Ebola natural history

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

Overview

Ebola infection rapidly progresses to death in the absence of supportive care. Ebola infection can be complicated by multiorgan failure and shock. Mortality rates, depending on the viral strain, can range between 25% - 90%.[1]

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".[2] 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.[3][4]

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.[5]
  • 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.[6]

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.[2][5]
  • Patients often report significant improvement in clinical symptoms with adequate food intake and mobility.[5]
  • 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, convlusions, encephalopathy, diffuse coagulopathy (disseminated intravascular coagulopathy), hypovolemic shock, and eventually death.[7][8][4]
  • 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.[3][4]
  • Patients typically experience rapid clinical deterioration and perish within 6 to 16 days following the onset of symptoms.

Complications

Complications of Advanced Disease

Ebola hemorrhagic fever usually leads to death by multiorgan failure and systemic complications. Complications that can develop in patients with advanced disease as a result of Ebola virus are[9]:

ENT

Cardiovascular system

Respiratory system

Gastrointestinal system

Genitourinary system

Neurological system

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

  • Persistent weight loss
  • Extreme fatigue
  • Anorexia
  • Fever
  • Headache

ENT

  • Hearing loss
  • Tinnitus
  • Suppurative parotitis
  • Gingival bleeding

Ocular disease

  • Conjunctivitis
  • Conjunctival bleeding
  • Vision loss
  • Uveitis

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 are typically worse in the morning and following exertion. Arthralgias are typically not accompanied by signs on physical exam.
  • Myalgias

Cardiovascular system

  • Pericarditis
  • Petechiae

Gastrointestinal system

  • Abdominal pain
  • Dysphagia
  • Hiccups
  • Melena
  • Hematemesis

Genitourinary

  • Unilateral orchitis
  • Amenorrhea

Neurological system

  • Myelitis
  • Psychosis

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)

References

  1. "CDC Ebola Hemorrhagic Fever Information Packet" (PDF). April 2010.
  2. 2.0 2.1 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.
  3. 3.0 3.1 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.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 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.
  5. 5.0 5.1 5.2 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.
  6. 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.
  7. 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.
  8. 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.
  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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