Filoviruses in bats: current knowledge and future directions

Abstract

Filoviruses, including Ebolavirus and Marburgvirus, pose significant threats to public health and species conservation by causing hemorrhagic fever outbreaks with high mortality rates. Since the first outbreak in 1967, their origins, natural history, and ecology remained elusive until recent studies linked them through molecular, serological, and virological studies to bats. We review the ecology, epidemiology, and natural history of these systems, drawing on examples from other bat-borne zoonoses, and highlight key areas for future research. We compare and contrast results from ecological and virological studies of bats and filoviruses with those of other systems. We also highlight how advanced methods, such as more recent serological assays, can be interlinked with flexible statistical methods and experimental studies to inform the field studies necessary to understand filovirus persistence in wildlife populations and cross-species transmission leading to outbreaks. We highlight the need for a more unified, global surveillance strategy for filoviruses in wildlife, and advocate for more integrated, multi-disciplinary approaches to understand dynamics in bat populations to ultimately mitigate or prevent potentially devastating disease outbreaks.

Figure 1

(A) The multiple transmission pathways are shown for Ebolavirus genera viruses. The role of vectors is unlikely, but not known (dashed line). Those pathways with epidemiological uncertainty are shown with question marks. Potential reservoir dynamics are shown in blue, spillover epidemics in small mammals (Africa), pigs (Reston ebolavirus only), duikers (Africa), primates and humans shown in red and ongoing human transmission in orange; (B) The multiple transmission pathways are shown for Marburgvirus genera viruses. The role of vectors is unlikely, but not known (dashed line). Those with epidemiological uncertainty are shown with question marks. Potential reservoir dynamics are shown in blue, spillover epidemics in primates and humans shown in red and ongoing human transmission in orange.

Figure 2

Differing antibody prevalence (as a proportion) from cross-sectional studies of two bat species from Ghana, West Africa. Epomophorus gambianus (left, Gambian epauletted fruit bat) roosts in low density, is non-migratory and has a high seroprevalence of anti-Ebolavirus antibodies. Eidolon helvum (right, Straw-colored fruit bat) roosts in high density, is migratory and has a low seroprevalence of anti-Ebolavirus antibodies, but high seroprevalence of antibodies against other RNA viruses. The viruses are: Lagos bat virus (LBV), Hendra virus (HeV), Nipah virus (NiV), and Ebolavirus (Ebola). Results are adapted from [75,76,82].

Figure 3

Geographic range for potential bat host species for (A) Marburgvirus marburgvirus; (B) Reston ebolavirus; (C) Lloviu virus; and (D) Zaire ebolavirus.

Figure 4

Methodology for determining potentially positive (i.e., cut-off values) for bat individuals using serological data. This figure highlights some of the challenges in interpreting filovirus serology (cut-off values) in bats, and why these data should be examined carefully. Distribution of Optical Density (OD) values from ELISA assay using 1:1 mixture of recombinant nucleoproteins for Reston + Zaire (R+Z) ebolavirus in Rousettus leschenautlii fruit bats. Data from [63], using methodology adapted from [77].Cut-off values were determined to be >0.454 for the R+Z ELISA using a maximum likelihood estimator, gamma distribution, and 95% risk of error.Pourrut et al. 2009 used an exponential distribution, but the data here are better fitted to a gamma distribution. This approach is less arbitrary than the standard approach of using a value 3× the OD value of negative control, as it uses the distribution of the data itself and a statistical framework to identify potential positive cut-off values. Grey bars = OD values from individual bats for the R+Z ELISA (without positive or negative controls); red line = gamma distribution; blue = 95% confidence of cutoff values; green = 99% confidence. After initial screening, 15 (11%) of 141 R. leschenaultii, 6 (8%) of 75 Cynopterus spp., and 4 (7%) of 56 Megaderma lyra bats were potentially positive at the 95% confidence level. However, only 5 (3.5%) of 141 (95% CI 1.5%–8.0%) of R. leschenaultii bats were reported as seropositive after additional testing by ELISAs and Western Blot [63].