What makes controlling Ebola virus challenging
The World Health Organization warns that the Ebola outbreak in the Democratic Republic of the Congo is on track to become the deadliest on record. Why is controlling the virus a major challenge? Are genome sequences published by researchers contributing to the development of treatments and vaccines? See infographics.
WHO warns that the Ebola outbreak in the Democratic Republic of the Congo (DRC) is on track to become the deadliest on record. (File) — Arunangshu Das
The Ebola outbreak in the Democratic Republic of the Congo (DRC) is on track to become the deadliest on record, warned the World Health Organization (WHO), adding that the epidemic, “at its current pace”, would “eclipse” that of the 2014-2016 occurrence, which killed at least 11,000 people.
The WHO declared the 17th outbreak of Ebola in DRC on May 17 as a public health emergency, for the first time without waiting to convene any emergency committee. But it is believed the outbreak began at least three months before it was detected. The current outbreak is primarily caused by Bundibugyo virus, a type of Ebola virus, in northeastern DRC and Uganda’s capital, Kampala.
Why is controlling the Bundibugyo virus a major challenge? Why is it difficult to precisely trace the natural reservoir of Ebola viruses? Are genome sequences published by researchers useful in developing treatments for Ebola virus infections?
DRC Ebola Outbreak: Explained
The search for Ebola’s precise natural reservoir
Mysterious deaths were first reported in Bundibugyo district in western Uganda, near the mountainous border with DRC, in November 2007. This was the 5th species of ebolavirus to be discovered involving 116 cases, including 39 deaths.
Scientific observations revealed that each member of each genus of different Ebola virus species were 30-40% divergent from one another. The degree of diversity signifies differences in the ecological niche they occupy during their evolutionary history. This suggests that differences among Ebola viruses, including differences in lethality, reflect where and how they have lived within their reservoir hosts.
There emerged a common pattern: close encounter with wild animals precedes Ebola outbreaks. For instance, major outbreaks in Africa were associated with reports of high mortality in the primate population, especially those of the great apes like chimpanzees and gorillas. The virus thus affects great apes perhaps more severely than humans, suggesting that they cannot be the natural reservoir of Ebola virus.
Yet, the precise reservoir host of ebolaviruses cannot be exactly determined after almost five decades since this deadly pathogen’s discovery. Bats are hypothesised to be the most probable natural host, but the debate is far from settled. A 2013 study in Bangladesh reported that approximately 4% of studied bats were seropositive (contains antibodies) to Zaire ebolavirus and Reston virus, though none were detected as nucleic acid positive in PCR tests- considered the gold standard for virus detection.
Thus, ebolavirus may be harboured across much larger geographic regions than assumed. Apart from Reston, the highly pathogenic lethal Zaire strain has also a potential connection with mainland Asia.
The complex pathways of Ebola transmission
In Bundibugyo, people live near national parks, where encounters with monkeys, baboons, fruit bats and other primates are frequent. A recent study published in the journal Current Biology illustrates the complexity of these ecological interactions.
Researchers set up cameras inside bat-infested caves. The footage caught an array of wildlife, including blue monkeys, eagles, monitor lizards, and leopards preying on bats in Python cave in Uganda’s Queen Elizabeth national park.
Such interactions complicate the potential transmission chain and make it difficult to trace the virus back to its original source. The situation is further complicated by the frequent visits by tourists, travellers, and schoolchildren to these caves without basic protective measures like face masks, despite warning boards placed outside the cave. Since 1967, 43% of 29 confirmed deadly Marburg virus outbreaks have been associated with visits to the Python cave.
Moreover, investigators have also identified a possible link between the current outbreak and a “superspreader event” on 5 May, traced through social media. Ebola virus diseases are transmitted through contact with blood, bodily fluids of an infected person or animals, and contaminated objects and surfaces.
In addition, across Africa, mining activity has expanded rapidly, especially for copper and cobalt – an indispensable component of lithium-ion batteries used in everything from mobile phones and laptops to electric cars. Vast stretches of aboriginal forests have been cleared for mineral harvesting. Such large-scale deforestation is recognised as a risk factor for zoonotic spillover.
Genetic clues to track Bundibugyo ebolavirus
Two teams of scientists from DRC and Uganda published three genome sequences online by May 18, which would help track how the Ebola virus is spreading. Combating Bundibugyo virus is proving to be a major challenge. The virus has apparently been spreading for some time undetected.
Two major outbreaks of Bundibugyo virus have been documented in 2007 and 2012. These limited outbreaks offer very little reliable information regarding its incubation period, epidemiology, and pathophysiology. The absence of approved vaccines and treatments, as well as a severe dearth of diagnostic tools and established protocols to handle it, adds to the existing challenges.
Ebola viruses belong to the family Filoviridae, which they share with another deadly pathogen, the Marburg virus. As its name suggests, filoviruses have a filamentous form, which can be twisted and shaped like an anguished worm. Ebola viruses contain a single-stranded RNA genome which encodes only 7 proteins.
Currently, six species/genera of Ebola virus are recognised: Zaire ebolavirus, Sudan ebolavirus, Tai Forest ebolavirus, Bundibugyo ebolavirus, Reston virus/ebolavirus and the Bombali virus/ebolavirus. Only the first four are known to infect humans and cause ebolavirus disease. Zaire ebolavirus is known to be the most pathogenic and has caused the largest number of outbreaks and recorded deaths. Irrespective of the species involved, ebolavirus disease can cause a severe and potentially fatal illness.
The limits of Ebola detection
Early symptoms of Ebola virus infection can resemble influenza and include high fever, vomiting, and diarrhoea. In some cases, the disease progresses to internal and external bleeding and can lead to liver and kidney malfunction. The cases with bleeding generally have the worst outcome. In severe cases, death usually results due to profound fluid loss, electrolyte imbalance, shock, and progressive multi-organ failure.
During the recent Ebola outbreaks, molecular investigators primarily relied on automated PCR machines called GeneXpert. But the reagents available for this technique are specific to Zaire ebolavirus, the strain that causes frequent outbreaks. For Bundibugyo ebolavirus, the absence of a specific reagent or kit led to no detection during the initial phases of the outbreak. The only alternative is the generic PCR-based kit for common detection of any ebolavirus called RADI-ONE.
Evolutionary biologists from the three published sequences are of the opinion that this same strain of virus may have caused multiple previous outbreaks that may have gone undetected. Its pattern of infection increasingly resembles that of a new (zoonotic) spillover.
Experimental therapies and vaccines to fight Ebola
The current treatment approach is largely supportive and directed towards management of immediate symptoms. The WHO is focusing on two separate rapid trials for treatment against filoviruses. One is the broad-spectrum antiviral remdesivir manufactured by Gilead Sciences. The other is MBP134, a mixture of two antibodies that recognises diverse Ebola viruses, and has been developed by Mapp Biopharmaceuticals.
The Remdesivir trial during the 2018-19 Zaire virus outbreak in Congo showed modest efficacy. MBP134, however, was not evaluated in a trial and has been made available on compassionate grounds, allowing people with life-threatening disease to receive investigational therapies. Hence, it was not possible to determine whether the drug worked or not. MBP134, however, has strong preclinical data from trials in monkeys and other animals, and has also shown activity against the Bundibugyo virus.
Several vaccine candidates and antiviral therapies are currently under development for Ebola virus infections. Experimental vaccines that protect non-human primates when administered both before and after exposure have been developed, but are not in trials yet.
Building new defences against Bundibugyo
The Africa Centres for Disease Control and Prevention (Africa CDC) and the WHO are focusing on evaluating the efficacy of Ervebo, the vaccine that provides protection against the Zaire strain of Ebola. Experts are of the opinion that the vaccine may be only 50% effective against Bundibugyo. Trials show that Bundibugyo is not completely lethal in monkeys
Researchers at the University of Oxford and the Serum Institute of India are also developing a vaccine based on a viral-vector platform, the same delivery technology used in the AstraZeneca Covid-19 vaccine. Meanwhile, the University of Science and Technology of China has developed a potential vaccine consisting of mRNA payload encoding glycoprotein of Zaire, Sudan, and Bundibugyo Ebola viruses.
On the antiviral front, Gilead Sciences’ oral small-molecule antiviral obeldesivir is being advanced by the Africa CDC. The drug works by inhibiting the RNA-dependent RNA polymerase enzyme of the virus. The clinical trial will test whether obeldesivir protects high-risk contacts of people with Bundibugyo virus disease.
Post read questions
1. Zoonotic diseases are increasingly becoming an ecological consequence of human transformation of natural landscapes. Discuss with reference to Ebola outbreaks in Central Africa.
2. The difficulty in identifying the natural reservoir of Ebola viruses illustrates the limitations of conventional approaches to emerging infectious disease surveillance. Discuss.
3. Great apes are both victims of Ebola outbreaks and potential indicators of ecological disruption. Discuss the implications of Ebola-associated mortality for biodiversity conservation in Africa.
4. Examine how deforestation, mining, habitat fragmentation and increasing human–wildlife interaction can alter the risk of zoonotic disease emergence. Illustrate with examples from Central Africa.
5. Pandemic preparedness cannot be reduced to vaccines alone. Discuss the role of surveillance, diagnostics, genomic sequencing, healthcare infrastructure and international cooperation in controlling emerging infectious diseases.
(Dr. Arunangshu Das is the Principal Project Scientist at the Centre for Atmospheric Sciences, Indian Institute of Technology, Delhi.)
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