Correspondence
Ebola in west Africa We have some concerns with your recent Editorial1 on the Ebola disease outbreak in west Africa. The piece did not recognise the importance of the work done by the numerous government and non-government organisations who have been striving since March to control the outbreak.2 The key deficiency identified by various organisations was community engagement (notwithstanding their efforts) and, as a result, the failure of the conventional model of isolation and case finding. Moreover, we feel that focusing your Editorial on unproven therapeutics was inappropriate. Several potential therapeutic candidates were not mentioned in the Editorial, including the pyrazinecarboxamide derivative T-705 (favipiravir) which induced rapid Ebola viral clearance in an animal model as late as day 6 of infection.3 Favipiravir is already licensed in Japan for the treatment of influenza that does not respond to conventional therapies and seems to be available in large quantities. The Editorial highlighted antibody-based therapies such as MB003 (ZMapp), the efficacy of which
substantially declined when given late in the course of experimental infection.1 We have not seen peerreviewed efficacy data but lay media reports suggest a 50% mortality at this time for treated individuals. In a recent statement, WHO eased the concerns about the ethical use of investigational agents in this outbreak.2 Putting competing commercial interests aside, now is the time for international agencies and research collaborations to come together to run well designed, comparative clinical trials to determine the safety and efficacy of these interventions in patients infected with Ebola virus. Lessons learned from the 2009 influenza A H1N1 pandemic include the opportunity lost to better understand the role of antiviral drugs. We still do not know if oseltamivir has any efficacy in patients with severe influenza.4 The experience with trovafloxacin in meningitis in west Africa is also instructive in that drugs which seem to have benefits for serious diseases with a high mortality can paradoxically be very harmful.5 Highlighting unproven therapeutics potentially distracts from the proven public health measures that have controlled every Ebola virus outbreak
since 1976. Global resources are being deployed in very difficult circumstances. If antiviral drugs are introduced into the west African response, organisations undertaking the response must ensure that efforts are not diverted from the key proven public health and infection prevention response. Although a randomised placebo-controlled trial might not be practical, we should at least work to optimise the results from real-world controlled comparative studies.
Lancet Infect Dis 2014 Published Online September 11, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70924-7
We declare no competing interests.
*Mohamad-Ali Trad, Dale Andrew Fisher, Paul Anantharajah Tambyah [email protected] National University Hospital, Singapore, Singapore 1 2
3
4
5
The Lancet Infectious Diseases. Ebola in west Africa. Lancet Infect Dis 2014; 14: 779. WHO. Global outbreak and response network. http://who.int/csr/disease/ebola/en (accessed Aug 20, 2014). Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014; 105: 17–21. Jefferson T, Doshi P. Multisystem faulure: the story of anti-influenza drugs. BMJ 2014; 348: g2263. Lenzer J. Pfizer settles with victims of Nigerian drug trial. BMJ 2011; 343: d5268.
www.thelancet.com/infection Published online September 11, 2014 http://dx.doi.org/10.1016/S1473-3099(14)70924-7
1
Ebola in west Africa We have some concerns with your recent Editorial1 on the Ebola disease outbreak in west Africa. The piece did not recognise the importance of the work done by the numerous government and non-government organisations who have been striving since March to control the outbreak.2 The key deficiency identified by various organisations was community engagement (notwithstanding their efforts) and, as a result, the failure of the conventional model of isolation and case finding. Moreover, we feel that focusing your Editorial on unproven therapeutics was inappropriate. Several potential therapeutic candidates were not mentioned in the Editorial, including the pyrazinecarboxamide derivative T-705 (favipiravir) which induced rapid Ebola viral clearance in an animal model as late as day 6 of infection.3 Favipiravir is already licensed in Japan for the treatment of influenza that does not respond to conventional therapies and seems to be available in large quantities. The Editorial highlighted antibody-based therapies such as MB003 (ZMapp), the efficacy of which
substantially declined when given late in the course of experimental infection.1 We have not seen peerreviewed efficacy data but lay media reports suggest a 50% mortality at this time for treated individuals. In a recent statement, WHO eased the concerns about the ethical use of investigational agents in this outbreak.2 Putting competing commercial interests aside, now is the time for international agencies and research collaborations to come together to run well designed, comparative clinical trials to determine the safety and efficacy of these interventions in patients infected with Ebola virus. Lessons learned from the 2009 influenza A H1N1 pandemic include the opportunity lost to better understand the role of antiviral drugs. We still do not know if oseltamivir has any efficacy in patients with severe influenza.4 The experience with trovafloxacin in meningitis in west Africa is also instructive in that drugs which seem to have benefits for serious diseases with a high mortality can paradoxically be very harmful.5 Highlighting unproven therapeutics potentially distracts from the proven public health measures that have controlled every Ebola virus outbreak
since 1976. Global resources are being deployed in very difficult circumstances. If antiviral drugs are introduced into the west African response, organisations undertaking the response must ensure that efforts are not diverted from the key proven public health and infection prevention response. Although a randomised placebo-controlled trial might not be practical, we should at least work to optimise the results from real-world controlled comparative studies.
Lancet Infect Dis 2014 Published Online September 11, 2014 http://dx.doi.org/10.1016/ S1473-3099(14)70924-7
We declare no competing interests.
*Mohamad-Ali Trad, Dale Andrew Fisher, Paul Anantharajah Tambyah [email protected] National University Hospital, Singapore, Singapore 1 2
3
4
5
The Lancet Infectious Diseases. Ebola in west Africa. Lancet Infect Dis 2014; 14: 779. WHO. Global outbreak and response network. http://who.int/csr/disease/ebola/en (accessed Aug 20, 2014). Oestereich L, Lüdtke A, Wurr S, Rieger T, Muñoz-Fontela C, Günther S. Successful treatment of advanced Ebola virus infection with T-705 (favipiravir) in a small animal model. Antiviral Res 2014; 105: 17–21. Jefferson T, Doshi P. Multisystem faulure: the story of anti-influenza drugs. BMJ 2014; 348: g2263. Lenzer J. Pfizer settles with victims of Nigerian drug trial. BMJ 2011; 343: d5268.
www.thelancet.com/infection Published online September 11, 2014 http://dx.doi.org/10.1016/S1473-3099(14)70924-7
1
