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| Name | Class |
|---|---|
| Centre Hospitalier Universitaire le Dantec (CHUD), Dakar, Senegal | UNKNOWN |
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This is a clinical trial in which healthy volunteers will be administered two experimental Ebola vaccines: ChAd3-EBO Z and MVA-EBO Z. Two groups of volunteers will be vaccinated with both vaccines one after the other in a prime/boost regimen.
All ChAd3-EBO Z doses are 2.5 x 10^10 - 3.7 x 10^10 vp and all MVA-EBO Z doses are 1.0 x 10^8 pfu.
All volunteers will receive a ChAd3-EBO Z priming vaccine and a MVA-EBO Z boosting vaccine 7 days later.
The site of administration of the MVA-EBO Z vaccine differs between the two groups:
Group 1 will receive the MVA-EBO Z vaccine in the same arm as the ChAd3-EBO Z vaccine.
Group 2 will receive the MVA-EBO Z vaccine in the opposite arm from the ChAd3-EBO Z vaccine.
The study will assess the safety of the vaccinations, and the immune responses to vaccination. Immune responses are measured by tests on blood samples.
The ChAd3-EBO Z and MVA-EBO Z vaccines are called viral vectored vaccines. They are made from viruses which are modified so that they cannot multiply. The viruses have extra DNA in them so that after injection, the body makes Ebola proteins (but Ebola does not develop), so that the immune system builds a response to Ebola without having been infected by it.
Healthy volunteers will be recruited in Dakar, Senegal. The study will be funded by GSK.
The CHUD study team will hold sensitisation meetings, in specific areas targeting specific populations, to explain the study to potential volunteers. During these meetings the investigators will explain the following: the need for a vaccine (including a simple picture of the burden of the Ebola disease and how it affects the community); the current status of vaccine development (including the fact that this is likely to be a prolonged process that probably will not influence the course of the current epidemic); the study screening and informed consent procedure; risks of vaccination and the unproven benefits of this vaccination. It will be stressed that this is an experimental vaccine and there is no current evidence that it will provide protection, and that it will therefore still be necessary to take preventive measures and to seek treatment if ill for any reason after vaccination.
After these sensitisation meetings, the CT team will actively identify. The study will be further explained to eligible participants on individual basis. Potential volunteers will be invited to the CHUD CT site for further discussion. Potential volunteers will be informed that they are free to withdraw from the CT at any time without giving any reason. Individuals who feel that the trial is appropriate for them will be invited to attend a formal screening visit.
Detailed information about the study will be provided in a Participant Information Sheet (PIS) at least 24 hours prior to the consent being undertaken. The informed consent process will start before the screening visit. The volunteer will be given the opportunity to ask about details of the trial, and will then have time to consider whether or not to participate. The investigators will ensure that the volunteers are briefed on the contents of the PIS in the language they understand. The investigators will also ensure that all volunteers fully understand the risks. Any volunteer who appears to have less than complete understanding will not be enrolled.
All volunteers will sign and date the informed consent form before any study specific procedures (including screening visit) are performed. If the volunteer is illiterate, s/he will sign the informed consent form; in the latter case a literate adult impartial witness will be present throughout the whole consenting process, write subject's name and date of signature and will sign and date the consent form. Volunteers will sign and date two copies of the consent form, one for them to take away and keep, and one to be stored in the subject's medical records.
Vaccinations in Group 1 can commence 7 days after vaccination after interim safety review of the first 5 volunteers receiving the same dose in the UK CT. The first 5 volunteers will be vaccinated in a staggered fashion.
The first volunteer to receive the ChAd63-EBO Z vaccine dose in Group 1 will be vaccinated alone and we will wait 24 hours before vaccinating subsequent volunteers in this group. Two further Group 1 volunteers will be vaccinated 24 hours after the first, and then at least another 24 hours gap will pass before vaccinating further subjects receiving the ChAd63-EBO Z vaccine in Groups 1 & 2.
The same staggered vaccine administration procedure will be adopted for vaccinations with the MVA-EBO Z vaccine. A total of 20 volunteers will be enrolled in this group.
In Group 2, vaccination can commence after 5 volunteers in Groups 1 have received the ChAd63-EBO Z vaccine dose. The same staggered vaccine administration procedure as for Group 1 will be adopted for vaccinations with the MVA-EBO Z vaccine. A total of 20 volunteers will be enrolled in this group.
Volunteers will be visited daily at home by a study field worker or nurse to record adverse events (solicited and unsolicited for six consecutive days after vaccination). Additional scheduled visits at the CHUD clinic will be at day 7, 14, 28, 35, 56, 90, 180 post-first vaccination during which interim history will be collected, physical examination and blood tests performed at the time-points indicated in the schedule of attendances. Blood will also be taken for exploratory immunology analysis.
All volunteers will be followed up for 6 months beginning from the day of the first vaccination.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group 1 | Active Comparator | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. Both vaccinations are administered in the same arm. |
|
| Group 2 | Active Comparator | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. The MVA-EBO Z is administered in the opposite arm to the ChAd3-EBO Z. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ChAd3-EBO Z | Biological | This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety and Tolerability of Administration of ChAd3-EBO Z and MVA-EBO Z 7 Days Later. This Will be Done by Recording the Number of Participants Who Experience Adverse Events and the Severity of Any Adverse Events. | The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed for both groups:
| 26 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| To Assess the Immunogenicity Generated by Heterologous Prime-boost Immunisation With Monovalent ChAd3-EBO Z (2.5 x 1010 vp - 3.7 x 1010vp) and MVA-EBO Z (1.0 x 108 Pfu) in Healthy Senegalese Volunteers Aged 18-50 Years | Ebolavirus specific immunogenicity will be assessed by a variety of immunological assays. The primary immunogenicity outcome measures are ELISA and neutralization antigen-specific assays for antibody responses and intracellular cytokine staining (ICS) assay for T cell responses. Exploratory outcome measures will include ex-vivo ELISPOT, plasma blast assays and flow cytometry performed with research samples collected at different study timepoints as well as other immunogenicity assays throughout the study. An evaluation of genetic factors associated with immune responses may be performed as exploratory evaluation. Vaccine-induced mRNA expression profiles during 1 week after vaccination may also be performed as an exploratory evaluation. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Souleymane Mboup, MD; PhD | Centre Hospitalier Universitaire le Dantec (CHUD), Dakar, Senegal | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre Hospitalier Universitaire le Dantec | Dakar | BP 7325 | Senegal |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 24964881 | Background | Dixon MG, Schafer IJ; Centers for Disease Control and Prevention (CDC). Ebola viral disease outbreak--West Africa, 2014. MMWR Morb Mortal Wkly Rep. 2014 Jun 27;63(25):548-51. | |
| 23001720 | Background | Kuhn JH, Bao Y, Bavari S, Becker S, Bradfute S, Brister JR, Bukreyev AA, Chandran K, Davey RA, Dolnik O, Dye JM, Enterlein S, Hensley LE, Honko AN, Jahrling PB, Johnson KM, Kobinger G, Leroy EM, Lever MS, Muhlberger E, Netesov SV, Olinger GG, Palacios G, Patterson JL, Paweska JT, Pitt L, Radoshitzky SR, Saphire EO, Smither SJ, Swanepoel R, Towner JS, van der Groen G, Volchkov VE, Wahl-Jensen V, Warren TK, Weidmann M, Nichol ST. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae. Arch Virol. 2013 Jan;158(1):301-11. doi: 10.1007/s00705-012-1454-0. Epub 2012 Sep 23. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. Both vaccinations are administered in the same arm. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
| FG001 | Group 2 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. The MVA-EBO Z is administered in the opposite arm to the ChAd3-EBO Z. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group 1 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. Both vaccinations are administered in the same arm. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Safety and Tolerability of Administration of ChAd3-EBO Z and MVA-EBO Z 7 Days Later. This Will be Done by Recording the Number of Participants Who Experience Adverse Events and the Severity of Any Adverse Events. | The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events. The following parameters will be assessed for both groups:
| Posted | Number | participants | 26 weeks |
|
Solicited adverse events will be recorded daily for 7 days post-vaccination Unsolicited AEs of all severities will be recorded from receipt of vaccination through 28 days post-vaccination. After study Day 28, only SAEs or new chronic medical conditions that require ongoing medical management will be recorded through to the last study visit.
There was no serious adverse event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group 1 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. Both vaccinations are administered in the same arm. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| headache | Vascular disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Adrian V Hill, DPhil FRCP | University of Oxford | vaccinetrials@ndm.ox.ac.uk |
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| ID | Term |
|---|---|
| D019142 | Hemorrhagic Fever, Ebola |
| ID | Term |
|---|---|
| D006482 | Hemorrhagic Fevers, Viral |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D007239 | Infections |
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| MVA-EBO Z | Biological | This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
|
| 26 weeks |
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| 15526058 | Background | Moorthy VS, Imoukhuede EB, Milligan P, Bojang K, Keating S, Kaye P, Pinder M, Gilbert SC, Walraven G, Greenwood BM, Hill AS. A randomised, double-blind, controlled vaccine efficacy trial of DNA/MVA ME-TRAP against malaria infection in Gambian adults. PLoS Med. 2004 Nov;1(2):e33. doi: 10.1371/journal.pmed.0010033. Epub 2004 Oct 26. |
| 16488059 | Background | Webster DP, Dunachie S, McConkey S, Poulton I, Moore AC, Walther M, Laidlaw SM, Peto T, Skinner MA, Gilbert SC, Hill AV. Safety of recombinant fowlpox strain FP9 and modified vaccinia virus Ankara vaccines against liver-stage P. falciparum malaria in non-immune volunteers. Vaccine. 2006 Apr 5;24(15):3026-34. doi: 10.1016/j.vaccine.2005.10.058. Epub 2006 Feb 2. |
| 22363582 | Background | Sheehy SH, Duncan CJ, Elias SC, Biswas S, Collins KA, O'Hara GA, Halstead FD, Ewer KJ, Mahungu T, Spencer AJ, Miura K, Poulton ID, Dicks MD, Edwards NJ, Berrie E, Moyle S, Colloca S, Cortese R, Gantlett K, Long CA, Lawrie AM, Gilbert SC, Doherty T, Nicosia A, Hill AV, Draper SJ. Phase Ia clinical evaluation of the safety and immunogenicity of the Plasmodium falciparum blood-stage antigen AMA1 in ChAd63 and MVA vaccine vectors. PLoS One. 2012;7(2):e31208. doi: 10.1371/journal.pone.0031208. Epub 2012 Feb 21. |
| 21862998 | Background | Sheehy SH, Duncan CJ, Elias SC, Collins KA, Ewer KJ, Spencer AJ, Williams AR, Halstead FD, Moretz SE, Miura K, Epp C, Dicks MD, Poulton ID, Lawrie AM, Berrie E, Moyle S, Long CA, Colloca S, Cortese R, Gilbert SC, Nicosia A, Hill AV, Draper SJ. Phase Ia clinical evaluation of the Plasmodium falciparum blood-stage antigen MSP1 in ChAd63 and MVA vaccine vectors. Mol Ther. 2011 Dec;19(12):2269-76. doi: 10.1038/mt.2011.176. Epub 2011 Aug 23. |
| 23526949 | Background | Ogwang C, Afolabi M, Kimani D, Jagne YJ, Sheehy SH, Bliss CM, Duncan CJ, Collins KA, Garcia Knight MA, Kimani E, Anagnostou NA, Berrie E, Moyle S, Gilbert SC, Spencer AJ, Soipei P, Mueller J, Okebe J, Colloca S, Cortese R, Viebig NK, Roberts R, Gantlett K, Lawrie AM, Nicosia A, Imoukhuede EB, Bejon P, Urban BC, Flanagan KL, Ewer KJ, Chilengi R, Hill AV, Bojang K. Safety and immunogenicity of heterologous prime-boost immunisation with Plasmodium falciparum malaria candidate vaccines, ChAd63 ME-TRAP and MVA ME-TRAP, in healthy Gambian and Kenyan adults. PLoS One. 2013;8(3):e57726. doi: 10.1371/journal.pone.0057726. Epub 2013 Mar 19. |
| 23089736 | Background | Sheehy SH, Duncan CJ, Elias SC, Choudhary P, Biswas S, Halstead FD, Collins KA, Edwards NJ, Douglas AD, Anagnostou NA, Ewer KJ, Havelock T, Mahungu T, Bliss CM, Miura K, Poulton ID, Lillie PJ, Antrobus RD, Berrie E, Moyle S, Gantlett K, Colloca S, Cortese R, Long CA, Sinden RE, Gilbert SC, Lawrie AM, Doherty T, Faust SN, Nicosia A, Hill AV, Draper SJ. ChAd63-MVA-vectored blood-stage malaria vaccines targeting MSP1 and AMA1: assessment of efficacy against mosquito bite challenge in humans. Mol Ther. 2012 Dec;20(12):2355-68. doi: 10.1038/mt.2012.223. Epub 2012 Oct 23. |
| 24284865 | Background | Ewer KJ, O'Hara GA, Duncan CJ, Collins KA, Sheehy SH, Reyes-Sandoval A, Goodman AL, Edwards NJ, Elias SC, Halstead FD, Longley RJ, Rowland R, Poulton ID, Draper SJ, Blagborough AM, Berrie E, Moyle S, Williams N, Siani L, Folgori A, Colloca S, Sinden RE, Lawrie AM, Cortese R, Gilbert SC, Nicosia A, Hill AV. Protective CD8+ T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation. Nat Commun. 2013;4:2836. doi: 10.1038/ncomms3836. |
| 21857654 | Background | Sullivan NJ, Hensley L, Asiedu C, Geisbert TW, Stanley D, Johnson J, Honko A, Olinger G, Bailey M, Geisbert JB, Reimann KA, Bao S, Rao S, Roederer M, Jahrling PB, Koup RA, Nabel GJ. CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates. Nat Med. 2011 Aug 21;17(9):1128-31. doi: 10.1038/nm.2447. |
| 16230147 | Background | Malaeb BS, Gardner TA, Margulis V, Yang L, Gillenwater JY, Chung LW, Macik G, Koeneman KS. Elevated activated partial thromboplastin time during administration of first-generation adenoviral vectors for gene therapy for prostate cancer: identification of lupus anticoagulants. Urology. 2005 Oct;66(4):830-4. doi: 10.1016/j.urology.2005.04.041. |
| 30407513 | Derived | Venkatraman N, Ndiaye BP, Bowyer G, Wade D, Sridhar S, Wright D, Powlson J, Ndiaye I, Dieye S, Thompson C, Bakhoum M, Morter R, Capone S, Del Sorbo M, Jamieson S, Rampling T, Datoo M, Roberts R, Poulton I, Griffiths O, Ballou WR, Roman F, Lewis DJM, Lawrie A, Imoukhuede E, Gilbert SC, Dieye TN, Ewer KJ, Mboup S, Hill AVS. Safety and Immunogenicity of a Heterologous Prime-Boost Ebola Virus Vaccine Regimen in Healthy Adults in the United Kingdom and Senegal. J Infect Dis. 2019 Apr 8;219(8):1187-1197. doi: 10.1093/infdis/jiy639. |
| BG001 | Group 2 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. The MVA-EBO Z is administered in the opposite arm to the ChAd3-EBO Z. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Group 2 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. The MVA-EBO Z is administered in the opposite arm to the ChAd3-EBO Z. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein |
|
|
| Secondary | To Assess the Immunogenicity Generated by Heterologous Prime-boost Immunisation With Monovalent ChAd3-EBO Z (2.5 x 1010 vp - 3.7 x 1010vp) and MVA-EBO Z (1.0 x 108 Pfu) in Healthy Senegalese Volunteers Aged 18-50 Years | Ebolavirus specific immunogenicity will be assessed by a variety of immunological assays. The primary immunogenicity outcome measures are ELISA and neutralization antigen-specific assays for antibody responses and intracellular cytokine staining (ICS) assay for T cell responses. Exploratory outcome measures will include ex-vivo ELISPOT, plasma blast assays and flow cytometry performed with research samples collected at different study timepoints as well as other immunogenicity assays throughout the study. An evaluation of genetic factors associated with immune responses may be performed as exploratory evaluation. Vaccine-induced mRNA expression profiles during 1 week after vaccination may also be performed as an exploratory evaluation. | Posted | Number | participants | 26 weeks |
|
|
|
| 0 |
| 20 |
| 0 |
| 20 |
| 17 |
| 20 |
| EG001 | Group 2 | ChAd3-EBO Z (2.5 - 3.7 x 10^10 vp) and MVA-EBO Z (1.0 x 10^8 pfu) 7 days later. The MVA-EBO Z is administered in the opposite arm to the ChAd3-EBO Z. ChAd3-EBO Z: This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein MVA-EBO Z: This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein | 0 | 20 | 0 | 20 | 18 | 20 |
| anaemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| warmth | General disorders | Systematic Assessment |
|
| itching | General disorders | Systematic Assessment |
|
| redness | General disorders | Systematic Assessment |
|
| myalgia | Nervous system disorders | Systematic Assessment |
|
| fatigue | General disorders | Systematic Assessment |
|
| nausea | General disorders | Systematic Assessment |
|
| malaise | General disorders | Systematic Assessment |
|
| Hyperbilirubinemia | Blood and lymphatic system disorders | Systematic Assessment |
|
| neutropenia | Immune system disorders | Systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | Systematic Assessment |
|
| Feverish | General disorders | Systematic Assessment |
|
| Dysmenorrhea | General disorders | Systematic Assessment |
|
| feverish/chills | General disorders | Systematic Assessment |
|
| tooth pain | General disorders | Systematic Assessment |
|
| unwell | General disorders | Systematic Assessment |
|
| diarrhoea | General disorders | Systematic Assessment |
|
Not provided
Not provided
Not provided
| D018702 |
| Filoviridae Infections |
| D018701 | Mononegavirales Infections |