Clusters of Influenza Virus

This image and description give details on how the influenza virus has evolved in clusters. Seasonal vaccinations increase the distance between clusters by selecting against certain strains.

Smith, D.J., A.S. Lapedes, J.C. de Jong, T.M. Bestbroer, G.F. Rimmelswaan, A.D.M.E. Osterhaus et.al. Mapping the Antigenic and Genetic Evolution of Influenza Virus. Science Magazine. 305(5682): 371-376, 2004.

Hannah Millimet

Cholera

V.  cholerae, bacteria responsible for cholera.

Photo taken from www.npr.org/blogs/health

Vibrio cholerae, the bacteria responsible for the disease cholera, claims over one hundred thousand lives every year and can spread explosively among populations. The virus is highly transmittable and must be ingested to spread infection. Many people act merely as carriers of the disease meaning they house the bacteria in their bodies but display no symptoms of infection, making the disease very difficult to eradicate. For those individuals unlucky enough to succumb to their bacterial guests, death comes as a result of dehydration caused by excessive watery diarrhea. The world has experienced 7 separate cholera pandemics since the 19th century.

http://nationalpostcomment.files.wordpress.com/2010/11/cholera1125.jpg

Due to its virulent nature and significant impact on human health and history, cholera has been studied and observed by the scientific community for quite some time. Scientists have developed used cholera to develop vaccines as well as learn more about the spread of diseases and the rapidity of bacterial evolution among infectious diseases. Much like Streptococcus pneumoniae, the bacteria responsible for diseases like pneumonia, V. cholerae evolves quickly to produce more effective and dangerous strains to infect human hosts. While the tendency of cholera causing bacteria to evolve rapidly may appear to have only negative implications, it actually helps epidemiologists track and control potential outbreaks. Scientists can draw on DNA databases filled with the genetic code for all current and past strains of V. cholerae to use as comparison with  new outbreaks of the disease. This allows governments to determine the cause and track the spread of the disease in order to contain and treat it. Recently this method of using genetic information to compare strains of V. cholerae helped the Haitian government track the cause of the recent 2010 outbreak of cholera to UN workers from Nepal. (http://www.bbc.co.uk/news/world-latin-america-21542842)

Sources:

http://www.cdc.gov/mmwr/preview/mmwrhtml/mm6117a4.htm

http://www.who.int/mediacentre/factsheets/fs107/en/index.html

http://www.npr.org/blogs/health/2010/10/29/130923065/tracking-the-origins-of-haiti-s-cholera-strain

http://www.pnas.org/content/100/3/1304.full.pdf

Is Pertussis Evolving to Fight Vaccines?

Pertussis, more commonly known as whooping cough, has unfortunately shown a strong resurgence within the past few years not only in the United States, but in countries across the globe as well.  In fact, there were a reported 27, 550 cases of pertussis in the United States in 2010, marking the year as that with the most numerous cases of the infection since 1959.  This new-found prominence in the disease has in turn resulted in a variety of public service announcements, on the radio and television, warning the general public of the symptoms and the importance of vaccination, especially for those with infants, as they tend to be the group most susceptible to the infection.  Without a doubt, the most resonating part of the segments are the sound bites of infants first going into coughing fits before beginning to gasp for air, the characteristic whooping sound, placed intermittently throughout the duration of the message.  If the information in the public service announcement does not catch your attention, the pained sounds of sick infants definitely will.

Pertussis is a highly contagious respiratory disease caused by an infection by the bacteria Bordetella pertussis.  The bacteria attack the upper respiratory system, releasing toxins that cause inflammation.  This in turn causes those infected to descend into bursts of rapid coughs which are then followed by a period of attempting to draw in as much air as possible in order to recover from the depletion in oxygen levels in the body due to the long coughing spells.  The disease often leads to the development of pneumonia, and in the worst cases the depletion in oxygen levels can lead to brain damage and even death.  For this reason, physicians highly recommend vaccination to those in direct contact with infants as it has shown to significantly decrease the chance of spreading the disease.

Despite the effectiveness of vaccination, public health studies have shown that pertussis has again begun to reemerge, but unexpectedly in countries with highly vaccinated populations.  Though factors such as decreases in vaccine coverage and vaccine quality could play a role in this resurgence of the disease, researchers in the Netherlands hypothesize that the bacteria has evolved to resist the effects of vaccines.

To test this theory, the researchers collected bacteria strains from 1949 to 1996, grouping them into periods of 5 to 8 years, and determined the frequency of different DNA fingerprint types within each of said periods.  The results showed a distinct difference between in the fingerprints types found before and after usage of the vaccine became widespread.  Moreover, the results showed that genotypic diversity drastically decreased soon after implementation of the vaccine, suggesting that only those bacteria with the correct genetic coding were able to resist being wiped out.  However, over the years the genotypic diversity has increased, implying that those surviving strains have continued to adapt and mutate so as to remain unaffected by vaccines.

In addition, the researcher also investigated the effects of the polymorphism observed in pertussis toxin and pertactin, two important virulence factors necessary for the bacteria to be able to bind to the host’s cells.  Results showed the polymorphisms were non-conservative for the most part, which would imply that Darwinian selection plays an important role in this adaption found in the bacterial DNA.  Specifically, results showed that tandem repeats in the coding existed near the RGD amino acid motif, making the area quite susceptible to mutation as a result of slipped-strand mispairing during DNA replication.  Said mutations affect areas of the bacteria related to binding with T-cells, causing those bacteria with sequences most distinct from those found in the pre-vaccination era selected to be selected.  Because of the mutations, the receptor binding area has changed such that the host’s T-cells can no longer bind to the bacteria, meaning that the bacteria no longer has to fear being eliminated from the host.

Though the usage of vaccines to help fight the spread of pertussis has without a doubt been quite beneficial at reducing the number of pertussis-related deaths over the decades, it would seem that yet again the bacteria are adapting and evolving to resist the effects of said vaccines.  Those bacteria able to survive the initial wave of vaccines have evolved and given way to new mutants that are beginning to show resistance against T-cells.  Though this is most likely not the only reason why pertussis has shown an increase in activity within the past few years, it does open up more doors towards the continued effort to eventually bring immunity towards the disease hopefully sometime in the future.

Danielle Spencer

Word Count:  760

References:

1.  http://www.cdc.gov/pertussis/

2.  Mooi, Frits R., Inge H. M. van Loo, Audrey J. King. Adaptation of Bordetella pertussis to Vaccination: A Cause for Its Reemergence? Emerging Infectious Diseases. 7(3, Supplement): 526-528, 2001.

Image from: http://medblog.medlink-uk.net/gangnamlad/files/2013/02/whooping-cough.jpg

A Race to Evolve - The Evolution of HIV in Response to Pharmaceuticals by Jesse Passman

One of the most publicized diseases of this day and age is the Human Immunodeficiency Virus, or HIV.  Since its emergence a few decades ago, the rise of its infection rates and total occurrence have been a concern, especially in developing nations.  HIV today infects 50,000 new individuals in the U.S. a year and the CDC estimates that 1,150,000 people area already infected in the U.S.  While many diseases that plague humanity have effective vaccines available, HIV still does not.  Treatments have been created for HIV infection; however they rarely work for long due to quick evolution of the virus.  This is concerning to all parties involved as without an effective cure or disease control program, the disease is destined to continue its spread.

HIV particles (green) budding from a cell.

HIV, which is spread through blood, semen, and other bodily fluids, is a prime example disease evolution in the modern age.  Its rapid and progressive change in the face of attempted cures has baffled scientists for years.  For instance, after the first antiretroviral drug active against HIV, zidovudine, came out, resistant HIV strains were found in new patients within six years.  But one may wonder why HIV is so much better at evolving in response to drugs than other bacteria and viruses.  The answer is two-fold.  The first aspect comes from just how virulent HIV is.  Its production of new virus and overall virus turnover is extraordinary.  According to Clavel and Hance, the lymphoid tissue of most untreated patients has between 10⁷ and 10⁸ infected cells, each of which has a half-life of one to two days.  To maintain this level, HIV must infect many new cells continuously. 

The second aspect is the rate of mutation between replications of the virus.  When HIV infects a human cell, it hijacks its machinery to create more HIV.  The reverse transcription process it uses, however, is very error prone.  For each copy of the virus that is created, at least one error occurs – a mutation.  While this may not seem significant, when it is extrapolated over the huge population of HIV found in someone’s body, it leads to a diverse set of HIV particles with a diverse set of traits.  Some of them are weaker than your average virus; some are stronger and more effective. 

Such genetic diversity means that many of the drugs coming out may already have HIV strains that are resistant to their effects.  The mutation rate means that those drugs that do not have any natural resistance can only hope that such a mutation will not pop up while treatment is occurring.

Ultimately, the best defense we have in this day and age is to use multiple drugs at once, which is known as highly active antiretroviral therapy (HAART).  This works because the odds that one HIV strain has resistance against all the actions of multiple drugs is much lower than it having resistance against just one action. 

But this strategy cannot work forever.  If we are ever to eradicate (or even cure) HIV, we will need to both crack its constantly changing genetic code and institute social changes to slow its diffusion amongst populations.  Until then, it will just be a constant battle between the rapidly evolving HIV genome and our research institutions.

Word Count: 539

Sources:

Clavel, Fracois, and Allan J. Hance.  "HIV drug resistance." New England Journal of Medicine 350.10 (2004): 1023-1035.

"HIV/AIDS Statistics and Surveillance." Centers for Disease Control and Prevention.  Centers for Disease Control and Prevention, 19 December 2012.  Web.  20 February 2013.

Image source: http://upload.wikimedia.org/wikipedia/commons/1/1a/HIV-budding-Color.jpg

The Evolution of Influenza

           Have you ever wondered why you need to get a new flu shot every year while most vaccinations last a lifetime? The reason for this is the quick evolution of the influenza virus. The virus evolves primarily through reassortment and genetic drift to adapt to vaccinations and other environmental factors. The virus changes structure so quickly that it becomes resistant to old vaccinations and new strains must be developed for each flu season. Current study results indicate that adaptive evolution occurs only sporadically in influenza viruses, and that influenza virus diversity and evolution is strongly affected by chance events, such as reassortment between strains coinfecting a host or the introduction of a particular variant from elsewhere. These factors make predicting future patterns of influenza evolution more difficult, and thus vaccine development is challenging.

            In depth studies of the evolution of the influenza virus have shown interesting trends. The strains tend to group in clusters rather than form a continuous antigenic lineage. This is based on the seasonal immunizations, which select against certain strains. There is a selective advantage for clusters farthest from those in the vaccination.

            The quick evolution of influenza poses a seemingly endless battle to the immune system. Influenza epidemics are estimated to cause 500,000 deaths worldwide per year. Certain strains of influenza have made their mark on human history by proving particularly fatal. These include the Spanish flu of 1918 that killed an estimated 50 million people worldwide, the Asian flu of 1957 that killed 2 million people, the Hong Kong flu in 1968 that killed 1 million people, and the swine flu of 2009, which killed an estimated 295,000 people. The global impact of this virus proves the importance of predicting its evolution to the best of our abilities in order to develop effective vaccinations. However, much of the evolution of influenza is due to random and unpredictable reassortments and genetic drifts, thereby making this task difficult.

Hannah Millimet

Word count: 356

References:

1. http://www.historyofinfluenza.com/

2. Smith, D.J., A.S. Lapedes, J.C. de Jong, T.M. Bestbroer, G.F. Rimmelswaan, A.D.M.E. Osterhaus et.al. Mapping the Antigenic and Genetic Evolution of Influenza Virus. Science Magazine. 305(5682): 371-376, 2004.

Images from:

1. http://medimoon.com/2012/08/fda-approves-vaccines-for-the-2012-2013-influenza-season/

2. http://en.wikipedia.org/wiki/1918_flu_pandemic

Why the hereditary disease hemochromatosis persists

Survival of the Sickest: the Surprising Connections between Disease and Longevity by Dr. Sharon Moalem and Jonathan Price explores the possible evolutionary pressures which have preserved diseases such as hemochromatosis, Type 1 diabetes, high cholesterol levels, and favism. The book gave interesting insights as to why diseases which are deadly today may have been potentiated. While the authors explored several different diseases, this review will focus on the explanations presented for the persistence of hemochromatosis.

Hemochromatosis:

Hemochromatosis, also called iron overload, is a hereditary condition which occurs when the body absorbs too much iron. The result is the accumulation of iron in organs such as the heart, liver, and pancreas, which in turn can lead to complications, including diabetes, liver failure, and heart failure. The symptoms of hemochromatosis can be alleviated through bloodletting, thereby reducing the amount of iron present, or through chelating agents which bind to iron and then may be excreted. If left untreated, hemochromatosis can be deadly.   

Dr. Moalem presents the hypothesis that hemochromatosis, while deadly today, originally protected people from the bubonic plague. Iron is targeted by bacteria, viruses, parasites, and cancer. Disease causing agents require it to persist, and they find it in the human tissue they infect. To combat this, iron is “locked up” when humans become sick in an effort to prevent the disease-causing organism from being able to survive. While people suffering from hemochromatosis have an excess of iron in many tissues, there is less iron than normal present in macrophages, a type of white blood cell. Because the bubonic plague utilized macrophages to spread through the body using the lymphatic system, people who had less iron present in macrophages were less likely to have the plague survive and multiply within the macrophages before it reached the lymph nodes. These people where therefore more likely to survive and pass on the gene for hemochromatosis.

The idea that iron-deficient macrophages are better at combating bacteria has been tested both in vivo and in vitro. In cell culture, iron-deficient macrophages are much more capable of successfully overcoming bacteria. Somali nomads who traditionally have had anemia became more susceptible to infection when given iron supplements. 

During the period of the Black Plague, one of the most famous outbreaks of the bubonic plague, young, healthy men were more likely to die than any other group. At the time, younger men would have been the least likely to have iron-deficiencies, and thus the most vulnerable to the plague. While this is not conclusive evidence as to why hemochromatosis was sustained within the population, it is an interesting hypothesis which is at least partially supported by studies today.

Claire Klimko

Word count: 440 words

Reference:

Moalem, Sharon and Jonathan Prince. Survival of the Sickest: the Surprising Connections between Disease and Longevity. New York: HarperCollins, 2007.

Image from http://en.wikipedia.org/wiki/File:Red_White_Blood_cells.jpg

Welcome!

Welcome to the Process of Evolution! During this semester, we hope to explore how evolution affects and shapes our daily lives through our class and this blog.