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Bluetongue in Belgium, 2006

Bluetongue has emerged recently in Belgium. A bluetongue virus strain was isolated and characterized as serotype 8. Two new real-time reverse transcription–quantitative PCRs (RT-qPCRs) that amplified 2 different segments of bluetongue virus detected this exotic strain. These 2 RT-qPCRs detected infection earlier than a competitive ELISA for antibody detection. Bluetongue is a noncontagious disease caused by an orbivirus of the family Reoviridae. The bluetongue virus (BTV) serogroup consists of 24 serotypes. BTV is transmitted by arthropods of the genus Culicoides and its distribution worldwide is restricted to regions that contain competent vectors. An outbreak of bluetongue was reported and confirmed in the Netherlands on August 17, 2006. Belgium reported its first cases of bluetongue 1 day later, and Germany and France reported outbreaks on August 21, 2006, and August 31, 2006, respectively. We report detection and characterization of a BTV strain and an overview of laboratory test results 4 weeks after the onset of the outbreak.

Twenty-one animals (16 cattle and 5 sheep) showing clinical signs suggestive of bluetongue were sampled by the Federal Agency for the Safety of the Food Chain on August 18, 2006, at 11 farms in northeastern Belgium. Two serologic tests that detect antibodies against the major serogroup antigen VP7 (bluetongue virus antibody competitive ELISA [cELISA]; Veterinary Medical Research and Development Inc., Pullman, WA, USA and competitive vp7 bluetongue kit; IDVET, Montpellier, France) identified 21 virus-positive animals. Two newly developed and validated reverse transcription–quantitative PCRs (RT-qPCRs) that detected BTV strains representing the 24 serotypes were then conducted to determine whether these seropositive animals also had viral RNA. The first assay (RT-qPCR_S1), which amplified a 357-nt fragment in segment 1, detected virus in erythrocytes of the 21 seropositive animals (mean cycle threshold [Ct] value 29.0). The second assay (RT-qPCR_S5), which amplified a 94-nt fragment in segment 5, detected virus in the same 21 seropositive animals (mean Ct value 26.5). The 2 serologic tests and the 2 molecular assays detected BTV in 21 animals from 11 Belgian farms within 14 hours.

Emerging Infectious Diseases
April 17, 2007

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Ewes get pregnant after uterus transplantation

Within the next few weeks scientists will attempt a uterus swap between two sheep in what they hope will be the first successfully transplanted uteruses in a large animal. Already, four ewes that had their uteruses removed and then reattached later to a different artery in their bodies are nearing the end of their pregnancies, the same team has announced. They plan to deliver the lambs from these ewes via caesarean section by the end of April 2007. Mats Brannstrom at the Sahlgrenska Academy in Gothenburg, Sweden, and colleagues removed the uteruses of 14 female sheep. Each five-hour surgical procedure involved delicately detaching the uterus and the ovary from the artery that supplies it with blood. The organ was preserved outside of the body and completely detached for about four hours, including at least an hour on ice.

Researchers then returned each uterus to the ewe from which it came in a seven-hour surgical operation. This ‘auto-transplantation’ avoids the possibility that the animals will reject the organ due to an immune reaction. Because the artery that supplies the uterus with blood is so delicate, Brannstrom’s team instead reattached the uterus to the artery that partly supplies blood to the legs. This involved stopping the flow in the artery temporarily and suturing the uterine vessels to it. Of the 14 ewes that underwent this auto-transplantation, five had complications as a result of the surgery and a further two developed severe intestinal problems. Those seven were euthanized. Researchers mated five of the remaining seven ewes with two rams, towards the end of 2006. Four of these ewes became pregnant as a result of this natural mating. The animals are now four-months-pregnant – one month away from full term, at which point they will undergo a caesarean section delivery.

Brannstrom’s team-mate Pernilla Dahm-Kahler is presenting details of the experiment this weekend at the first annual symposium of uterine transplantation taking place in Sweden. The team previously showed that mice that receive uterine transplants can successfully become pregnant and give birth. They say that the pregnancies in sheep represent a significant advance as the animals are larger, making the transplantation procedure more similar to one that might work in humans. Their next step will be to swap the uterus organs of two sheep in the next few weeks. These sheep will have to receive drugs that suppress the immune system, to prevent their bodies rejecting the foreign transplants. A successful outcome of this follow-up experiment could bolster hopes that uterine transplants will become a viable option for humans.

Women who suffer from a condition called Rokitansky syndrome are born without a uterus, while some women must have theirs removed due to cancer, fibrous growths or rupturing during childbirth. Some women who lack a womb hope that a transplant procedure may restore their ability to become pregnant. Kutluk Oktay at Weil Medical College of Cornell University in New York, US, says the sheep pregnancies are impressive and, he believes, unique. But he cautions that a non-vital procedure in humans can carry potentially fatal risks, including blood clotting complications. And the drugs patients must take to protect against tissue rejection puts them at higher risk of cancer later in life. Even if the womb recipients do become pregnant, these drugs could result in lower birth weight or premature delivery of their babies, he warns. In 2000, for example, surgeons transplanted a uterus into a 26-year-old woman. But a few months later the organ had to be removed because of the formation of a dangerous clot. Still, surgeons at the New York Downtown Hospital have received approval from the hospital’s review board to carry out a womb transplant and say they are interviewing women who would like to receive a donated uterus.

New Scientist
April 17, 2007

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Chernobyl haunts the Norwegian uplands

Tougher controls on the slaughter of sheep have been imposed in Norway after they were found to be contaminated with unusually high levels of radioactivity from the Chernobyl disaster in 1986. The Norwegian Radiation Protection Authority (NRPA) says the problem has arisen because the sheep have feasted on an unusually large crop of mushrooms, which were more plentiful than usual because of wet weather. Previous research has shown that fungi take up more radioactivity from the soil than grasses or other plants. There are 36 areas of upland Norway where Chernobyl contamination still requires controls on sheep. According to the NRPA, levels of caesium-137 from the Chernobyl disaster reached 7000 becquerels per kilogram in sheep this year, more than twice maximum levels in previous years.

Farmers can reduce the level of radioactivity in sheep by giving them non-contaminated food for a month before slaughter. For some farmers, this period will now have to be doubled to reduce caesium-137 levels to below Norway’s safety limit of 600 bq/kg. Per Strand, the NRPA’s head of environmental radioactivity, stresses that the precautions mean that lamb on the market is safe to eat. He says, though, that the discovery of such high levels of radioactivity so long after the Chernobyl accident came as a surprise. “No one at the time expected contamination to be so high more than 20 years after the event,” he says.

New Scientist
November 6, 2006

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Bluetongue outbreak has African roots

The deadly livestock virus that has taken the Netherlands, Belgium, and Germany by surprise this month did not come from southern Europe, as researchers had suspected. A genetic analysis, announced yesterday, has shown that the Bluetongue virus almost certainly originated in Africa, deepening the mystery of how it reached northern Europe. First seen in the Netherlands on 14 August, the virus, which infects ruminants and is transmitted by Culicoides biting midges, has spread to more than 70 farms in Belgium, the Netherlands, and Germany (ScienceNOW, 25 August). Bluetongue sickens primarily sheep and goats and is not harmful to humans. There are 24 known “serotypes” of the virus, and over the past 8 years, a handful of them had made dramatic incursions from Turkey and the Middle East into southern European countries such as Greece, Italy, Spain, and the Balkan nations. Hence, scientists had assumed that the disease’s arrival in northern Europe marked another leap north from one of these areas.

The leap is much bigger than they thought. Frantic days of genetic testing, completed very early Saturday morning at the Institute for Animal Health (IAH) in Pirbright, United Kingdom, has revealed the virus to be of serotype 8, previously known to occur only in sub-Saharan Africa, South America, and the Indian subcontinent, says Peter Mertens, who heads IAH’s arthropod-borne virus research group. Its genetic fingerprint is closest to that of a virus isolated in Nigeria in 1982, which means it almost certainly came from Africa, Mertens says.

But how? There’s almost no traffic of ruminants between Africa and Europe, says epidemiologist Aline de Koeijer of the Central Institute for Animal Disease Control (CIDC) in Lelystad, the Netherlands. Perhaps an imported zoo animal was infected, she suggests; veterinary authorities in the affected countries are trying to track down possible culprits. An infected midge may also have hitched a ride on an airplane, as happens occasionally with malaria-infected mosquitoes. Yet it would then have to find its way to a farm. The current outbreak is unusual in that some cows have gotten sick–normally, they are infected without clinical symptoms–but it’s unclear whether this is typical of serotype 8, which has been studied very little, says CIDC virologist Eugène van Rooij.

Once introduced, the virus may have benefited from the warm weather, which speeds up its life cycle, says medical and veterinary entomologist Willem Takken of Wageningen University in the Netherlands; July was the hottest month on record in the affected areas. Scientists are certain that the outbreak will subside as temperatures drop; they can only hope that the northern European winter will kill off all infected midges and prevent a 2007 sequel.

ScienceNow
September 26, 2006

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Researchers discover that sheep need retroviruses for reproduction

A team of scientists from Texas A&M University and The University of Glasgow Veterinary School in Scotland has discovered that naturally occurring endogenous retroviruses are required for pregnancy in sheep. In particular, a class of endogenous retroviruses, known as endogenous retroviruses related to Jaagsiekte sheep retrovirus or enJSRVs, are critical during the early phase of pregnancy when the placenta begins to develop. Retroviruses, such as human immunodeficiency virus or HIV, are one class of viruses. They are best known for their ability to cause diseases, said Dr. Thomas Spencer, a reproductive biologist with the Texas Agricultural Experiment Station and Texas A&M University.

Findings published Sept. 11 in the Proceedings of the National Academy of Sciences demonstrate enJSRVs are essential for the development of the placenta in sheep. Retroviruses are unique for their ability to permanently insert their genetic material into the DNA of host cells, he said. During evolution of mammals, some retroviruses infected the germline (cells of the ovary and testis that have genetic material that are passed to their offspring) of the host, which is then inherited by their children. These retroviruses, known as endogenous retroviruses, are present in the genome of all mammals, including humans. Consequently, endogenous retroviruses can be considered remnants of ancient retroviral infections, Spencer said.

Many scientists believed these endogenous retroviruses were junk DNA, he said. “Indeed, these endogenous retroviruses are usually harmless and generally contain mutations that prevent them from producing infectious retroviruses,” he said. However, several endogenous retroviruses appear to provide protection from infection and are involved in reproduction. For instance, the exogenous Jaagsiekte Sheep Retrovirus or JSRV causes lung tumors in sheep and led to the death of Dolly, the world’s first mammal cloned from an adult cell. The idea that endogenous retroviruses are important for reproduction in mammals has been around for about 30 years, Spencer said. Studies in cultured cells have shown that a protein of a human endogenous retrovirus might have a role in development of the human placenta.

The team blocked expression of the envelope of the enJSRVs using morpholino antisense oligonucleotides, which inhibit translation of specific messenger RNA. When production of the envelope protein was blocked in the early placenta, the growth of the placenta was reduced and a certain cell type, termed giant binucleate cells, did not develop. The result was that embryos could not implant and the sheep miscarried, Spencer said. “Our research supports the idea that endogenous retroviruses shaped the evolution of the placenta in mammals and then became indispensable for pregnancy, and thus may be why they are expressed in the placenta of many mammals,” he said.

Further, Palmarini said, “The enJSRVs arose from ancient infections of small ruminants during their evolution,” said Dr. Massimo Palmarini, a virologist at The University of Glasgow Veterinary School. “This infection was beneficial to the host and was then positively selected for during evolution. In other words, animals with enJSRVs were better equipped than those without. Therefore, enJSRVs became a permanent part of the sheep genome and, in these days, sheep can’t do without them.”

Science Daily
September 26, 2006

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A virus moves north

The sudden emergence of an insect-borne disease of livestock in northern Europe has plunged the agricultural sectors of three countries into crisis. At least 45 farms in the Netherlands, Germany, and Belgium have so far been affected by bluetongue disease, which infects ruminants such as cows, sheep, goats, and deer. Scientists are trying to find out how the disease, which had made inroads into southern Europe over the past 8 years, made the giant leap north, and what its potential for further spread is. The disease was first discovered in sheep on a farm in the Netherlands on 14 August. On 21 August, the European Union announced a series of measures to contain it, including an export ban on ruminants–as well as their semen, ova, and embryos–in a 150-kilometer radius around stricken areas.

The Bluetongue Virus, carried by tiny insects called biting midges, causes severe and sometimes fatal disease–including a blue tongue, caused by bleeding–in sheep and goats; cows are reservoirs but usually don’t get sick. The virus occurs in many parts of the world, including sub-Saharan Africa, Turkey, and the Middle-East. But until recently, it was rare in Europe. From 1998 on, however, different subtypes of the virus started spreading into Greece, Italy, Spain, Portugal, and the Balkan countries. Still, its sudden jump north–by some 10 degrees of latitude–is “very surprising,” says Bethan Purse of the University of Oxford, who studies bluetongue epidemiology.

In southern Europe, bluetongue’s main vector is a species called Culicoides imicola, which doesn’t occur in the newly affected countries. A team led by medical and veterinary entomologist Willem Takken of Wageningen University in the Netherlands is trapping insects around Dutch farms to determine the most likely vector there. So far, the team has found predominantly C. obsoletus–which lab studies have shown to be a potential vector for bluetongue–as well as nine other Culicoides species, Takken says. Studies to determine whether they carry the virus are still underway.

Meanwhile, virologists are trying to determine which of the 24 subtypes of the virus is involved. The fact that several cows in the Netherlands have fallen ill suggests that it may be an unusual one, Takken says. Researchers aren’t sure why bluetongue is moving north. In a paper published last year, Purse and colleagues suggested climate change might have triggered its recent spread into southern Europe. Other explanations, such as a more virulent strain or changes in land use, agriculture, or animal health systems, seemed implausible, they said, and the disease had struck primarily in those areas that had heated up the most.

ScienceNow
September 12, 2006

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Genetically modified goats may help fight diarrhea-causing pathogens in underdeveloped countries

Milk may do a body good, but transgenic researchers are trying to make it do a body better. A new study shows that goat’s milk engineered to be more similar to human breast milk reduces the amount of harmful bacteria in piglet guts. Eventually, such dairy animals might improve the health of children in undeveloped countries. The World Health Organization estimates that approximately 2 million people a year die from bacterial infections that cause diarrhea and dehydration. Young children in developing countries are at greatest risk. That’s because, after a child is weaned, it is no longer exposed to a variety of helpful proteins in mother’s milk that fight diarrhea-causing pathogens, such as coliform bacteria. One of these proteins, lysozyme, is present in human breast milk at 1600 to 3000 times the concentration found in cow’s or goat’s milk. But breastfeeding only goes on for so long, and geneticist James Murray and colleagues at the University of California, Davis, have been working to develop goats that produce more humanlike milk for older children.

In 1999, the researchers engineered a dairy goat to make human lysozyme in the same mammary cells that generate other milk proteins, and at about two-thirds the amount as in human milk. Subsequent work showed that the transgenic milk reduced bacterial growth in laboratory cultures, so the team wanted to know if the same would happen in a real gut. To find out, the researchers fed four 2-week old pigs pasteurized transgenic milk and another group pasteurized regular milk for 16 days. Then the team measured the amount of coliform bacteria in the animals’ intestines. The piglets drinking regular milk had, on average, between 100 to 4000 times the amount of coliform bacteria in their guts as did those drinking transgenic milk, the team reports in today’s issue of Transgenic Research. Although the experiments still need to be done, Murray believes children would also be protected by the transgenic milk because “pigs are very similar to humans in the kinds of E. coli bacteria they harbor.”

“This is the first transgenic [animal] to have true benefit for the consumer,” says Bill Muir, a population geneticist and environmental risk assessor of transgenics at Purdue University in West Lafayette, Indiana. Other transgenic animals, such as glow-in-the-dark pet fish or fast-growing salmon, might prove economically valuable, but Murray’s goat “addresses the dysentery pathogen taking up residence in the gut.” Animal scientist Matt Wheeler at the University of Illinois, Urbana/Champaign, says this demonstration of safety and efficacy is the first step before any scientific review boards or the U.S. Food and Drug Administration will allow human consumption of the milk.

ScienceNow
August 29, 2006

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Go-ahead for ‘pharmed’ goat drug

The first medicine produced from a genetically modified animal has been recommended for use in Europe. The European Medicines Agency (EMEA) has reversed an earlier decision not to issue a licence for the drug, ATryn, after taking further expert advice. The drug is extracted from the milk of goats engineered to carry a human gene involved in inhibiting blood clots. ATryn will be used during surgery on patients with a rare condition that makes their blood clot too easily. About one person in every 3,000-5,000 is in this position. They are born missing a copy of the gene that makes a protein called anti-thrombin, an anticoagulant – a substance that prevents coagulation of the blood. Normally, vulnerable patients are maintained on blood thinners such as Warfarin but if they are giving birth or undergoing surgery this is deemed too risky, and they are given replacement anti-thrombin.

Currently, anti-thrombin is extracted from human blood plasma; but fears about the possible transmission of disease, such as vCJD, make doctors unwilling to expose their patients to plasma products unless they have no choice. The US-based company GTC Biotherapeutics set out to address this problem by producing a human version of anti-thrombin in animals. They genetically modified goats to contain the human gene that codes for anti-thrombin. The transgenic animals produce the protein in their milk. The EMEA turned down in February this year the company’s original application to market the drug processed from the milk. It is a good day for European patients with congenital anti-thrombin deficiency and for their physicians. It said the company had not presented enough scientific evidence that the medicine’s benefits outweighed its risks. But after re-examining the application data and meeting with experts, the EMEA has now given the drug the go-ahead for use in Europe, subject to final approval later this year.

Tom Newberry of GTC Biotherapeutics said the approach of using transgenic animals would lead to lower development costs and a broader range of treatments for patients. GTC claims one goat produces the equivalent of 90,000 blood collections. “This is a technology which has the potential to dramatically change the way in which expensive biological drugs are developed for the commercial marketplace,” he told the BBC News website. In a statement on the company’s website, Professor Isobel Walker, consultant haematologist at the Glasgow Royal Infirmary, UK, said: “It is a good day for European patients with congenital anti-thrombin deficiency and for their physicians.”

BBC News
June 20, 2006

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New evidence questions the simple link between prion proteins and vCJD

While newly published research confirms that under laboratory circumstances prion-protein can be absorbed across the gut, it also shows that this is unlikely to occur in real life. In addition, the results show that the places in the gut that do take up these disease-associated proteins are different from the locations where infectivity is known to be amplified. The findings will be published in the Journal of Pathology. Since the outbreak of BSE in cattle and vCJD in humans, scientists have struggled to make sense of how an abnormal variation of a normal protein can trigger an infectious disease. Some are questioning whether this simple relationship exists at all. This paper adds new evidence that can inform the debate.

Firstly, it is known that individual people and animals have different levels of genetic susceptibility to this group of diseases, but no one knows how this resistance is achieved. One option is that resistant people do not absorb the disease-associated prion protein (PrP) from their guts. To test this, the researchers worked with 50 sheep, with different degrees of genetic resistance to scrapie – the sheep form of the disease. When they injected material containing abnormal prion protein (PrP) into the sheep’s gut, it was equally absorbed by all sheep. “This clearly shows that resistance is not achieved by blocking uptake of abnormal proteins from the gut – it must be achieved by some other mechanism,” says lead author Dr Martin Jeffrey.

Secondly, they looked in more detail at the route of absorption in the gut. Using surgically modified sheep, they loaded a small area of the gut with a fluid mixture containing 0.5 grams of scrapie infected brain containing a large amount of the disease specific variant of the PrP protein and watched how it was taken up. They saw the abnormal PrP was rapidly taken up by finger-like projections called villi and passed in to the lymph. It was not, however, taken up by structures called Peyer’s nodules, that are believed to be the places where animals amplify the infective agent. “The fact the PrP isn’t taken up by the Peyer’s nodules questions whether PrP is really infectious, or whether PrP is really just a secondary marker of the presence of the scrapie agent,” says Jeffrey.

His belief in this need to reappraise the fundamental understanding of prion diseases is enhanced by one more observation published in this same paper. The team pre-digested a mixture containing disease specific PrP with standard stomach contents, and then injected the resulting mixture into the gut. No PrP transferred into the villi. When they used a highly sensitive version of Western Blot analysis to examine the contents of this pre-digested mixture, they found only the faintest suggestion that some of the PrP had survived. This was despite the fact that the original mixture had a contained a high level of PrP. “Think about it – a sheep grazing in a field is not naturally exposed to highly infected brain and could only pick up a tiny amount of PrP from other tissues. This will then be exposed to 48 hours or more digestion before it arrives in the gut, and our experiments show that after this, the chance of there being more than an unmeasurably small amount of PrP left to absorb is very small,” says Jeffrey.

“As sheep can become infected, the theoretical probability of this being due to an invisible sub-fraction of digestion resistant PrP molecules is unlikely. The possibility of there being infectious molecules other than PrP must therefore be seriously considered,” says Jeffrey. “A lot of people are completely wedded to the prion hypothesis of diseases like vCJD, but the more you deal with whole animals as opposed to relying purely on in vitro studies, the more cautious you are about saying that prion proteins alone cause the disease,” says Martin Jeffrey. In a commentary published in the same edition of the journal Dr Nicole Sales of the Department of Infectology, at the Scripps Research Institute Jupiter, Florida, suggests that one possible explanation that keeps with the prion hypothesis is that infection occurs as PrPs are absorbed in the mouth, rather than in the gut. Dr Jeffrey, however, is not convinced by this argument. “Were infection to be acquired from the mouth then the first tissues to accumulate infectivity would be lymph nodes in the throat or the tonsils. But we don’t tend to see this in animals, and have no reason to believe it would be different in humans,” comments Jeffrey.

Source: John Wiley & Sons, Inc.

Bio com
April 11, 2006

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Easy-breeding goats may make a cheaper source for some pharmaceuticals

An application to market a drug made in the milk of genetically modified (GM) goats was turned down this week. The decision means that, despite more than a decade of work using GM animals to produce drugs, no products have yet been approved for use. GTC Biotherapeutics of Framingham, Massachusetts, has spent almost 15 years developing a herd of genetically modified goats whose milk contains a human anticoagulant called anti-thrombin. The company planned to market the drug under the name ATryn. But the London-based European Medicines Agency (EMEA) turned down their request on 23 February, saying the product hadn’t been tested enough. “It’s important to stress that the grounds for refusal have nothing to do with the use of a transgenic animal,” says Martin Harvey Allchurch, spokesman for the EMEA.

ATryn was designed for people lacking a working anti-thrombin gene, who can have an increased risk of blood clots. At the moment they are given blood-thinning drugs such as Warfarin, but this can raise the risk of bleeding to death during childbirth or surgery. At such times anti-thrombin itself is used, the only present source of which is human blood. GTC spokesman Tom Newberry says that goats’ milk is an ideal place to make these proteins, because it can deliver large quantities relatively cheaply and reliably. Some therapeutic proteins are currently produced in bioreactors, huge brewing vats that typically contain cultured Chinese hamster ovary cells. But large, complex proteins such as anti-thrombin are difficult to make this way. And breeding goats is easier than building reactors.

GTC added a copy of the human anti-thrombin gene to a goat gene that makes milk. The engineered DNA was injected into an embryo, and a goat herd built up by conventional breeding. “Getting the protein into the milk is the easiest part,” says Newberry. The difficult part is purifying the proteins and doing enough clinical trials, he adds. The EMEA recommended that GTC test their drug on 12 patients undergoing surgery. But the company only presented evidence from five cases, which the EMEA says is too few. Newberry says that the drug also tested positively during nine childbirths, but that the EMEA excluded these from the surgical tally.

The agency also pointed out that the marketed product would have an extra filtration step that was not included in the trials. Finally, they said that GTC had done too few studies to assess whether patients developed antibodies in response to ATryn. Despite the setback, the next such application is just around the corner. Pharming, a biotech company based in Leiden, the Netherlands, is awaiting approval from the US Food and Drug Administration for an antibacterial agent called lactoferrin, which they produce in the milk of GM cows. Samir Singh, chief business officer with Pharming, believes the company will get a positive response by the end of this year. As human lactoferrin would be a ‘nutriceutical’ — a food additive intended to boost health — it has fewer hurdles to clear than a drug.

Nature
March 14, 2006

Original web page at Nature

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Rift Valley fever in small ruminants

During the 2003 rainy season, the clinical and serologic incidence of Rift Valley fever was assessed in small ruminant herds living around temporary ponds located in the semi-arid region of the Ferlo, Senegal. No outbreak was detected by the surveillance system. Serologic incidence was estimated at 2.9% (95% confidence interval 1.0–8.7) and occurred in 5 of 7 ponds with large variations in the observed incidence rate (0%–20.3%). The location of ponds in the Ferlo Valley and small ponds were correlated with higher serologic incidence (p = 0.0005 and p = 0.005, respectively). Rift Valley fever surveillance should be improved to allow early detection of virus activity. Ruminant vaccination programs should be prepared to confront the foreseeable higher risks for future epidemics of this disease.

Rift Valley fever (RVF) is an arbovirosis caused by a phlebovirus (Bunyaviridae). In ruminants, RVF causes mass abortions and deaths in newborn kids and lambs. Human disease is often limited to a flulike syndrome, but severe forms have been reported. In West Africa, domestic ruminants are the main hosts of the virus, which is transmitted between animals by mosquitoes, particularly those belonging to the Culex and Aedes genera. Transmission is mostly horizontal, but a vertical mode was described for some Aedes species. Human cases are mainly caused by virus exposure after abortion or slaughtering of viremic animals.

A large RVF epidemic occurred in 1987 in southern Mauritania, with >200 reported human deaths. In the following years, several animal and human outbreaks occurred in Mauritania, Senegal, which emphasizes the need for understanding and modeling the risk for RVF in this region before implementing more efficient surveillance and control measures. For this purpose, a survey was conducted in the pastoral area of the Ferlo in northern Senegal. During the rainy season, this agro-ecosystem depends on the availability of surface water in temporary ponds that are flooded after the first rainfalls. These ponds also constitute a favorable habitat for RVF vectors. Previous studies showed that Barkedji, a village located in the central part of the Ferlo, was an area with active viral circulation. The purpose of this study was to assess RVF activity in the area of Barkedji during the 2003 rainy season and to identify risk factors for its transmission to livestock.

Emerging Infectious Diseases
November 22, 2005

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World’s largest database on sheep genetics

Australia launched the world’s largest database on sheep genetics, with the aim of improving breeding and boosting returns for producers. More than two million sheep, drawn from Australia’s 100 million-strong flock, will be incorporated into the database, which brings together the fragmented genetic records used in the past to produce a new comprehensive national system. “We have some tremendously exciting opportunities,” Australia’s Agriculture Minister Peter McGauran said. The new, consolidated service would allow stud breeders, sheep classers and commercial sheep producers to compare animals from different flocks on genetic merit for the first time, McGauran said, helping them to improve their revenue.

The new system will work with sheep producers, using scientific evaluation of their sheep to produce the best breeding outcomes. For example, the characteristics of sheep can be fed into the database, desired traits selected and a match produced for the most appropriate breeding rams. The new system, called Sheep Genetics Australia, is a joint initiative of the wool industry’s main marketing and research body Australian Wool Innovation and the meat industry’s marketing body Meat & Livestock Australia. Variations between genetic systems in the past had held back the industry’s development, McGauran said.

Reuters
November 8, 2005

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Cells from amniotic fluid used to tissue-engineer a new trachea

Researchers at Children’s Hospital Boston report using tissue engineering to reconstruct defective tracheas (windpipes) in fetal lambs, first using cells from the amniotic fluid to grow sections of cartilage tube, and then implanting these living grafts into the lambs while still in the womb. The tracheal repair technique is one of several tissue-engineering approaches pioneered at Children’s that use the fetus’s own cells, drawn from the amniotic fluid that surrounds it, to create patches to fix birth defects — in this case, even before birth. Pediatric surgeon Dario Fauza, MD, who led the study, will present the team’s work on October 8 at the American Academy of Pediatrics annual conference in Washington, DC.

Amniotic fluid is easily collected during pregnancy and contains unspecialized cells, known as mesenchymal stem cells, that can make many of the tissues needed to perform repairs, Fauza says. While tracheal defects are rare, they’re life-threatening: babies born with incomplete, malformed or missing tracheas cannot breathe and must immediately go on heart-lung bypass, which can cause neurologic and other complications. Surgeons have tried various fixes, such as grafting in pieces of the baby’s rib or pelvic bone, using synthetic substances like Teflon, or implanting stents (in the hope that tissue would scar around the stents and form a tube), but with limited success.

“These are all makeshift solutions, and they’re fraught with complications — infection, narrowing of the trachea, reoperation,” Fauza says. Working with sheep, considered a good model for humans (lambs grow quickly and are similar in size to human babies), Fauza’s team obtained a small quantity of amniotic fluid and isolated mesenchymal stem cells. Mesenchymal stem cells descend directly from embryonic stem cells and are abundant in the amniotic fluid. They specialize in making connective tissues, including muscle, bone, cartilage, fat and tendon. Fauza’s team multiplied the amniotic mesenchymal cells in culture, then “seeded” them onto biodegradable tubes of the needed dimensions and shape. The tubes and cells were then exposed to growth factors that caused the mesenchymal cells to differentiate into cartilage cells. When the engineered grafts were ready, they were used to reconstruct defective tracheas in seven fetal lambs. Four to five weeks later, the lambs were born, and all five lambs that survived to term were able to breathe spontaneously at birth, four of them with no sign of respiratory distress. (The other two lambs, twins, were born prematurely and did not survive.)

While many congenital defects can be safely repaired after birth, Fauza’s goal is to fix tracheal defects in utero. Once the baby is born, tracheal surgery requires that the baby be intubated and ventilated long after the operation while the trachea heals; this can lead to many complications, including failure of the repair. Fetal surgery would eliminate these interventions and their resulting problems. “The fetus doesn’t need the trachea, so the repair would have time to heal in utero,” Fauza explains. “And fetal healing is very good — it’s better than adult healing.” Fauza, whose research lab works closely with Children’s Advanced Fetal Care Center, has been investigating the idea of growing new tissues and organs for these tiny patients for eight years. Since the tissue-engineered grafts are made from the baby’s own cells, taken before birth, there would be no risk of the immune system rejecting the tissues, and since fetal cells are immature and not fully specialized, they can be used to generate a variety of tissues.

Currently, most tissue engineers use adult cells to create their lab-grown tissues. While Fauza has also used cells from the ear and from the bone marrow to derive cartilage cells, amniotic fluid is much more readily available.
Millions of pregnant women elect to have amniotic fluid drawn to test for chromosome defects, the procedure known as amniocentesis. And when a prenatal ultrasound exam reveals fetal malformations, amniocentesis is usually recommended. Complications are rare. “In many cases, the amniotic fluid is collected anyway,” says Fauza. “It’s a precious resource that’s thrown out now, but shouldn’t be.”

Less than two tablespoons of amniotic fluid provide enough fetal cells to repair a malformation in utero or after birth — potentially, even years later, Fauza says. He envisions a future in which amniotic fluid is banked for everyone’s use. “Fetal cells are the best cells you can have for tissue engineering,” he says. “They grow very well, and they’re very plastic — you can coach them to do what you want.” Last year, Fauza reported using similar techniques in newborn lambs to repair congenital diaphragmatic hernia (CDH), or a hole in the diaphragm that separates the lungs from the visceral organs. If the hole is large enough, the stomach and other visceral organs can end up in the chest cavity, crowding the lungs and stunting their growth. Using mesenchymal stem cells from amniotic fluid, Fauza’s team engineered a tendon patch for the diaphragm; a year later, the lambs’ diaphragms showed good healing.

The FDA is now reviewing Fauza’s application to conduct a clinical trial in human babies with a prenatal ultrasound diagnosis of CDH; the amniotic fluid would be collected several months before birth and a tissue-engineered patch made ready for use soon after delivery. His team is also working on stem-cell-based, tissue-engineered grafts to fix spina bifida (in which the spinal column doesn’t close fully during fetal development) and structural cardiac defects, using similar principles.

Science Daily
November 8, 2005

Original web page at Science Daily

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A sheep with a heart attack can be helped to heal with mouse stem cells

Embryonic stem cells from mice can help mend the broken hearts of sheep. This cross-species experiment is one more step in finding out whether human embryonic stem cells can mend the damage done by heart attacks. A heart attack damages the muscle and blood vessels that allow a heart to pump blood around the body. Doctors have long sought a way to repair this damage, and some experts say that embryonic stem cells hold the answer. These cells have the potential to turn into any type of cell needed, such as heart-muscle cells. Studies have already shown that embryonic stem cells can improve blood flow after an attack in small animals, such as rodents. But in people, ethical controversies have slowed research into the benefits of embryonic stem cells for ailing hearts.

In human trials scientists have used stem cells from a patient’s bone marrow to help the healing. These cells are not as flexible as embryonic ones, but can sometimes be persuaded to turn into the desired cell types. Patients treated this way are able to pump more blood after a heart attack than those who don’t get the treatment. But researchers hope that embryonic stem cells might have a greater effect. Michel Pucéat of the French National Centre for Scientific Research in Montpellier and his colleagues decided to test embryonic stem cells in sheep to see how well they work in large mammals. Because there is not much call for sheep embryonic stem cells, they are hard to source, so the team used mouse cells instead.

hns Hopkins University School of Medicine in Baltimore, Maryland. For the moment, the improvement is of the same order of magnitude as that achieved in humans with bone marrow transplants. But Hare says that the healing should increase over time: other studies have shown the biggest benefit from stem cells two months after injections. Pucéat says that this form of cardiac therapy holds much future promise. He and his colleagues are currently conducting tests to assess the healing power of human embryonic stem cells in baboons.

Nature
October 11, 2005

Original web page at Nature

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Whole-ovary transplant successful in sheep

Whole, frozen and then thawed ovaries have been successfully transplanted in sheep, resulting in viable embryos. The technique offers the hope of motherhood to young women about to undergo cancer therapies known to cause infertility. Aggressive radiation or chemotherapy treatments for cancer can destroy ovaries. Unfortunately just 2% of human eggs, or oocytes, survive the freezing and thawing process necessary to preserve them for future use. Fertilised eggs have a much better track record, but for that, a woman must already have chosen the father.

The best treatment so far is frozen and thawed ovarian grafts. These small sections of tissue are harvested before cancer treatment and then transplanted back into the body – into the ovaries, arm or abdomen – when treatment is finished. Two direct grafts back onto ovaries have resulted in successful, natural pregnancies in humans. But without built-in blood vessels, up to half of the surviving follicles –sacs of cells in the ovary, each containing a maturing ovum – die immediately after transplantation due to lack of blood supply. Grafts also tend to be short lived. “The benefit of transplanting the whole ovary, the organ and blood vessels, is that you have immediately renewed blood flow. There is a much better chance of survival for the follicles,” says co-author Yehudit Nathan at IMT Ltd in Ness Ziona, Israel, a research company specialising in cryobiology.

Nathan and her colleagues removed both ovaries from eight sheep, being careful to take the delicate blood vessels attached to the right ovary, too. They then slowly froze the right ovaries at a steady rate to control ice crystal growth – if crystals grow too large, they can damage and kill fragile cells. Two weeks later, they thawed and implanted the ovaries back into the sheep, into the place previously occupied by the left ovary. Five of the eight ovaries showed immediate blood flow and were considered a success. One month later, the team successfully retrieved egg cells from two of the sheep. At four months, one of these two ewes produced another four egg cells. The team used chemicals to mimic fertilisation – to avoid the complications of varying sperm quality – and found that all eggs grew into viable embryos. Three years on, and MRI imaging and hormone tests showed that the ovaries were still functioning normally.

The feat, previously only accomplished in rats, is a “significant step forward”, says ovarian cryopreservation expert Kutluk Oktay at Weill Medical College at Cornell University, US. But he warns that the benefits of whole-ovary transplant must be weighed against the risks: it is literally putting half a woman’s eggs in one vulnerable basket. Human ovaries are three to four times larger than sheep ovaries and may not survive freezing and thawing so well, as size is a crucial variable to success – the bigger they are, the more difficult to safely freeze. Preserving grafts may end up being safer and more effective in the end. “One would need a head-to-head comparison of those two techniques. But if the survival rate after freezing is similar then the [whole-ovary] technique would be superior,” Oktay told New Scientist.

Source: journal Human Reproduction

New Scientist
September 27, 2005

Original web page at New Scientist

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Sheep can pass BSE to their lambs

BSE has been shown to spread naturally between sheep for the first time. It passed from mother to lamb, before or during birth, in an experimentally infected flock. But if the study shows the infection spreads more generally within the flock, that means BSE could still be lurking in Europe’s sheep, possibly posing a greater health risk to people than that from “mad” cows.

Scientists found in 1996 that sheep develop a disease similar to BSE if they eat infected cattle tissue. But feeding cattle remains to sheep was banned in Britain in 1988, and in the EU in 1994. All the sheep infected before then should be gone by now. So there should be no more BSE sheep – unless they can transmit BSE to each other. Cattle cannot do this, but sheep transmit a related disease called scrapie between themselves, apparently when they eat placentas and other birthing remains in the field. If BSE also spreads “horizontally” in this way – between other members of the flock – it might have kept spreading in sheep even after the feed ban.

And because the symptoms of BSE in sheep resemble scrapie, “mad” sheep might not have been noticed. Nearly 2700 sheep with apparent scrapie have now been tested for BSE in the UK. None so far had clear BSE, though two are being tested further. BSE-infected goats, which are biologically similar to sheep, were found in France and possibly the UK in 2005. BSE-infected sheep are potentially more dangerous to human consumers than BSE-infected cows, as they carry the infection in more of the tissues people eat.

Sue Bellworthy and colleagues at the UK’s Veterinary Laboratories Agency (VLA) report that two ewes experimentally infected with BSE in a flock in Warwickshire in 2000 gave birth to lambs in 2003 that died of BSE this year. This is the first confirmation of “vertical” transmission of BSE from mother to offspring. It has been suspected but never proved in cattle. In sheep, given how scrapie spreads, “this was expected,” Danny Matthews, a BSE expert at the VLA, told New Scientist. “But vertical transmission alone would not be enough to keep BSE going in the sheep population after the feed ban.” Transmission would be limited to one family line, which would die out as animals die of BSE or are eaten. The experimental herd is now being watched to see if adults can transmit BSE horizontally to other ewe’s lambs now being born and raised within the flock. So far none has, and no uninfected adult sheep have caught the disease from experimentally infected sheep. But it’s still “too early to say”, cautions Matthews.

Journal reference: Veterinary Record

New Scientist
September 13, 2005

Original web page at New Scientist