F-106 Ebola and lassa fever: Lessons learned, continuing challenges (2019)

The 2013–2016 West African Ebola outbreak was the largest, most geographically dispersed and deadliest on record. Since the West Africa outbreak began 4 independent outbreaks of Ebola have occurred, all in the Democratic Republic of the Congo (DRC). The last outbreak was detected only a week after the previous outbreak was declared over. Ebola is not the only global health challenge that is emerging with increasing frequency. During 2018 Nigeria experienced an unprecedented increase in Lassa fever cases. Nearly 500 cases have been diagnosed by August, more than reported in any previous year. While confirmed Lassa fever cases are concentrated in the southwest states of Edo (42%) and Ondo (24%), and the southeast state of Ebonyi (15%), additional cases have originated in 18 other states country-wide. Emerging viruses such as Ebola virus (EBOV) and Lassa virus (LASV) present enormous challenges to global public health. Numerous gaps exist in our understating of the factors that drive viral emergence and may be responsible for the increased frequency of Ebola outbreaks and the geographic expansion of LASV. For example, the EBOV strains that emerged in DRC in 2014 and during the latest 2018 outbreak in eastern DRC (North Kivu, virological.org/t/drc-2018-viral-genome-characterization/230) are phylogenetically most similar to EBOVs isolated during the 1995–1996 outbreaks in Middle Africa, rather than more recent isolates. EBOVs from the 2017 DRC outbreak in northern DRC (Yambuko) and 2018 outbreak in western DRC (Bikoro) also cluster in a manner that further challenges a simple monophyletic clock. The now uncertain evolutionary trajectory of EBOV is only one of many conundrums surrounding Ebola emergence. In contrast to EBOV whose reservoir is currently unknown, most LASV infections result from contact with Mastomys natalensis, the major natural reservoir. Previous phylogenetic investigations of LASV reported extensive viral genetic diversity and established the presence of at least 6 viral lineages across West Africa. The surge of Nigerian Lassa fever cases in 2018 is not attributable to a single Lassa virus strain, nor has it been sustained by human-to-human transmission (Siddle et al, accepted). Extensive viral diversity structured by geography, with major rivers appearing to act as barriers to migration of the rodent vector. Together these results suggest that the 2018 Lassa fever surge was driven by cross-species transmission of multiple viral strains from local rodent populations. The rapid availability of genomic sequence information for the recent Ebola outbreaks and the Lassa surge in Nigeria highlights the fact that there have been fundamental changes in the ways that the international community responds to outbreaks. At the beginning of the West African outbreak governments, often acting on the advice of outside “special” advisors, withheld information on actual numbers of cases. The threat of spread of the virus was minimized because it was felt that the outbreak would “burnout” within a timeframe of a few weeks, and that releasing actual case numbers would have a deleterious effect on the already fragile economies. Real-time case reporting has since become the norm. In prior outbreaks it was argued that no research, including genomic sequencing, should be done in an outbreak, so as not to impede the public health response. Promising experimental treatment and vaccines were withheld from Africans, including researchers with long experience with VHFs. While some trials of vaccines and drugs did occur late in the outbreak, in most cases definite results of effectiveness were not obtained due to diminishing case numbers. It is encouraging that a rVSV-ZEBOV vaccine is being rapidly deployed in the most recent outbreaks with apparent success. Experimental drugs, including monoclonal antibody therapies, are now being used in African patients. The World Health Organization (WHO) and the Coalition for Epidemic Preparedness Innovations (CEPI) have each now ranked LASV as a priority pathogen. These rankings are based on the potential for further geographic expansion of the rodent reservoirs, the ease of procurement and weaponization of the virus, the frequent importation to North America and Europe, and the emergence of novel strains in densely populated West Africa. The Food and Drug Administration recently recognized Lassa fever as a neglected tropical disease, which could also spur development of countermeasures. Reclassifying LASV as a Tier 1 Select Agent should now become a priority of the Centers for Disease Prevention and Control and the United States Department of Agriculture (USDA), a change which would also accelerate development of much needed vaccines and therapeutics. Lessons learned may improve the next response to an international health crisis caused by a viral pathogen that emerges in a region of the world with a severely limited health care infrastructure. However, predicting when the next new human viral pathogen will mutate or where it will emerge in people is not achievable. There are far too many possible pathogens and too little known about the changes that may determine the ability of animal viruses to jump to humans. Rather, the most effective way to prepare for the inevitable emergence of new pathogens is surveillance of humans, particularly those living in locations that are most vulnerable. Isolation of a novel pathogen from a person exhibiting symptoms or animals experiencing die-offs can occur in literally a matter of days. Scarce resources should be prioritized to surveillance efforts for known pathogens such as EBOV and LASV. Employing rapid and effective point-of-care diagnostics designed for environments that lack advanced laboratory infrastructure will greatly aid in early detection and containment efforts during future outbreaks.