Abstract
BACKGROUND: From 2004 to 2005, an outbreak of Marburg virus, a filovirus, in Angola led to a case-fatality rate of 90 percent. However, little information is available regarding the virulence of the Angola strain from this outbreak compared with the virulence of other strains. Therefore, we sought to assess time to selected outcomes in non-human primates (NHPs) experimentally infected with either Angola or Musoke Marburg strains. METHODS: Between 2012 and 2017, nine therapeutic trials at the US Army Medical Research Institute of Infectious Diseases were conducted in Macaca fascicularis monkeys challenged with 1 to 10,000 plaque forming units of Marburg virus administered intramuscularly. The current study population was comprised of 90 control NHPs, of which, 61 were administered Angola strain in four separate trials and 29 with Musoke strain in five trials. Clinical responses including development of rash and oral intake were collected following infection. The primary outcome of interest was time to death or euthanasia post-inoculation between strains evaluated using Cox proportional hazards regression. Secondary endpoints included time to development of a petechial rash and time to decreased appetite. RESULTS: Following Marburg virus challenge, all NHPs died and most NHPs experienced decreased food consumption (97%), and petechial rash (96%). The median time to death for Angola-infected NHPs was 8.9 days (25th, 75th percentiles: 7.9, 9.3), whereas Musoke-infected NHPs survived for a median of 10.0 days (25th, 75th percentiles: 9.0, 10.9) (Figure 1). Irrespective of strain, petechial rash was preceded by decreased food consumption by 0.7 days (SD 1.5) on average. Angola strain was associated with statistically significant earlier death (adjusted HR = 21.8; 95% CI: 8.9, 53.2), earlier development of petechiae (adjusted HR = 17.6; 95% CI: 7.0, 44.5) and earlier loss of appetite (adjusted HR = 5.8; 95% CI: 2.9,11.7). CONCLUSION: This was the first study to compare survival and clinical characteristics in NHPs between these strains. Despite sharing the similar genetic lineage, our data strongly supports increased virulence of Angola strain compared with Musoke strain. Pathophysiological mechanisms involved in increased virulence require further study. DISCLOSURES: All authors: No reported disclosures.