title: The face of Ebola: changing frequency of haemorrhage in the West African compared with Eastern-Central African outbreaks.
abstract: BACKGROUND
  The West-African (WA) Zaire Ebolavirus disease (EVD) outbreak was characterized by an exceptionally high number of cases and deaths as compared with the Eastern-Central African (ECA) outbreaks. Despite the Zaire Ebolavirus being the most lethal for humans, case-fatality rate, close to 80 % in ECA outbreaks, almost halved to 47 % in Guinea-Liberia-Sierra Leone (WA). Such an improvement was due to the remarkable implementation of international humanitarian aids. Some studies also suggested that the long human-to-human transmission cycle occurred in WA, gave rise to human adaptation and consequent immune escape. Haemorrhage, the main feature in seriously infected EVD patients, is due to the immune system that triggers the infected endothelial cells which expose the spike-like glycoprotein (GP) of the virion on their surface. If the human adaptation hypothesis holds true, the proportion of EVD patients with haemorrhage in the WA outbreak should be lower than in the ECA outbreaks due to immune escape. Therefore, the aim of this meta-analysis was to compare the relative frequencies of three typical haemorrhagic symptoms (conjunctival -CB, nasal -NB, gingival -GB- bleedings) in the ECA and WA outbreaks.
  
  
  METHODS
  Literature searches were performed through PubMed and Scopus using generic keywords; surveys including at least ten patients reporting CB, NB, GB relative frequencies were extracted and split into ECA and WA. The meta-analytical methods chosen were based on the levels of between-study heterogeneity and publication bias. Pooled CB, NB, GB relative frequencies in ECA and WA were estimated and compared. Subgroup analysis including only studies on Zaire Ebolavirus also was performed.
  
  
  RESULTS
  Fifteen studies (10 ECA, 5 WA) were located with 4,867 (CB), 3,859 (NB), 4,278 (GB) EVD patients overall. GB pooled relative frequency was 45.3 % (95 % confidence interval -95 CI, 34.7-56.1 %) and 18.0 % (95 CI, 6.0-34.5 %), in ECA and WA; NB was 10.6 % (95 CI, 5.7-16.8 %) and 1.3 % (1.0-1.8 %); GB was 24.2 % (95 CI, 11.9-39.2 %) and 1.9 % (95 CI, 1.4-2.4 %). Subgroup analysis confirmed these results.
  
  
  CONCLUSIONS
  During the WA outbreak the relative frequency of GB decreased by two thirds, while NB and GB almost disappeared, suggesting that the Zaire Ebolavirus human adaptation hypothesis is plausible.
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. stefano.petti@uniroma1.it.
authors.forename: Stefano
authors.initials: S
authors.lastname: Petti
authors.affiliation: Department of Public Health and Infectious Diseases, Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy. giuseppe.messano@uniroma1.it.
authors.forename: Giuseppe Alessio
authors.initials: GA
authors.lastname: Messano
authors.affiliation: Ophthalmology Department, Sapienza University, Viale del Policlinico 155, 00186, Rome, Italy. enzomaria.vingolo@uniroma1.it.
authors.forename: Enzo Maria
authors.initials: EM
authors.lastname: Vingolo
authors.affiliation: Department of Biomedicine and Prevention, Tor Vergata University, Viale Oxford 81, 00133, Rome, Italy. marsella.luigi@gmail.com.
authors.forename: Luigi Tonino
authors.initials: LT
authors.lastname: Marsella
authors.affiliation: University College London, Gower Street WC1E 6BT, London, UK. crispian.scully@ucl.ac.uk.
authors.forename: Crispian
authors.initials: C
authors.lastname: Scully
mesh_terms: D044383:Black People; D016208:Databases, Factual; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000235:genetics / Q000302:isolation & purification; D006470:Hemorrhage / Q000209:etiology*; D019142:Hemorrhagic Fever, Ebola / Q000150:complications / Q000453:epidemiology* / Q000821:virology; D006801:Humans; D009154:Mutation; D012807:Sierra Leone / Q000453:epidemiology