The Mosquitos-Men Foe: the story of Malaria

The Mosquitos-Men Foe: the story of Malaria

Mayleen Lee

To many humans, Mosquitos seem harmless in any possible way: tiny, soft, and squishable.

The reality, however, is unfortunately very ironic.

Mosquitoes have caused more human suffering than any other organism in the human history – more than one million people die from mosquito-transmitted diseases worldwide every year since ancient time.

Malaria perfect demonstrates this formidable foe between mosquitos and men.  Malaria, caused by infection from Plasmodium parasites, is transmitted to people through the bites of infected mosquitoes.  The stings, particularly from Anopheles mosquitoes, would normally lead to seemly mild symptoms such as fever and headache, making them difficult to be recognized as Malaria.  According to the World Health Organization (WHO), untreated Malaria can progress in 24 hours and lead to death.  This makes Malaria the deadliest infectious disease in history, taking 1.2 million lives per year.

The medical world has put lots of efforts into creating effective vaccine for Malaria.  It turns out that, despite our advanced scientific knowledge and technology, we failed at outfoxing evolution - when we attack Malaria germs with drugs, the germs fight back.  Scientists have discovered that the Plasmodium parasites have repeatedly evolved to resist the front-line treatments. The mosquitoes that carry the parasites have rapidly evolved to resist the insecticides we poison them with.  And now, scientist has found that some malaria parasite can cause disease severe enough to cause evolutionary selection pressures in human populations!

Dr. Anna Rosana-Urgell and her collegues from PNG Institute In Medical Research found that Plasmodium vivax malaria is the reason behind the abnormally high rates of Southeast Asian Ovalovytosis (SAO), a hereditary erythrocytes (red blood cell) disorder, in the Asian and Oceanic region.    

In SAO, the red blood cells are a different shape (elliptical) from the usual biconcave disc shape.  This genetic defect is carried by up to 35% of people living on the coasts of Papua New Guinea, an area happened to have high malaria endemic.  The researchers performed genetic tests in 1,975 children and found that nearly 50% of children in Papua New Guinea aged 0-14 years are SAO-positive and immune to P. vivax.  This means that SAO genetic defect may have protective effect against malaria caused by P.vivax by altering the ability of the parasite to develop within the red blood cell.  These findings indicated that P.vivax have caused enough evolutionary pressure that it has influence genetic adaption of the human population.

As Professor Andrew Read, a biologies and entomologist from Penn State University, presented at TEDMED: disease superbugs have the ability to mutate faster than treatments are developed, and understanding natural selection can help scientists fight back and control antibiotic resistance.

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 Phyo, A.P. et al. Emergence of artemisinin-resistant malaria on the western border of Thailand: a longitudinal study, The Lancet, Volume 379, Issue 9830, 26 May–1 June 2012, Pages 1960-1966,(http://www.sciencedirect.com/science/article/pii/S014067361260484X)
 

Rosanas-Urgell A, Lin E, Manning L, Rarau P, Laman M, et al. (2012) Reduced Risk of Plasmodium vivax Malaria in Papua New Guinean Children with Southeast Asian Ovalocytosis in Two Cohorts and a Case-Control Study. PLoS Med 9(9): e1001305. doi:10.1371/journal.pmed.1001305

Chytridomycosis: Bad News for Amphibians

Amphibians have been disappearing from around the world at an alarming rate. There is currently a global decline of amphibian populations, which is affecting over 30% of amphibian species. (Stuart 2004) This enormous loss of species is caused by a single disease: Chytridiomycosis.

The disease Chytridiomycosis is caused by the fungus Batrachochytrium dendrobatidis, which attacks the layers of skin on the amphibian. It deprives them of oxygen, and is currently a leading cause of death of frogs. The massive amount of death by Chytridiomycosis is causing a huge loss of diversity of amphibian species. This leads to a homogenization across the community of species where Chytridiomycosis is present. A study by Smith et al. showed these exact results when studying Chytridiomycosis in Costa Rica and Panama. The extinction rates at these sites were determined to be nonrandom, due to the Chytridiomycosis. This disease also targeted mainly riparian species, leading to riparian species loss and an increase in terrestrial organisms. The amphibians were more similar at the family level, creating more phylogenetic similarity. Smith et al. also determined that this specialized extinction caused more species loss than a random extinction would. This leads to an enormous loss of biodiversity, and could also reflect a loss of amphibians at a global scale. As Chytridiomycosis continues to spread, there could be a global extinction of certain amphibian species.

Word Count: 224

Sources: 

Smith, K. G., Lips, K.R., Chase J.M. (2009) Selecting for extinction: nonrandom disease-associated extinction homogenizes amphibian biotas. Ecology Letters 12: 1069-1078.

Stuart, S. N., J. S. Chanson, et al. (2004). "Status and trends of amphibian declines and extinctions worldwide." Science 306: 1783-1786

Whole Genome Construction of Chlamydia Phylogeny

Contributed by: Tom Xia

Everyone thinks of HIV when he or she thinks of sexually transmitted infections (STIs), but at-risk college students need to be aware of Chlamydia. Caused by the bacterium Chlamydia trachomatis, Chlamydia is the most common bacterial STI (1). As of 2010, sexually transmitted Chlamydia effects 3.1% of the world’s population, and the Center of Disease Control and Prevention estimates an incidence rate of 2.8 million new cases per year in the United States, which is nearly 60 times greater than the incidence rate of HIV (2, 3). Chlamydia can be transmitted through vaginal, anal, and oral sex and can lead to diseases of the genitals and eyes (1). While the prognosis for Chlamydia is generally pretty good, a recent study has found that Chlamydia evolves differently than previously expected, which has great significance in the diagnosis and treatment of the bacterium.

Historically, the diversity of C. trachomatis was characterized by the major outer membrane protein and its gene, ompA. However, attempts to use ompA sequences to construct the C. trachomatis species phylogeny have been unsuccessful due to lack of agreement between trees produced using other gene sets (4). Harris et al. constructed a phylogeny using genome-wide single nucleotide polymorphisms (SNPs) and showed that ompA serotyping does not match the evolutionary structure of C. trachomatis because many serotypes appeared on multiple distinct branches of the tree (Fig. 1).

Figure 1. Maximum likelihood reconstruction of the species phylogeny (a) and plasmid phylogeny (b) of C. trachomatis with recombinations removed. (Harris et al (4)).

Interestingly, the whole genome analysis showed very high occurrence of homoplasic SNPs, or identical SNPs that occur independently on different branches of the phylogenetic tree (Fig. 2). Researchers found dense clusters of compatible homoplasies, which suggest that recombination was the cause of the homoplasies rather than convergent selection. This is a momentous finding as recombination events were previously thought to be very rare in C. trachomatis. In fact, recombination is most likely an ongoing process because many recombination events have occurred in recent evolutionary divergences (4).

Figure 2. Reconstruction of recombination events on the species phylogeny of C. trachomatis. (From Harris et al. (4)).

This study shows the error of using ompA serotyping to characterize different strains of Chlamydia and calls for the use of whole genome data. Current methods cannot detect subtle changes outside ompA and can potentially lead to proliferation of drug resistance. Recombination occurs frequently between different strains of Chlamydia, even those that invade different tissues, hinting at a lack of absolute barriers to the exchange of genetic data (5). Efforts must be made to improve the diagnosis of Chlamydia to include identification of different strains, and recombination events need to be thoroughly studied in anticipation of the evolution of drug resistance.

Word Count: 414

References

1. Stamm WE, Batteiger BE (2009) Chlamydiatrachomatis (trachoma,perinatal infections, lymphogranuloma venereum, and other genital infections). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 7th ed. Philadelphia, Pa: Elsevier Churchill Livingstone; chap 180.

2. Vos, T (2012) Years lived with disability (YLDs) for1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis forthe Global Burden of Disease study 2010. Lancet 380(9859):2163-96.

3. STD Trends in the United States: 2010 national Datafor Gonorrhea, Chlamydia, and Syphilis (2010) Center for Disease Control and Prevention (CDC). Retrieved Feb. 22, 2013.

4. Harris SR, Clarke IN, Seth-Smith HMB, Solomon AW, Cutcliffe LT, Marsh P, Skilton RJ, Holland MJ, Mabey D, Peeling RW, Lewis DA, Spratt BG, Unemo M, Persson K, Bjartling C, Brunham R, de Vries HJC, Morre SA, Speksnijder A, Bebear CM, Clerc M, de Barbeyrac B, Parkhill J, Thomson NR (2012) Whole genomeanalysis of diverse Chlamydia trachomatis strains identifies phylogeneticrelationships masked by current clinical typing. Nat Genet 44(4):413-S1.

5. STD tracing shows Chlamydia evolved more actively than thought (2012) Redorbit. Retrieved Feb. 22, 2013. 

What I Wish I Knew Then About Lice By Rebecca Isaac

I remember the first, last, and only time I was told that I had lice (Pediculus humanus capitis). I was in the 2^nd grade and my head had been itching so much, and deep down in my 9 year old self I knew that I had lice. Kids can be so mean, and even after I had endured the terrible Nix lice head comb, the burning Nix head shampoo treatment, and my parents and I had washed EVERYTHING in the house (including furniture) with scalding hot water—kids taunted me for weeks. Little did we all know that those lice were more than just microscopic, ectoparasitic members of the Phthiraptera order; through evolutionary study we could actually help tell the story of the evolution and migration of the human race. So yes, there was some slight discomfort when my 9 year old long hair and scalp were shoved under the scalding hot faucet, but there should also be molecular evolution papers in Nature being written about those special inhabitants I had. They not only linked me to my ancestors, but my ancestors from 100,000 years ago, it turns out (Kittler, et al. 2003).

Figure 1 (Kitler, et al. 2003)

According to an article published by Current Biology, scientists studied the mtDNA and nuclear DNA segments from human head and body lice from all different parts of the world in order to determine if the evolution of body lice transpired from the migration of humans out of Africa (Kittler, et al. 2003). In other words, scientists were curious to see if the evolutionary traits of lice matched with the evolutionary history of their human hosts dating back to their time in Africa and perhaps even before.  Their materials and methods included “a global sample of 40 head and body lice” and using a chimpanzee louse for the outgroup (Kittler, et al. 2003). They used statistical analysis such as Tajima’s D as well as compared the known mtDNA sequence data and used Poisson amino acid data for dating the nodes of the generated and linearized mtDNA tree (Kittler, et al. 2003).  Based on the generated phylogenetic tree shown, these scientists believed that what the molecular evolutionary data of these lice supports the evolutionary data found amongst humans. Lice, just like their human hosts, originated in Africa. Additionally, the molecular evolutionary data supported the widely accepted scientific belief that body lice evolved from head lice and that this finding corresponds with the development of the earliest known forms of human clothing, which falls within the reasonable estimation of 72,000±32,000 years. The earliest known gadgets being used to create clothing are roughly 40,000 years (Kittler et al., 2003).  

Thus, it seems that the molecular evolutionary data suggests that lice developed, and were closely influenced, by the changing cultural and migratory patterns of our ancestors from Africa. With a little bit of patient analysis and persistent evolutionary observation, all of that corroborating evidence was found, and supported, by something smaller than the already microscopic Pediculus humanus capitalis—mitochondrial and nuclear DNA. Had my 9-year old self been able to understand that, maybe that brief moment of stress in my childhood would have seemed a little cooler then….or maybe not. The point is, despite the fact that lice are vectors for infectious diseases such as epidemic typhus fever, epidemic relapsing fever, and trench fever, which are terrible for sure; however, they also carry a whole lot of human evolutionary information that can be valuable if we can manage to look a little deeper past the nuisance and into the significance of what these, and other pests, can share with us about our own evolution and history.

Word Count: 610

Citation: Kittler, Ralf, Manfred Kayser, and Mark Stoneking. "Molecular Evolution of  Pediculum humanus and the Origin of Clothing." Current Biology. 13. (2003): 1414-1417. Print.

The Evolution of Influenza: Predicting and Preventing Epidemics

by Kelsey Wooddell

Each year, experts from the Food and Drug Administration (FDA), World Health Organization (WHO), U.S. Centers for Disease Control and Prevention (CDC), and other institutions study virus samples collected from around the world in order to identify the influenza viruses that are most likely to cause illness during the upcoming flu season.  Vaccines cannot be manufactured in real time with enough supplies to go around, so scientists have to predict which strains are most likely to outbreak, and how they will evolve.  There are more than 100 national influenza centers in more than 100 countries that conduct year-round surveillance for influenza viruses and disease activity, and these centers then send viruses for additional analyses to the five WHO Collaborating Centers for Reference and Research on Influenza.  In varies between countries, but in the U.S. the FDA determines what viruses will be used in U.S.-licensed vaccines.

A three-component (trivalent) vaccine has been used since the early 1980’s in order to protect against each of the two three main groups of influenza (A,B, and C) circulating in humans.  Human influenza A and B viruses cause seasonal epidemics almost every winter in the U.S. and the most common are therefore protected by the vaccine, whereas type C infections cause a mild respiratory illness and are not thought to cause epidemics.  The emergence of a new and very different influenza virus can cause an influenza pandemic.  This occurred in 2009 with the outbreak of what is now called the “2009 H1N1”, a type of influenza A virus, which caused the first influenza pandemic in over 40 years.  As of June 2012, it is estimated that the virus killed between 151,700 and 575,400 people worldwide, with young people being hit unusually hard.

Influenza A viruses are divided into subtypes based on two proteins on the surface of the virus: the hemagglutinin (H), which has 17 subtypes, and the neuraminidase (N), which has 10 subtypes.  Currently, the two types of influenza subtypes circling the population are influenza A (H1N1) and influenza A (H3N2).  The 2009 H1N1, however, was very different from the regular human influenza A (H1N1), and has now replaced the H1N1 that was previously circulating in humans.

Vaccines are looked down upon by many people for fear that they will create a super-virus, one selectively created by vaccines to be super-infections and super-resistant.  If a vaccinated person becomes infected with the virus, the body mounts an immune response that was created when the vaccine previously introduced the virus so it could begin to formulate antibodies.  However, that pressure from the immune system can provoke the virus to mutate into a slightly different - and possibly more infectious - form.

One study from MIT reveals the mechanism behind this phenomenon to be antigenic drift and analyzed which amino acids that made up the viral protein were most likely to undergo mutation that improve the viruses’ ability to infect new hosts.  This knowledge could help vaccine designers produce vaccines that don’t induce an evolution of fitter viruses.

Influenza A virus is such an effective virus because it has the ability to evade antibodies specific for its attachment protein, the hemagglutinin (HA).  The antigenic drift is a result of accumulating several substitutions of the HA epitope, the part of the virus that the immune system recognizes.  This means that the immune system no longer recognizes the virus, and therefore the antibodies cannot fight it.  If no vaccines can be specifically formulated to target the specific amino acids that tend to acquire substitutions, there is another option to increase the effectiveness of the vaccine.

Antigenic drift, according to the same study, can be mitigated most effectively by decreasing the number of passages of the influenza A virus between immune and nonimmune individuals, which in humans essentially means children.  Therefore, increasing the number of pediatric influenza A vaccination rates would likely slow antigenic drift and temporally extend the effectiveness of influenza vaccines.  Additionally, monitoring the most commonly mutating amino acids may assist in accurately predicting the strains of the influenza A virus with the greatest epidemic potential.

Word Count: 678

Sources:

“CDC - Seasonal Influenza (Flu) - First Global Estimates of 2009 H1N1 Pandemic Mortality Released by CDC-Led Collaboration.” Web. 3 Mar. 2013.

“CDC - Seasonal Influenza (Flu) - Types of Influenza Viruses.” Web. 3 Mar. 2013.

“CDC - Seasonal Influenza (Flu) - Vaccine Virus Selection for the 2012-2013 Influenza Season.” Web. 3 Mar. 2013.

Hensley, Scott E. et al. “Hemagglutinin Receptor Binding Avidity Drives Influenza A Virus Antigenic Drift.” Science 326.5953 (2009): 734–736. Web. 3 Mar. 2013.

“Stopping Influenza Evolution Before It Starts - MIT News Office.” MIT’s News Office. Web. 3 Mar. 2013.