Showing posts with label infectious diseases. Show all posts
Showing posts with label infectious diseases. Show all posts
Tuesday, September 1, 2009
Monday, May 25, 2009
New jab shows promise for CMV prevention
Medical Tribune May 2009 P12
David Brill
American researchers have scored “a home run” in the quest to prevent congenital cytomegalovirus (CMV) infections – a leading cause of birth defects in newborns.
In a recent phase II trial they found that a new vaccine was 50 percent effective at preventing CMV infection among women, after a minimum of 1 year follow-up.
Just 18 of 234 women who were vaccinated went on to develop CMV infection, compared to 31 of 230 women in the placebo group. [N Engl J Med 2009 Mar 19;360(12):1191-9]
Further trials are now needed to confirm whether immunizing mothers will actually translate to a reduction in congenital infections, said lead researcher Dr. Robert Pass.
With phase III trials also required it is likely to be at least 5 years before the vaccine is licensed, he said. It also remains unclear whether CMV immunity persists or would need boosters.
Successful CMV vaccines have so far proved elusive: none are currently licensed despite more than 30 years of research and a ‘top priority’ listing by the US Institute of Medicine in 2001.
“CMV is a very complex virus which has a long-standing relationship with its host,” said Pass, who is professor of pediatrics at the University of Alabama at Birmingham, US.
“When this trial was initiated most people did not think we would find any efficacy for prevention of maternal infection. So to find that the vaccine was actually able to prevent infection in women was essentially a home run.”
Around 0.7 percent of babies are born with a congenital CMV infection – 11 percent of whom are symptomatic at birth. Fetal damage typically occurs in cases where the infection is acquired during pregnancy: around 0.5 percent of such babies die and up to 20 percent have permanent disabilities. [N Engl J Med 2009 Mar 19;360(12):1250-2]
CMV is endemic in Singapore – the virus was present in 87 percent of antental women screened at KK Women’s and Children’s Hospital (KKH) from 1997 to 1998. [Singapore Med J 2000 Apr;41(4):151-5]
Dr. Lai Fon Min, a consultant and head of the antenatal risk assessment unit at KKH, said that there is an important need for CMV vaccines since there are limitations to both maternal and fetal screening, and no accepted therapy for congenital infections.
“If a highly effective vaccine for CMV is developed there may be justification in introducing it in Singapore as we have a high prevalence rate,” he said, but added that it “remains to be seen” whether routine vaccination would be cost effective.
The vaccine tested by Pass and colleagues comprises 0.02 mg of CMV envelope glycoprotein B, along with 13.25 mg of a squalene-in-water emulsion known as MF59. The rights are owned by Sanofi Pasteur.
The study was not designed to assess outcomes among newborns but the findings appear promising: just one of 81 babies born to vaccinated mothers had CMV, whereas three of 97 babies born to placebo-group mothers were infected.
The trial enrolled CMV-seronegative women who had given birth within the previous year. They were vaccinated at 0, 1 and 6 months, and tested quarterly for CMV infections over 42 months.
Injection-site reactions were more common in the vaccinated women but overall adverse event rates were not significantly different to placebo.
Pass added that vaccination could either be performed in pre-teen girls – potentially in combination with the human papillomavirus vaccine – or in very young children, since they are the main source of CMV infections for pregnant women.
Just 18 of 234 women who were vaccinated went on to develop CMV infection, compared to 31 of 230 women in the placebo group. [N Engl J Med 2009 Mar 19;360(12):1191-9]
Further trials are now needed to confirm whether immunizing mothers will actually translate to a reduction in congenital infections, said lead researcher Dr. Robert Pass.
With phase III trials also required it is likely to be at least 5 years before the vaccine is licensed, he said. It also remains unclear whether CMV immunity persists or would need boosters.
Successful CMV vaccines have so far proved elusive: none are currently licensed despite more than 30 years of research and a ‘top priority’ listing by the US Institute of Medicine in 2001.
“CMV is a very complex virus which has a long-standing relationship with its host,” said Pass, who is professor of pediatrics at the University of Alabama at Birmingham, US.
“When this trial was initiated most people did not think we would find any efficacy for prevention of maternal infection. So to find that the vaccine was actually able to prevent infection in women was essentially a home run.”
Around 0.7 percent of babies are born with a congenital CMV infection – 11 percent of whom are symptomatic at birth. Fetal damage typically occurs in cases where the infection is acquired during pregnancy: around 0.5 percent of such babies die and up to 20 percent have permanent disabilities. [N Engl J Med 2009 Mar 19;360(12):1250-2]
CMV is endemic in Singapore – the virus was present in 87 percent of antental women screened at KK Women’s and Children’s Hospital (KKH) from 1997 to 1998. [Singapore Med J 2000 Apr;41(4):151-5]
Dr. Lai Fon Min, a consultant and head of the antenatal risk assessment unit at KKH, said that there is an important need for CMV vaccines since there are limitations to both maternal and fetal screening, and no accepted therapy for congenital infections.
“If a highly effective vaccine for CMV is developed there may be justification in introducing it in Singapore as we have a high prevalence rate,” he said, but added that it “remains to be seen” whether routine vaccination would be cost effective.
The vaccine tested by Pass and colleagues comprises 0.02 mg of CMV envelope glycoprotein B, along with 13.25 mg of a squalene-in-water emulsion known as MF59. The rights are owned by Sanofi Pasteur.
The study was not designed to assess outcomes among newborns but the findings appear promising: just one of 81 babies born to vaccinated mothers had CMV, whereas three of 97 babies born to placebo-group mothers were infected.
The trial enrolled CMV-seronegative women who had given birth within the previous year. They were vaccinated at 0, 1 and 6 months, and tested quarterly for CMV infections over 42 months.
Injection-site reactions were more common in the vaccinated women but overall adverse event rates were not significantly different to placebo.
Pass added that vaccination could either be performed in pre-teen girls – potentially in combination with the human papillomavirus vaccine – or in very young children, since they are the main source of CMV infections for pregnant women.
Monday, April 13, 2009
Action needed on S. aureus in developing SE Asian countries
Medical Tribune March 2009 P12
David Brill
The burden of Staphylococcus aureus in low-income south and east Asian countries is poorly understood and could pose a threat to the health of both developed and developing countries, an international team of researchers has warned.
The lack of data on drug resistance rates in particular could exacerbate the problem if a strategic research program is not defined, the group wrote in a recent review in The Lancet Infectious Diseases. [2009 Feb;9(2):130-135]
The regional prevalence of methicillin-resistant S. aureus (MRSA), for example, remains largely unknown, although surveillance data from India and China suggest that the strain represents a substantial and rising proportion of the overall S. aureus burden. This knowledge gap could be contributing to the lack of recognition given to the problem by healthcare workers and the public, the study authors say.
The unregulated sale of cheap, substandard over-the-counter antibiotics could also be fuelling the emergence of MRSA in these countries, they add.
Mortality data on S. aureus in developing Asian countries are also scarce, but one study from a Thai hospital found that the death rate from bacteremia could be as high as 48 percent. [Lancet Infect Dis 2006 Feb;6(2):70-1] A comparable study in the US reported a mortality of just 22 percent. [Arch Intern Med 2003 Sep 22;163(17):2066-72]
Children seem particularly vulnerable to S. aureus in low-income countries in south and east Asia, unlike in high-income countries where the incidence of the bug appears largely to increase with age. The same study from Thailand found that S. aureus infections were most common in neonates, who made up 25 percent of all cases, while another study from Laos demonstrated that S. aureus was the number one cause of bacteremia in children aged under 1 year. [Am J Trop Med Hyg 2006 Nov;75(5):978-85]
“The burden of S. aureus disease in developing regions is inadequately appreciated or understood. An initiative is needed to raise the profile of S. aureus disease in developing countries, and to fund studies to better define the healthcare challenges and potential practical solutions relating to this important global pathogen,” wrote the authors, who hail from the Mahidol University in Bangkok, Thailand, the University of Oxford, UK, and the University of Washington in Seattle, US.
A total of 96 papers were included in the literature review – comprising published data from 20 low-income or lower-middle income countries including Indonesia, the Philippines, Vietnam and Cambodia.
Besides establishing the prevalence of MRSA, future research should also be directed at identifying risk factors for S. aureus and implementing cheap but effective mechanisms for infection control, the authors wrote.
The lack of data on drug resistance rates in particular could exacerbate the problem if a strategic research program is not defined, the group wrote in a recent review in The Lancet Infectious Diseases. [2009 Feb;9(2):130-135]
The regional prevalence of methicillin-resistant S. aureus (MRSA), for example, remains largely unknown, although surveillance data from India and China suggest that the strain represents a substantial and rising proportion of the overall S. aureus burden. This knowledge gap could be contributing to the lack of recognition given to the problem by healthcare workers and the public, the study authors say.
The unregulated sale of cheap, substandard over-the-counter antibiotics could also be fuelling the emergence of MRSA in these countries, they add.
Mortality data on S. aureus in developing Asian countries are also scarce, but one study from a Thai hospital found that the death rate from bacteremia could be as high as 48 percent. [Lancet Infect Dis 2006 Feb;6(2):70-1] A comparable study in the US reported a mortality of just 22 percent. [Arch Intern Med 2003 Sep 22;163(17):2066-72]
Children seem particularly vulnerable to S. aureus in low-income countries in south and east Asia, unlike in high-income countries where the incidence of the bug appears largely to increase with age. The same study from Thailand found that S. aureus infections were most common in neonates, who made up 25 percent of all cases, while another study from Laos demonstrated that S. aureus was the number one cause of bacteremia in children aged under 1 year. [Am J Trop Med Hyg 2006 Nov;75(5):978-85]
“The burden of S. aureus disease in developing regions is inadequately appreciated or understood. An initiative is needed to raise the profile of S. aureus disease in developing countries, and to fund studies to better define the healthcare challenges and potential practical solutions relating to this important global pathogen,” wrote the authors, who hail from the Mahidol University in Bangkok, Thailand, the University of Oxford, UK, and the University of Washington in Seattle, US.
A total of 96 papers were included in the literature review – comprising published data from 20 low-income or lower-middle income countries including Indonesia, the Philippines, Vietnam and Cambodia.
Besides establishing the prevalence of MRSA, future research should also be directed at identifying risk factors for S. aureus and implementing cheap but effective mechanisms for infection control, the authors wrote.
Monday, March 16, 2009
Experts fear rise of drug-resistant superbug
Medical Tribune January 2009 P1&6
David Brill
Rising levels of drug resistance among Acinetobacter Baumannii are causing serious concern among infectious disease experts, who are calling for urgent international attention to the issue.
The bug is particularly prevalent in hospitals in Southeast Asia, with Taiwan and Korea seemingly the worst affected.
The rapidly dwindling number of treatment options could soon herald the dawn of the “post-antibiotic era,” according to a specialist from Singapore, where extensively drug-resistant strains have already been reported.
A. Baumannii resistance rates are increasing globally, with around half of strains presently thought to be resistant to at least one antibiotic. Nearly 20 percent of strains are resistant to all but one or two agents.
Reports have already emerged of pandrug resistant strains, which – although rare at present – will beome increasingly common if the problem is not addressed, said Professor Matthew Falagas, an international expert who published a recent high-profile review calling for more research into treatment options. [Lancet Infect Dis 2008 Dec;8(12):751-62]
“We should be worried because we have never heard before of bugs which affect humans where we do not have an antibiotic to provide,” he told Medical Tribune.
“The issue of pan-drug resistance needs international attention. Public health organizations and local infection controls at the country level should disseminate guidelines on this issue,” he said, adding that in some hospitals the significance of the bug is already on a par with methicillin-resistant S. Aureus (MRSA).
A. Baumannii mainly affects seriously ill patients in intensive care units and burn wards. Although less common than other hospital-based infections, the bug can cause significant morbidity and mortality, placing a heavy drain upon hospital resources through repeated hospitalizations and increased lengths of stay.
A Singapore study found that 69 percent of A. Baumannii strains in one intensive care unit were resistant to carbapenem. Nearly 20 percent of isolates from all the nation’s hospitals were resistant to everything except the polymixins, which can cause significant toxicity to the brain and kidneys. [Emerg Infect Dis 2007 Dec;13(12):1944-7]
“Its ability to acquire resistance is a big concern because there aren’t going to be many treatment options available,” said Dr. Tan Thuan Tong, an infectious diseases consultant at Singapore General Hospital.
“We foresee a time when you get strains that are not treatable and you just try your luck with various combinations that might act in a synergistic manner,” he said, adding that such a scenario could arise in Singapore within the next 5 years.
Around 30 to 40 percent of patients who get a multidrug-resistant A. Baumannii bloodstream infection may die, according to Tan, but he added that the directly attributable mortality is not clear-cut since patients are often critically ill for other reasons.
Falagas, meanwhile, called on hospitals worldwide to decrease the usage of antibiotics and promote stricter infection prevention and control measures, particularly with regard to hand hygiene. He added that research is now ongoing to find new antibiotics for Gram-negative bacteria, but said that the process has been too slow getting started.
“The scientific community and the pharmaceutical companies have focused attention on Gram-positives without understanding the significance of Gram-negatives as healthcare-associated infections, and especially A. Baumannii,” said Falagas, who is director of the Alfa Institute of Biomedical Sciences in Athens, Greece, and an adjunct associate professor at Tufts University
School of Medicine, Boston, US.
Singapore has already begun to acknowledge the growing problem of antimicrobial resistance, with a group of experts publishing a recent position paper advocating stricter controls on the use of antibiotics. [Singapore Med J 2008 Oct;49(10):749-55]
“In the 18th and 19th century, there were no antibiotics and treatment was with drainage of pus, amputation and other surgical approaches. If you have infections with these untreatable bugs, then you are back to the days when you can’t do anything,” added Tan.
David Brill
Rising levels of drug resistance among Acinetobacter Baumannii are causing serious concern among infectious disease experts, who are calling for urgent international attention to the issue.
The bug is particularly prevalent in hospitals in Southeast Asia, with Taiwan and Korea seemingly the worst affected.
The rapidly dwindling number of treatment options could soon herald the dawn of the “post-antibiotic era,” according to a specialist from Singapore, where extensively drug-resistant strains have already been reported.
A. Baumannii resistance rates are increasing globally, with around half of strains presently thought to be resistant to at least one antibiotic. Nearly 20 percent of strains are resistant to all but one or two agents.
Reports have already emerged of pandrug resistant strains, which – although rare at present – will beome increasingly common if the problem is not addressed, said Professor Matthew Falagas, an international expert who published a recent high-profile review calling for more research into treatment options. [Lancet Infect Dis 2008 Dec;8(12):751-62]
“We should be worried because we have never heard before of bugs which affect humans where we do not have an antibiotic to provide,” he told Medical Tribune.
“The issue of pan-drug resistance needs international attention. Public health organizations and local infection controls at the country level should disseminate guidelines on this issue,” he said, adding that in some hospitals the significance of the bug is already on a par with methicillin-resistant S. Aureus (MRSA).
A. Baumannii mainly affects seriously ill patients in intensive care units and burn wards. Although less common than other hospital-based infections, the bug can cause significant morbidity and mortality, placing a heavy drain upon hospital resources through repeated hospitalizations and increased lengths of stay.
A Singapore study found that 69 percent of A. Baumannii strains in one intensive care unit were resistant to carbapenem. Nearly 20 percent of isolates from all the nation’s hospitals were resistant to everything except the polymixins, which can cause significant toxicity to the brain and kidneys. [Emerg Infect Dis 2007 Dec;13(12):1944-7]
“Its ability to acquire resistance is a big concern because there aren’t going to be many treatment options available,” said Dr. Tan Thuan Tong, an infectious diseases consultant at Singapore General Hospital.
“We foresee a time when you get strains that are not treatable and you just try your luck with various combinations that might act in a synergistic manner,” he said, adding that such a scenario could arise in Singapore within the next 5 years.
Around 30 to 40 percent of patients who get a multidrug-resistant A. Baumannii bloodstream infection may die, according to Tan, but he added that the directly attributable mortality is not clear-cut since patients are often critically ill for other reasons.
Falagas, meanwhile, called on hospitals worldwide to decrease the usage of antibiotics and promote stricter infection prevention and control measures, particularly with regard to hand hygiene. He added that research is now ongoing to find new antibiotics for Gram-negative bacteria, but said that the process has been too slow getting started.
“The scientific community and the pharmaceutical companies have focused attention on Gram-positives without understanding the significance of Gram-negatives as healthcare-associated infections, and especially A. Baumannii,” said Falagas, who is director of the Alfa Institute of Biomedical Sciences in Athens, Greece, and an adjunct associate professor at Tufts University
School of Medicine, Boston, US.
Singapore has already begun to acknowledge the growing problem of antimicrobial resistance, with a group of experts publishing a recent position paper advocating stricter controls on the use of antibiotics. [Singapore Med J 2008 Oct;49(10):749-55]
“In the 18th and 19th century, there were no antibiotics and treatment was with drainage of pus, amputation and other surgical approaches. If you have infections with these untreatable bugs, then you are back to the days when you can’t do anything,” added Tan.
Sunday, March 15, 2009
The meteoric rise of HIV
Healthy Times December 2008
David Brill (aka David Wise)
December 1 is World Aids Day. To mark the event medical journalist David Wise looks at the humble origins of this global killer and its journey from an isolated outbreak to a worldwide pandemic.
Léopoldville may not be a familiar name to many, yet the city played host to one of the defining events of mankind’s recent history. The former Belgian colonial capital – now known as Kinshasa, Democratic Republic of the Congo – is thought to be the birthplace of HIV, the virus responsible for the AIDS pandemic which is currently affecting over 33 million people worldwide.
The precise origins of HIV remain a mystery but new research allows scientists to paint a more detailed picture than ever before. They now believe that the virus first reached humans in Léopoldville around 100 years ago, where it found a foothold among the booming population of the newly-founded city.
It is likely that HIV spread slowly at first, experts say, while the fact that symptoms differ widely between individuals may have prevented it from being recognized for many years. It was not until 1981 that French scientists Françoise Barré-Sinoussi and Luc Montagnier formally identified the virus – a discovery that was honored this year with the award of the Nobel Prize for medicine.
The true beginning of the story, however, begins not with humans but with our primate cousins. Today there are several different types of HIV, each of which may have its own tale to tell, but the particular strain responsible for the current pandemic seems to have evolved from a virus which naturally infects chimpanzees. In 2006 researchers announced that they had found this HIV forefather – the Simian Immunodeficiency Virus (SIV) – among wild chimps living in southeast Cameroon.
Most scientists accept that SIV became HIV, but how it first crossed the species barrier is largely a matter for speculation, according to Professor Robin Weiss, an HIV expert from University College London, UK.
“The most likely explanation is that it began with the butchering of apes,” he explains. “There was blood and splintered bones and goodness knows what lying around, and then the virus got transferred into small cuts or abrasions on the skin. If you wanted to be lurid you could raise a King Kong scenario of sex with a great ape but I think that’s a bit sensational myself.”
The first known case of HIV comes from a preserved tissue specimen dating back to 1959, which was found in the archives at the University of Kinshasa. In 2000, Betty Korber and her team at the Los Alamos National Laboratory, US, published an important research paper analyzing the genetic sequence of this virus. Their calculations, they said, suggested that the virus had likely been born around 1931 – back when Kinshasa was still known as Léopoldville.
But this information begged an important question which has only recently been answered: how did the slaughtering of chimps in southeastern Cameroon lead to the infection of humans in Léopoldville some 700km away?
The answer was provided in October of this year when Michael Worobey and his colleagues from the University of Arizona, writing in the journal Nature, announced that they had found another early HIV specimen lurking in the archives at Kinshasa. The tissue sample – a lymph node taken from an adult woman – had been fixed in preservative back in 1960.
This discovery enabled the team to compare the virus with Korber’s specimen from 1959. By looking at genetic differences between the two samples and tracing their family trees backwards, they established that the viruses must have shared a common ancestor between 1884 and 1924. Their best estimate puts the birth of HIV at 1908 – some 23 years earlier than previously thought.
Worobey’s team went one step further and placed their genetic studies alongside demographic data on the growth of cities in west-central Africa. They found that their estimate of 1908 coincided with a period of population boom in Léopoldville, suggesting that growth of the city provided the necessary kick-start for HIV to spread. Before 1900, there was not one settlement in the area with more than 10,000 people, but by 1910 Léopoldville had established itself as the region’s major city.
As the colonial outpost grew, so it continued to flourish as an administrative and trading center. With transportation at the time largely restricted to boats, Léopoldville found itself ideally situated on the Congo River – the final destination of many of the tributaries that run through the forests of Cameroon. The identity of the person that first contracted SIV may remain a mystery, but their arrival in the city now seems the likely trigger for the modern-day AIDS pandemic.
This newfound understanding of where HIV came from can provide important insights into the evolution of future pandemics, according to Weiss.
“These examples of particular viruses help to inform our general thinking about the origins of infections that come from animals. And for sure we’ve haven’t seen the last one – there’ll be some other disease like SARS or something that we haven’t even thought about today,” he says.
“And looking back at HIV in its very humble, small beginnings… who would have guessed that this would turn out to be the major killer at the end of the 20th century?”
David Brill (aka David Wise)
December 1 is World Aids Day. To mark the event medical journalist David Wise looks at the humble origins of this global killer and its journey from an isolated outbreak to a worldwide pandemic.
Léopoldville may not be a familiar name to many, yet the city played host to one of the defining events of mankind’s recent history. The former Belgian colonial capital – now known as Kinshasa, Democratic Republic of the Congo – is thought to be the birthplace of HIV, the virus responsible for the AIDS pandemic which is currently affecting over 33 million people worldwide.
The precise origins of HIV remain a mystery but new research allows scientists to paint a more detailed picture than ever before. They now believe that the virus first reached humans in Léopoldville around 100 years ago, where it found a foothold among the booming population of the newly-founded city.
It is likely that HIV spread slowly at first, experts say, while the fact that symptoms differ widely between individuals may have prevented it from being recognized for many years. It was not until 1981 that French scientists Françoise Barré-Sinoussi and Luc Montagnier formally identified the virus – a discovery that was honored this year with the award of the Nobel Prize for medicine.
The true beginning of the story, however, begins not with humans but with our primate cousins. Today there are several different types of HIV, each of which may have its own tale to tell, but the particular strain responsible for the current pandemic seems to have evolved from a virus which naturally infects chimpanzees. In 2006 researchers announced that they had found this HIV forefather – the Simian Immunodeficiency Virus (SIV) – among wild chimps living in southeast Cameroon.
Most scientists accept that SIV became HIV, but how it first crossed the species barrier is largely a matter for speculation, according to Professor Robin Weiss, an HIV expert from University College London, UK.
“The most likely explanation is that it began with the butchering of apes,” he explains. “There was blood and splintered bones and goodness knows what lying around, and then the virus got transferred into small cuts or abrasions on the skin. If you wanted to be lurid you could raise a King Kong scenario of sex with a great ape but I think that’s a bit sensational myself.”
The first known case of HIV comes from a preserved tissue specimen dating back to 1959, which was found in the archives at the University of Kinshasa. In 2000, Betty Korber and her team at the Los Alamos National Laboratory, US, published an important research paper analyzing the genetic sequence of this virus. Their calculations, they said, suggested that the virus had likely been born around 1931 – back when Kinshasa was still known as Léopoldville.
But this information begged an important question which has only recently been answered: how did the slaughtering of chimps in southeastern Cameroon lead to the infection of humans in Léopoldville some 700km away?
The answer was provided in October of this year when Michael Worobey and his colleagues from the University of Arizona, writing in the journal Nature, announced that they had found another early HIV specimen lurking in the archives at Kinshasa. The tissue sample – a lymph node taken from an adult woman – had been fixed in preservative back in 1960.
This discovery enabled the team to compare the virus with Korber’s specimen from 1959. By looking at genetic differences between the two samples and tracing their family trees backwards, they established that the viruses must have shared a common ancestor between 1884 and 1924. Their best estimate puts the birth of HIV at 1908 – some 23 years earlier than previously thought.
Worobey’s team went one step further and placed their genetic studies alongside demographic data on the growth of cities in west-central Africa. They found that their estimate of 1908 coincided with a period of population boom in Léopoldville, suggesting that growth of the city provided the necessary kick-start for HIV to spread. Before 1900, there was not one settlement in the area with more than 10,000 people, but by 1910 Léopoldville had established itself as the region’s major city.
As the colonial outpost grew, so it continued to flourish as an administrative and trading center. With transportation at the time largely restricted to boats, Léopoldville found itself ideally situated on the Congo River – the final destination of many of the tributaries that run through the forests of Cameroon. The identity of the person that first contracted SIV may remain a mystery, but their arrival in the city now seems the likely trigger for the modern-day AIDS pandemic.
This newfound understanding of where HIV came from can provide important insights into the evolution of future pandemics, according to Weiss.
“These examples of particular viruses help to inform our general thinking about the origins of infections that come from animals. And for sure we’ve haven’t seen the last one – there’ll be some other disease like SARS or something that we haven’t even thought about today,” he says.
“And looking back at HIV in its very humble, small beginnings… who would have guessed that this would turn out to be the major killer at the end of the 20th century?”
Wednesday, February 18, 2009
Dengue epidemic avoided in Singapore
Medical Tribune November 2008 SFXII
David Brill
Efforts to control dengue in Singapore appear to have been a success this year, with early fears of a repeat outbreak proving to be premature.
Last year saw levels pass the epidemic threshold in early July, when 432 cases of dengue fever and dengue hemorrhagic fever were reported in a single week.
This year, however, the combined number of cases has so far remained comfortably below the warning level of 279 cases in a week.
That same week in July, the peak for 2007, saw just 160 cases reported in 2008, according to Ministry of Health (MOH) statistics.
Experts had raised concerns about the possibility of another epidemic when more cases were reported in the first 3 months of this year than last year.
In response the National Environment Agency (NEA) invested more resources into the Campaign Against Dengue, intensifying operations to identify and destroy mosquito breeding habitats.
In a joint statement with the MOH, the NEA said that this could be one of the reasons for the lower number of cases observed this year.
They also said that their annual ‘Intensive Source Reduction Exercise’ – an initiative targeting the town councils who manage the public housing estates – was launched earlier this year than last.
“We should nonetheless continue to monitor the dengue situation closely and sustain our efforts against the vector because the secular disease trend remains in the upward direction and epidemic transmission continues to be a problem,” the statement concluded.
Associate Professor Leo Yee Sin, head of the department of Infectious Diseases at Tan Tock Seng Hospital, said that the dengue patterns observed so far for 2008 are similar to typical non-epidemic years.
She also noted that last year’s outbreak was preceded by a distinct switch in the predominant circulating dengue strain from DEN-1 to DEN-2. The lack of epidemic this year could therefore be attributable to growing herd immunity against this strain, she said.
Leo added that the outbreak of the chikungunya virus in January this year prompted “massive search and destroy efforts” targeting the Aedes aegypti mosquito, which is also responsible for spreading dengue.
The worldwide incidence of dengue has “grown dramatically” in recent years according to the WHO, who estimate that two fifths of the global population is now at risk.
Singapore has experienced regular dengue epidemics since the first reported outbreak in 1901. These typically occur when there is a shift in the balance between the virus strains, all four of which are present in the country.
A recently-published analysis of the 2005 epidemic found that DEN-1 was responsible for 71.2 percent of cases and DEN-2 just 9.2 percent – a predominance that appears to have reversed in 2007. The development of an effective vaccine against all the strains could be the only definitive way to control dengue in Singapore in the long-term, the authors wrote. [Ann Acad Med Singapore 2008 Jul;37(7):538-45]
David Brill
Efforts to control dengue in Singapore appear to have been a success this year, with early fears of a repeat outbreak proving to be premature.
Last year saw levels pass the epidemic threshold in early July, when 432 cases of dengue fever and dengue hemorrhagic fever were reported in a single week.
This year, however, the combined number of cases has so far remained comfortably below the warning level of 279 cases in a week.
That same week in July, the peak for 2007, saw just 160 cases reported in 2008, according to Ministry of Health (MOH) statistics.
Experts had raised concerns about the possibility of another epidemic when more cases were reported in the first 3 months of this year than last year.
In response the National Environment Agency (NEA) invested more resources into the Campaign Against Dengue, intensifying operations to identify and destroy mosquito breeding habitats.
In a joint statement with the MOH, the NEA said that this could be one of the reasons for the lower number of cases observed this year.
They also said that their annual ‘Intensive Source Reduction Exercise’ – an initiative targeting the town councils who manage the public housing estates – was launched earlier this year than last.
“We should nonetheless continue to monitor the dengue situation closely and sustain our efforts against the vector because the secular disease trend remains in the upward direction and epidemic transmission continues to be a problem,” the statement concluded.
Associate Professor Leo Yee Sin, head of the department of Infectious Diseases at Tan Tock Seng Hospital, said that the dengue patterns observed so far for 2008 are similar to typical non-epidemic years.
She also noted that last year’s outbreak was preceded by a distinct switch in the predominant circulating dengue strain from DEN-1 to DEN-2. The lack of epidemic this year could therefore be attributable to growing herd immunity against this strain, she said.
Leo added that the outbreak of the chikungunya virus in January this year prompted “massive search and destroy efforts” targeting the Aedes aegypti mosquito, which is also responsible for spreading dengue.
The worldwide incidence of dengue has “grown dramatically” in recent years according to the WHO, who estimate that two fifths of the global population is now at risk.
Singapore has experienced regular dengue epidemics since the first reported outbreak in 1901. These typically occur when there is a shift in the balance between the virus strains, all four of which are present in the country.
A recently-published analysis of the 2005 epidemic found that DEN-1 was responsible for 71.2 percent of cases and DEN-2 just 9.2 percent – a predominance that appears to have reversed in 2007. The development of an effective vaccine against all the strains could be the only definitive way to control dengue in Singapore in the long-term, the authors wrote. [Ann Acad Med Singapore 2008 Jul;37(7):538-45]
Friday, February 6, 2009
Healthcare systems urged to vaccinate workers
Medical Tribune August 2008 P7
David Brill
Widespread vaccination programs should be introduced for all healthcare workers and backed by the WHO, according to an infectious diseases expert from Mexico City.
Describing healthcare as “a very risky activity,” Dr. Samuel Ponce de Leon told the ICID that death and disease among personnel can have serious consequences for systems that are already short of important resources.
“Healthcare workers are an endangered species and a very reluctant one to be protected. A total of 57 countries, mostly in sub-Saharan Africa but also some Asian countries, face crippling healthcare worker shortages.
“Every health system, hospital, institute and outpatient clinic, private or public, should establish a program to vaccinate all healthcare workers as part of a comprehensive healthcare program,” he said, adding that “the WHO should establish obligatory regulation to protect healthcare workers.”
Hepatitis B, influenza, measles, rubella, tetanus and diphtheria – just some of the diseases faced by healthcare workers – should form the very minimum components of vaccination programs, according to Ponce de Leon.
Workers risk catching a wide range of infectious diseases from their patients if they are not vaccinated, and can be responsible for passing these on to other patients, medics and the community at large.
Compliance to healthcare worker vaccination schemes is typically poor, he said, suggesting that poor communication and lack of knowledge are typically responsible. Workers may also be reluctant to give up their time, have a fear of needles, or perceive vaccination as dangerous or unnecessary.
“Healthcare workers should be clear that compliance to be vaccinated is an ethical duty,” he said.
Despite the obstacles, vaccine uptake can be successfully promoted said Ponce de Leon, citing the example of a hospital campaign in Korea which boosted influenza vaccination rates among workers from 27 to 52 percent. [Infect Control Hosp Epidemiol 2006 Jun;27(6):612-7]
Beyond the basic schedule, vaccination programs could be extended to include hepatitis A, varicella and pneumoccocus, he said.
He added that avian influenza is also an area to consider but several issues remain unresolved as to what the best vaccine is and when best to use it.
David Brill
Widespread vaccination programs should be introduced for all healthcare workers and backed by the WHO, according to an infectious diseases expert from Mexico City.
Describing healthcare as “a very risky activity,” Dr. Samuel Ponce de Leon told the ICID that death and disease among personnel can have serious consequences for systems that are already short of important resources.
“Healthcare workers are an endangered species and a very reluctant one to be protected. A total of 57 countries, mostly in sub-Saharan Africa but also some Asian countries, face crippling healthcare worker shortages.
“Every health system, hospital, institute and outpatient clinic, private or public, should establish a program to vaccinate all healthcare workers as part of a comprehensive healthcare program,” he said, adding that “the WHO should establish obligatory regulation to protect healthcare workers.”
Hepatitis B, influenza, measles, rubella, tetanus and diphtheria – just some of the diseases faced by healthcare workers – should form the very minimum components of vaccination programs, according to Ponce de Leon.
Workers risk catching a wide range of infectious diseases from their patients if they are not vaccinated, and can be responsible for passing these on to other patients, medics and the community at large.
Compliance to healthcare worker vaccination schemes is typically poor, he said, suggesting that poor communication and lack of knowledge are typically responsible. Workers may also be reluctant to give up their time, have a fear of needles, or perceive vaccination as dangerous or unnecessary.
“Healthcare workers should be clear that compliance to be vaccinated is an ethical duty,” he said.
Despite the obstacles, vaccine uptake can be successfully promoted said Ponce de Leon, citing the example of a hospital campaign in Korea which boosted influenza vaccination rates among workers from 27 to 52 percent. [Infect Control Hosp Epidemiol 2006 Jun;27(6):612-7]
Beyond the basic schedule, vaccination programs could be extended to include hepatitis A, varicella and pneumoccocus, he said.
He added that avian influenza is also an area to consider but several issues remain unresolved as to what the best vaccine is and when best to use it.
Hygiene and education key to reducing catheter-related infections
Medical Tribune August 2008 P7
David Brill
Some 250,000 catheter-related bloodstream infections (BSIs) occur each year in the US, with mortality as high as 35 percent and avoidable costs totaling around US$6.25 billion.
Pic: hospital patient with a catheter line
However the number of infections can be dramatically reduced by following a range of simple steps, according to Trish Perl who is Professor of medicine, pathology and epidemiology at Johns Hopkins Hospital (JHH) in Baltimore.
Since introducing measures to reduce the rates of catheter-related BSIs, JHH has seen a 75 percent decrease across all of their adult intensive care units in the past 6 years, she said. The hospital published a report in 2004 in which they estimate that 43 BSIs, 8 deaths and nearly US$2 million dollars in costs have been prevented each year by the intervention strategy. [Crit Care Med 2004 Oct;32(10):2014-20]
Perl outlined three major contamination sites that can cause BSIs: the skin and insertion site, the catheter hub and the infusate. Each of these points provides a focal target for prevention strategies, she said, noting that the former two are of the greatest concern in developed countries whereas the latter is more of a problem in the developing world.
“It remains important to cleanse your hands … that recommendation actually has the strongest evidence,” said Perl, adding that employing maximal barrier precautions and educating health care workers who place catheters can also help to avoid skin-derived infections.
“These three recommendations are highly, highly supported by the evidence and should be in place in all settings. Knowledge and adherence to guidelines for all persons placing lines has also been shown to decrease your BSI rates,” she said.
Suggested maximal barrier precautions include wearing sterile gloves and gowns and tight-fitting non-sterile masks and hats, and covering the patient’s body with a sterile drape. Consideration should also be given to the site of catheter insertion, as the subclavian vein is associated with lower infection rates than the internal jugular and femoral veins she said.
Beyond the insertion site, catheter hubs and infusates are also an important source of infections said Perl, citing a study of four pediatric hospitals in Mexico City which found that 70 percent of injection ports and 7 percent of infusates were contaminated. [Infect Control Hosp Epidemiol 2004 Mar;25(3):226-30]
“Coated catheters have been shown to decrease BSI rates but given the cost we need to determine the high-risk patients and ensure that other prevention strategies are in place,” she said, adding that the use of antiseptic ports and caps and new stopcock models seem to cut infection rates.
BSI rates also seem to increase when nursing staff levels are low, and ensuring adequate levels of care at all times may also be an important prevention strategy.
Perl noted, however, that certain newer models of needleless connectors have actually led to increased infection rates.
“I think we have to really start considering whether or not the technology can actually contribute to BSIs,” she said.
Perl concluded by adding that future infection control programs should use standard definitions, so that feedback can be easily provided to the healthcare workers who are responsible for the placement of catheters.
David Brill
Some 250,000 catheter-related bloodstream infections (BSIs) occur each year in the US, with mortality as high as 35 percent and avoidable costs totaling around US$6.25 billion.
Pic: hospital patient with a catheter line
However the number of infections can be dramatically reduced by following a range of simple steps, according to Trish Perl who is Professor of medicine, pathology and epidemiology at Johns Hopkins Hospital (JHH) in Baltimore.
Since introducing measures to reduce the rates of catheter-related BSIs, JHH has seen a 75 percent decrease across all of their adult intensive care units in the past 6 years, she said. The hospital published a report in 2004 in which they estimate that 43 BSIs, 8 deaths and nearly US$2 million dollars in costs have been prevented each year by the intervention strategy. [Crit Care Med 2004 Oct;32(10):2014-20]
Perl outlined three major contamination sites that can cause BSIs: the skin and insertion site, the catheter hub and the infusate. Each of these points provides a focal target for prevention strategies, she said, noting that the former two are of the greatest concern in developed countries whereas the latter is more of a problem in the developing world.
“It remains important to cleanse your hands … that recommendation actually has the strongest evidence,” said Perl, adding that employing maximal barrier precautions and educating health care workers who place catheters can also help to avoid skin-derived infections.
“These three recommendations are highly, highly supported by the evidence and should be in place in all settings. Knowledge and adherence to guidelines for all persons placing lines has also been shown to decrease your BSI rates,” she said.
Suggested maximal barrier precautions include wearing sterile gloves and gowns and tight-fitting non-sterile masks and hats, and covering the patient’s body with a sterile drape. Consideration should also be given to the site of catheter insertion, as the subclavian vein is associated with lower infection rates than the internal jugular and femoral veins she said.
Beyond the insertion site, catheter hubs and infusates are also an important source of infections said Perl, citing a study of four pediatric hospitals in Mexico City which found that 70 percent of injection ports and 7 percent of infusates were contaminated. [Infect Control Hosp Epidemiol 2004 Mar;25(3):226-30]
“Coated catheters have been shown to decrease BSI rates but given the cost we need to determine the high-risk patients and ensure that other prevention strategies are in place,” she said, adding that the use of antiseptic ports and caps and new stopcock models seem to cut infection rates.
BSI rates also seem to increase when nursing staff levels are low, and ensuring adequate levels of care at all times may also be an important prevention strategy.
Perl noted, however, that certain newer models of needleless connectors have actually led to increased infection rates.
“I think we have to really start considering whether or not the technology can actually contribute to BSIs,” she said.
Perl concluded by adding that future infection control programs should use standard definitions, so that feedback can be easily provided to the healthcare workers who are responsible for the placement of catheters.
Community-acquired MRSA: The new breed of nosocomial pathogen
Medical Tribune August 2008 P9
David Brill
The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as a nosocomial pathogen presents a range of new challenges for both prevention and management, according to a leading infectious disease specialist.
Professor Richard Wenzel, president of the International Society for Infectious Diseases, told the audience at the ICID that CA-MRSA appears to be more virulent than other nosocomial strains and has an unknown epidemiology.
He described the case that first “gave him respect for CA-MRSA:” a 22-year old male who deteriorated rapidly and died within 36 hours.
The patient had normal heart sounds on admission, yet developed a systolic murmur and symptoms of endocarditis after 16 hours. CT at presentation was also normal, yet MRI performed shortly before death showed around 100 brain abscesses which were later confirmed by biopsy.
It is unclear exactly what makes CA-MRSA so virulent, said Wenzel. The Panton-Valentine leucocidin (PVL) gene and alpha hemolysin have both been implicated in animal models, but their precise roles remain unclearly defined.
Screening also appears to be a complicated issue: a prospective cohort study of 51 CA-MRSA patients found that only 41 percent were nasal carriers, while a report of five patients who received the infection via heterosexual transmission revealed that only one was a nasal carrier.
Screening would therefore underestimate the prevalence of the USA-300 and USA-400 strains, Wenzel said, whereas in cases of nosocomial MRSA the majority of patients test positive for USA-100.
“This is important because people in the US are saying we just have to screen people so we know who’s out there. But it’s not that simple,” he said.
The antiobiogram for CA-MRSA also seems to differ from other types of infection, and the optimal treatment strategy remains unclear.
“The problem is what drugs do you use? I want to tell you this is getting complicated,” said Wenzel, who is chairman of the department of internal medicine at Virginia Commonwealth University, US.
“For life-threatening infections, antibiotics that inhibit protein synthesis and intravenous immunoglobulin may be useful,” he said, but noted that side effects are an issue with many of the available drug treatments.
“Linezolid we think is a relatively good drug but neuropathy, lactic acidosis and serotonin syndrome have all been described.
“Daptomycin looks good in comparative trials for skin and soft tissue. However, it’s not recommended for pneumonia because surfactant inhibits the antibacterial activity.”
He added that vancomycin can lead to renal failure when given with amino glycosides, while trimethoprim causes hyperkalemia in the majority of patients.
Definitive answers are still lacking on what treatments to use either for preventative prophylaxis of CA-MRSA or for treating ventilator-associated pneumonia, Wenzel said, noting that there are currently no clinical trials which can inform these decisions.
Improving our knowledge of resistant pathogens, drug interactions and the adverse events of antibiotics may help in future, he said.
“The plans for changing the prophylactic and empirical therapy for nosocomial infections need to begin right now,” he concluded.
David Brill
The emergence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) as a nosocomial pathogen presents a range of new challenges for both prevention and management, according to a leading infectious disease specialist.
Professor Richard Wenzel, president of the International Society for Infectious Diseases, told the audience at the ICID that CA-MRSA appears to be more virulent than other nosocomial strains and has an unknown epidemiology.
He described the case that first “gave him respect for CA-MRSA:” a 22-year old male who deteriorated rapidly and died within 36 hours.
The patient had normal heart sounds on admission, yet developed a systolic murmur and symptoms of endocarditis after 16 hours. CT at presentation was also normal, yet MRI performed shortly before death showed around 100 brain abscesses which were later confirmed by biopsy.
It is unclear exactly what makes CA-MRSA so virulent, said Wenzel. The Panton-Valentine leucocidin (PVL) gene and alpha hemolysin have both been implicated in animal models, but their precise roles remain unclearly defined.
Screening also appears to be a complicated issue: a prospective cohort study of 51 CA-MRSA patients found that only 41 percent were nasal carriers, while a report of five patients who received the infection via heterosexual transmission revealed that only one was a nasal carrier.
Screening would therefore underestimate the prevalence of the USA-300 and USA-400 strains, Wenzel said, whereas in cases of nosocomial MRSA the majority of patients test positive for USA-100.
“This is important because people in the US are saying we just have to screen people so we know who’s out there. But it’s not that simple,” he said.
The antiobiogram for CA-MRSA also seems to differ from other types of infection, and the optimal treatment strategy remains unclear.
“The problem is what drugs do you use? I want to tell you this is getting complicated,” said Wenzel, who is chairman of the department of internal medicine at Virginia Commonwealth University, US.
“For life-threatening infections, antibiotics that inhibit protein synthesis and intravenous immunoglobulin may be useful,” he said, but noted that side effects are an issue with many of the available drug treatments.
“Linezolid we think is a relatively good drug but neuropathy, lactic acidosis and serotonin syndrome have all been described.
“Daptomycin looks good in comparative trials for skin and soft tissue. However, it’s not recommended for pneumonia because surfactant inhibits the antibacterial activity.”
He added that vancomycin can lead to renal failure when given with amino glycosides, while trimethoprim causes hyperkalemia in the majority of patients.
Definitive answers are still lacking on what treatments to use either for preventative prophylaxis of CA-MRSA or for treating ventilator-associated pneumonia, Wenzel said, noting that there are currently no clinical trials which can inform these decisions.
Improving our knowledge of resistant pathogens, drug interactions and the adverse events of antibiotics may help in future, he said.
“The plans for changing the prophylactic and empirical therapy for nosocomial infections need to begin right now,” he concluded.
Singapore joins UK on infectious disease research
Medical Tribune August 2008 SFI
David Brill
Singapore and the UK are to invest a total of $6m in infectious disease research as part of a collaborative project unveiled recently at Biopolis.
The Agency for Science, Technology and Research (A*STAR) and the UK’s Medical Research Council (MRC) are to contribute $3m each to the fund.
The money will be spent directly on joint research projects, which are expected to focus on the identification of disease biomarkers and the development of new vaccines and diagnostic tests.
“This joint collaborative research fund bears testimony to the success of the ‘UK-Singapore Partners in Science’ programme and builds on the excellent exchange and interactions between the scientists from both sides,” said Mr. Lim Chuan Poh, chairman of A*STAR.
“The collaboration will also lead to more opportunities for our A*STAR scholars to pursue research attachments and training respectively at MRC units in the UK, as well as develop new PhD projects between the supervisors in Singapore and their partner supervisors in UK universities,” he said.
The announcement was made ahead of a roundtable discussion to further develop ideas and agree on a course of action for tackling infectious diseases. Other attendees included Mr. Ian Pearson, the UK Minister of State for Science and Innovation, and Professor Sir Roy Anderson, a prominent expert on infectious diseases and the incoming Rector of Imperial College, London.
Pearson, who co-hosted the discussion with Lim, said: "This significant new collaborative fund brings the best of Singapore and UK science together to fight infectious diseases.
“I would like to see similar partnerships tackling problems in other scientific fields.”
Infectious diseases are estimated to account for 20 percent of all deaths worldwide, and are the leading cause of mortality in developing countries according to WHO data.
David Brill
Singapore and the UK are to invest a total of $6m in infectious disease research as part of a collaborative project unveiled recently at Biopolis.
The Agency for Science, Technology and Research (A*STAR) and the UK’s Medical Research Council (MRC) are to contribute $3m each to the fund.
The money will be spent directly on joint research projects, which are expected to focus on the identification of disease biomarkers and the development of new vaccines and diagnostic tests.
“This joint collaborative research fund bears testimony to the success of the ‘UK-Singapore Partners in Science’ programme and builds on the excellent exchange and interactions between the scientists from both sides,” said Mr. Lim Chuan Poh, chairman of A*STAR.
“The collaboration will also lead to more opportunities for our A*STAR scholars to pursue research attachments and training respectively at MRC units in the UK, as well as develop new PhD projects between the supervisors in Singapore and their partner supervisors in UK universities,” he said.
The announcement was made ahead of a roundtable discussion to further develop ideas and agree on a course of action for tackling infectious diseases. Other attendees included Mr. Ian Pearson, the UK Minister of State for Science and Innovation, and Professor Sir Roy Anderson, a prominent expert on infectious diseases and the incoming Rector of Imperial College, London.
Pearson, who co-hosted the discussion with Lim, said: "This significant new collaborative fund brings the best of Singapore and UK science together to fight infectious diseases.
“I would like to see similar partnerships tackling problems in other scientific fields.”
Infectious diseases are estimated to account for 20 percent of all deaths worldwide, and are the leading cause of mortality in developing countries according to WHO data.
New bird flu vaccine promises broad immunity and rapid manufacture
Medical Tribune August 2008 SFXII
David Brill
A new vaccine against the avian influenza H5N1 virus has been shown to be well tolerated and induce high levels of immunogenicity against a variety of strains.
The vaccine is derived from continuous cell culture and could be produced up to 3 months quicker than by using traditional methods, the manufacturers suggest.
Mr. Peter Carrasco, Policy Advisor on Vaccine Security for WHO, said that the vaccine could be useful for protecting against viruses that are currently circulating in infected birds, but added that more research is needed with larger study groups to reconfirm the trial’s findings.
The vaccine was tested in a randomized phase I and II trial involving 275 subjects who received two doses 21 days apart. The results were published in The New England Journal of Medicine.
A dosage of 7.5 mcg without adjuvant induced a neutralizing-antibody response in 76.2 percent of subjects – equivalent to a seroconversion rate of 69 percent. Immunogenicity was seen not only against the clade 1 strain used to produce the vaccine (A/Vietnam/1203/2004), but also extended to the clade 2 and 3 strains.
Conventional H5N1 vaccines are produced using embryonated chicken eggs – a technique that requires the use of an attenuated version of the virus. Cell culture, however, can be used to generate a vaccine from the wild type, thereby eliminating the delay while a modified virus is produced.
“The lag time between receipt of a new virus and delivery of a new vaccine is only something like 12 weeks using our technology, which is about 3 months quicker than can be done with the egg technology,” said Dr. Noel Barrett from the Department of Global Research and Development at Baxter BioScience, who developed the vaccine.
“We’re faster, we’re more flexible, and the process is much more robust in that we’re not dependent on the supply of hen’s eggs, which is an uncertain factor in the event of a pandemic caused by an avian virus.”
Baxter have submitted a licensing application for the vaccine to the European Medicines Agency (EMEA), and expect a decision early next year.
The company has reached agreements with some countries to provide the vaccine in the event of a pandemic and already has the manufacturing capacity to deliver in a relatively short time, Barrett said. The decision whether to implement pre-pandemic vaccination remains a matter of government policy, he added.
One potential drawback to the new vaccine is the need for enhanced biosafety facilities which can handle the virulent wild type virus.
“There are very few facillities which are biosafety level 3, and these are expensive to maintain,” said Associate Professor Paul Ananth Tambyah, head of the Division of Infectious Diseases at the National University Hospital in Singapore, who was also one of the authors of the study.
“Without them it is not safe to manufacture this vaccine,” he said, adding that these manufacturing hurdles would need to be overcome before the vaccine could be used routinely.
David Brill
A new vaccine against the avian influenza H5N1 virus has been shown to be well tolerated and induce high levels of immunogenicity against a variety of strains.
The vaccine is derived from continuous cell culture and could be produced up to 3 months quicker than by using traditional methods, the manufacturers suggest.
Mr. Peter Carrasco, Policy Advisor on Vaccine Security for WHO, said that the vaccine could be useful for protecting against viruses that are currently circulating in infected birds, but added that more research is needed with larger study groups to reconfirm the trial’s findings.
The vaccine was tested in a randomized phase I and II trial involving 275 subjects who received two doses 21 days apart. The results were published in The New England Journal of Medicine.
A dosage of 7.5 mcg without adjuvant induced a neutralizing-antibody response in 76.2 percent of subjects – equivalent to a seroconversion rate of 69 percent. Immunogenicity was seen not only against the clade 1 strain used to produce the vaccine (A/Vietnam/1203/2004), but also extended to the clade 2 and 3 strains.
Conventional H5N1 vaccines are produced using embryonated chicken eggs – a technique that requires the use of an attenuated version of the virus. Cell culture, however, can be used to generate a vaccine from the wild type, thereby eliminating the delay while a modified virus is produced.
“The lag time between receipt of a new virus and delivery of a new vaccine is only something like 12 weeks using our technology, which is about 3 months quicker than can be done with the egg technology,” said Dr. Noel Barrett from the Department of Global Research and Development at Baxter BioScience, who developed the vaccine.
“We’re faster, we’re more flexible, and the process is much more robust in that we’re not dependent on the supply of hen’s eggs, which is an uncertain factor in the event of a pandemic caused by an avian virus.”
Baxter have submitted a licensing application for the vaccine to the European Medicines Agency (EMEA), and expect a decision early next year.
The company has reached agreements with some countries to provide the vaccine in the event of a pandemic and already has the manufacturing capacity to deliver in a relatively short time, Barrett said. The decision whether to implement pre-pandemic vaccination remains a matter of government policy, he added.
One potential drawback to the new vaccine is the need for enhanced biosafety facilities which can handle the virulent wild type virus.
“There are very few facillities which are biosafety level 3, and these are expensive to maintain,” said Associate Professor Paul Ananth Tambyah, head of the Division of Infectious Diseases at the National University Hospital in Singapore, who was also one of the authors of the study.
“Without them it is not safe to manufacture this vaccine,” he said, adding that these manufacturing hurdles would need to be overcome before the vaccine could be used routinely.
New partnership launched to accelerate TB drug research
Medical Tribune August 2008 P13
David Brill
A new collaboration was announced in Singapore last month that aims to facilitate the development of new drugs for tuberculosis (TB).
The 5-year agreement will allow information and ideas to be shared between the Novartis Institute for Tropical Diseases (NITD) and the Global Alliance for TB Drug Development (GATB), with a particular view to discovering drugs that work on resistant strains of TB.
“TB as an area is in desperate need of new drugs,” said Professor Paul Herrling, chairman of the board of the NITD.
“The essence of this is that we open our entire research protocol to the GATB. If we have a drug that looks promising for full development in TB, based on this agreement we can give them the exclusive license. It’s a very good thing.”
Shortening the duration of treatment is one of the major aims of the research, Herrling said. Current anti-TB drugs typically need to be taken for 6 to 9 months but resistance can develop when patients do not complete the course.
The project also seeks to find new drugs that are cheap to produce, easy to use, and do not interfere with HIV combination therapy.
The GATB – a not-for profit group which works with both private and public laboratories – is experienced in the later stages of drug development and in delivering new products to patients, Herrling said, whereas the NITD focuses on the early stages from the basic science through to proof of concept in humans.
“They really need a constant inflow of new compounds, and we are one of the suppliers. So it’s win-win in the sense that we produce what they want, and then they take our compounds and move them on beyond the stage that we would,” said Herrling, who is also a former vice president of the board at GATB.
TB was responsible for 1.7 million deaths in 2006, according to data from the World Health Organization. Almost half a million new cases each year are multidrug-resistant, with the highest-ever rates reported in 2008.
“One of the important changeovers [in drug discovery] is between the research part and what comes after,” said Herrling, adding that the new collaboration should speed up this part of the process.
“If you don’t do it well you lose a year or two or maybe even more at this interface, and that’s a bad idea because while you wait people are dying at the other end,” he concluded.
David Brill
A new collaboration was announced in Singapore last month that aims to facilitate the development of new drugs for tuberculosis (TB).
The 5-year agreement will allow information and ideas to be shared between the Novartis Institute for Tropical Diseases (NITD) and the Global Alliance for TB Drug Development (GATB), with a particular view to discovering drugs that work on resistant strains of TB.
“TB as an area is in desperate need of new drugs,” said Professor Paul Herrling, chairman of the board of the NITD.
“The essence of this is that we open our entire research protocol to the GATB. If we have a drug that looks promising for full development in TB, based on this agreement we can give them the exclusive license. It’s a very good thing.”
Shortening the duration of treatment is one of the major aims of the research, Herrling said. Current anti-TB drugs typically need to be taken for 6 to 9 months but resistance can develop when patients do not complete the course.
The project also seeks to find new drugs that are cheap to produce, easy to use, and do not interfere with HIV combination therapy.
The GATB – a not-for profit group which works with both private and public laboratories – is experienced in the later stages of drug development and in delivering new products to patients, Herrling said, whereas the NITD focuses on the early stages from the basic science through to proof of concept in humans.
“They really need a constant inflow of new compounds, and we are one of the suppliers. So it’s win-win in the sense that we produce what they want, and then they take our compounds and move them on beyond the stage that we would,” said Herrling, who is also a former vice president of the board at GATB.
TB was responsible for 1.7 million deaths in 2006, according to data from the World Health Organization. Almost half a million new cases each year are multidrug-resistant, with the highest-ever rates reported in 2008.
“One of the important changeovers [in drug discovery] is between the research part and what comes after,” said Herrling, adding that the new collaboration should speed up this part of the process.
“If you don’t do it well you lose a year or two or maybe even more at this interface, and that’s a bad idea because while you wait people are dying at the other end,” he concluded.
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