Wednesday, 22 January 2014

Dengue in Viet Nam
In some, maybe the majority of cases, economic development tends to improve a country's situation regarding infectious disease; a proper sewerage system, for example, may decrease the incidence of diseases associated with the contamination of water sources. Where dengue virus is concerned this is not the case. Dengue is a human virus spread by mosquitoes of the genus Aedes (in particular A. aegypti), which happily breed in dirty water. Economic development tends to result in increased urbanisation and, as a result, ideal breeding conditions are generated for the mosquitoes (tin cans, old tyres etc.). Together, the result is a dense population of humans in the same location as the mosquitoes: in the absence of a vaccine or antivirals dengue has thus thrived. Whilst the conditions are favourable for dengue in general, there are inevitably more specific drivers of transmission and outbreaks.

A recently published study in PLOS Neglected Tropical Diseaes by Rabaa et al looked into what the drivers are for dengue in Viet Nam. The situation in Viet Nam can broadly be regarded as the south (tropical) region being endemic, whilst the north (sub-tropical) is not endemic, but experiences frequent introductions. In central Viet Nam the virus can persist for more extended periods of time, perhaps due to more favourable conditions for transmission and, ultimately, a higher level of immunity. As an illustration as to the impact of urbanisation, Ho Chi Minh city in the south is highly endemic and represents a large source of viruses for the rest of Viet Nam.

The authors compared the dengue serotype 1 (DENV-1) sequences of the envelope (E) gene.
Using a maximum likelihood approach to get an additional grasp of geographical relationships, they found that, perhaps unsurprisingly, all of the sequences belonged to the Southeast Asia subtype of Genotype I.

Phylogeography of DENV-1 genotype 1 in Southeast Asia, 1998-2009. A) Map of north (red) central (yellow) and south (blue) Viet Nam. The colours match in the graphs of mean min/max temperature (B, top graph) and mean precipitation (B, bottom graph), and branches in the maximum clade credibility phylogenetic tree (C). Purple branches represent Singapore sequences.

On the whole, DENV-1 seems to invade subtropical northern Viet Nam regularly, but never seems to become endemic - most likely due to the cold winter temperatures resulting in conditions that are refractory to continued transmission. Such invasions also occur in the central regions, although these persist for longer.
Interestingly, although (as may be expected) within a particular region the diversity among viruses was limited,  on a broader scale Ho Chi Minh City in the south was found to act as a source of virus throughout Viet Nam.

On the other hand, despite local diversity being low, it's interesting that geographically long distance movements were observed in a time-scale that precludes the hypothesis that it's merely natural spread via vectors. Instead, it appears that the movement of infected humans is responsible for seeding at least some of the regions. This is one route by which the north can be seeded. However, because the north is sub-tropical, there comes a time in the year when the vectors die off and transmission is reduced; a familiar scenario with non-tropical arboviruses. 

As interesting a piece of work as this is in itself, it arguably demonstrates something important at a more global level. Clearly DENV can be seeded in different regions by people moving around Viet Nam; if this can happen within Viet Nam, then it's not a massive step to extend Viet Nam to the world.

Maia A. Rabaa, Cameron P. Simmons, Annette Fox, Mai Quynh Le, Thuy Thi Thu Nguyen, Hai Yen Le, Robert V. Gibbons, Xuyen Thanh Nguyen, Edward C. Holmes, John G. Aaskov (2013). Dengue Virus in Sub-tropical Northern and Central Viet Nam: Population Immunity and Climate Shape Patterns of Viral Invasion and Maintenance PLOS Neglected Tropical Diseases DOI: 10.1371/journal.pntd.0002581

Friday, 3 January 2014

Bats vs. Rats
If I had to name one book that got me interested in viruses it would be 'Virus X: understanding the real threat of the new pandemic plagues', by Frank Ryan. The book largely concentrates upon virus emergence; why it happens, where the viruses come from, and what that might mean for the future. Whether or not I now agree fully with everything that's hypothesised is a different matter, although an honest evaluation is difficult considering the advances in science since its publication (1997). Nevertheless, it got me interested at the time.

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Flicking back through it last night I read a line regarding virus reservoirs that stood out. "The threat to humanity derives in particular from rodents". This was the logical conclusion derived from the fact that rodents are the most numerous mammal, which is fair enough. Nowadays it's almost all about bats. In the book Ryan does point out the suspicions of bats as reservoirs, but overall in this book the potential significance of bats is over shadowed by a focus on rodents.

With our current knowledge of virus natural reservoirs (a term itself worthy of debate), a suggestion that anything other than bats are the most important source of viruses as far as public health is concerned, is likely to be met with an element of scorn. Bats do indeed harbor a lot of viruses, as was published earlier this year. In this particular paper the authors also estimated the numbers of viruses still to be discovered (320,000), although wisely they also stated that such a calculation was based upon some rather large assumptions:

"Several important limitations must be considered in our extrapolations, including (i) the assumption that a mean of 58 viruses per species is a reasonable estimate and that host populations are panmictic with respect to viral transmission (such that expanded geographic sampling would not influence viral detections), (ii) the assumption that viruses are not shared by more than one host species, (iii) that only those viruses within the nine families are considered in this estimation, (iv) that the results are limited by the sensitivity and specificity of our tests, and (v) that a similar mean cost of sample collection is incurred across all species."  (Anthony et al. 2013, mBio) 

Nevertheless, it's a useful number to have.
Bats have long been suspected as reservoirs, and in the case of rabies it had been firmly established, but I'm not sure when exactly they became so popular for virus hunters. Perhaps around the time of Nipah and Hendra emergence. Nowadays everybody seems to be hunting for viruses in bats specifically.

Bats, it can safely be said, represent an important source of novel as well as known viruses. In terms of virus emergence and spread however, there is more to it. Yes, bats may harbor a lot of viruses. And perhaps yes for one reason or another those viruses may have a higher chance of being unpleasant. But there is more to epidemiology than simply the source. Spillovers in a forest/rural setting are inevitable, and in this case bats pose as much of a risk as rodents. However, the majority of people live in urban areas. And from this perspective, rodents are surely of greater importance for transmission as their populations are so intimately linked with humans. More contact means a greater likelihood of transmission. One of the worst epidemics in history, the Black Death (admittedly caused by a bacterium), was closely linked with rats. More recent, viral, examples include the Sin Nombre hantavirus in New Mexico, and the Arenaviruses (e.g. Lassa fever virus).

It could be argued that, because we've had so much interaction with rats over the years we're unlikely to find anything new. That doesn't mean they're of lesser importance; Lassa fever and Sin Nombre are responsible for the death of more people than those caused by more exotic viruses such as Ebola virus.

Global air travel: 'emergence hotspots' such as South East Asia experience more international travel than central Africa. Image: Max Planck Institute for Dynamics and Self-Organisation/ Dirk Brockmann
It is clear that the jungles and savannas of Central Africa harbor bats with viruses of great danger to humans. But is this more important than, say, the populations of rats in densely populated urban centers in South East Asia? Human traffic to and from such urban areas is higher, enhancing the probability of an infection spreading to other parts of the world; would SARS, for example, have spread so far if it had emerged in Uganda? In the future it may be that the world is equally connected. For now though, some places remain more connected than others, and this should be remembered when people decide what's more important: bats or rats.

Anthony SJ, Epstein JH, Murray KA, Navarrete-Macias I, Zambrana-Torrelio CM, Solovyov A, Ojeda-Flores R, Arrigo NC, Islam A, Ali Khan S, Hosseini P, Bogich TL, Olival KJ, Sanchez-Leon MD, Karesh WB, Goldstein T, Luby SP, Morse SS, Mazet JA, Daszak P, & Lipkin WI (2013). A strategy to estimate unknown viral diversity in mammals. mBio, 4 (5) PMID: 24003179