Clinical trial NCT02431923: Ebola Virus Disease Survivors: Clinical and Immunologic Follow-up
Official title: Partnership for Research on Ebola Virus (PREVAIL) Prevail III: Ebola Natural History Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Ebola Virus Disease
Keywords: Sequelae
Seroprevalence
Household Contacts
Natural History
Lead sponsor: National Institutes of Health Clinical Center (CC)
Sponsor class: NIH
First posted: 2015-05-01
Enrollment: 4043
Sex: ALL
Maximum age (years): 100
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Survivors of EVD, household contacts, non EVD Controls

Brief summary: Background:

- Ebola is a lethal disease. A lot is still unknown about Ebola and its long-term effects. Researchers want to learn what ill health conditions Ebola survivors have. They want to learn if Ebola survivors can infect others in their household through close contact. They also want to learn if Ebola survivors are immune from getting Ebola again. To learn these things, they want to follow people in Liberia for 5 years.

Objectives:

- To learn how Ebola affects the health of survivors and the people they live with.

Eligibility:

- People in Liberia who had Ebola in the past 2 years, who share a household with someone who had Ebola, or who got ill and went to an Ebola Treatment Unit but were sent home because they did not have Ebola.

Design:

* Participants will be screened with family illness history, physical exam, and blood tests. They may have an eye exam.
* Ebola survivors and those who went to a Treatment Unit but did not have Ebola will visit a clinic at 3, 6, and 12 months, then every 6 months for 5 years. At each visit, they will repeat the screening tests.
* Participants who live with someone who had Ebola will have only the screening visit. But they may be asked to return for follow-up visits. These visits will help researchers learn more about the differences between those who have had Ebola and those who have not.
* Participants brought to the NIH Clinical Center will have documentation of positive Ebola virus PCR and a clinical syndrome compatible with acute EVD.
* The study will last 5 years.

Detailed description: Between 1994 and the present, there have been several Ebola virus outbreaks affecting mostly countries in Central Africa. However, the 2014 West African outbreak significantly exceeds all previous outbreaks in geographic range and number of individuals affected. Ebola virus disease (EVD) is highly lethal with case fatality rates of 70-80% in the current West African outbreak. While the clinical manifestations of acute Ebola virus infection are well documented, little is known about long-term sequelae, ability to transmit Ebola, or long-term protective immunity in survivors from EVD. The purpose of this protocol is to study these questions in a cohort of EVD survivors from Liberia.

Eligibility criteria: * INCLUSION CRITERIA FOR EVD SURVIVORS

A volunteer of any age with a diagnosis of EVD within the past 2 years who is on the Ministry of Health (MOH) Registry of EVD survivors is eligible to participate.

* Willingness to participate in examinations at one of the participating health facilities
* Willingness to provide informed consent/assent

Individuals on the MOH Registry were PCR positive for EVD and treated at an Ebola Treatment Unit (ETU), Community Care Center (CCC) or holding center. Periodically, participants enrolled will be matched against the MOH Registry to verify that those enrolled are EVD survivors. If a participant enrolled is not on the registry, their antibody levels at baseline will be assessed. If antibody levels are present, the participant will continue to be followed as an EVD survivor. If antibody levels are not present, the participants will no longer be followed as an EVD survivor and may be withdrawn from the study. Participants brought to the NIH Clinical Center will have documentation of positive Ebola virus PCR and a clinical syndrome compatible with acute EVD.

EXCLUSION CRITERION FOR EVD SURVIVORS

Any condition in the judgment of the study staff that would make the volunteer unable to participate in the study.

Primary outcomes:
measure: To characterize the clinical sequelae seen in convalescent Ebola virus disease (EVD) patients.
timeFrame: Throughout
measure: Assess whether convalescent EVD patients can transmit infection to household and sexual contacts as determined by development of EVD or Ebola seroconversion in contacts
timeFrame: Throughout
Secondary outcomes:
measure: Better define the immune response in EVD survivors.
timeFrame: Throughout
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institutes of Health Clinical Center
state: Maryland
city: Kakata
country: Liberia
facility: CH Rennie Hospital
city: Monrovia
country: Liberia
facility: Duport Clinic
city: Monrovia
country: Liberia
facility: JFK Hospital
Study officials:
affiliation: National Institute of Allergy and Infectious Diseases (NIAID)
name: Michael C Sneller, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Rowe AK, Bertolli J, Khan AS, Mukunu R, Muyembe-Tamfum JJ, Bressler D, Williams AJ, Peters CJ, Rodriguez L, Feldmann H, Nichol ST, Rollin PE, Ksiazek TG. 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 Epidemies a Kikwit. J Infect Dis. 1999 Feb;179 Suppl 1:S28-35. doi: 10.1086/514318.
citation: Kibadi K, Mupapa K, Kuvula K, Massamba M, Ndaberey D, Muyembe-Tamfum JJ, Bwaka MA, De Roo A, Colebunders R. Late ophthalmologic manifestations in survivors of the 1995 Ebola virus epidemic in Kikwit, Democratic Republic of the Congo. J Infect Dis. 1999 Feb;179 Suppl 1:S13-4. doi: 10.1086/514288.
citation: Postnikova EN, Pettitt J, Van Ryn CJ, Holbrook MR, Bollinger L, Yu S, Cai Y, Liang J, Sneller MC, Jahrling PB, Hensley LE, Kuhn JH, Fallah MP, Bennett RS, Reilly C. Scalable, semi-automated fluorescence reduction neutralization assay for qualitative assessment of Ebola virus-neutralizing antibodies in human clinical samples. PLoS One. 2019 Aug 27;14(8):e0221407. doi: 10.1371/journal.pone.0221407. eCollection 2019.
citation: PREVAIL III Study Group; Sneller MC, Reilly C, Badio M, Bishop RJ, Eghrari AO, Moses SJ, Johnson KL, Gayedyu-Dennis D, Hensley LE, Higgs ES, Nath A, Tuznik K, Varughese J, Jensen KS, Dighero-Kemp B, Neaton JD, Lane HC, Fallah MP. A Longitudinal Study of Ebola Sequelae in Liberia. N Engl J Med. 2019 Mar 7;380(10):924-934. doi: 10.1056/NEJMoa1805435.
citation: Kelly JD, Weiser SD, Wilson B, Cooper JB, Glayweon M, Sneller MC, Drew C, Steward WT, Reilly C, Johnson K, Fallah MP. Ebola virus disease-related stigma among survivors declined in Liberia over an 18-month, post-outbreak period: An observational cohort study. PLoS Negl Trop Dis. 2019 Feb 27;13(2):e0007185. doi: 10.1371/journal.pntd.0007185. eCollection 2019 Feb.