Links, news, and paper highlights: January 2016

I’m trying to do a better job of keeping up with parasite ecology and epidemiology related news this year. Here’s some recent work that might be of interest:

Links:

Tasmanian devils have TWO types of infectious cancer!

Romans were wormy, despite relatively good hygienic practices.

The West African Ebola outbreak is over.

It looks like the mosquito-borne Zika virus is the likely culprit of the rapid increase in microcephaly in infants born in Brazil.

Paper highlights:

Pertussis, also known as whooping cough, kills tens of thousands of children per year, despite high global vaccination coverage. Additionally, developed countries with high pertussis vaccine coverage – like the United States – have experienced bigger outbreaks in recent years. Many hypotheses have been suggested to explain the “resurgence” of pertussis: (1) there is waning immunity to the vaccines and adults act as bacterial reservoirs; (2) the new acellular vaccine isn’t as good as the previous whole-cell vaccine; (3) the vaccines protect against infection but not transmission; and (4) there isn’t really a resurgence; we’re just better at detecting pertussis now than we used to be. A recent paper argues that all of those commonly held views are wrong and proposes some new hypotheses. Cool stuff!

Antibiotic resistance is a huge challenge facing global medicine. We usually assume that when bacteria evolve resistance to a given antiobiotic, the mutation that provides resistance is costly. Because we assume that those resistance mutations are costly, we also assume that if we stop using an antibiotic, the bacteria populations will evolve back to their susceptible state by acquiring compensatory mutations that restore the function(s) lost by resistance mutations. But resistance mutations vary in how costly they are. Some aren’t costly at all. And there are only so many compensatory mutations that can restore a given function. So, we can’t necessarily expect a resistant population to revert to susceptibility, whether a compensatory mutation pops up in the population or not. Furthermore, there are many other possible mutations that can reduce or eliminate any cost of resistance just by increasing overall bacterial fitness, without actually returning lost functions. We might be overlooking the importance of those “generally beneficial mutations” in the evolution and subsequent loss of antibiotic resistance in bacterial populations. Check it out.

The Eradication of Infectious Diseases

Did you know that “Guinea worm disease,” also called dracunculiasis, is about to become the second infectious disease of humans to be fully eradicated by a disease control program? Humans become infected by the nematode that causes the disease when they drink unfiltered water that contains the intermediate host for the nematode: copepods. To reduce human infection rates, the Carter Center’s Guinea Worm Eradication Program has led an international effort to educate people about the importance of filtering their water. For instance, a simple straw containing a filter can prevent people from ingesting the copepods that transmit the nematode larvae. The control program has been very successful! Since 1986, the yearly number of reported Guinea worm cases has dropped by 99.99%! Just 126 cases were reported in 2014. We’re so close!

The first human disease to be fully eradicated was smallpox. If you don’t know much about smallpox, here’s the quick version: having smallpox was awful, and the disease was often fatal. But we couldn’t prevent smallpox transmission by giving people special straws with filters. The smallpox virus was transmitted directly between people, and the best way to stop transmission was to vaccinate a sufficient proportion of the population so that they would no longer be susceptible to the disease. In the late 1970s, the whole world hit that vaccination target, and smallpox was eradicated.

Also, here’s an interesting tidbit: recent work coming out of the Democratic Republic of the Congo suggests that during the time of the mass vaccination campaigns, the smallpox virus was actually working double duty by protecting people from the monkeypox virus. Since the 1980s, the incidence of monkeypox has increased dramatically in that region. People who live in forested regions are the most likely to become infected by monkeypox, because the virus is typically hosted by (you guessed it) monkeys (Rimoin et al. 2010). But it turns out that prior vaccination with the smallpox vaccine also reduces monkeypox infection risk. That means that people who weren’t born during the years of mass vaccination (i.e., young people) have a higher risk of becoming infected (Rimoin et al. 2010).

Finally, let’s talk about one more incredible eradication program, but this time let’s focus on a pathogen that didn’t infect humans. Rinderpest, or cattle plague, was a viral disease that infected both wildlife (e.g., wildebeest, buffalo) and cattle. The disease often caused high cattle mortality rates, which resulted in huge economic losses for humans. But after a massive vaccination program, rinderpest was officially declared as eradicated in 2011.

So, there you have it. We have almost eradicated Guinea worms via a long-term education program. And we have successfully eradicated two important viral diseases (smallpox and rinderpest) via massive vaccination programs. Next stop – HIV vaccine?

SuperVaccine

Vaccination Coverage and Herd Immunity

I’ve talked about vaccination and herd immunity on this blog before, but I think it’s important for me to emphasize how INCREDIBLY IMPORTANT it is to get vaccinated.  The importance of vaccinating most of the population is usually explained using mathematics, because scientists study the spread of pathogens by using mathematics.  But today, I’m going to try to explain it with cartoons and pictures, instead of math.

herdimmunity1

herdimmunity2

Without explaining the math, I’ll say that there are some “magic numbers” for vaccination.  These numbers are unique to each pathogen/disease.  For instance, for whooping cough, a disease that can make make babies very sick, the “magic number” is between 92 and 94.  That is, 92-94% of people must be vaccinated in order to prevent disease epidemics of whooping cough.  If that magic number – called the herd immunity threshold – is reached, babies are indirectly protected from whooping cough.  If not, you can expect outbreaks of whooping cough.

So, you might be wondering if there will be outbreaks of whooping cough where you live.  Check out this graphic that was published in Scientific American last year.  If your state’s bar is red – that is, if you live anywhere except Nebraska – you can expect epidemics of whooping cough in your state in the near future.  And while it looks like nobody will be seeing Mumps epidemics any time soon, you can expect to see Measles epidemics in many states.

vaccination coverage

At one point, we’d nearly eliminated whooping cough in the United States by vaccinating children with the DTP vaccine.  Here’s a graph from the CDC showing that after we started using the DTP vaccine around 1950, whooping cough (also called pertussis) almost completely disappeared.  But in the past decade or so, the number of cases reported each year has been increasing. That is likely due to a decline in the effectiveness of the newer pertussis vaccine, rather a decline in vaccination coverage.

pertussis

Vaccination, Herd Immunity, Economics, and International Cooperation

Herd immunity and the herd immunity threshold:

Herd immunity is a type of “immunity” or protection against infection that occurs when so many members of the population have been vaccinated that nonvaccinated individuals have reduced risk of infection.  In earlier posts, I’ve talked about R0, and how parasites/pathogens cannot persist in a closed population if Ro < 1.  Ro depends on the number of susceptible individuals in the population.  Therefore, if we reduce the number of susceptible individuals below some threshold – alternatively, if we increase the proportion of vaccinated individuals to the herd immunity threshold – then R0 < 1, and the parasite/pathogen cannot persist.  The herd immunity threshold varies for each parasite/pathogen, and you can find lists of herd immunity thresholds for common parasites/pathogens on the web (see the wikipedia page, for instance).

Herd immunity explanation from NIAID.

GET VACCINATED:

If you click through to wikipedia, you’ll see that the herd immunity thresholds are pretty high for our bigname parasites/pathogens; 75-94% of the population must be immunized for things like polio, measles, and smallpox.  I’m going to stand on my soapbox for eight sentences:

In 1998, a very unethical man by the name of Andrew Wakefield published a paper where he fraudulently linked the MMR vaccine and autism in children.  Unfortunately, this and the following media frenzy made people question vaccine safety, which made people refuse to get themselves and their children vaccinated.  Even though there is proof that Wakefield fabricated data and was being paid to make this fraudulent link, public uncertainty about vaccination is still high.

When people do not get vaccinated, two things happen.  First, those unvaccinated people are the ones who will be infected by the parasite/pathogen.  Second, the proportion of vaccinated individuals may drop below the herd immunity threshold, allowing the parasite/pathogen to spread through the population and persist.  That means that those individuals who are physically unable to be vaccinated – the very young, the very old, and the immunosuppressed – are no longer protected against infection because individuals who can be vaccinated chose not to be.  So, if any readers of this blog were thinking about forgoing vaccination, please remember that it is not only you and your children at risk, but also all of the people who cannot be vaccinated for medical reasons (like lack of a functioning immune system).

Herd Immunity, Economics, and International Cooperation:

The rest of this post is about a really cool talk I saw at EEID 2013.  It was presented by Petra Klepac, and was titled, “Free ride or vaccinate? Cooperation in control of immunizing infections.”  If you’re interested in the economic/political side of vaccination, you should check out some of her publications.

Typically, when we think about vaccination programs, we think about things at the national level.  Nations need to balance two things when it comes to developing vaccination programs.  They need to try to vaccinate their target proportion of the population, which may mean vaccinating up to the herd immunity threshold, or it may mean vaccinating enough people to go from a “severe” to a “small” epidemic.  That requirement is often influenced by the second requirement: the need to minimize cost.  Sometimes, vaccinating to the herd immunity threshold also minimizes cost.  This is especially true if a disease is particularly harmful economically.  But other times, countries may find that minimum costs can be found when vaccinating less than the herd immunity threshold.  This may occur when a nation is not wealthy enough to invest in high vaccination coverage, when vaccination for a given parasite/pathogen is particularly expensive, when the herd immunity threshold is particularly high, etc.

What if you’re a relatively wealthy nation that can afford to vaccinate to the herd immunity threshold, but a neighboring nation can’t/won’t vaccinate to the herd immunity threshold?  Your vaccination coverage insures that the parasite/pathogen will not persist in your population, but in less you vaccinate 100% of individuals, people may still get sick if travelers carry the parasite/pathogen into your nation.   What to do?!

Petra used game theory models to evaluate how nations should cooperate or cheat when it came to vaccination coverage.  She found that 1) by forming international coalitions that agree on some level of vaccination coverage, nations could reduce costs.  2)  Sometimes, the most cost-effective way to spend vaccination funds was to pay for vaccination programs in a neighboring nation!!!!  3)  The bigger an international coalition became, the cheaper it got to be a “cheating” nation which did not adhere to the same vaccination coverage goal.  Cool stuff!

T-cell Vaccines and Host Pathology

This is one of several posts that I’ll write about the Ecology and Evolution of Infectious Disease conference (EEID).  I’m starting with the very first talk at the conference, because I’m not feeling particularly creative, and chronological order is my default.  🙂

Let’s talk about vaccines.  The vaccines that you’re familiar with are probably vaccines that cause antibody immunity.  For instance, you might be given a bit of dead pathogen, and your immune system learns how to make antibodies that target the pathogen.  For instance, vaccines for influenza, chickenpox, polio, and hepatitis B are meant to help you develop antibody immunity.

But what if the pathogen mostly hangs out in your cells, and antibodies won’t cut it?  This happens with many pathogens that have persistent infections, like HIV and malaria.  As you know, we don’t have vaccines for malaria and HIV, because these antibody-type vaccines won’t work (yet? ever?).

People are working on a different type of vaccine, called a T-cell vaccine.  T-cells are immune cells that find and kill host cells that are infected with pathogens.  The hope is that T-cell vaccines will better enable T-cells to recognize infected cells.

But here’s the problem.  Some people have found that vaccines for these pathogens that hang out inside of cells can actually cause disease/pathology.  That is, individuals (e.g., mice) have greater pathology when they are exposed to a pathogen after being vaccinated than if they hadn’t been vaccinated.  (Note:  I’m talking about vaccines that are still being developed, not ones that we currently use.)  Obviously, we can’t develop useful vaccines until we figure out why they may be increasing infection and causing pathology.

To work on this, Johnson et al. (2011) made a model (which parallels experimental data) of lymphocytic choriomeningitis virus in mice.  What they found was that at low and high densities of T-cells, pathology was low.  But at intermediate levels of T-cells, pathology was high.  In this case, “pathology” was measured in terms of the number of functional host cells, where few functional host cells means high pathology.

Image

My cartoon of Rustom Antia’s graph.

Why should the number of T-cells matter?  Rustom Antia suggested that at low T-cell numbers/density, the virus kills some host cells and the T-cells don’t kill many host cells.  At high T-cell numbers/density, the virus kills few host cells, but the T-cells kill more host cells.  In both cases, not too many host cells are killed.  At intermediate T-cell numbers/density, both the virus and the T-cells kill many host cells, which ends up being detrimental to the host.  Tada!

So, there you have it.  Now, since this isn’t my area of expertise, I recommend checking out the paper that Rustom based his talk on to find out more.

What do you think?  Will we figure out how to use T-cell vaccines in the near future?

References:

Rustom, Antia. 2013. An immuno-epidemiological approach to understanding vaccine efficacy. EEID.

Johnson et al. 2011. Vaccination Alters the Balance between Protective Immunity, Exhaustion, Escape, and Death in Chronic Infections. Journal of Virology 85(11): 5565–5570.