Ebola viruses — Questions

The current emergency is caused by Bundibugyo virus, for which no vaccine or specific therapeutic is licensed; the licensed countermeasures protect only against Zaire ebolavirus.

Sudan virus also has no licensed vaccine but is not the cause here, Reston is non-pathogenic in humans, and Taï Forest has caused only a single case.

The licensed antibodies Inmazeb and Ebanga target the Zaire glycoprotein, so for Sudan and Bundibugyo virus disease there is no licensed specific treatment, and broadly reactive agents such as the monoclonal MBP134 and the antiviral remdesivir are being evaluated in trials.

Ervebo prevents rather than treats infection, and ribavirin has no established role in filovirus disease.

Blood RT-PCR can be negative in the first days of symptoms because viraemia may be below the detection threshold, so a symptomatic contact who tests negative early should be retested after about 72 hours before Ebola is excluded.

Discharge, IgG serology, routine-laboratory culture and antigen testing alone are all inadequate for exclusion at that stage.

Inside the acidifying endosome, cathepsins B and L trim the glycoprotein, removing the glycan cap and mucin-like domain to expose the site that binds the intracellular receptor NPC1, which then triggers fusion.

Entry does not depend on surface furin cleavage, neuraminidase, plasma-membrane fusion, or a single specific surface receptor; attachment is promiscuous.

Necrosis of the adrenal cortex impairs the cortisol-dependent control of blood pressure, compounding the hypovolaemic and distributive shock of severe disease.

The thyroid, pituitary, pancreas and spleen are not the principal contributors to the shock.

At a run of seven uridines the polymerase stutters and inserts an extra nucleotide, shifting the reading frame so one gene yields both the structural spike GP1,2 and a secreted decoy glycoprotein, sGP. Marburg virus lacks this editing and makes no sGP.

The mechanism is cotranscriptional editing, not splicing, stop-codon read-through, a second gene, or cleavage by the receptor NPC1.

Ebola disease is a Category 1 Notifiable Medical Condition, requiring immediate reporting on clinical suspicion, before laboratory confirmation, so that isolation and the outbreak response can begin without delay.

Waiting for confirmation, reporting weekly or monthly, or reporting only fatal cases would all breach the immediate-notification requirement.

The 1976 Yambuku outbreak was amplified by the reuse of unsterilised needles and syringes, which spread the virus among patients and staff and gave an early lesson in health-care transmission.

Ebola virus is not airborne and is not spread by mosquitoes or by water; contact with an animal source seeds the index case but does not sustain hospital amplification.

The bleeding tendency reflects disseminated intravascular coagulation triggered by tissue factor released from infected macrophages, which consumes clotting factors and platelets; overt haemorrhage is a minority, late feature.

It is not caused by direct endothelial lysis, anti-platelet autoantibodies, vitamin K deficiency, or hepatic failure alone.

Filoviruses are enveloped filaments of uniform ~80 nm diameter and highly variable length, often bent into U-shapes or a figure-of-six, with a helical nucleocapsid inside; the thread-like shape gives the family its name.

They are not icosahedral, brick-shaped (poxviruses), bullet-shaped (rhabdoviruses) or compact spheres.

Aggressive replacement of fluid and electrolytes, matching the losses from vomiting and diarrhoea, is the backbone of care and reduces mortality on its own, independent of any specific drug.

Antibiotics, corticosteroids, routine transfusion and ribavirin are not the primary intervention.

The genome is a single molecule of negative-sense, non-segmented RNA of about 19 kilobases, the largest of the nonsegmented negative-strand RNA viruses, with the gene order NP, VP35, VP40, GP, VP30, VP24, L.

It is not positive-sense, segmented, DNA or ambisense; segmented and ambisense genomes belong to the arenaviruses and bunyaviruses.

VP40 is the matrix protein: it lines the envelope, organises assembly and drives budding of progeny filaments through the host ESCRT machinery, and can release particles on its own.

VP35 is the polymerase cofactor and an interferon antagonist, VP30 the transcription activator, VP24 a nucleocapsid-associated interferon antagonist, and NP the nucleoprotein.

Taï Forest virus has caused one recorded human infection, which was non-fatal, in an ethologist who autopsied a chimpanzee in Côte d’Ivoire in 1994.

Sudan and Bundibugyo viruses cause severe epidemic disease, Reston is non-pathogenic in humans, and Bombali is known only from bats.

Bombali virus was identified in insectivorous bats in Sierra Leone in 2018, the first ebolavirus described from its animal host before any human infection was known.

Reston, Sudan, Zaire and Taï Forest viruses were each first recognised through disease in humans or non-human primates.

Zabdeno (Ad26.ZEBOV) followed by Mvabea (MVA-BN-Filo) is a two-dose prophylactic regimen, suited to preventive protection of at-risk groups, in contrast to the single-dose rVSV vaccine Ervebo used reactively in outbreaks.

There is no licensed inactivated, mRNA or live-attenuated whole-virus Ebola vaccine.

The admission or peak viral load is the most consistent predictor of death, with acute kidney injury and central-nervous-system involvement also marking a poor prognosis.

Age, rash, fever height and sex are far weaker predictors of outcome.

Overt haemorrhage occurs in only a minority of patients and is usually a late sign, reflecting consumptive coagulopathy and thrombocytopenia; death is driven by fluid loss, shock and multi-organ failure.

Bleeding is not universal, does not arise from a single organ, and is not due to direct endothelial lysis.

Patients are not infectious during the incubation period, and infectiousness rises with the viral load, so the sickest patients and freshly deceased bodies are the most dangerous sources.

Asymptomatic carriage does not drive transmission, infectivity is not constant, and the corpse remains highly infectious after death, which is why safe burial matters.

The basic reproduction number is modest, around 1.5 to 2, and transmission requires direct contact with infected fluids, so interrupting those contacts through isolation, safe burial and contact tracing halts spread.

Patients are not infectious before symptoms, herd immunity is not reached quickly, environmental stability is not the decisive factor, and most infections are symptomatic.