August, 1976. A new infection was causing panic in Zaire. Hospitals became death zones, as both patients and medical staff succumbed to the disease. Reports of nightmarish symptoms trickled in to scientists in Europe and the US, who sent investigators to determine the cause and stem the epidemic. Concurrently, they would find out, the same thing was happening hundreds of miles to the north in Sudan. In all, 284 would be infected in that country, and another 358 in Zaire–over 600 cases (and almost 500 deaths) due to a mysterious new disease in just a few months’ time.
The new agent was Ebola, but remarkably, the outbreaks were unrelated, at least as far as any direct epidemiological links go. No one had brought the virus from Sudan to Zaire, or vice-versa. Molecular analysis showed that the viruses causing the outbreaks were two distinct subtypes, subsequently named for their countries of origin, Ebola Zaire and Ebola Sudan.
While Uganda is currently battling another outbreak of Ebola Sudan, rumors in the past week have suggested that this virus may have spread to former Zaire (now the Democratic Republic of Congo), where Ebola has reappeared 4 additional times since the first discovery there in 1976. It’s now been confirmed that Ebola is again present in the DRC, with an (unconfirmed) 6 deaths. However, it’s not related to the Uganda outbreak. Reminiscent of 1976, the strain that’s circulating currently in the DRC is the Bundibugyo subtype, which was first identified in Uganda in a 2007-8 outbreak in that country, rather than the Sudan type causing the current Ugandan epidemic. Interestingly, every previous outbreak of Ebola in the DRC has been caused by the Zaire type of Ebola, so the appearance of Bundibugyo is a first–though not altogether surprising given that the outbreak province borders Uganda.
Is this just coincidence that Ebola has twice now broken out in two different places at the same time, but with different viral subtypes? Hard to say. Though we can now say it’s fairly likely that bats are a reservoir host for Ebola and other filoviruses, we can’t say for sure that bats are the *only* reservoir. Indeed, we know that some outbreaks have occurred because the index case was in contact with an infected ape or their meat–were these animals originally infected by a bat, or by another source? How does the ecology of an area affect the chances of an outbreak occurring? Were there reasons that humans might be increasingly exposed to the virus in these different areas–Zaire and Sudan in 1976, DRC and Uganda in 2012–at the same time? Weather conditions? Trade/industry? Host migration or dispersal? We know with another bat-borne virus, Nipah, that changes in farming practices led to increased proximity of fruit bats and farmed pigs–allowing pigs to come into contact with virus-laden bat guano, become infected with Nipah, and subsequently transmit the virus to farmers. Things that may seem completely inconsequential–like the placement of fruit trees–can actually be risk factors for viral emergence. Is there a common factor here, or just bad luck? Only additional hard-won knowledge of filovirus ecology will be able to tell.
Typically when we think of flying things and influenza viruses, the first images that come to mind are wild waterfowl. Waterbirds are reservoirs for an enormous diversity of influenza viruses, and are the ultimate origin of all known flu viruses. In birds, the virus replicates in the intestinal tract, and can be spread to other animals (including humans) via fecal material.
However, a new paper expands a chapter on another family of flying animals within the influenza story: bats.
I’ve written previously about the enormous diversity of microbes that bats possess. This shouldn’t be surprising–after all, bats are incredibly diverse themselves, encompassing about a fifth of all known mammalian species. Though rabies is probably the most famous bat-associated virus, other viruses that have been isolated from bats include Nipah and Hendra viruses, SARS coronavirus, Chikungunya virus, Japanese and St. Louis encephalitis viruses, Hantaan virus (a relative of the Sin Nombre hantavirus), and filoviruses, among many others. And of course, a bat->pig->human cross-species infection ended up being a plot line in the recent movie, Contagion (modeled after Nipah virus). However, bats still remain chronically under-studied, despite the fact that they can carry so many potential human pathogens.
This new research expands our knowledge of bat viruses a bit. The authors examined 316 bats from eight locations in Guatemala in 2009-10. Rectal swabs were obtained and screened for influenza virus using molecular methods (looking for influenza virus RNA). Three of the samples tested positive, and all were from little yellow-shouldered bats (Sturnira lilium). This could indicate some clustering and transmission of the virus within bat colonies–and indeed, two of the bats were from the same area in the same year (2009). However, the third bat was captured in 2010 at a location 50 km away from the other two, suggesting that the virus may be more widespread than in just one colony.
When we discuss the epidemiology of influenza viruses, we talk about two genes: the HA gene, which encodes the hemagglutinin protein and allows the virus to bind to host cells; and the NA gene, which encodes the neuraminidase protein and allows the virus to leave an infected cell and spread to others. This is where the “H1N1” or “H5N1” nomenclature come from. The novel bat virus was a completely new H type–type 17 (provisional, they note, pending further analyses). The NA gene was also highly divergent, but they are awaiting further analyses to more definitively classify this gene. (Currently there are 9 recognized types of NA genes).
Though they weren’t able to culture out the flu viruses, the authors did do some molecular work suggesting that these novel bat viruses could combine with human viruses and form a functional recombinant virus. What implications could this have for human health? Well, hard to say. We still know very little about all the implications of any distinct type of avian influenza virus, or swine influenza virus, much less something completely foreign like bat flu. It’s interesting that, like birds, influenza virus in bats was found in the intestine (though lung samples were also positive). Can it cause an intestinal infection as well as an upper respiratory infection (the latter being more common in other mammal species)? Does it cause any signs of disease in infected bats at all? If they can get this bat virus to grow, all sorts of interesting lines of research are just waiting.
The article also mentions that seroepidemiological studies are currently being carried out to better understand the epidemiology of bat flu. Looking at PubMed, there is one reference to some similar studies carried out in the early 1980s, but I can’t access anything beyond the title. There also is a report of H3N2 influenza in bats in Kazakhstan, but that article is in Russian and also not readily available. Either way, everything old is new again, and it looks like interest in bat influenza has resurfaced after a 30-year lull. Who knows what else we’ll find lurking out there as interest continues to increase in the wildlife microbiome.
Suxiang Tong, Yan Li, Pierre Rivailler, Christina Conrardy, Danilo A. Alvarez Castillo, Li-Mei Chen, Sergio Recuenco, James A. Ellison, Charles T. Davis, Ian A. York, Amy S. Turmelle, David Moran, Shannon Rogers, Mang Shi, Ying Tao, Michael R. Weil, Kevin Tang, Lori A. Rowe, Scott Sammons, Xiyan Xu, Michael Frace, Kim A. Lindblade, Nancy J. Cox, Larry J. Anderson, Charles E. Rupprecht, & Ruben O. Donis (2012). A distinct lineage of influenza A virus from bats PNAS Link.