J Vet Res | year= 2012 | volume= 79 | issue= 2 | pages= 451 | pmid=23327370 | doi=10.4102/ojvr.v79i2.451 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23327370  }} </ref>
*In the minority of cases, patients recover during this phase and survive. However, the majority of cases progress into developing life-threatening complications.
 
===Phase 2: Life-threatening Signs and Symptoms===
*A second phase of manifestations, characterized by hemorrhagic and neurological manifestations, typically develops during the peak of the illness.
* Approximately 50% of patients develop mucosal and visceral hemorrhage.
*At advanced stages, patients' symptoms worsen; and patients develop multisystem failure (renal failure, hepatic failure, and pancreatitis), dyspnea, convulsions, encephalopathy, diffuse coagulopathy (disseminated intravascular coagulopathy), hypovolemic shock, and eventually death.<ref name="pmid9988154">{{cite journal| author=Peters CJ, LeDuc JW| title=An introduction to Ebola: the virus and the disease. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= ix-xvi | pmid=9988154 | doi=10.1086/514322 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988154  }} </ref><ref name="pmid17940939">{{cite journal| author=Feldmann H, Geisbert T, Kawaoka Y| title=Filoviruses: recent advances and future challenges. | journal=J Infect Dis | year= 2007 | volume= 196 Suppl 2 | issue=  | pages= S129-30 | pmid=17940939 | doi=10.1086/520550 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17940939  }} </ref><ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
* In contrast to early leucopenia, the late course of the disease is often characterized by prolonged prothrombin time (PT) and partial thromboplastin time (PTT), neutrophilia with left shift and atypical lymphocytes, thrombocytopenia, elevated liver enzymes, hyperproteinemia, and proteinuria.<ref name="pmid9988184">{{cite journal| author=Ksiazek TG, West CP, Rollin PE, Jahrling PB, Peters CJ| title=ELISA for the detection of antibodies to Ebola viruses. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S192-8 | pmid=9988184 | doi=10.1086/514313 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988184  }} </ref><ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
* Patients typically experience rapid clinical deterioration and perish within 6 to 16 days following the onset of symptoms.
 
==Complications==
===Acute Complications of Advanced Disease===
Ebola hemorrhagic fever usually leads to death by multiorgan failure and systemic complications. Infectious (overwhelming [[sepsis]]) and hemorrhagic (visceral bleeding and [[disseminated intravascular coagulopathy]]) complications are the most significant life-threatening causes of death associated with Ebola virus disease.<ref name="pmid25253023">{{cite journal| author=Parkes-Ratanshi R, Ssekabira U, Crozier I| title=Ebola in West Africa: be aware and prepare. | journal=Intensive Care Med | year= 2014 | volume= 40 | issue= 11 | pages= 1742-5 | pmid=25253023 | doi=10.1007/s00134-014-3497-z | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=25253023  }} </ref> Generally, the following complications have been reported in patients with advanced Ebola virus disease<ref name="pmid9988155">{{cite journal| author=Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y et al.| title=Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S1-7 | pmid=9988155 | doi=10.1086/514308 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988155  }} </ref>:


==Natural history==
====ENT====
===Cultural impact===
*[[Tinnitus]]
[[Image:Stuffed ebola.jpg|thumb|An Ebola virus cuddly toy]]
*[[Hearing loss]]
Ebola and Marburg have served as a rich source of ideas and plotlines for many forms of entertainment. The infatuation with the virus is likely due to the high mortality rate of its victims, its mysterious nature, and its tendency to cause gruesome bleeding from bodily orifices.
*Sudden bilateral [[blindness]]


In the movie ''[[Outbreak (film)|Outbreak]]'', the virus looks the same as the Ebola virus.{{Or|date=March 2008}} In fact, the entire movie's made up virus "Motaba" is based very closely on Ebola.{{Or|date=March 2008}} The symptoms and area of infection had relevance.
====Cardiovascular system====
*[[Hypovolemic shock]]
*[[Disseminated intravascular coagulopathy]] ([[DIC]])
*Acute [[heart failure]]
*[[Myocarditis]]
*Serous [[pericardial effusion]]


The Rage Virus from the movies [[28 Days Later]] and [[28 Weeks Later]] is a modified version of the Ebola virus.
====Respiratory system====
*[[Epistaxis]]
*[[Acute respiratory distress syndrome]] ([[ARDS]])
*[[Pulmonary edema]]
*[[Respiratory tract infection]]s


In the book ''[[Outbreak (novel)|Outbreak]]'', by [[Robin Cook (novelist)| Robin Cook]], the Ebola virus is used in name as a possible weapon, with criminal intent. This book is different from the movie ''[[Outbreak (film)|Outbreak]]'' of the same name
====Gastrointestinal system====
*[[Hemoptysis]]
*[[Hematemesis]]
*[[Hematochezia and melena]]
*[[Pancreatitis]]
*[[Hepatitis]]


Biological warfare using airborne modifications of the Ebola virus was a main theme in [[Tom Clancy]]'s novels ''[[Executive Orders]]'' and ''[[Rainbow Six (novel)|Rainbow Six]]''.
====Genitourinary system====
*[[Fetal loss]]
*[[Orchitis]]
*[[Hematuria]]
*[[Oligouria and anuria]]
*[[Urinary tract infection]]s


In ''[[Resident Evil]]'', the T-Virus is a modified version of the Progenitor Virus, created by inserting it with Ebola genes.<ref>{{cite web |url=http://www3.capcom.co.jp/bio/weskars/index.html |title=Capcom.co.jp "Wesker's Report II"  |accessdate=2008-04-12}}</ref>
====Neurological system====
*[[Hiccups]] (may herald further neurological symptoms and death)
*[[Dysesthesia]] and burning skin sensation
*[[Convulsions]]
*[[Meningitis]]
*[[Encephalopathy]]
*[[Coma]]


[[Tomb Raider: The Cradle of Life]] features a biological weapon<ref>{{cite web |url=http://www.jesusfreakhideout.com/movies/TombRaider2.asp |title=Jesusfreakhideout.com "Lara Croft Tomb Raider: The Cradle of Life" Movie Review |accessdate=2008-03-11 |format= |work= }}</ref> consisting of a greatly accelerated form of Ebola, capable of causing death within minutes.
===Late Complications Among Survivors===
Survivors of Ebola hemoarrhagic fever may present with late [[complications]] of the disease that are not related to the acute illness. However, the majority of these symptoms seem to resolve by 1-2 years.<ref name="pmid9988162">{{cite journal| author=Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D et al.| title=Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S28-35 | pmid=9988162 | doi=10.1086/514318 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988162  }} </ref> The most common long-term complication of Ebola virus among survivors is arthralgias of the large joints that are not accompanied by physical exam findings. Other unexplained reported complications that have occurred between 2 weeks to 2 months<ref name="pmid9988155">{{cite journal| author=Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y et al.| title=Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S1-7 | pmid=9988155 | doi=10.1086/514308 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988155  }} </ref>, at 6-months, and 21-month follow-up of the acute Ebola infection are listed below<ref name="pmid9988162">{{cite journal| author=Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D et al.| title=Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit. | journal=J Infect Dis | year= 1999 | volume= 179 Suppl 1 | issue=  | pages= S28-35 | pmid=9988162 | doi=10.1086/514318 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=9988162  }} </ref>:
====Constitutional signs and symptoms====
*Persistent [[weight loss]]
*Extreme [[fatigue]]
*[[Anorexia]]
*[[Fever]]
*[[Headache]]


Much of the representation of the Ebola virus in fiction and the media is considered [[apocryphal|exaggerated or myth]].{{Fact|date=June 2007}} One pervasive myth follows that the virus kills so fast that it has little time to spread. Victims die very soon after contact with the virus. In reality, the incubation time is usually about a week. The average time from onset of early symptoms to death varies in the range 3-21 days, with a mean of 10.1.  Although this would prevent the transmission of the virus to many people, it is still enough time for some people to catch the disease.
====ENT====
*[[Hearing loss]]
*[[Tinnitus]]
*[[Suppurative parotitis]]
*[[Gingival bleeding]]


Another myth states that the virus causes patients to melt, liquefy, or bleed profusely. In depictions of this type, victims of Ebola suffer from squirting blood, liquefying flesh, [[zombie]]-like faces and dramatic projectile bloody vomiting, at times, from even recently deceased. In actual fact, only a fraction of Ebola victims have severe bleeding, and most accounts of the course of the disease describe patients as dull and lethargic. Approximately 10% of patients suffer some bleeding, but this is often internal or subtle, such as bleeding from the gums. Ebola symptoms are usually limited to extreme exhaustion, vomiting, diarrhea, abdominal pain, a high fever, headaches and other body pains.
====Ocular disease====
*[[Conjunctivitis]]
*[[Conjunctival bleeding]]
*[[Vision loss]]
*[[Uveitis]]


The following is an excerpt from an interview with Philippe Calain, M.D. Chief Epidemiologist, CDC Special Pathogens Branch, Kikwit 1996:
====Musculoskeletal system====
*Migratory [[arthralgia]]s. Notably, arthralgias are the most common non-acute complication of Ebola virus. Arthralgias usually involve the large joints (knees, back, hips). Joint pain may be symmetric and is typically worse in the morning and following exertion. Arthralgias are typically not accompanied by signs on physical exam.
*[[Myalgias]]


{{cquote|''At the end of the disease the patient does not look, from the outside, as horrible as you can read in some books. They are not melting. They are not full of blood. They're in shock, muscular shock. They are not unconscious, but you would say 'obtunded', dull, quiet, very tired. Very few were hemorrhaging. Hemorrhage is not the main symptom. Less than half of the patients had some kind of hemorrhage. But the ones that had bled, died.''}}
====Cardiovascular system====
*[[Pericarditis]]
*[[Petechiae]]


==Complications==
====Gastrointestinal system====
Survivors may have unusual problems, such as hair loss and sensory changes. There are also some late complications that may occur due to ebola. They are:
*[[Abdominal pain]]
*[[Dysphagia]]
*[[Hiccups]]
*[[Melena]]
*[[Hematemesis]]


*[[Hearing]] loss
====Genitourinary system====
*Unilateral [[orchitis]]
*Unilateral [[orchitis]]
*[[Headache]]
*[[Fatigue]]
*[[Myalgias]]
*[[Tinnutis]]
*[[Amenorrhea]]
*[[Amenorrhea]]
*[[Bulimia]]
*Suppurative [[parotitis]]


==Prognosis==
====Neuropsychiatric system====
The prognosis for a patient infected with the ebola virus is typically not good. The mortality rate from ebola can be as high as 90%. Many times patients will die from [[shock]] rather than [[blood]] loss. It should be noted that patients who are able to survive with ebola for two weeks are usually able to slowly recover.
*[[Myelitis]]
*[[Psychosis]]
 
== Prognosis ==
* Ebola infection is associated with poor survival. [[Case-fatality rate]]s is highly dependent on the [[species]] of [[virus]]:<ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
:* '''''Zaire Ebola''''' virus species: case-fatality rate of 60 - 90%
:* '''''Sudan Ebola''''' virus species: case-fatality rate 40 - 60%
:* '''''Bundibugyo Ebola''''' virus species: case-fatality rate 25%
:* '''''Côte d’Ivoire Ebola''''' virus: case-fatality rate 0% (only 1 case reported)
:* '''''Reston Ebola''''' virus: case-fatality rate 0% (Reston virus seems to be relatively harmless to humans)
* Patients who survived Ebola infection for two weeks are usually able to recover slowly, despite potential [[complications]].<ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
* Survival for 11 days is generally associated with recovery.
* [[Desquamation]] of the [[maculopapular rash]] by the 5th or 7th day is often associated with survival.<ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>
* [[Tachypnea]] is the strongest correlate of fatal outcome. It often appears a few hours before [[death]]. Other correlates of fatal outcome are [[hypotension]], [[tachycardia]] and [[anuria]].
* Severe [[hemorrhage|hemorrhagic]] [[complications]] such as [[hematemesis]], [[melena]], [[epistaxis]], [[ear bleeding]] and [[hematuria]] are associated with a poorer [[prognosis]] and are often associated with death within a week.<ref name="pmid2749110">{{cite journal| author=Sureau PH| title=Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire. | journal=Rev Infect Dis | year= 1989 | volume= 11 Suppl 4 | issue=  | pages= S790-3 | pmid=2749110 | doi= | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2749110  }} </ref> 
* In pregnant women, there is an increased risk of miscarriage.<ref name="pmid21084112">{{cite journal| author=Feldmann H, Geisbert TW| title=Ebola haemorrhagic fever. | journal=Lancet | year= 2011 | volume= 377 | issue= 9768 | pages= 849-62 | pmid=21084112 | doi=10.1016/S0140-6736(10)60667-8 | pmc=PMC3406178 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21084112  }} </ref>


==References==
== References ==
{{Reflist|2}}
{{Reflist|2}}
[[Category:Mononegavirales]]
[[Category:Viral diseases]]
[[Category:Biological weapons]]
[[Category:Zoonoses]]
[[Category:Hemorrhagic fevers]]
[[Category:Needs overview]]
[[Category:Disease]]
[[Category:Needs content]]
{{WH}}
{{WS}}

Latest revision as of 17:38, 18 September 2017

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Michael Maddaleni, B.S.; Guillermo Rodriguez Nava, M.D. [2]; João André Alves Silva, M.D. [3]; Yazan Daaboul, M.D.

Overview

The natural history of Ebola hemorrhagic fever is highly dependent on the Ebola virus species and the host immunity. The symptoms of Ebola hemorrhagic fever usually develop 2 to 21 days following exposure to Ebola virus. The clinical course of Ebola hemorrhagic fever has 2 phases, which may possibly be separated by a phase of "pseudoremission". The majority of patients develop severe symptoms that gradually worsen with time. Patients with non-fatal disease typically develop isolated high-grade fever that resolves within 7 to 10 days of disease onset. In contrast, fatal disease is associated with early clinical signs and symptoms, and these patients typically experience rapid clinical deterioration, including hemorrhagic, infectious, and neurological complications, and die 6 to 16 days following the onset of symptoms. Recovery from Ebola depends on good supportive care and the patient’s immune response. People who recover from Ebola infection develop antibodies that last for at least 10 years, possibly longer. It is not known if people who recover are immune for life or if they can become infected with a different species of Ebola. Patients who survive are susceptible to late complications that are not related to the acute illness. The most common long-term complication of Ebola virus among survivors is arthralgia of the large joints that is usually not accompanied by findings on physical examination.

Natural History

The natural history of Ebola hemorrhagic fever is highly dependent on the Ebola virus species and the host immunity. The symptoms of Ebola hemorrhagic fever usually develop 2 to 21 days following exposure to Ebola virus. The clinical course of Ebola hemorrhagic fever has 2 phases, which may possibly be separated by a phase of "pseudoremission".[1] The clinical course of Ebola virus is a spectrum of manifestations. If left untreated, patients may remain asymptomatic or develop mild non-fatal disease, but the majority of patients develop severe symptoms that gradually worsen with time. Patients with non-fatal disease typically develop isolated high-grade fever that resolves within 7 to 10 days of disease onset. In contrast, fatal disease is associated with early clinical signs and symptoms, and these patients typically experience rapid clinical deterioration and die 6 to 16 days following the onset of symptoms.[2][3]

Phase 1: Early, Non-specific Signs and Symptoms

  • Early symptoms include high-grade fever, chills, myalgias, arthritis, and generalized fatigue that typically develop within 6 to 13 days of viral incubation (incubation period ranges from 2 to 21 days). Early symptoms typically persist for approximately one week.[4]
  • Without treatment, patients subsequently develop non-specific multisystem symptoms, including constitutional (asthenia and anorexia), respiratory (cough and nasal discharge), and gastrointestinal (abdominal pain, nausea, and vomiting) manifestations.
  • During this phase, work-up is usually remarkable for leucopenia with lymphopenia.
  • At day 5-7 following onset of symptoms, patients may develop cutaneous flushing or a characteristic desquematous, maculopapular, non-pruritic, erythematous rash with a centripetal distribution.
  • Patients with non-fatal disease usually develop non-life-threatening symptoms that self-resolve approximately 7 to 10 days following onset of symptoms. When no improvement is observed within one week of phase 1 symptoms, patients are more likely to deteriorate into the potentially fatal phase 2 symptoms.[5]

Pseudoremission Phase

  • A phase of pseudoremission, that typically occurs at day 7-8 of symptoms onset and lasts for 1 to 2 days, may be observed prior to the development of neurological and hemorrhagic manifestations.[1][4]
  • Patients often report significant improvement in clinical symptoms with adequate food intake and mobility.[4]
  • In the minority of cases, patients recover during this phase and survive. However, the majority of cases progress into developing life-threatening complications.

Phase 2: Life-threatening Signs and Symptoms

  • A second phase of manifestations, characterized by hemorrhagic and neurological manifestations, typically develops during the peak of the illness.
  • Approximately 50% of patients develop mucosal and visceral hemorrhage.
  • At advanced stages, patients' symptoms worsen; and patients develop multisystem failure (renal failure, hepatic failure, and pancreatitis), dyspnea, convulsions, encephalopathy, diffuse coagulopathy (disseminated intravascular coagulopathy), hypovolemic shock, and eventually death.[6][7][3]
  • In contrast to early leucopenia, the late course of the disease is often characterized by prolonged prothrombin time (PT) and partial thromboplastin time (PTT), neutrophilia with left shift and atypical lymphocytes, thrombocytopenia, elevated liver enzymes, hyperproteinemia, and proteinuria.[2][3]
  • Patients typically experience rapid clinical deterioration and perish within 6 to 16 days following the onset of symptoms.

Complications

Acute Complications of Advanced Disease

Ebola hemorrhagic fever usually leads to death by multiorgan failure and systemic complications. Infectious (overwhelming sepsis) and hemorrhagic (visceral bleeding and disseminated intravascular coagulopathy) complications are the most significant life-threatening causes of death associated with Ebola virus disease.[8] Generally, the following complications have been reported in patients with advanced Ebola virus disease[9]:

ENT

Cardiovascular system

Respiratory system

Gastrointestinal system

Genitourinary system

Neurological system

Late Complications Among Survivors

Survivors of Ebola hemoarrhagic fever may present with late complications of the disease that are not related to the acute illness. However, the majority of these symptoms seem to resolve by 1-2 years.[10] The most common long-term complication of Ebola virus among survivors is arthralgias of the large joints that are not accompanied by physical exam findings. Other unexplained reported complications that have occurred between 2 weeks to 2 months[9], at 6-months, and 21-month follow-up of the acute Ebola infection are listed below[10]:

Constitutional signs and symptoms

ENT

Ocular disease

Musculoskeletal system

  • Migratory arthralgias. Notably, arthralgias are the most common non-acute complication of Ebola virus. Arthralgias usually involve the large joints (knees, back, hips). Joint pain may be symmetric and is typically worse in the morning and following exertion. Arthralgias are typically not accompanied by signs on physical exam.
  • Myalgias

Cardiovascular system

Gastrointestinal system

Genitourinary system

Neuropsychiatric system

Prognosis

  • Zaire Ebola virus species: case-fatality rate of 60 - 90%
  • Sudan Ebola virus species: case-fatality rate 40 - 60%
  • Bundibugyo Ebola virus species: case-fatality rate 25%
  • Côte d’Ivoire Ebola virus: case-fatality rate 0% (only 1 case reported)
  • Reston Ebola virus: case-fatality rate 0% (Reston virus seems to be relatively harmless to humans)

References

  1. ↑ 1.0 1.1 Ndambi R, Akamituna P, Bonnet MJ, Tukadila AM, Muyembe-Tamfum JJ, Colebunders R (1999). "Epidemiologic and clinical aspects of the Ebola virus epidemic in Mosango, Democratic Republic of the Congo, 1995". J Infect Dis. 179 Suppl 1: S8–10. doi:10.1086/514297. PMID 9988156.
  2. ↑ 2.0 2.1 Ksiazek TG, West CP, Rollin PE, Jahrling PB, Peters CJ (1999). "ELISA for the detection of antibodies to Ebola viruses". J Infect Dis. 179 Suppl 1: S192–8. doi:10.1086/514313. PMID 9988184.
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 Feldmann H, Geisbert TW (2011). "Ebola haemorrhagic fever". Lancet. 377 (9768): 849–62. doi:10.1016/S0140-6736(10)60667-8. PMC 3406178. PMID 21084112.
  4. ↑ 4.0 4.1 4.2 Muyembe-Tamfum JJ, Mulangu S, Masumu J, Kayembe JM, Kemp A, Paweska JT (2012). "Ebola virus outbreaks in Africa: past and present". Onderstepoort J Vet Res. 79 (2): 451. doi:10.4102/ojvr.v79i2.451. PMID 23327370.
  5. ↑ Casillas AM, Nyamathi AM, Sosa A, Wilder CL, Sands H (2003). "A current review of Ebola virus: pathogenesis, clinical presentation, and diagnostic assessment". Biol Res Nurs. 4 (4): 268–75. PMID 12698919.
  6. ↑ Peters CJ, LeDuc JW (1999). "An introduction to Ebola: the virus and the disease". J Infect Dis. 179 Suppl 1: ix–xvi. doi:10.1086/514322. PMID 9988154.
  7. ↑ Feldmann H, Geisbert T, Kawaoka Y (2007). "Filoviruses: recent advances and future challenges". J Infect Dis. 196 Suppl 2: S129–30. doi:10.1086/520550. PMID 17940939.
  8. ↑ Parkes-Ratanshi R, Ssekabira U, Crozier I (2014). "Ebola in West Africa: be aware and prepare". Intensive Care Med. 40 (11): 1742–5. doi:10.1007/s00134-014-3497-z. PMID 25253023.
  9. ↑ 9.0 9.1 Bwaka MA, Bonnet MJ, Calain P, Colebunders R, De Roo A, Guimard Y; et al. (1999). "Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo: clinical observations in 103 patients". J Infect Dis. 179 Suppl 1: S1–7. doi:10.1086/514308. PMID 9988155.
  10. ↑ 10.0 10.1 Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D; et al. (1999). "Clinical, virologic, and immunologic follow-up of convalescent Ebola hemorrhagic fever patients and their household contacts, Kikwit, Democratic Republic of the Congo. Commission de Lutte contre les Epidémies à Kikwit". J Infect Dis. 179 Suppl 1: S28–35. doi:10.1086/514318. PMID 9988162.
  11. ↑ Sureau PH (1989). "Firsthand clinical observations of hemorrhagic manifestations in Ebola hemorrhagic fever in Zaire". Rev Infect Dis. 11 Suppl 4: S790–3. PMID 2749110.

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