Tuesday, December 22, 2015

The Curious Case of Declining Measles Infections

So I had an interesting conversation recently with Destroyed by Science and The Technical Skeptic on the topic of measles death statistics. We were trying to reconcile the US death rate and those published by the WHO. Eventually it dawned on us what the big differences between the two numbers were, so I thought I'd write up a post to discuss it.

The US death rate is 1-2 deaths out of 1,000 cases (0.1 to 0.2%). This makes the measles seem like it really isn't that bad. However, the worldwide death rate is more troubling. Out of 266,701 reported cases there were 145,700 deaths for a rate of 54.6%; this was the source of our confusion. You don't have to be a mathematical genius to realize that 54.6% is not the same as 0.1%. Digging deeper the reasons for this difference becomes quite clear.

A big reason for the dichotomy is because the WHO data is worldwide and is a total. The number of cases and the number of deaths are much lower in developed nations compared to developing nations.

Number of Reported Measles Cases with onset date from May 2015 to Oct 2015 (6M period). 

Because most of the cases are happening in places where the healthcare systems are not as developed, fatalities from the virus are much higher. A big part of this is pneumonia, which occurs in 1 out of every 20 children who contract measles, either from the measles virus itself or as a secondary infection from other viruses or bacteria. Pneumonia is in fact the leading cause of death with the measles. In developed nations hospital care, and antibiotics for cases of bacterial pneumonia, is available for patients which reduces the impact of pneumonia whereas this is not the case in developing countries.

Another factor that reduces the impact of measles in developed nations is the improved nutrition whereas developing nations suffer from malnutrition and deficiencies. In particular, Vitamin A deficiency increases the fatality rate of measles. One of the areas with high numbers of measles cases, SE Asia, also suffers from Vitamin A deficiency despite the availability of a source for Vitamin A that would help alleviate the deficiency: Golden Rice.  This makes opponents of Golden Rice, like GreenPeace, doubly damned as they are not only allowing blindness from Vitamin A deficiency to languish but risking the lives of millions of children to complications from measles.

The final factor that impacts the death rate is the vaccination rate. In most developed nations, or at least until recently, vaccination rates for measles were above 90% which reduces the severity of the disease and reduces the death rate if at least one vaccination dose has been administered and of course more doses offer a higher degree of protection. This has been changing recently with the WHO, The Gates Foundation and others pushing for measles vaccination in developing nations.

Immunization coverage with first measles vaccine dose in infants, 2014

This push for immunization has resulted in dramatic results that cannot be disputed: measles cases worldwide have dropped dramatically since the vaccination program was initiated.

Trend of measles cases compared to vaccination rates worldwide.

So the take away message here is that you can't use the rates in developed nations as the sole determinant for how bad measles can be. After all, measles has a long and brutal history of killing large numbers of peoples exposed to it for the first time. Measles is highly contagious and those exposed to it without the protective antibodies from a vaccine, for example, are very likely to get infected. I won't rest easy around measles until it has gone the way of smallpox or rinderpest (a relative of measles). We also learned that trying to do math late at night is a recipe for disaster.

Sunday, December 13, 2015

What to do when the norovirus comes to visit

So with the Chipotle norovirus outbreak and the fact that everyone in my family, except for me, are suffering from the effects of norovirus infection (most likely a matter of time for me as you can see by the picture it's hard to say no to that face), I thought I'd share some ways to help limit the spread and some general information about the norovirus.

The source of the TMV family norovirus outbreak

The name norovirus refers to the genus norovirus in the family Caliciviridae which has a single species, the Norwalk virus. Within this species there are numerous strains from five genotypes, including a mouse genotype that is used as a model to study the species. For simplicity, I'll refer to the virus by norovirus as that is what it is called in the media most often. They all cause pretty similar symptoms: vomiting and diarrhea that can vary in severity, stomach pain, fever, headache, and body aches.

So how does one avoid the norovirus? One of the simplest measures to limit spread is to wash your hands with soap and water frequently. Washing fruits and vegetables can also help as can avoiding certain foods like oysters that serve as a host for the norovirus (the virus sticks to the oyster). Above all, avoid touching strange surfaces or letting toddlers put random things into their mouths (say in the waiting room of a doctors office). So let's say for example, that your toddler caught the norovirus and is sharing with the whole family. How can you limit the spread so that you don't share with other families? Again, the easiest way is to wash your hands thoroughly with soap and hot water. Alcohol rubs don't do much on their own but may (or may not) be used in conjunction with thorough hand washing. All laundry needs to be washed thoroughly as soon as possible on the longest cycle possible and machine dried. Also, all potentially contaminated surfaces need to be disinfected with bleach (bleach is the best) but do not use disinfectant wipes as they won't do much. Lysol spray is effective and can be used on surfaces that cannot be bleached (such as a carpet). Carpets should be steam cleaned at the end of the outbreak to prevent further spread. But one of the most important things that can be done to limit the spread of the norovirus is to not prepare food for others. This is how norovirus outbreaks are happening in restaurant settings, with a sick or recently sick person coming into work and handling food. A person can shed enough norovirus to be contagious for two days after symptoms have disappeared and the virus can be found in the stool for up to two weeks after as well. A vaccine for the norovirus has been elusive so other than taking precautions before and during an outbreak, there isn't much that can be done. However, there might be hope on the horizon for a vaccine due to some recent developments (a vaccine candidate is in Phase I trials). Until then, wash your hands and be mindful of the risks of certain foods, like oysters.

Thursday, December 10, 2015

Chipotle needs to clean house (literally)

So Chipotle is back in the news for yet another norovirus outbreak. This is in addition to the E. coli outbreak that occurred in several states back in October. So far, 120 Boston College students have been sicked with the norovirus after eating at a Boston Chipotle and have been tested for E. coli as well (those tests are still being processed).
People stand inside a closed Chipotle restaurant Monday in the Cleveland Circle neighborhood of Boston. Steven Senne / AP
Essentially, Chipotle is in serious trouble here due to a mess of their own making. They created a marketing campaign against genetically modified organisms (only removing a few and keeping the majority of them in their soda and cheese) based entirely upon providing food with integrity. Yet they have had serious issues with food safety since they launched the campaign. Some people are claiming a crazy conspiracy against Chipotle is being orchestrated by Monsanto et al.
An example of the conspiracy theories being used here. Hat tip to A Science Enthusiast and The Credible Hulk
However, it is far more likely that employees are not washing their hands and cross contaminating vegetables with raw meat than a company about the size of Whole Foods is riding dirty. Not to be out done, Chipotle is blaming both the media and the CDC for bad PR they are experiencing. They are upset at the media for reporting on outbreaks originating in their stores and they are mad at the CDC for reporting the outbreak statistics each week (based on the numbers they receive from healthcare officials) rather than wait until the end of the outbreak to report the total number. First of all, that is an insane suggestion and will never happen. The CDC releases these weekly numbers so that healthcare officials know what to look for in the case of a large scale outbreak from say a restaurant chain. Second, the CDC and the media are not to blame for Chipotle having what appears to be substandard policies for enforcing the health codes in their restaurants. Chipotle is in serious trouble unless they make some serious changes here. You cannot have food with integrity when you have routine outbreaks of food-borne pathogens.

Wednesday, December 9, 2015

Impact factors are not the same thing as reliability

A very common issue that I see among scientists and science lovers (skeptics, enthusiasts, etc.) is this idea that impact factors are useful in determining the quality and reliability of a scientific study. Some take it to the point that anything with an impact factor less than 10 is questionable. Unfortunately, there are issues with this idea that become apparent once what an impact factor really means is defined. An impact factor is the number of times that the articles in a journal are cited the previous two years divided by the number of articles published that year.

This is the calculation used:
Figure 1: Calculation for journal impact factor.
A= total cites in 1992
B= 1992 cites to articles published in 1990-91 (this is a subset of A)
C= number of articles published in 1990-91
D= B/C = 1992 impact factor

All this means is that the impact factor is telling you how popular the previous year's articles were in the community (as measured by number of citations). Because of how simple this calculation is, it is prone to manipulations that artificially inflate it. There have been quite a few articles and papers detailing the issues with the impact factor including a recent one that talks about some of the damage that impact factor mania leads to. It has gotten to the point where some just accept science in high impact factor journals like Science, Nature and Cell without examining the science despite the dangers of this. Even worse, the impact factor has become part and parcel of the process of getting grants, positions, and tenure despite some people decrying this practice.

How did we get to the point where the impact factor is the end all be all of academic progress and the sole measure of reliability? Part of the problem is that some institutions, grant panels, and science communicators have used the impact factor as a quick measure of reliability. Take what this blogger has said about the impact factor:

"One of the better ways to ascertain scientific research quality to examine the quality of the journal where the research was published. Articles in high quality journals are cited more often, because those journals attract the best scientific articles (which are cited more). Yes, it’s a self-fulfilling system, but that’s not all bad. Some of the most prestigious journals have been around for a century or more, and their reputation is deserved.

Obviously, the best articles are sent to these journals partially because of the prestige of the journal, but also because the peer review is so thorough. Journals use a metric called “impact factor” that essentially states how many times an average article is cited by other articles in an index (in this case for all medical journals).

Not only is this an incorrect explanation of what an impact factor is (remember it is a measure of the number of citations the previous year divided by the number of articles published the previous two years (not the average number of citations per article as stated), but it sets the impact factor on the same level as quality of peer review and reliability. Although it might be true that journals like Cell, Nature and Science are harder to publish in, they also are very specific in what they are interested in publishing (known in academia as scope) and tend to publish flashier pieces. For example, 30 years ago it would be common to publish either the complete or partial genome of a virus in Science or Nature. These days you are more likely to publish such a paper in Genome Announcements or Archives of Virology. Does this mean that the peer review in GA of AoV is not rigorous or that the research published there is lesser quality than those published previously in Science or Nature? It is not likely to be the case due to the advancements in technology that eliminated the novelty (a big draw for journals like Science and Nature) in fact it is likely that the genome coverage is higher and the sequences are more reliable in recent papers than the days when a researcher called the bases on a long polyacrylamide sequencing gel. Does this mean that one journal is better than the other? No, they just have different scopes and therefore foci.

The aforementioned blogger does mention that impact factors aren't the sole determinant of reliability; however, they then come back to impact factors as a shortcut for determining reliability.

"As an independent, objective method to judge the quality of published research, Impact Factor is one of the best available."

Sadly nothing could be further from reality. This makes the assumption that journals with high impact factors never have to retract articles due to fraud. This is not the case as high impact factor journals have more retractions on average than lower impact factor journals. One possible explanation is that journals with a high impact factor have more concrete plans to deal with retractions; however, this has thus far only been studied in high impact factor journals with similar editorial practices regarding retractions and does not account for the increase in retractions as the impact factor increases.

Photo caption: Correlation between impact factor and retraction index. The 2010 journal impact factor s plotted against the retraction index as a measure of the frequency of retracted articles from 2001 to 2010 (see text for details). Journals analyzed were Cell, EMBO Journal, FEMS Microbiology Letters, Infection and Immunity, Journal of Bacteriology, Journal of Biological Chemistry, Journal of Experimental Medicine, Journal of Immunology, Journal of Infectious Diseases, Journal of Virology, Lancet, Microbial Pathogenesis, Molecular Microbiology, Nature, New England Journal of Medicine, PNAS, and Science. Credit: Fang et al., 2011, Figure 1.

Another variable in this discussion of impact factors is that it is very dependent on the field and the focus of the journal. A perfect example of this is the impact factor of journals focusing on entomology. Even the best of these journals only reaches an impact factor of 1-2. Does this mean the research in these journals are not reliable and therefore suspect? Of course not, and here is why. The researchers that will read and cite articles from entomology journals are either entomologists or work in a closely related field. A biomedical researcher is not likely to cite from an entomology journal unless they work with arthropods. It quickly becomes apparent that this is a numbers game. If a field has more people working in it, there will be more citations for journals in that field. Likewise, if a journal has a broader audience base, then they will have more people reading it and citing it.

So how do the virology journals make out in this impact factor game? I've put together a list of the 2014 impact factors for the virology-specific journals I could find. Note: I did not include general focus journals that include papers on virology in this list to help illustrate how field-specific journals suffer from this system.

*Journal publisher is on Beall's List of Predatory Publishers

If you notice, none of these journals, even the review journals, has an impact factor above 10, which people often use as their minimum for trustworthiness. So does this mean that these journals are automatically suspect? What are we to make of a journal published by a publisher on Beall's List having as high of an impact factor as other highly respected virology journals? The answer to both of these questions is simple: there must be something else going on here. In order to determine exactly what is going on, we need to dig deeper into what the impact factor was meant to convey and how it originated.  

The idea of the impact factor dates back to the 1920's with the proposal to produce an index for university librarians to determine which journals were worth purchasing. In 1955, it was mentioned by Dr. Eugene Garfield with the intention of building an index for scientific papers so that outdated or fraudulent work could be put to rest. This original index had the idea of individual papers being cataloged and the number of citations that they had being recorded. This idea lives on in google scholar citations, ResearchGate, Web of Science and several others. Take my google scholar page for example. One can easily see which papers I have published and how many times they have been cited.The original idea for the impact factor was to make citing work easier for researchers. Over time, the idea of the impact factor evolved from comparing individual papers to journals. Dr. Garfield originally intended the journal impact factor to be used to evaluate an author when their most recent papers had not had time to be cited. Dr. Garfield also had this to say about comparing journals across disciplines: "In any case, comparisons should not be made across disciplines unless the data are normalized in to take into account the various parameters that affect impact." This is something that is not done as the raw impact factors are used for the comparisons. 

The usefulness of the impact factor is hotly debated among bibliometricians, with some pointing out rather large flaws in the system. Among the flaws are the ease of impact factor manipulation, the evolution from the journal impact factor from being used as a selective criteria for purchasing to the end all, be all of academia, negative citations carry the same weight as positive citations, that the importance of papers may be noticed after the impact factor, and that some papers that are not cited actually have an impact on the field. A recurring theme among the bibliometricians is that the impact factor is being misused to judge quality of a journal and not the influence. Some are quite blunt in their disapproval of this practice. Take what Dr. Anthony van Raan, director of the Center for Science and Technology Studies at Leiden University in the Netherlands has said about this habit: "If there is one thing every bibliometrician agrees, it is that you should never use the journal impact factor to evaluate research performance for an article or for an individual — that is a mortal sin." Several other alternatives have been proposed, but they would suffer the same fate as the impact factor in that they would be misappropriated as a way to judge quality.  
So what can we do? There is no easy answer or shortcut in determining the quality of a particular paper. The only surefire way to judge an article's quality is to examine its methods, results and conclusions. Another option is to look for a meta analysis or a review covering the article in question as these are often written by experts who have an intimate knowledge of the topic and can determine the impact of the article. However, this runs into the issue that scientists are human with jealousies and grudges that can color their views on work by those they dislike. There really isn't an easy way around it. Sometimes, you just have to go to the data to see the quality of a paper.

So what's the take away from this? From my research on the history and intended use of the impact factor I found that:
  1. The impact factor does not measure reliability, just journal popularity
  2. Higher impact factor journals have higher retraction rates that cannot be explained away as differences in editorial practices as only high impact factor journals have been studied for this
  3. Just because a journal has a high impact factor it does not mean that the articles published there are of high quality
  4. The impact factor of journals in different disciplines and scopes cannot be directly compared without further mathematical adjustment 
  5. There is no real shortcut for determining the quality of a research paper other than examining it critically