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…

Aedes aegypti in San Mateo County

The mosquito, Aedes aegypti, which is the vector for a number of world scourges (e.g., dengue, yellow fever), has been found in San Mateo County (just across San Francisquito Creek from Stanford) for the first time since 1979. That makes three counties in California where the mosquito has been found. While not a panic-inducing development, it would be most excellent if the good people of San Mateo and Santa Clara counties would make sure their yards are free of mosquito breeding habitat!

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.

On The Dilution Effect

A new paper written by Dan Salkeld (formerly of Stanford), Kerry Padgett (CA Department of Public Health), and myself just came out in the journal Ecology Letters this week.

One of the most important ideas in disease ecology is a hypothesis known as the “dilution effect”. The basic idea behind the dilution effect hypothesis is that biodiversity — typically measured by species richness, or the number of different species present in a particular spatially defined locality — is protective against infection with zoonotic pathogens (i.e., pathogens transmitted to humans through animal reservoirs). The hypothesis emerged from analysis of Lyme disease ecology in the American Northeast by Richard Ostfeld and his colleagues and students from the Cary Institute for Ecosystem Studies in Millbrook, New York. Lyme disease ecology is incredibly complicated, and there are a couple different ways that the dilution effect can come into play even in this one disease system, but I will try to render it down to something easily digestible.

Lyme disease is caused by a spirochete bacterium Borrelia burgdorferi. It is a vector-borne disease transmitted by hard-bodied ticks of the genus >Ixodes. These ticks are what is known as hemimetabolous, meaning that they experience incomplete metamorphosis involving larval and nymphal stages. Rather than a pupa, these larvae and nymphs resemble little bitty adults. An Ixodes tick takes three blood meals in its lifetime: one as a larva, once as a nymph, once as an adult. At different life-cycle stages, the ticks have different preferences for hosts. Larval ticks generally favor the white-footed mouse (Peromyscus leucopus) for their blood meal and this is where the catch is. It turns out that white-footed mice are extremely efficient reservoirs for Lyme disease. In fact, an infected mouse has as much as a 90% chance of transmitting infection to a larva feeding on it. The larvae then molt into nymphs and overwinter on the forest floor. Then, in spring or early summer a year after they first hatch from eggs, nymphs seek vertebrate hosts. If an individual tick acquired infection as a larva, it can now transmit to its next host. Nymphs are less particular about their choice of host and are happy to feed on humans (or just about any other available vertebrate host).

This is where the dilution effect comes in. The basic idea is that if there are more potential hosts such as chipmunks, shrews, squirrels, or skunks, there are more chances that an infected nymph will take a blood meal on a person. Furthermore, most of these hosts are much less efficient at transmitting the Lyme spirochete than are white-footed mice. This lowers the prevalence of infection and makes it more likely that it will go extinct locally. It’s not difficult to imagine the dilution effect working at the larval stage blood-meal too: if there are more species present (and the larvae are not picky about their blood meal), the risk of initial infection is also diluted.

In the highly-fragmented landscape of northeastern temperate woodlands, when there is only one species in a forest fragment, it is quite likely that it will be a white-footed mouse. These mice are very adaptable generalists that occur in a wide range of habitats from pristine woodland to degraded forest. Therefore, species-poor habitats tend to have mice but no other species. The idea behind the dilution effect is that by adding different species to the baseline of a highly depauperate assemblage of simply white-footed mice, the prevalence of nymphal infection will decline and the risk for zoonotic infection of people will be reduced.

It is not an exaggeration to say that the dilution-effect hypothesis is one of the two or three most important ideas in disease ecology and much of the explosion of interest in disease ecology can be attributed in part to such ideas. The dilution effect is also a nice idea. Wouldn’t it be great if every dollar we invested in the conservation of biodiversity potentially paid a dividend in reduced disease risk? However, its importance to the field or the beauty of the idea do not guarantee that it is actually scientifically correct.

One major issue with the dilution effect hypothesis is its problem with scale, arguably the central question in ecology. Numerous studies have shown that pathogen diversity is positively related to overall biodiversity at larger spatial scales. For example, in an analysis of global risk of emerging infectious diseases, Kate Jones and her colleagues form the London Zoological Society showed that globally, mammalian biodiversity is positively associated with the odds of an emerging disease. Work by Pete Hudson and colleagues at the Center for Infectious Disease Dynamics at Penn State showed that healthy ecosystems may actually be richer in parasite diversity than degraded ones. Given these quite robust findings, how is it that diversity at a smaller scale is protective?

We use a family of statistical tools known as “meta-analysis” to aggregate the results of a number of previous studies into a single synthetic test of the dilution-effect hypothesis. It is well known that inferences drawn from small samples generally have lower precision (i.e., the estimates carry more uncertainty) than inferences drawn from larger samples. A nice demonstration of this comes from the classical asymptotic statistics. The expected value of a sample mean is the “true mean” of a normal distribution and the standard deviation of this distribution is given by the standard error, which is defined as the standard deviation of the distribution divided by the square root of the sample size. Say that for two studies we estimate the standard deviation of our estimate of the mean to be 10. In the first study, this estimate is based on a single observation, whereas in the second, it is based on a sample of 100 observations. The estimated of the mean in the second study is 10 times more precise than the estimate based on the first because $10/\sqrt{1} = 10$ while $10/\sqrt{100} = 1$.

Meta-analysis allows us to pool estimates from a number of different studies to increase our sample size and, therefore, our precision. One of the primary goals of meta-analysis is to estimate the overall effect size and its corresponding uncertainty. The simplest way to think of effect size in our case is the difference in disease risk (e.g., as measured in the prevalence of infected hosts) between a species rich area and a species poor area. Unfortunately, a surprising number of studies don’t publish this seemingly basic result. For such studies, we have to calculate a surrogate of effect size based on the reported test statistics of the hypothesis that the authors report. This is not completely ideal — we would much rather calculate effect sizes directly, but to paraphrase a dubious source, you do a meta-analysis with the statistics that have been published, not with the statistics you wish had been published. On this note, one of our key recommendations is that disease ecologists do a better job reporting effect sizes to facilitate future meta-anlayses.

In addition to allowing us to estimate the mean effect size across studies and its associated uncertainty, another goal of meta-analysis is to test for the existence of publication bias. Stanford’s own John Ioannidis has written on the ubiquity of publication bias in medical research. The term “bias” has a general meaning that is not quite the same as the technical meaning. By “publication bias”, there is generally no implication of nefarious motives on the part of the authors. Rather, it typically arises through a process of selection at both the individual authors’ level and the institutional level of the journals to which authors submit their papers. An author, who is under pressure to be productive by her home institution and funding agencies, is not going to waste her time submitting a paper that she thinks has a low chance of being accepted. This means that there is a filter at the level of the author against publishing negative results. This is known as the “file-drawer effect”, referring to the hypothetical 19 studies with negative results that never make it out of the authors’ desk for every one paper publishing positive results. Of course, journals, editors, and reviewers prefer papers with results to those without as well. These very sensible responses to incentives in scientific publication unfortunately aggregate into systematic biases at the level of the broader literature in a field.

We use a couple methods for detecting publication bias. The first is a graphical device known as a funnel plot. We expect studies done on large samples to have estimates of the effect size that are close to the overall mean effect because estimates based on large samples have higher precision. On the other hand, smaller studies will have effect-size estimates that are more distributed because random error can have a bigger influence in small samples. If we plot the precision (e.g., measured by the standard error) against the effect size, we would expect to see an inverted triangle shape — or a funnel — to the scatter plot. Note — and this is important — that we expect the scatter around the mean effect size to be symmetrical. Random variation that causes effect-size estimates to deviate from the mean are just as likely to push the estimates above and below the mean. However, if there is a tendency to not publish studies that fail to support the hypothesis, we should see an asymmetry to our funnel. In particular, there should be a deficit of studies that have low power and effect-size estimates that are opposite of the hypothesis. This is exactly what we found. Only studies supporting the dilution-effect hypothesis are published when they have very small samples. Here is what our funnel plot looked like.

Note that there are no points in the lower right quadrant of the plot (where species richness and disease risk would be positively related).

While the graphical approach is great and provides an intuitive feel for what is happening, it is nice to have a more formal way of evaluating the effect of publication bias on our estimates of effect size. Note that if there is publication bias, we will over-estimate our precision because the studies that are missing are far away from the mean (and on the wrong side of it). The method we use to measure the impact of publication bias on our estimate of uncertainty formalizes this idea. Known as “trim-and-fill“, it uses an algorithm to find the most divergent asymmetric observations. These are removed and the precision of the mean effect size is calculated. This sub-sample is known as the “truncated” sample. Then a sample of missing values is imputed (i.e., simulated from the implied distribution) and added to the base sample. This is known as the “augmented” sample. The precision is then re-calculated. If there is no publication bias, these estimates should not be too different. In our sample, we find that estimates of precision differ quite a bit between the truncated and augmented samples. We estimate that between 4-7 studies are missing from the sample.

Most importantly, we find that the 95% confidence interval for our estimated mean effect size crosses zero. That is, while the mean effect size is slightly negative (suggesting that biodiversity is protective against disease risk), we can’t confidently say that it is actually different than zero. Essentially, our large sample suggests that there is no simple relationship between disease risk and biodiversity.

On Ecological Mechanisms One of the main conclusions of our paper is that we need to move beyond simple correlations between species richness and disease risk and focus instead on ecological mechanisms. I have no doubt that there are specific cases where the negative correlation between species richness and disease risk is real (note our title says that we think this link is idiosyncratic). However, I suspect where we see a significant negative correlation, what is really happening is that some specific ecological mechanism is being aliased by species richness. For example, a forest fragment with a more intact fauna is probably more likely to contain predators and these predators may be keeping the population of efficient reservoir species in check.

I don’t think that this is an especially controversial idea. In fact, some of the biggest advocates for the dilution effect hypothesis have done some seminal work advancing our understanding of the ecological mechanisms underlying biodiversity-disease risk relationships. Ostfeld and Holt (2004) note the importance of predators of rodents for regulating disease. They also make the very important point that not all predators are created equally when it comes to the suppression of disease. A hallmark of simple models of predation is the cycling of abundances of predators and prey. A specialist predator which induces boom-bust cycles in a disease reservoir probably is not optimal for infection control. Indeed, it may exacerbate disease risk if, for example, rodents become more aggressive and are more frequently infected in agonistic encounters with conspecifics during steep growth phases of their population cycle. This phenomenon has been cited in the risk of zoonotic transmission of Sin Nombre Virus in the American Southwest.

I have a lot more to write on this, so, in the interest of time, I will end this post now but with the expectation that I will write more in the near future!

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!

Measuring Epidemiological Contacts in Schools

I am happy to report that our paper describing the measurement of casual contacts within an American high school is finally out in the early edition of PNAS. Stanford’s great social science reporter, Adam Gorlick, has written a very nice overview of our paper for the Stanford Report (also here in the LA Times and here on Medical News Today). The lead author, and general force of nature behind this paper, is Marcel Salathé, who until recently was a post-doc here at Stanford in Marc Feldman‘s lab.  This summer, Marcel moved to the Center for Infectious Disease Dynamics at Penn State, a truly remarkable place and now all the better for having Marcel.  From the Penn State end, there is a nice video describing our results as well as well as a brief note on Marcel’s blog.  This paper has not been picked up quite like our paper on plague dynamics this summer, probably because measuring casual contacts in an American high school generally does not involve carnivorous mice.

With generous NSF funding, we were able to buy a lot of wireless sensor motes — enough to outfit every student, teacher, and staff member at a largish American high school so that we could record all of their close contacts in a single, typical day. By “close contact,” we mean any more-or-less face-to-face interaction within a radius of three meters.  As Marcel was putting together this project, we were (once again) exceptionally lucky to find ourselves at Stanford along with one of the world authorities on wireless sensor technology, Phil Levis, of Stanford’s Computer Science department.  Phil and his students, Maria and Jung Woo Lee, made this work come together in ways that I can’t even begin to fathom.  This actually leads me to a brief diversion to reflect on the nature of collaboration.  As with our plague paper or SIV mortality paper, this paper is one where collaboration between very different types of researchers (viz., Biologists, Computer Scientists, Anthropologists) is absolutely fundamental to the success of the work.  In coming up for tenure — and generally living in an anthropology department — the question of what I might call the partible paternity of papers (PPP) comes up fairly regularly. “I see you have a paper with five co-authors; I guess that means you contributed 17% to this paper, no?”  Well, no, actually.  I call this the “additive fallacy of collaboration.” When a paper is truly collaborative, then the contributions of the paper are not mutually exclusive from each other and so do not simply sum.  To use a familiar phrase, the whole is greater than the sum of the parts.  Our current paper is an example of such a truly collaborative project.  Without the contributions of all the collaborators, it’s not that the paper would be 17% less complete; it probably wouldn’t exist. I can’t speak particularly fluently to what Phil, Maria, and Jung Woo did other than by saying, “wow” (thus our collaboration), but I can say that we couldn’t have done it without them.

I’ll talk more about our actual results later.  For now, you’ll either have to read the paper (which is open access), watch the video, or read the overview in the Stanford Report.