Archive for April 2008

Looking at the Rotavirus

History

One of Flewett's original electron micrographs

One of Flewett’s original electron micrographs

Computer reconstruction of a rotavirus particle

Computer reconstruction of a rotavirus particle

In 1943, Jacob Light and Horace Hodes proved that a filterable agent, in the faeces of children with infectious diarrhoea, also caused scours (livestock diarrhoea) in cattle.[11] Three decades later, preserved samples of the agent were shown to be rotavirus.[12] In the intervening years, a virus in mice[13] was shown to be related to the virus causing scours.[14] In 1973, related viruses were described by Ruth Bishop in children with gastroenteritis, in Australia.[4][15]

In 1974, Thomas Henry Flewett suggested the name rotavirus after observing that, when viewed through an electron microscope, a rotavirus particle looks like a wheel (rota in Latin);[16][17] the name was officially recognised by the International Committee on Taxonomy of Viruses four years later.[18] In 1976, related viruses were described in several other species of animals.[14] These viruses, all causing acute gastroenteritis, were recognised as a collective pathogen affecting humans and animals worldwide.[16] Rotavirus serotypes were first described in 1980,[19] and in the following year, rotavirus from humans was first grown in cell cultures derived from monkey kidneys, by adding trypsin, (an enzyme now known to be essential for rotavirus to replicate and found in the duodenum of mammals), to the culture medium.[20] The ability to grow rotavirus in culture accelerated the pace of research, and by the mid-1980s the first candidate vaccines were being evaluated.[21]

In 1998, a rotavirus vaccine was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100% effective at preventing severe diarrhoea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects.[22][23] The manufacturer, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, a type of bowel obstruction, in one of every 12,000 vaccinated infants.[24] The experience provoked intense debate about the relative risks and benefits of a rotavirus vaccine.[25] In 2006, two new vaccines against rotavirus A infection were shown to be safe and effective in children.[26]

Signs and symptoms

Rotavirus gastroenteritis is a mild to severe disease characterised by vomiting, watery diarrhoea, and low-grade fever. Once a child is infected by the virus, there is an incubation period of about two days before symptoms appear.[27] Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea. Dehydration is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection.[28]

Rotavirus A infections can occur throughout life: the first usually produces symptoms, but subsequent infections are typically asymptomatic,[29] as the immune system provides some protection.[2] Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age.[30][31] Infection in newborn children, although common, is often associated with mild or asymptomatic disease;[32][33] the most severe symptoms tend to occur in children six months to two years of age, the elderly, and those with compromised or absent immune system functions. Asymptomatic infections in adults may maintain the transmission of infection in the community.[34] Symptomatic reinfections are often due to a different rotavirus A serotype.[3][35]

Transmission

Rotavirus A from the faeces of an infected child

Rotavirus A from the faeces of an infected child

Rotavirus is transmitted by the faecal-oral route, via contact with contaminated hands, surfaces and objects,[36] and possibly by the respiratory route.[1] The faeces of an infected person can contain more than 10 trillion infectious particles per gram;[29] only 10–100 of these are required to transmit infection to another person.[37]

Rotaviruses are stable in the environment and have been found in estuary samples at levels as high as 1–5 infectious particles per US gallon.[38] Sanitary measures adequate for eliminating bacteria and parasites seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar.[1]

Disease mechanisms

Electron micrograph of a rotavirus infected enterocyte (top) compared to an uninfected cell (bottom). The bar = approx. 500 nm

Electron micrograph of a rotavirus infected enterocyte (top) compared to an uninfected cell (bottom). The bar = approx. 500 nm

The diarrhoea is caused by multiple activities of the virus. Malabsorption occurs because of the destruction of gut cells called enterocytes. The toxic rotavirus protein NSP4 induces age- and calcium ion-dependent chloride secretion, disrupts SGLT1 transporter-mediated reabsorption of water, apparently reduces activity of brush-border membrane disaccharidases, and possibly activates the calcium ion-dependent secretory reflexes of the enteric nervous system.[39][40] Healthy enterocytes secrete lactase into the small intestine; milk intolerance due to lactase deficiency is a particular symptom of rotavirus infection,[41][42] which can persist for weeks.[43] A recurrence of mild diarrhoea often follows the reintroduction of milk into the child’s diet, due to bacterial fermentation of the disaccharide lactose in the gut.[44]

Norman Ernest Borlaug

Norman Ernest Borlaug (born March 25, 1914) is an American agricultural scientist, humanitarian, Nobel laureate, and has been called the father of the Green Revolution. Borlaug is one of five people in history to have won the Nobel Peace Prize, the Presidential Medal of Freedom and the Congressional Gold Medal.

Borlaug received his Ph.D. in plant pathology and genetics from the University of Minnesota in 1942. He took up an agricultural research position in Mexico, where he developed semi-dwarf high-yield, disease-resistant wheat varieties.

During the mid-20th century, Borlaug led the introduction of these high-yielding varieties combined with modern agricultural production techniques to Mexico, Pakistan, and India. As a result, Mexico became a net exporter of wheat by 1963. Between 1965 and 1970, wheat yields nearly doubled in Pakistan and India, greatly improving the food security in those nations. These collective increases in yield have been labeled the Green Revolution, and Borlaug is often credited with saving over a billion people from starvation. He was awarded the Nobel Peace Prize in 1970 in recognition of his contributions to world peace through increasing food supply.

More recently, he has helped apply these methods of increasing food production to Asia and Africa. Borlaug has continually advocated the use of his methods and biotechnology to decrease world famine. His work has faced environmental and socioeconomic criticisms, including charges that his methods have created dependence on monoculture crops, unsustainable farming practices, heavy indebtedness among subsistence farmers, and high levels of cancer among those who work with agriculture chemicals. He has emphatically rejected many of these as unfounded or untrue. In 1986, he established the World Food Prize to recognize individuals who have improved the quality, quantity or availability of food around the globe.

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