Inside Science News Briefs -- Sept. 26, 2008

Inside Science News Briefs

Sept. 26, 2008

By Jason Socrates Bardi
Inside Science News Service

Hidden Numbers in Cholera Outbreaks

One of the worst outbreaks in human history swept the globe 175 years ago. It was cholera, emerging in the river communities within the Ganges delta in India and swiftly crossing over into modern-day Afghanistan. From there it followed the trade routes into Russia then spread west into Scandinavia and south into North Africa. Huge epidemics erupted in Germany, France, Britain, and Spain in the 1830s. European immigrants carried it to the United States, Cuba, and Mexico, killing tens of thousands with each visitation.

This particular outbreak was unusual in its severity, but not in its origins. Six of the seven large, worldwide cholera pandemics of the last 200 years originated in the same region in India. There, cholera has remained a widespread problem in between each episodic global outbreak. Beginning in 1891 and continuing for a half century until the beginning of World War II, the British administration in India recorded monthly counts of people who died of cholera in 26 districts in Bengal. Now a new mathematical analysis of this rich data suggests that getting an understanding of the extent of a cholera outbreak may not be as simple as counting the number of people in hospital wards. The analysis provides a new way of thinking about managing cholera outbreaks too.

Scientists at the University of Michigan and the University of London used a new statistical method called "iterated filtering" that allowed them to model the data in new ways. It revealed that the traditional focus on the most severely afflicted cases may bias our view of this disease. Symptomless cases -- unobserved or "inapparent" infections -- are far more prevalent than fatal ones. Indeed, the new analysis suggests that fatal cases may account for a mere 0.4 percent of all infections. This is in contrast to the prevailing wisdom that as many as 1 in 3 infections lead to severe symptoms.

The work, published in the journal Nature last month, suggests inapparent infections provide natural vaccination, which has historically helped control cholera epidemics. This gives the scientists a better way to predict outbreaks and renewed hope for vaccination programs, says ecologist Aaron King, the first author on the paper. "Existing vaccines, if delivered in a timely fashion, even to as few as 1/3 of the population, could be very effective at forestalling predicted outbreaks," he says.

A Parasite that Dupes to Conquer

If microbes seem cruel in their attempt to survive by establishing infections, they lose no love from their hosts. Humans have numerous "innate" immune defense mechanisms that can be downright hostile to pathogens, automatically responding to a foreign invader and often wiping them out. In the intricate opera of the natural world, however, pathogens can adapt and reemerge to enjoy a strong second act-sometimes even evolving the ability to use the human immune system to their own advantage.

A recent study by researchers at the National Institute of Allergy and Infectious Diseases (NIAID) published in the journal Science last month demonstrates one such adaptation in Leishmania parasites. Common in parts of North Africa, Asia, and the Americas, these parasites invade when someone is bitten by a sand fly, which have these parasites growing in their digestive tract. While the sand fly is feeding, these parasites get expelled into the skin and cause a painful ulcerous disease that strikes more than a million people a year.

Taking advantage of major advances in microscopes in the last decade that allow them to directly visualize the parasite in living tissue, the NIAID researchers took time-lapse 3D video images of the parasite as they established infections in mice. Cells within the mice were prepared with chemicals designed to absorb light and glow with a certain characteristic color. What the videos reveal is that one of the main immune cells that acts as a first line of defense and is supposed to protect against invading parasites is actually critical for the establishment of Leishmania infection.

Called neutrophils, the human body makes billions of these cells every day. Their lives, to borrow a phrase from Thomas Hobbes, are nasty, brutish, and short. Usually living for less than a day, they troll the bloodstream and tissues in search of foreign pathogens and toxic matter, which they normally engulf and destroy with an onslaught of toxic chemicals. Neutrophils cannot destroy Leishmania, however, and the parasites use them as safe havens until they are eventually released and taken up by the definitive host cell for the parasite, a second type of immune cell in the skin called the macrophage. Inside macrophage cells, the parasites find a long-term home for the infection—but only if the neutrophils are there first.

In the end, what this means is that the bite of a sand fly stings twice. First, the creature expels parasites where it bites. And second, in biting, the sand fly attracts the very cells the parasites need to initiate an infection. The researchers say that this insight may influence how they design vaccines in the future. "A vaccine that works against parasites inoculated by a needle may not work against those transmitted by a sand fly," says Nathan Peters, who led the research. A jab, after all, is not the same as a bite.

Viruses Infecting Viruses

Among pathogens, viruses are unique in their collective ability to infect all types of organisms. There are plant viruses, insect viruses, fungal viruses, and even viruses that infect only amoeba and bacteria. Now a group of researchers at the Centre National de la Recherche Scientifique in France has made the startling discovery that even some viruses can have viruses.

In a paper in Nature last month, the group described how they identified a giant mimivirus in a cooling tower in France. Mimiviruses are the largest viruses known to exist—so big they are visible under a normal optical microscope (usually much higher resolution electron microscopes are needed to view them). The new virus, large even by mimivirus standards, was appropriately named "mamavirus." In the same cooling tower, the French group also discovered a second, tiny virus that infects the giant mamavirus. This they named "Sputnik."

Sputnik is unusual because it is the first virus ever discovered that is a parasite of another virus. When it reproduces in a cell infected by the larger virus, its action impairs the reproduction of mamavirus particles. The group sequenced Sputnik's genetic code and discovered that a number of its gene sequences are similar to those found in a massive survey of genetic material taken from oceans all over the globe. This suggests that a whole class of viruses might exist that infect other viruses.

Moreover, the discovery rekindles the debate over whether viruses are alive. Viruses are often not considered living organisms because they lack their own cellular structure and the ability to metabolize food -- traits common to all known forms of life. The ability of one virus to infect another calls into question the possibility that viruses should be considered forms of life -- though this is no great revelation for some. "For me it is does not change anything," says Bernard Lascola, who was the first author on the paper. "I always considered that viruses are alive."


This Science Briefs column is provided for media use by the Inside Science News Service, which is supported by the American Institute of Physics, a not-for-profit publisher of scientific journals. Contact: Jim Dawson, news editor, at jdawson@xxxxxxxx
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