Emergence of Marburg virus: a global perspective on fatal outbreaks and clinical challenges

Abstract

The Marburg virus (MV), identified in 1967, has caused deadly outbreaks worldwide, the mortality rate of Marburg virus disease (MVD) varies depending on the outbreak and virus strain, but the average case fatality rate is around 50%. However, case fatality rates have varied from 24 to 88% in past outbreaks depending on virus strain and case management. Designated a priority pathogen by the National Institute of Allergy and Infectious Diseases (NIAID), MV induces hemorrhagic fever, organ failure, and coagulation issues in both humans and non-human primates. This review presents an extensive exploration of MVD outbreak evolution, virus structure, and genome, as well as the sources and transmission routes of MV, including human-to-human spread and involvement of natural hosts such as the Egyptian fruit bat (Rousettus aegyptiacus) and other Chiroptera species. The disease progression involves early viral replication impacting immune cells like monocytes, macrophages, and dendritic cells, followed by damage to the spleen, liver, and secondary lymphoid organs. Subsequent spread occurs to hepatocytes, endothelial cells, fibroblasts, and epithelial cells. MV can evade host immune response by inhibiting interferon type I (IFN-1) synthesis. This comprehensive investigation aims to enhance understanding of pathophysiology, cellular tropism, and injury sites in the host, aiding insights into MVD causes. Clinical data and treatments are discussed, albeit current methods to halt MVD outbreaks remain elusive. By elucidating MV infection's history and mechanisms, this review seeks to advance MV disease treatment, drug development, and vaccine creation. The World Health Organization (WHO) considers MV a high-concern filovirus causing severe and fatal hemorrhagic fever, with a death rate ranging from 24 to 88%. The virus often spreads through contact with infected individuals, originating from animals. Visitors to bat habitats like caves or mines face higher risk. We tailored this search strategy for four databases: Scopus, Web of Science, Google Scholar, and PubMed. we primarily utilized search terms such as "Marburg virus," "Epidemiology," "Vaccine," "Outbreak," and "Transmission." To enhance comprehension of the virus and associated disease, this summary offers a comprehensive overview of MV outbreaks, pathophysiology, and management strategies. Continued research and learning hold promise for preventing and controlling future MVD outbreaks. GRAPHICAL ABSTRACT.

Keywords: Marburg virus; epidemic; filovirus; pathogenesis; treatment; vaccine.

GRAPHICAL ABSTRACT

Figure 1

The structure of the Marburg virus and the organization of its genome are depicted in the figure. The upper portion of the figure shows the structure of the virus and identifies the structural proteins. The genomic organization of the seven-gene Marburg virus strain is depicted in the lower section of the figure, which has been crudely scaled. Light blue boxes indicate non-coding regions, whereas colored boxes depict the coding sections of genes. Except for the overlap between VP24 and VP30, which is depicted as a black triangle, the genes are separated by intergenic regions, as shown by the black arrows. At the ends, the 3′ and 5′ trailer sequences are also displayed. Bio render software was used to create this figure (Abir et al., 2022).

Figure 2

The image shows the distribution of confirmed Marburg virus disease (MVD) cases and associated fatalities. The image illustrates that the MVD outbreak in Tanzania was confined to a distinct region, with reported cases concentrated in the Kigoma region. Additionally, the image underscores the ongoing MVD outbreak in Equatorial Guinea, characterized by a broader geographical spread of cases. Moreover, the image also denotes further instances of MVD outbreaks across different African regions (Abir et al., 2022).

Figure 3

African fruit bats serve as reservoirs for the Marburg virus, which is conveyed by direct contact, sexual contact, or biting. Humans and non-human primates can contract the virus through viral-contaminated fruit consumption or direct contact with the reservoir hosts. Disease transmission can also occur through direct contact between NHPs and humans, or from NHPs to humans through bushmeat consumption. The image was created using Bio render software.

Figure 4

The pathogenesis of Marburg virus (MV) hemorrhagic fever in humans involves a complex sequence of interactions with various cell types. MV predominantly targets dendritic cells, monocytes, liver parenchymal cells, adrenocortical cells, and diverse lymphoid tissues. Dendritic cell infection results in compromised T lymphocyte stimulation, inducing lymphocyte apoptosis and subsequent immune suppression. This state amplifies cytokines/chemokines levels, culminating in shock and multiorgan damage. T lymphocytes and endothelial cells continue to suffer damage as a result of macrophage or monocyte infection, which sets off an unchecked cascade of cytokines and chemokines. Hemorrhaging is facilitated by endothelial cell infection, which increases blood vessel permeability and causes disseminated intravascular coagulopathy (DIC). Systemic replication may arise from endothelial cell infection. Parenchymal cell infection within the liver diminishes coagulation factors, potentially leading to later hemorrhage events. Infection of adrenocortical cells within the adrenal gland results in metabolic disturbances and dysregulated blood pressure, which can ultimately culminate in hemorrhage. Lymphoid tissue infections, especially those that affect the lymph nodes and spleen, cause tissue necrosis and impair adaptive immunity. In the later stages of the illness, shock and harm to the lymphoid organs can appear.