Ebola: Hot in the Headlines But, As Yet, Less So in the Literature

September 2014

Towards the end of his life, almost two millennia ago now, the naturalist Pliny the Elder noted that there was always something new coming out of Africa. Today’s virologists would surely agree. The many novel viral infections emerging from that continent include HIV/AIDS and Lassa, Marburg, and Ebola fevers. The last of these is named after the River Ebola in northern Zaire (now the Democratic Republic of the Congo) in a village near which the first cases were recorded in 1976. Ebola virus is one of three filoviruses (the other two are Marburgvirus and “Cuevavirus”), and five Ebola virus species are known, the main ones being Zaire, Sudan (where there was an outbreak in 1976 also), and Bundibugyo. The often fatal illness associated with this viral infection was initially labelled Ebola hemorrhagic fever. However, hemorrhage is a feature of only 50% or so of cases. To date all outbreaks of Ebola virus disease (EVD), as it is now called, have been in one or more of a swath of countries in sub-Saharan Africa. The prognosis varies in severity with the virus species.

For this report, ScienceWatch turns to the Web of Science to check on the latest literature as well as foundational papers covering earlier outbreaks. Observation suggests that, despite a proliferation of papers in recent years, Ebola has yet to register as a “hot” topic according to the customary Thomson Reuters citation measures.

MAJOR OUTBREAKS

Apart from 1976, there have been major (more than 100 cases) outbreaks in 1995, 2000, 2003, and 2007 with a puzzling absence of any recorded cases in the 14 years 1980-93. The current focus of concern is Guinea, Liberia, and Sierra Leone (lately joined by Nigeria) and by the third week of August, 2014, EVD, which was first spotted in February/March, had resulted in more than 3,000 cases, with deaths exceeding 1,500. WHO updates the figures every two or three days (http://www.who.int/csr/don/archive/disease/ebola/en/). The 2014 case fatality rate of 55% is closer to that associated with Sudan ebolavirus (54% over all outbreaks) than with Zaire ebolavirus (79%), the presumed species in this instance.

We do not yet have a vaccine, though this preventive approach is feasible (A. Marzi, H. Feldmann, Expert Rev. Vaccines, 13[4]: 521-31, 2014). Nor is there any specific treatment. Even so, previous outbreaks have been brought under control. The number of cases still being reported in August of 2014 suggests that the three countries most severely affected are not yet out of the woods. This is already by far the largest known outbreak of EVD, and Dr. Margaret Chan, secretary-general of the World Health Organization, has expressed the fear that it had been spreading more quickly than efforts to control it. On July 31, WHO announced a joint $100 million response, much of it for the extra staff needed to implement control and surveillance measures, and a few days later the outbreak was officially declared an international public-health emergency.

The clinical picture is not diagnostic by itself, and laboratory confirmation of infection with this highly dangerous pathogen took time to become routine. Seroepidemiology hints at other foci of Ebola infection. For example, when Randal J. Schoepp and colleagues investigated cases of suspected but later unconfirmed Lassa fever referred in 2006-08, they found evidence for several different viral infections, including filoviruses. The authors noted, presciently, that this finding “extends the Ebola virus geographic region to Sierra Leone,” a country which, like Guinea, had not until this year registered cases of EVD (R.J. Schoepp, et al., Emerg. Infect. Dis., 20[7]: 1176-82, 2014). The possibility of natural immunity to infection was raised by, for example, studies in Ebola epidemic and non-epidemic areas of Gabon (P. Becquart, et al., PLOS One, 5[2] e9126, 2010).

The exact classification of the 2014 virus has been debated but it appears to be related to the Zaire strain. The forested region of southeast Guinea is some 1,500 miles from the nearest point in the Democratic Republic of Congo (formerly Zaire). How the virus travelled so far is just one of the intriguing questions raised by Ebola virus’s latest tragic emergence (D.G. Bausch, L. Schwarz, PLOS Negl. Trop. Dis., 8[7]: e3056, 2014). A WHO map shows the range of one genus of fruit bat (a very probable candidate as a reservoir for Ebola viruses), and this range encloses outbreak areas and countries with serologic (only) evidence of infection.

PAPERS, BUT FEW HIGHLY CITED

Papers indexed in the Web of Science since 1976 on Ebola viruses and EVD (i.e., with “Ebola” mentioned in the title, abstract, or keywords) now exceed 2,200, and the annual output has increased markedly since the late 1990s, although the number for each of the last three years has remained around 170. However, only eight papers published in the last decade have been formally designated by Essential Science Indicators as “highly cited” (that is, ranking among the top 1% most cited for their field and year of publication).  Furthermore, automated analysis of citation patterns has identified only one current Research Front devoted to Ebola. Of only three “core” papers for this research cluster, two provide specifics on viral infection while the third offers a broader overview.

In the lay press, the topic of Ebola fever may have been grabbing headlines this summer but, given the comparatively recent time window for the latest outbreak, no official Hot Papers (highly cited within two years of publication) have yet surfaced. In all, it appears that, at least as of this writing, Ebola as a research area is still shy of the critical mass that constitutes a true hot topic. Perhaps, depending on how the current crisis plays out, this will abruptly change.

The table below provides a few sources for descriptions of EVD outbreaks over the years.

Selected Publications on Outbreaks of Ebola Virus Disease in Africa, 1976 – 2014

(Including citation totals, for those papers that have accrued them to date)

Country/Topic Publication Citations
Zaire
(1976)
Anon., “Ebola haemorrhagic fever in Zaire, 1976,” Bull. World Health Org., 56(2): 271-93, 1978. 257
Sudan
(1976)
Anon., “Ebola haemorrhagic fever in Sudan, 1976,” Bull. World Health Org., 56(2): 247-70, 1978. 206
Sudan
(1979)
R.C. Baron, et al., “Ebola virus disease in southern Sudan,” Bull. World Health Org., 61(6): 997-1003, 1983. 109
Uganda
(2007)
J.S. Towner, et al., “Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda,” PLOS Pathog., 4(11): e1000212, 2008. 148
Guinea
(2014)
S. Baize, et al., “Emergence of Zaire Ebola virus disease in Guinea,” New Engl. J. Med., Epub, 2014. -
Review H. Feldmann, T.W. Geisbert, “Ebola haemorrhagic fever,” Lancet, 377(9768): 849-62, 2011. 89
Review D. Gatherer, “The 2014 Ebola virus outbreak in West Africa,” J. Gen. Virol., 95(8): 1619-24, 2014. -
Source: Thomson Reuters Web of Science

Horrible though the infection is, there have been insufficient cases to make EVD an attractive candidate for conventional pharmaceutical research and development. However, such research is being done, some of it prompted by the sickening thought that filoviruses might be used as biologic warfare agents. WHO and others have been discussing the thorny question of providing unproven treatments to the countries affected in 2014. No drug has yet been licensed but several candidates have been reviewed in the Thomson Reuters Life Sciences “Focus on Ebola” report, and Canada has agreed to donate 800 to 1,000 doses of ZMapp for use in West Africa. Further supplies are not available. This is the drug given to two healthcare workers repatriated to the USA in July.

WHO decided on August 12 that “in the circumstances of this outbreak, it is ethical to offer unproven interventions with as yet unknown efficacy and adverse effects” but in a press release a few days later WHO was anxious that too much might be being expected of experimental drugs and vaccines. It remains to be seen how many of the candidate drugs, apart from ZMapp, will be tried in patients during the current outbreak.


A former deputy editor of The Lancet,David W. Sharp, M.A. (Cambridge), is a freelance writer living in Minchinhampton, Gloucestershire, UK.

The data and citation records included in this report are from Thomson Reuters Web of ScienceTM. Web of ScienceTM is a registered trademark of Thomson Reuters. All rights reserved.