Federal officials reported this week that at least 36 children have died in the US as result of the 2009 pandemic swine flu virus A(H1N1), two thirds of whom had one or more high risk medical conditions. Over 90 per cent of the children who had medical conditions had neurodevelopmental disorders such as developmental delay or cerebral palsy and health-care professionals are urged to be aware of the potential for more severe illness, including death, among these children.
The report also shows that most of the children with neurodevelopmental conditions who died had more than one neurodevelopmental diagnosis and/or pulmonary conditions.
In addition, doctors should be aware of the higher risk of severe bacterial coinfections in children who have flu and treat accordingly. Over 40 per cent of the reported deaths for which lab results were reported, showed the children also had bacterial coinfections.
The figures appear in this week's MMWR report from the US Centers for Disease Control and Prevention, which details results of surveillance for pediatric deaths linked to the 2009 pandemic swine flu from April to August.
As of 8th August, the CDC said it had received reports of 477 deaths linked to pandemic swine flu, including 36 deaths among children aged under 18 years of age. The youngest patient was 2 months old, and the oldest was 17. The figures also show that 7 of the children were under 5 years old (5 were under 2 years old).
The deaths of the 36 children were reported from 15 state and local authorities. Half were male, 42 per cent were non-Hispanic white and 33 per cent were Hispanic. Six deaths occurred in May, 25 in June, and 5 in July.
24 of the 36 children who died of swine flu had at least one high risk medical condition, including three children under 5. Of the children with high risk medical conditions, the vast majority (22 children, 92 per cent) had neurodevelopmental conditions (such as developmental delay or cerebral palsy).
13 of the 22 children with neurodevelopmental conditions had more than one such diagnosis and 9 of them had neurodevelopmental and chronic pulmonary conditions.
8 of the 36 children who died of swine flu were aged 5 years and over and had no reported high risk conditions. Although two of these children were reported as obese, no data was given on their height and weight.
The children were ill for a median of 6 days (ranging from 1 to 28 days) before death occurred. Early diagnosis of flu means children at greater risk or who are severely ill have a greater chance of being treated effectively with antivirals, yet among the 19 children reported to have received antiviral treatment, only four of them started treatment within 2 days of falling ill with swine flu.
An editorial note pointed out that 28 (nearly 80 per cent) of the 36 children who died of swine flu were in one of two groups already known to be at higher risk from seasonal flu: they were either under 5 years old or they had a pre-existing medical condition. However, the percentage of children with high risk medical conditions who died of swine flu is higher than the percentage reported in recent flu seasons and this needs to be monitored to see if this and other differences between seasonal flu and swine flu are important.
The report also highlights the prominence of laboratory-confirmed bacterial coinfections, which were found in 10 (43 per cent) of the 23 children who had culture or pathology results reported. 6 children aged 5 and over with no high risk medical condition had an invasive bacterial coinfection, suggesting that swine flu combined with bacterial infection can result is severe illness in otherwise healthy children.
When reading the report people should bear in mind that the figures may not be accurate for a number of reasons. For example, cases of flu deaths among children may be under-reported, for instance because there is a low level of flu testing among children. Also it is difficult to compare swine flu cases with seasonal flu cases because of the difference in availability of reliable diagnostic tools.
The best way to stop people getting swine flu and its complications is to vaccinate them, said the CDC, who recommend that everyone between the age of 6 months and 24 years should be vaccinated against the 2009 H1N1 swine flu virus, for which vaccine doses should be available in mid-October. People who live with or care for babies under 6 months old should also be vaccinated, regardless of their age.
CDC Morbidity and Mortality Weekly Report, September 4, 2009 / 58(34); 941-947
Showing posts with label PhD. Show all posts
Showing posts with label PhD. Show all posts
Discovery Of New HIV Antibodies Opens Door To Effective AIDS Vaccine
By examining blood samples donated by infected people in developing countries, US researchers have found two new powerful antibodies to HIV that open the door to a new and effective AIDS vaccine. The antibodies, called PG9 and PG16, are of a type known as bNAbs (broadly neutralizing antibodies) and exploit an "Achilles heel" or vulnerable spot in the HIV that could be an effective target for a vaccine, said the researchers.
The discovery was made by researchers working at and with the International AIDS Vaccine Initiative (IAVI), at The Scripps Research Institute, and at the biotechnology companies Theraclone Sciences and Monogram Biosciences, and was published on 3 September as an online advanced issue in Science.
Co-principal investigator Wayne Koff, who is senior vice president of research and development at IAVI in New York, told the media:
"The findings themselves are an exciting advance toward the goal of an effective AIDS vaccine because now we've got a new, potentially better target on HIV to focus our efforts for vaccine design."
He said now they've found this target they can look for more, and speed up global efforts to develop an effective AIDS vaccine.
The discovery relied on a global collaboration that developed a new way of looking for bNAbs, and the researchers fully expect more to be found, revealing further vulnerable spots on HIV for vaccines to target.
Only a small proportion of people infected with HIV produce bNAbs, a range of antibodies that are different to other antibodies because they effectively neutralize a high proportion of the HIV types in circulation around the world.
Animal experiments suggest that if the body can "learn" to produce these types of antibody, which is what an effective AIDS vaccine induces, then it is able to protect itself from infection by HIV.
Other bNAbs against HIV have been discovered before, but PG9 and PG16 are the first to be isolated in over 10 years from donors in developing countries, where most new HIV infections occur. Also, the previously identified bNAbs bind to spots on the virus that are hard to target with vaccines.
One of the other co-principal investigators, Dennis Burton, who is professor of immunology and microbial science and scientific director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, California, said:
"These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design."
"So now we may have a better chance of designing a vaccine that will elicit such broadly neutralizing antibodies, which we think are key to successful vaccine development," added Burton, who is also a member of the newly established Ragon Institute of MGH, MIT and Harvard.
For a vaccine to be effective it must be able to stimulate the immune system to make broad spectrum antibodies that can effectively neutralize as many forms of the virus as possible. Ability to stimulate high potency antibodies also makes it more likely that the vaccine does not need to stimulate production of too many antibodies to make it effective.
One of the features of HIV that gives it an advantage, is a viral "spike" that it uses to invade cells. The "spike" foils attack by the immune system because it relies on two glycoproteins, gp120 and gp41, which keep changing. This is a successful tactic for HIV because by the time the immune system has noticed the new version of the spike and made new antibodies to attack it, the virus has invaded enough host cells to allow it to replicate in large numbers and overwhelm the immune system.
But PG9 and PG16 attack a part of the "viral spike" of the HIV: specifically they attack regions of gp120 that don't change, and this is probably why they are broad spectrum neutralizers.
There are probably two main reasons why the researchers were able to discover PG9 and PG16: one was the high number of blood samples they were able to access from a range of developing countries, and the other was they used a new way of testing whether bNAbs bind to gp120 and gp41.
The blood samples the researchers used were donated by HIV-infected volunteers from IAVI-supported clinical research centers based in seven sub-Saharan countries as well as in Thailand, Australia, the UK and the US.
The conventional way of testing the ability of bNAbs to bind to gp120 and gp41 uses soluble forms of the proteins, and if Koff, Burton and colleagues had used it they would probably have rejected PG9 and PG16 as candidate bNAbs because they bind weakly to soluble forms of the proteins. But they used a new method that relies on a micro-neutralization assay developed jointly by Monogram Biosciences and IAVI which they ran in parallel with the standard binding assays.
This new method is likely to make a significant difference to the way bNAbs are screened in the future, because it allows researchers to screen bNAbs directly for their ability to block HIV infection.
Another important aspect of the work was the contribution of Theraclone Sciences, a company that was initially working outside of the HIV field, but they had a relevant and unique high throughput process that could be adapted to isolate the effective bNAbs in a much shorter time. Funding from IAVI's Innovation Fund, which is co-funded by the Bill & Melinda Gates Foundation helped to pay for the adaptation.
The process that the Theraclone team used exposes all the antibodies in a blood sample from an HIV infected person, identifies those with broadly neutralizing potential and traces them to their corresponding antibody-forming cells. With recombinant DNA technology, they isolated genes from the candidate bNAbs so they could clone them in large numbers for testing.
Chief scientific officer and senior vice president of Theraclone Sciences, Matthew Moyle, said:
"It is exciting that we were able to use our technology to identify and isolate these new bNAbs, which may offer important clues that could help create an effective AIDS vaccine."
"Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target."
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W. Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton.
Science, Published online September 3, 2009.
DOI:10.1126/science.1178746
The discovery was made by researchers working at and with the International AIDS Vaccine Initiative (IAVI), at The Scripps Research Institute, and at the biotechnology companies Theraclone Sciences and Monogram Biosciences, and was published on 3 September as an online advanced issue in Science.
Co-principal investigator Wayne Koff, who is senior vice president of research and development at IAVI in New York, told the media:
"The findings themselves are an exciting advance toward the goal of an effective AIDS vaccine because now we've got a new, potentially better target on HIV to focus our efforts for vaccine design."
He said now they've found this target they can look for more, and speed up global efforts to develop an effective AIDS vaccine.
The discovery relied on a global collaboration that developed a new way of looking for bNAbs, and the researchers fully expect more to be found, revealing further vulnerable spots on HIV for vaccines to target.
Only a small proportion of people infected with HIV produce bNAbs, a range of antibodies that are different to other antibodies because they effectively neutralize a high proportion of the HIV types in circulation around the world.
Animal experiments suggest that if the body can "learn" to produce these types of antibody, which is what an effective AIDS vaccine induces, then it is able to protect itself from infection by HIV.
Other bNAbs against HIV have been discovered before, but PG9 and PG16 are the first to be isolated in over 10 years from donors in developing countries, where most new HIV infections occur. Also, the previously identified bNAbs bind to spots on the virus that are hard to target with vaccines.
One of the other co-principal investigators, Dennis Burton, who is professor of immunology and microbial science and scientific director of the IAVI Neutralizing Antibody Center at The Scripps Research Institute in La Jolla, California, said:
"These new antibodies, which are more potent than other antibodies described to date while maintaining great breadth, attach to a novel, and potentially more accessible site on HIV to facilitate vaccine design."
"So now we may have a better chance of designing a vaccine that will elicit such broadly neutralizing antibodies, which we think are key to successful vaccine development," added Burton, who is also a member of the newly established Ragon Institute of MGH, MIT and Harvard.
For a vaccine to be effective it must be able to stimulate the immune system to make broad spectrum antibodies that can effectively neutralize as many forms of the virus as possible. Ability to stimulate high potency antibodies also makes it more likely that the vaccine does not need to stimulate production of too many antibodies to make it effective.
One of the features of HIV that gives it an advantage, is a viral "spike" that it uses to invade cells. The "spike" foils attack by the immune system because it relies on two glycoproteins, gp120 and gp41, which keep changing. This is a successful tactic for HIV because by the time the immune system has noticed the new version of the spike and made new antibodies to attack it, the virus has invaded enough host cells to allow it to replicate in large numbers and overwhelm the immune system.
But PG9 and PG16 attack a part of the "viral spike" of the HIV: specifically they attack regions of gp120 that don't change, and this is probably why they are broad spectrum neutralizers.
There are probably two main reasons why the researchers were able to discover PG9 and PG16: one was the high number of blood samples they were able to access from a range of developing countries, and the other was they used a new way of testing whether bNAbs bind to gp120 and gp41.
The blood samples the researchers used were donated by HIV-infected volunteers from IAVI-supported clinical research centers based in seven sub-Saharan countries as well as in Thailand, Australia, the UK and the US.
The conventional way of testing the ability of bNAbs to bind to gp120 and gp41 uses soluble forms of the proteins, and if Koff, Burton and colleagues had used it they would probably have rejected PG9 and PG16 as candidate bNAbs because they bind weakly to soluble forms of the proteins. But they used a new method that relies on a micro-neutralization assay developed jointly by Monogram Biosciences and IAVI which they ran in parallel with the standard binding assays.
This new method is likely to make a significant difference to the way bNAbs are screened in the future, because it allows researchers to screen bNAbs directly for their ability to block HIV infection.
Another important aspect of the work was the contribution of Theraclone Sciences, a company that was initially working outside of the HIV field, but they had a relevant and unique high throughput process that could be adapted to isolate the effective bNAbs in a much shorter time. Funding from IAVI's Innovation Fund, which is co-funded by the Bill & Melinda Gates Foundation helped to pay for the adaptation.
The process that the Theraclone team used exposes all the antibodies in a blood sample from an HIV infected person, identifies those with broadly neutralizing potential and traces them to their corresponding antibody-forming cells. With recombinant DNA technology, they isolated genes from the candidate bNAbs so they could clone them in large numbers for testing.
Chief scientific officer and senior vice president of Theraclone Sciences, Matthew Moyle, said:
"It is exciting that we were able to use our technology to identify and isolate these new bNAbs, which may offer important clues that could help create an effective AIDS vaccine."
"Broad and Potent Neutralizing Antibodies from an African Donor Reveal a New HIV-1 Vaccine Target."
Laura M. Walker, Sanjay K. Phogat, Po-Ying Chan-Hui, Denise Wagner, Pham Phung, Julie L. Goss, Terri Wrin, Melissa D. Simek, Steven Fling, Jennifer L. Mitcham, Jennifer K. Lehrman, Frances H. Priddy, Ole A. Olsen, Steven M. Frey, Phillip W. Hammond, Protocol G Principal Investigators, Stephen Kaminsky, Timothy Zamb, Matthew Moyle, Wayne C. Koff, Pascal Poignard, and Dennis R. Burton.
Science, Published online September 3, 2009.
DOI:10.1126/science.1178746
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