# Selection is What Matters

This has to be a quick one, but I wanted to go on the record is noting my frustration at the current concern that Ebola might “mutate” into something far worse, like a pathogen that is efficiently transmitted by aerosol. For example, Michael Osterholm wrote in the New York Times yesterday, “The second possibility is one that virologists are loath to discuss openly but are definitely considering in private: that an Ebola virus could mutate to become transmissible through the air.”  I heard Morning Edition host David Greene ask WHO Director Margaret Chan last week, “Is this virus mutating in a way that could be very dangerous, that could make it spread faster?”

I agree, Ebola Virus becoming more easily transmitted by casual contact would be a ‘nightmare scenario.’ However, what we need to worry about is not mutation per se, but selection! Yes, the virus is mutating. It’s a thing that viruses do. Ebola Virus is a Filovirus. It is composed of a single strand of negative-sense RNA. Like other viruses, and particularly RNA viruses, it is prone to high mutation rates. This is exacerbated by the fact that RNA polymerases lack the ability to correct mistakes. So mutations happen fast and they don’t get cleaned up. Viruses also have very short generation times and can produce prodigious copies of themselves. This means that there is lots of raw material on which selection can act, because variation is the foundation of selection. Add to that heritability, which pretty much goes without saying since we are talking about the raw material of genetic information here, and differential transmission success and voilà, selection!

And virulence certainly responds to selection. There is a large literature on experimental evolution of virulence. See for example the many citations at the linked to Ebert’s (1998) review in Science here. There are lots of different specific factors that can favor the evolution of greater or lesser virulence and this is where theoretical biology can come in and make some sense of things. Steve Frank wrote a terrific review paper in 1996, available on his website, that describes many different models for the evolution of virulence. Two interesting regularities in the the evolution of virulence may be relevant to the current outbreak of EVD in West Africa. The first comes from a model developed by van Baalen & Sabelis (1995). Noting that there is an inherent trade-off between transmissibility of a pathogen and the extent of disease-induced mortality that it causes (a virus that makes more copies of itself is more likely to be transmitted but more viral copies means the host is sicker and might die), they demonstrate that when the relative transmissibility of a pathogen declines, its virulence will increase. They present a marginal value theorem solution for optimal virulence, which we can represent graphically in the figure below. Equilibrium virulence occurs where a line, rooted at the origin, is tangent to the curve relating transmissibility to disease-induced mortality. When the curve  is shifted down, the equilibrium mortality increases. EVD is a zoonosis and it’s reasonable to think that when it makes the episodic jump into human populations, it is leaving the reservoir species the biology of which it is adapted to and entering a novel species to which it is not adapted. Transmission efficiency very plausibly would decrease in such a case and we would expect higher virulence.

The second generality that may be of interest for EVD is discussed by Paul Ewald in his book on the evolution of infectious disease and (1998) paper. Ewald notes that when pathogens are released of the constraint between transmissibility and mortality — that is, when being really sick (or even dead) does not necessarily detract from transmission of the pathogen — then virulence can increase largely without bound. Ewald uses the difference in virulence between waterborne  and directly-transmitted pathogens to demonstrate this effect. At first glance, this seems to contradict the van Baalen & Sabelis model, but it doesn’t really. The constraint is represented by the curve in the above figure. When that constraint is released, the downward-sloping curve becomes a straight line (or maybe even an upward-sloping curve) and transmissibility continues to increase with mortality. There is no intermediate optimum, as predicted by the MVT, so virulence increases to the point where host mortality is very high.

A hemorrhagic fever, EVD is highly transmissible in the secretions (i.e., blood, vomit, stool) of infected people. Because these fluids can be voluminous and because so many of the cases in any EVD outbreak are healthcare workers, family members, and attendants to the ill, we might imagine that the constraints between transmissibility and disease-induced mortality on the Ebola Virus could be released, at least early in an outbreak. As behavior changes over the course of an outbreak — both because of public health interventions and other autochthonous adaptations to the disease conditions — these constraints become reinforced and selection for high-virulence strains is reduced.

These are some theoretically-informed speculations about the relevance of selection on virulence in the context of EVD. The reality is that while the theoretical models are often supported by experimental evidence, the devil is always in the details, as noted by Ebert & Bull (2003). One thing is certain, however. We will not make progress in our understanding of this horrifying and rapidly changing epidemic if all we are worried about is the virus mutating.

Selection is overwhelmingly the most powerful force shaping evolution. The selective regimes that pathogens face are affected by the physical and biotic environments in which pathogens are embedded. Critically, they are also shaped by host behavior. In the case of the current West African epidemic of EVD, the host behavior in question is that of many millions of people at risk, their governments, aid organizations, and the global community. People have a enormous potential to shape the selective regime that will, in turn, shape the pathogen that will infect future victims. This is what we need to be worrying about, not whether the virus will mutate. It saddens and frustrates me that we live in a country where evolution is so profoundly misunderstood that even our most esteemed, and otherwise outstanding sources of information and opinion don’t understand the way nature works and the way that human agency can change its workings for our benefit or detriment.

# Quick and Dirty Analysis of Ebola

I've been traveling all summer while this largest Ebola Virus Disease (EVD) outbreak in recorded history has raged in the West African countries of Guinea, Sierra Leone, Liberia, and (worryingly) Nigeria. My peripatetic state has meant that I haven't been able to devote as much attention to this outbreak as I would like to. There is a great deal of concern -- some might say hysteria -- about EVD and the possibility that it may go pandemic. Tara Smith at least, on her Aetiology blog, has written something sensible, noting that EVD, while terrifying, is controllable with careful public health protective measures, as the historical record from Uganda shows. A recent post by Greg Laden got me to thinking about the numbers from the current EVD outbreak and what we might be able to learn.

EVD was the model disease for the terrible (1995) Dustin Hoffman movie, Outbreak. As we learned in the much more scientifically-accurate (2011) movie Contagion (which is based on an equally terrifying aerosolized Nipah virus), one of the key pieces of information regarding an epidemic is the basic reproduction number, $R_0$. The basic reproduction number tells us how many secondary infections are expected (i.e., on average) to be produced by a single, typical case at the outset of an epidemic before the pool of susceptible people has been depleted.  $R_0$ provides lots of information about epidemics, including: (1) the epidemic threshold (i.e., whether or not an epidemic will occur, which happens in the deterministic case when $R_0 > 1$), (2) the initial rate of increase of an epidemic, (3) the critical vaccination threshold (i.e., what fraction of the population you need to vaccinate to prevent an outbreak), (4) the endemic equilibrium of an infection (i.e., the fraction of the population that is infected in between outbreaks), and (5) the final size of the epidemic (i.e., the fraction of the total population that is ever infected when the epidemic is over).

Thus, for a novel outbreak, it's good to have an idea of $R_0$. I've been a bit out of the loop this summer and haven't seen any estimates so I figured that I would see what I could do. I fully realize that someone may have already done this and that I am not yet aware of it. I also recognize that, if someone has done this, they've probably done it better. This is a blog, not a peer-reviewed paper, and I am away from my usual resources, so please take this in the back-of-the-envelope spirit in which it is intended. I reserve the right to retract, etc. I will also post the R code that I used to make the calculations. I hope that this may prove helpful to others interested in the dynamics of outbreaks.

In their terrific (2003) paper on the SARS outbreak, Marc Lipsitch and colleagues provided a method for estimating the reproduction number from outbreak data. Note that this is a more generalized reproduction number, which we call $R$, than is the basic reproduction number, $R_0$. The key difference is that a reproduction number can be calculated at any point in an outbreak, whereas $R_0$ is only technically correct at the outset (the zero index in $R_0$ indicates the "generation" of the outbreak where "0" refers to the index case, a.k.a., "patient zero"). I've simply used the count of total cases from this week. It is straightforward to extend the calculation to previous counts. I haven't yet had a chance to do this because there is no convenient collection of data that I can find with my current access constraints.

The method involves equating $R_0$ for a simplified SEIR system to the observed rate of increase of the outbreak at some point in time $t$, using the fact that the reproduction number is approximately equivalent to the growth rate of the epidemic. See the supplementary information from Lipsitch et al. (2003) for details of the method. In brief, we calculate the dominant eigenvalue of the linearized SEIR model, for which it is straightforward to write an analytical formula, and equate this to $log[Y(t)]/t$, the empirical growth rate of the epidemic (where $Y(t)$ is the cumulative number of cases at time $t$). Lipsitch et al. (2003) note that using the standard formula for the characteristic equation of the eigenvalues of the linearized SEIR model, we can solve for the reproduction number as:

where $V$ is the serial interval (i.e., the summed duration of the incubation period, $L$, and the duration of the infectious period, $D$), $\lambda$ is the positive root of the characteristic equation which we set equal to $\log[Y(t)]/t$, and $f$ is the ratio of the infectious period of the serial interval.

I got the case data from the weekly WHO outbreak report for 11 August 2014. For this week $Y(t)=1848$. For the start time of the epidemic in the currently afflicted countries, I used the date of 10 March 2014, taken from this week's NEJM paper by Blaize et al. (2014). For the serial interval data, I used the values provided by the Legrand et al. (2007). Because Legrand et al. (2007) provide mean values of the relevant parameters -- and this is a different epidemic -- I used a variety of values for $D$ and $L$ to calculate $R$. It turns out that it doesn't matter all that much; the estimates of $R$ are pretty stable.

I plot the values of $R$ against the duration of the latent period. The different lines are for the different values of the duration of infectiousness. $R$ increases with both. What we see is that at this point in the epidemic at least, $R$ ranges from around 1.3 to 2.6, depending on specifics of the course of the disease. This is not all that high -- about the same as various flavors of influenza and considerably less than, say, pertussis. This is good news for potential control, if we could just rally some more international support for control of this serious infection...

Here is the R code for doing the calculations and creating this figure:

R:
1. library(lubridate)
2. # number of cases as of 11 August 2014
3. # http://www.who.int/csr/don/2014_08_11_ebola/en/
4. cases <- 1848
5.
6. # start of epidemic in Guinea: 10 March 2014
7. # Blaize et al. (2014), NEJM. DOI: 10.1056/NEJMoa1404505
8. s <- dmy("10-03-14")
9. e <- dmy("11-08-14")
10. t <- e-s
11. # Time difference of 154 days
12.
13. ## incubation period 2-21 days
14. ## http://www.who.int/mediacentre/factsheets/fs103/en/
15. ## duration of infectiousness: virus detected in of lab-infected man 61 days!
16.
17. ## Legrande et al. (2007) use L=7 and D=10
18. ## doi:10.1017/S0950268806007217
19.
20. lambda <- log(cases)/t
21.
22. ## From Lipsitch et al. (2003)
23. ## lambda is the dominant eigenvalue of the linearized SEIR model
24. ## V is the serial interval V = D + L
25. ## D is duration infectious period, L is duration of latent period
26. ## f is the ratio of the the infectious period to the serial interval
27. ## to solve for R set the eigenvalue equal to the observed exponential growth rate of the epidemic log(Y(t))/t
28. Rapprox <- function(lambda,V,f) 1 + V*lambda + f*(1-f)*(V* lambda)^2
29.
30. RR <- matrix(0, nr=10, nc=10)
31. L <- seq(3,12)
32. D <- seq(5,14)
33. for(i in 1:length(L)){
34. for(j in 1:length(D)){
35. RR[i,j] <- Rapprox(lambda,L[i]+D[j],D[j]/(L[i]+D[j]))
36. }
37. }
38.
39. cols <- topo.colors(10)
40.
41. png(file="Ebola-R0-plot1.png")
42. plot(L, RR[1,], type="n", xlab="Duration of Incubation", ylab="Reproduction Number",ylim=c(1,2.5))
43. for(i in 1:10) lines(L, RR[i,], lwd=2, col=cols[i])
44. dev.off()

# EEID 2014 Wrap-Up

It's been a long time since I've written in monkey's uncle. Life has gotten pretty busy and my seeming inability to write brief entries has led me to neglect the blog this year. However, I am freshly back from the Ecology and Evolution of Infectious Disease Conference in Fort Collins, Colorado and feel compelled to give my annual run-down. The conference was hosted by friend and colleague Mike Antolin, Sue Vandewoude, and my erstwhile post-doc, now CSU researcher, Dan Salkeld. Nice job, folks, on a very successful conference.

EEID is pretty much the best meeting. As I noted in last year's post, I love its future-orientation. EEID is a meeting that foregrounds the work of junior scientists and there was, as ever, a tremendous array of human capital on display at this meeting. This drives home to me the importance of investment in professional training and research programs that specifically develop human capital. This community exists in large measure because of the innovative program jointly offered by NSF and NIH. Thanks as ever to the vision and hard work of Josh Rosenthal, Sam Scheiner, and all the funders (e.g., support from The Gates Foundation can be found all around this conference) for this area. It's always great to catch up with smart, fun friends. Plenty of time was spent talking science and drinking craft beer (what a beer town Ft. Collins is!) with the likes of Peter Hudson, Jessica Metcalf, Ottar Bjornstad, Aaron King, Mike Antolin, Tony Goldberg, Issa Cattadori, Maciej Boni, Marm Kilpatrick and, of course, Dan Salkeld. It was nice to meet and chat, if only briefly, with my sometime remote collaborator Paul Sharp, who gave what I understand to be an extremely stimulating keynote on the complicated and surprising evolution of malaria (alas, I missed it as I was delayed getting to Ft. Collins). I also spent some quality time learning about acquired immunity in dogs with Colin Parrish. This may come in handy for some ideas that Jess Metcalf and I have been playing around with.

There is a great tradition of the EEID hike and closing banquet/dance. Ft. Collins provided a beautiful and challenging hike out in Lory State Park. The view from the top of Arthur's Peak was pretty amazing.

At Wednesday's banquet, I'm afraid to say that Princeton once again dominated the dance floor as we all rocked out to the amazing Denver funk/rock/jam band Kinetix (great choice, Mike). The Stanford showing was disappointing in part because of the early departure of some of our most enthusiastic dancers. Don't get cocky though, Princeton. We'll be gunning for you next year.

The entirety of Tuesday morning's session was given over to communicating science. Dan Salkeld warmed up the crowd with some hilarious examples of the reporting frenzy that ensued following the publication of our paper on plague dynamics in prairie dog towns or, more recently, Hillary Young's work showing that excluding large ruminants increases rodent density in Kenya. Wow. Dan also used my Stanford colleague Rebecca Bird's work as an example of how an unexpected story can engage readers and listeners. My collaborator Tony Goldberg gave a talk that was also not lacking in ridiculous headlines thanks to his "viral" nose-tick work. David Quammen, author of outstanding popular science books such as The Song of the Dodo and Spillover (which Bill Durham and I use for our class on environmental change and emerging infectious disease), gave a terrific presentation in which he consolidated a lot of nice, practical advice on the craft of writing engaging work into 18 points, amply illustrated by anecdotes of characters from our field. Sonia Altizer from the University of Georgia introduced the crowd to the opportunities (and pitfalls) of citizen science and suggested that it might just be possible to engage the public in disease ecology data collection. Some examples she identified included the granddaddy of citizen-science in the US run by the Laboratory of Ornithology at Cornell, the ZomBee Watch at SFSU, and her own Project MonarchHealth. If I had to summarize this session in one pithy phrase, I think it would have to be "Yay, ecologists!"

Quammen took to Twitter to call us out for being behind the curve with respect to social media.

While there were, in fact, a few of us tweeting the occasional tidbit from the conference, I think his general point is valid. This stuff is intrinsically interesting and we can do a much better job communicating to broad publics.

Some talks that really caught my attention.

Ary Hoffmann gave a great talk about the complexities of using bacteria of the genus Wolbachia to control the Aedes mosquitoes that transmit dengue in Australia (and elsewhere). Wolbachia infects mosquitoes and can have a variety of effects on their biology. The reason artificial infection of mosquitoes wit this bacterium seems so promising as a means of biological control is that the offspring of crosses between infected and uninfected mosquitoes are not viable. This is obviously a very substantial fitness cost to the mosquitoes and this creates serious challenges for getting the infected mosquitoes to persist and take over local populations. Hoffmann presented a cool result about the invasibility of infected mosquitoes wherein in the early phases of introduction there is an unstable point in the mosquito dynamics. At this point, if the infected mosquitoes are above a threshold, they will successfully invade, otherwise, they will die out because of the inherent fitness costs of the Wolbachia infection. One policy challenge that arises is that to get a local population of mosquitoes above the invasibility threshold, researchers and vector-control specialists have to sometimes introduce a lot of mosquitoes. This means that the number of mosquitoes locally can increase substantially and, as you can imagine, this isn't always popular with communities.

Fellow Anthropologist Aaron Blackwell from UCSB gave a fantastic talk on our "old friends", the helminths (cue the freaky electron micrograph of a helminth's mouth!). Aaron participates in the Tsimane Health and Life History Project which was started by colleagues Mike Gurven (also at UCSB) and Hilly Kaplan (New Mexico). Using sophisticated multi-state Markov hazard models (go Anthropology!), Aaron showed that co-infection with helminths and Giardia is less frequent than expected among this population that experiences ubiquitous exposure to both pathogens and that, in fact, infection with the one appears to be protective against infection with the other. One of the most provocative results he presented showed that helminth infection actually lowered systolic blood pressure in men by an amount equivalent to the increase that comes from aging ten years. Chronic helminthic infection may be a reason why Tsimane men's systolic blood pressure does not rise precipitously with age as it does in the US. This result, which may provide fresh insights into the mechanisms of hypertension, a major source of morbidity in the US, struck me as particularly poignant given the demeaning comments made about NSF funding for work among the Tsimane from none other than Lamar Smith (R–TX), the chair of the House Committee on Science, Space, and Technology.

Anna Savage, a post-doc with the National Zoo in Washington DC, gave an awesome talk on the comparative immunogenetics of of frogs with respect to infection with the devastating fungal infection, chytridiomycosis. Chytridiomycosis has been identified as a major cause of amphibian extinction worldwide and Anna showed surprising heterogeneity in immune response across frog species. This is a subject with which I have only passing familiarity, but her talk demonstrated an amazing sophistication in integrating different levels of biological organization and making sense of a dauntingly complex problem. I would wager that Dr. Savage is one to keep an eye on.

The organizers tried a scheduling format that was a bit different from last year, wherein each session started with two half-hour talks generally given by somewhat more senior people. The second half of each session was then given over to brief ten-minute talks, typically delivered by more junior people. This format is nicely in keeping with the great EEID tradition of promoting the research of junior scientists. A few short talks that I found especially interesting included one by Sarah Hamer, from Texas A&M, on Chagas disease in the United States. She presented sobering data from national blood-bank surveillance showing a surprising number of Chagas-infected samples coming from donors with no history of travel to Latin America. When pushed by a questioner, she suggested that she would consider Chagas to be endemic in the US, at least in dogs and possibly even in people. Carrie Cizauskas, formerly of Wayne Getz's shop at Berkeley and now with Andy Dobson and Andrea Graham at Princeton, give a nice talk on the role of both stress and sex hormones in mediating macroparasite infection in wild ungulates in Etosha National Park, Namibia. Romain Garnier from Princeton described a very nifty image-processing approach to scanning large volumes of histological slides for indications of infection.

I perhaps didn't see as many posters as I should have. The problem with the poster sessions is that one keeps running into various people one wants to talk to. I did manage to check out the poster of my former freshman advisee and current Princeton EEB student Cara Brook. She's got an awesome PhD project studying the multi-host ecology of infectious disease in Malagasy fruit bats.

I'm looking forward to next year's meeting at the University of Georgia already. I'm also looking forward to resuscitating the pedagogical workshop that used to be a signature feature of this EEID meeting. More on that later...

# Ecology and Evolution of Infectious Disease

I am recently back from the 2013 Ecology and Evolution of Infections Disease Conference at Penn State University. This was quite possibly the best meeting I have ever attended, not even for the science (which was nonetheless impeccable), but for the culture. I place the blame for this awesome culture firmly on the shoulders of the leaders of this field and, in particular, the primary motivating force behind the recent emergence of this field, Penn State's Peter Hudson. Since I had attended the other EEID conference at UGA earlier this Spring (another great conference), I had no intention on attending the Penn State conference this year. Then, one day in late March, Nita Bharti asked me if I was going and mentioned, "You know it's Pete's 60th birthday, right?" Well that sealed it; I really had no choice.  I simply had to go if for no other reason than to pay my due respect to this man I admire so greatly. Pete has the most relentless optimism about the future of science and a willingness to make things happen that I have ever encountered and, in this way, has provided me one of my primary role models as a university professor and mentor. He has played a role in developing so many of the brilliant people who make this field so exciting, it's amazing (just a sample that comes immediately to mind: Ottar Bjornstad, Matt Ferrari, Nita Bharti, Marcel Salathé, Isabella Cattadori, Jamie Lloyd-Smith, Shweta Bansal, Jess Metcalf...). Of course, even as I write this, I realize the joint influence of another major player in the field, Bryan Grenfell, formerly of Penn State but now at Princeton, becomes obvious. A great scientist in his own right, Pete is the master facilitator, providing the support (and institutional interference!) that allows young scholars to thrive. He is a talent-spotter extraordinaire.

The tone set by these great mentors carries through to the whole culture of the conference, where senior people attended the poster sessions, sat with students at lunches and dinners, and schmoozed at the plentiful open-bar mixers. For example, on the first full day of the conference, there was an afternoon poster session that started at 4:30 (we had been in back-to-back sessions since 8:30). This session was preceded by an hour-long poster-teaser session in which grad students and post-docs got up and presented 60-second (and, as Andrew Read noted, not one nanosecond more) teasers of their posters. Bear in mind, this session was entirely comprised of students and post-docs. It was striking that essentially every seat in the house was occupied and all the major players were present. The teasers were great – many were very funny, including a haiku apparently written by a triatomine bug and translated to us by Princeton EEB student Jennifer Peterson.

After the teasers, the conference went en masse to the fancy new Millenium Science Complex (it turns out that Pete Hudson has physical capital projects in addition to human capital ones!). There, participants milled about the 150 posters. After spending quite a bit of time doing this – and dutifully getting pictures of all my lab with their posters – I thought to check the time and realized it was nearly 6:30. The poster session had been going for two hours and nearly everyone was still there, including all the luminaries. It helped that there was free beer. I tweeted my amazement at this realization:

That is, in fact, Princeton's Bryan Grenfell moving fast in the middle of the picture, apparently making a bee-line for Michigan's Aaron King. Andrew Read is in the far background, talking to a poster-presenter (he has that posture).

Scientific highlights for me included Caroline Buckee's talk about measuring mobility in the context of malaria transmission in Kenya and Derek Cummings's talk on the Fluscape Project to measure spatial heterogeneity in influenza transmission in China. I am a long-time fan of this project and it's nice to see the great work that has come out of it. These talks were right in my wheelhouse of interest, but there were plenty other cool ones including Britt Koskella's talk on the dynamics of bacteria and phage on tree leaves.

Stanford was exceedingly well represented at this conference. My lab had no fewer than five posters. Ashley Hazel presented on her work with Carl Simon on modeling gonorrhea transmission dynamics in Kaokoland, Namibia. Whitney Bagge presented her work on remote-sensing of rodent-borne disease in Kenya. Alejandro Feged presented work on the transmission dynamics of malaria in the Colombian Amazon among the indigenous Nukak people. Laura Bloomfield presented her remote sensing and spatial analysis work from our project on the spillover of primate retroviruses in Western Uganda. I closed things out with a minimalist poster on simple graphical models for multiple attractors in vector-borne disease dynamics in multi-host ecologies. In addition to my lab group, Giulio De Leo (with whom I have been running a weekly disease ecology workshop at Woods since winter quarter) was there, helping to bridge all sorts of structural holes in our collective collaboration graphs.

The other thing that comes out of these meetings, especially more intimate ones like EEID, is some actual work on collaborative projects. I managed to find some time to sit down and discuss plans with collaborators as well as do some shameless recruitment for my planned re-submission of the Stanford Biodemography Workshops. I'm really excited about some of these collaborations, including one that brings together my two major areas of interest: biodemography and life history theory and infectious disease ecology.

Oh, and I'm convinced that there must be an interpretive dance component to the Ph.D. exam in the Grenfell lab. This is certainly the most parsimonious explanation for much of what I saw Wednesday night.

# Ecology and Evolution of Infectious Disease, 2013

I am recently back from the Ecology and Evolution of Infectious Disease (EEID) Principal Investigators' Meeting hosted by the Odum School of Ecology at the University of Georgia in lovely Athens. This is a remarable event, and a remarkable field, and I can't remember ever being so energized after returning from a professional conference (which often leave me dismayed or even depressed about my field). EEID  is an innovative, highly interdisciplinary funding program jointly managed by the National Science Foundation and the National Institutes of Health. I have been lucky enough to be involved with this program for the last six years. I've served on the scientific review panel a couple times and am now a Co-PI on two projects.

We had a big turn-out for our Uganda team in Athens and team members presented no fewer than four posters. The Stanford social networks/human dimensions team (including Laura Bloomfield, Shannon Randolph and Lucie Clech) presented a poster ("Multiplex Social Relations and Retroviral Transmission Risk in Rural Western Uganda") on our preliminary analysis of the social network data. Simon Frost's student at Cambridge, James Lester, presented a poster ("Networks, Disease, and the Kibale Forest") analyzing our syndromic surveillance data. Sarah Paige from Wisconsin presented a poster on the socio-economic predictors of high-risk animal contact ("Beyond Bushmeat: Animal contact, injury, and zoonotic disease risk in western Uganda") and Maria Ruiz-López, who works with Nelson Ting at Oregon, presented a poster on their work on developing the resources to do some serious population genetics on the Kibale red colobus monkeys ("Use of RNA-seq and nextRAD for the development of red colobus monkey genomic resource").

Parviez Hosseini, from the EcoHealth Alliance, also presented a poster for our joint work on comparative spillover dynamics of avian influenza ("Comparative Spillover Dynamics of Avian Influenza in Endemic Countries"). I'm excited to get more work done on this project which is possible now that new post-doc Ashley Hazel has arrived from Michigan. Ashley will oversee the collection of relational data in Bangladesh and help us get this project into high gear.

The EEID conference has a unique take on poster presentations which make it much more enjoyable than the typical professional meeting. In general, I hate poster sessions. Now, don't get me wrong: I see lots of scientific value in them and they can be a great way for people to have extended conversations about their work. They can be an especially great forum for students to showcase their work and start the long process of forming professional networking. However, there is an awkwardness to poster sessions that can be painful for the hapless conference attender who might want, say, to walk through the room in which a poster session is being held. These rooms tend to be heavy with the smell of desperation and one has to negotiate a gauntlet of suit-clad, doe-eyed graduate students desperate to talk to anyone who will listen about their work. "Please talk to me; I'm so lonely" is what I imagine them all saying as I briskly walk through, trying to look busy and purposeful (while keeping half an eye out for something really interesting!).

The scene at EEID is much different. All posters go up at the same time and the site-fidelity of poster presenters is the lowest I have ever seen. It has to be since, if everyone stuck by their poster, there wouldn't be anyone to see any of them! What this did was allow far more mixing than I normally see at such sessions and avoid much of the inherent social awkwardness of a poster session. Posters also stayed up long past the official poster session. I continued to read posters for at least a day after the official session ended. Of course, it helps that there was all manner of great work being presented.

There were lots of great podium talks too. I was particularly impressed with the talks by Charlie King of Case Western on polyparasitism in Kenya, Maria Diuk-Wasser of Yale on the emergence of babesiosis in the Northeast, Jean Tsao (Michigan State) and Graham Hickling's (Tennessee) joint talk on Lyme disease in the Southeast, and Bethany Krebs's talk on the role of robin social behavior in West Nile Virus outbreaks. Laura Pomeroy, from Ohio State, represented one of the other few teams with a substantial anthropological component extremely well, talking about the transmission dynamics of foot-and-mouth disease in Cameroon. Probably my favorite talk of the weekend was the last talk by Penn State's Matt Thomas. They done awesome work elucidating the role of temperature variability on the transmission dynamics of malaria.

It turns out that this was the last EEID PI conference. Next year, the EEID PI conference will be combined with the other EEID conference which was originally organized at Penn State (and is there again this May). This combining of forces is, I'm sure, a good thing as it will reduce confusion and probably make it more likely that all the people I want to see have a better chance of showing up. I just hope that this new, larger conference retains the charms of the EEID PI conference.

EEID is a new, interdisciplinary field that has grown thanks to some disproportionately large contributions of a few, highly energetic people. One of the principals in this realm is definitely Sam Scheiner, the EEID program officer at NSF.  The EEID PI meeting has basically been Sam's baby for the past 10 years. Sam has done an amazing job creating a community of interdisciplinary scholars and I'm sure I speak for every researcher who has been heavily involved with EEID when I express my gratitude for all his efforts.

# New Publication, Emerging infectious diseases: the role of social sciences

This past week, The Lancet published a brief commentary I wrote with a group of anthropologist-collaborators. The piece, written with Craig Janes, Kitty Corbett, and Jim Trostle, arose from a workshop I attended in lovely Buenos Aires back in June of 2011. This was a pretty remarkable meeting that was orchestrated by Josh Rosenthal, acting director of the Division of International Training and Research at the Fogarty International Center at NIH, and hosted in grand fashion by Ricardo Gürtler of the University of Buenos Aires.

Our commentary is on a series of papers on zoonoses, a seemingly unlikely topic for about which a collection of anthropologists might have opinions. However, as we note in our paper, social science is essential for understanding emerging zoonoses. First, human social behavior is an essential ingredient in $R_0$, the basic reproduction number of an infection (The paper uses the term "basic reproductive rate," which was changed somewhere in production from the several times I changed "rate" to "number"). Second, we suggest that social scientists who participate in primary field data collection (e.g., anthropologists, geographers, sociologists) are in a strong position to understand the complex causal circumstances surrounding novel zoonotic disease spill-overs.

We note that there are some challenges to integrating the social sciences effectively into research on emerging infectious disease. Part of this is simply translational. Social scientists, natural scientists, and medical practitioners need to be able to speak to each other and this kind of transdisciplinary communication takes practice. I'm not at all certain what it takes to make researchers from different traditions mutually comprehensible, but I know that it's more likely to happen if these people talk more. My hypothesis is that this is best done away from anyone's office, in the presence of food and drink. Tentative support for this hypothesis is provided by the wide-ranging and fun conversations over lomo y malbec. These conversations have so far yielded at least one paper and laid the foundations for a larger review I am currently writing. I know that various permutations of the people in Buenos Aires for this meeting are still talking and working together, so who knows what may eventually come of it?

# New Grant, Post-Doc Opportunity

Biological and Human Dimensions of Primate Retroviral Transmission
One of the great enduring mysteries in disease ecology is the timing of the AIDS pandemic. AIDS emerged as a clinical entity in the late 1970s, but HIV-1, the retrovirus that causes pandemic AIDS, entered the human population from wild primates many decades earlier, probably near the turn of the 20th century. Where was HIV during this long interval? We propose a novel ecological model for the delayed emergence of AIDS. Conceptually, in a metapopulation consisting of multiple, loosely interconnected sub-populations, a pathogen could persist at low levels indefinitely through a dynamic balance between localized transmission, localized extinction, and long-distance migration between sub-populations. This situation might accurately describe a network of villages in which population sizes are small and rates of migration are low, as would have been the case in Sub-Saharan Africa over a century ago.
We will test our model in a highly relevant non-human primate system. In 2009, we documented three simian retroviruses co-circulating in a metapopulation of wild red colobus monkeys (Procolobus rufomitratus) in Kibale National Park, Uganda, where we have conducted research for over two decades. We will collect detailed data on social interactions, demography, health, and infection from animals in a core social group.
We will also study a series of 20 red colobus sub-populations, each inhabiting a separate, isolated forest fragment. We will determine the historical connectivity of these sub-populations using a time series of remotely sensed images of forest cover going back to 1955, as well as using population genetic analyses of hypervariable nuclear DNA markers. We will assess the infection status of each animal over time and use viral molecular data to reconstruct transmission pathways.
Our transmission models will define the necessary conditions for a retrovirus to persist, but they will not be sufficient to explain why a retrovirus might emerge. This is because human social factors ultimately create the conditions that allow zoonotic diseases to be transmitted from animal reservoirs and to spread. We will therefore conduct an integrated analysis of the root eco-social drivers of human-primate contact and zoonotic transmission in this system. We will study social networks to understand how social resources structure key activities relevant to human-primate contact and zoonotic transmission risk, and we will explore knowledge, beliefs, and perceptions of human-primate contact and disease transmission for a broad sample of the population. We will reconcile perceived risk with actual risk through a linked human health survey and diagnostic testing for zoonotic primate retroviruses.
The ultimate product of our research will a data-driven set of transmission models to explain the long-term persistence of retroviruses within a metapopulation of hosts, as well as a linked analysis of how human social factors contribute to zoonotic infection risk in a relevant Sub-Saharan African population. Our study will elucidate not only the origins of HIV/AIDS, but also how early-stage zoonoses in general progress from "smoldering" subclinical infections to full-fledged pandemics.

I am thrilled to report that our latest EID project proposal, Biological and Human Dimensions of Primate Retroviral Transmission, has now been funded (by NIAID nonetheless!).  I will briefly describe the project here and then shamelessly tack on the full text of our advertisement for a post-doc to work as the project manager with Tony Goldberg, PI for this grant, in the College of Veterinary Medicine, University of Wisconsin, Madison.  This project will complement the ongoing work of the Kibale EcoHealth Project. The research team includes: Tony, Colin Chapman (McGill), Bill Switzer (CDC), Nelson Ting (Iowa), Mhairi Gibson (Bristol), Simon Frost (Cambridge), Jennifer Mason (Manchester), and me. This is a pretty great line-up of interdisciplinary scholars and I am honored to be included in the list.

Biological and Human Dimensions of Primate Retroviral Transmission

One of the great enduring mysteries in disease ecology is the timing of the AIDS pandemic. AIDS emerged as a clinical entity in the late 1970s, but HIV-1, the retrovirus that causes pandemic AIDS, entered the human population from wild primates many decades earlier, probably near the turn of the 20th century. Where was HIV during this long interval? We propose a novel ecological model for the delayed emergence of AIDS. Conceptually, in a metapopulation consisting of multiple, loosely interconnected sub-populations, a pathogen could persist at low levels indefinitely through a dynamic balance between localized transmission, localized extinction, and long-distance migration between sub-populations. This situation might accurately describe a network of villages in which population sizes are small and rates of migration are low, as would have been the case in Sub-Saharan Africa over a century ago.

We will test our model in a highly relevant non-human primate system. In 2009, we documented three simian retroviruses co-circulating in a metapopulation of wild red colobus monkeys (Procolobus rufomitratus) in Kibale National Park, Uganda, where we have conducted research for over two decades. We will collect detailed data on social interactions, demography, health, and infection from animals in a core social group.

We will also study a series of 20 red colobus sub-populations, each inhabiting a separate, isolated forest fragment. We will determine the historical connectivity of these sub-populations using a time series of remotely sensed images of forest cover going back to 1955, as well as using population genetic analyses of hypervariable nuclear DNA markers. We will assess the infection status of each animal over time and use viral molecular data to reconstruct transmission pathways.

Our transmission models will define the necessary conditions for a retrovirus to persist, but they will not be sufficient to explain why a retrovirus might emerge. This is because human social factors ultimately create the conditions that allow zoonotic diseases to be transmitted from animal reservoirs and to spread. We will therefore conduct an integrated analysis of the root eco-social drivers of human-primate contact and zoonotic transmission in this system. We will study social networks to understand how social resources structure key activities relevant to human-primate contact and zoonotic transmission risk, and we will explore knowledge, beliefs, and perceptions of human-primate contact and disease transmission for a broad sample of the population. We will reconcile perceived risk with actual risk through a linked human health survey and diagnostic testing for zoonotic primate retroviruses.

The ultimate product of our research will a data-driven set of transmission models to explain the long-term persistence of retroviruses within a metapopulation of hosts, as well as a linked analysis of how human social factors contribute to zoonotic infection risk in a relevant Sub-Saharan African population. Our study will elucidate not only the origins of HIV/AIDS, but also how early-stage zoonoses in general progress from "smoldering" subclinical infections to full-fledged pandemics.

Post Doctoral Opportunity

The Goldberg Lab at the University of Wisconsin-Madison invites applications for a post-doctoral researcher to study human social drivers of zoonotic disease in Sub-Saharan Africa.   The post-doc will be an integral member of a new, international, NIH-funded project focused on the biological and human dimensions of primate infectious disease transmission in Uganda, including social drivers of human-primate contact and zoonotic transmission.  This is a unique opportunity for a post-doctoral scholar with training in the social sciences to study human-wildlife conflict/contact and health and disease in a highly relevant ecological setting.  The following criteria apply.

1. Candidates must have completed or be near to completing a PhD in the social sciences, in a discipline such as anthropology, geography, sociology, behavioral epidemiology, or a relevant discipline within the public health fields.
2. Candidates must have a demonstrated interest in health and infectious disease.
3. Candidates must have prior field experience in Sub-Saharan Africa.
4. Candidates must be willing to relocate to Madison, Wisconsin for three years.
5. Candidates must be willing to spend substantial time abroad, including in Sub-Saharan Africa and at partner institutions in the United Kingdom.
6. Candidates must have experience with collection and analysis of both quantitative and qualitative data.  Familiarity with methods such as social network analysis, GIS, participatory methods, and survey design would be advantageous.

The successful candidate will help lead a dynamic international team of students and other post-docs in a multi-institutional, multidisciplinary project.  Duties involve a flexible combination of fieldwork, analyses, and project coordination, in addition to helping to mentor students from North America, Europe, and Africa.  The successful applicant will be expected to explore new research directions of her/his choosing, assisted by a strong team of collaborators.

University of Wisconsin-Madison is a top-notch institution for research and training in the social and health sciences.  Madison, WI, is a vibrant city with outstanding culture and exceptional opportunities for outdoor recreation.

Applicants should send a current CV, a statement of research interests and qualifications (be sure to address the six criteria above), and a list of three people (names, addresses, e-mails) who can serve as references.

Materials and inquiries should be sent to Dr. Tony L. Goldberg (tgoldberg@vetmed.wisc.edu).  Application materials must be received by September 12, 2011 for full consideration; the position is available starting immediately and requires a three-year commitment.

# A New Vector for Leishmania

It isn't every day that we learn about the discovery of an entirely new vector for an important vector-borne disease. A new report by the Australian Department of Agriculture and Fisheries has identified a new species of Leishmania that is transmitted by midges, not the usual vector, sandflies. Leishmania is a vector-borne protozoan parasite that causes an ulcerative disease known as Leishmaniasis or Kala-azar. Leishmaniasis is a disease primarily of the tropics and subtropics and is considered one of the most neglected infectious diseases in the world. The usual vectors are phlebotomine sandflies.

Australia (along with Antarctica) was thought to be the only continent free of Leishmania when locally-acquired infection was detected in kangaroos in Northern Territory in 2003.  Researchers investigating this infection thought that the local sandflies (Sergentomyia spp.) seemed highly unlikely vectors because they show a strong preference for feeding on reptiles. Indeed, screening for Leishmania in 3046 Sergentomyia sandflies yielded none infected with Leishmania. This led the researchers to expand the vectors tested. What they found was an unnamed species of day-feeding midge (Lasiohelea sp.) that was infected with a prevalence of up to 15 percent. This is the first identified vector for Leishmania that is not a phlebotomine sandfly. Not much is known about this midge.  The researchers were unable to find breeding sites, for example. The presence of prolegs on the midge larvae suggest that it is not aquatic but is terrestrial or semi-acquatic.  The authors suggest looking for midge breeding sites in the moist soil near water troughs where kangaroos drink.

Finding a totally new vector for a disease carries with it implications for eradication and control. One possibility raised by this work is that the difficulty some control programs have experienced may reflect the fact that Leishmania is being transmitted by multiple vectors. This is an hypothesis well worth investigating in areas other than Australia.

This work formed the basis of the Ph.D. dissertation for Annette Dougall at Charles Darwin University, Menzies School of Health Research.  Nice work, Annette!

# Mutant Fungus Threatening World Wheat Supplies

A mutant strain of the wheat stem rust fungus, Puccinia graminis f. sp. tritici, has emerged that threatens as much as 60 million tons of world wheat production.  The story of this emergence can be found here.  There is a clearinghouse of information on the Borlaug Global Rust Initiative website. The emergence of such a potentially devastating crop pathogen highlights once again the practical importance of evolutionary biology for understanding major world problems.

# Pssst, Swine Flu is Still Here

The coming Aporkalypse appears to have faded into last week's obscurity. With WHO raising the pandemic alert from 3 to 5 in the span of about 24 hours, it seemed that Oinkmageddon was upon us.  But now it's hard to find a news piece on swine flu, let alone an inflammatory one. This is something that worries me and lots of other public health professionals. Not so much the lack of inflammatory new pieces. More, I worry that people are going to see this incident of just another case of health officials needlessly pushing the panic button.  There is always the possibility that the public health measures enacted to control extensive spread of Influenza A(H1N1) may have actually worked! The epidemic fizzling when the alert goes to level 5 is really the best possible case, right? Alas, I doubt that it's really the case.  As I noted before, it seems unlikely that we will have extensive sustained transmission in the northern hemisphere at this late date. But case counts continue to grow globally and the austral flu season starts in the not-too-distant future.

WHO publishes case counts each day, and I have plotted them from 30 April through 13 May.  These are the worldwide confirmed cases as of this morning.

We can see that the case count does, in fact, increase each day and shows no sign of slowing down. This is true, incidentally, whether one plots the cumulative number of the incident number -- clearly this plot is more dramatic, but the incidence does not show any obvious sign of decline. Of course, there is an inherent lag in the reporting of confirmed cases, so it is at least possible that the number of cases has peaked.  But I doubt it.  Recent analysis by an international team of epidemiologists suggests that the reproduction number (the average number of secondary cases produced by a single primary case in a completely susceptible population) is substantially greater than that of seasonal flu.  The reproduction number tells us how fast and how far an infectious disease will spread and how many people will ultimately be infected and higher values of the reproduction number mean faster, further and more. This team also found that the estimated case fatality ratio is less than that of the 1918 pandemic strain but comparable to the 1957 pandemic strain.  So, given proper environmental conditions for transmission, this variant of the flu looks like it could spread rapidly, widely, and cause a decent amount of mortality.  It seems entirely possible that this is exactly what will happen in the southern hemisphere in the coming months, after which it will come back and hit here in the north.

As I noted before, I can hope is that people have not become inured to warnings of epidemics because of our recent experience with H5N1 bird flu and this new H1N1 swine flu (there is also the last swine flu scare of 1976).  Some saner press coverage would help. Of course, it would mean less grist for the mills of John Stewart and Stephen Colbert, but it might mean a public better prepared for a potentially real public health emergency that we still may face.