Children younger than 13 shed the pandemic H1N1 influenza virus over a longer period of time than older children and adults, a Taiwanese study showed.
Although the median duration of viral shedding was nine days, it was significantly longer in younger children (11 days versus seven, P<0.001), according to Kuender Yang, MD, PhD, of Chang Gung Memorial Hospital-Kaohsiung Medical Center in Taiwan, and colleagues.
"Why children have a longer period of viral shedding is unknown," the researchers wrote in the August issue of Emerging Infectious Diseases. "Delayed cell-mediated immunity in children responding to a novel virus may explain, in part, their longer viral shedding time."
The researchers also found that patients who developed pneumonia had significantly higher viral loads than those with upper respiratory tract infections (P<0.001) or bronchitis (P=0.002).
Taken together, the researchers wrote, "these results suggest that younger children may require a longer isolation period and that patients with pneumonia may require treatment that is more aggressive than standard therapy for pandemic (H1N1) 2009 virus."
Yang and colleagues tested 1,052 patients treated at their center for the presence of influenza using real-time reverse-transcription polymerase chain reaction; 602 were infected with the pandemic strain.
Of those with confirmed H1N1, 86.4% went to the hospital within two days of the onset of fever. All received oseltamivir (Tamiflu) for five days.
Overall, 3.4% had severe illness, including pneumonia and meningoencephalitis. There were no deaths.
In patients with confirmed infection with the pandemic strain, viral load was inversely correlated with the number of days after the onset of fever (P<0.001). Viral load was high for the first three days.
The reason patients with pneumonia had higher viral loads than those with other respiratory infections "may be a reflection of disease severity or impaired host immunity, requiring immediate attention and aggressive treatment," according to Yang and his colleagues.
The median duration of viral shedding (nine days) was longer than that seen in previous studies.
The researchers noted that that could be because of the younger age of this study population (median age 10.1) compared with other studies. Age was the only independent predictor of the duration of viral shedding.
Nearly nine out of every 10 children younger than 13 had detectable viral RNA for at least a week, and 36% had detectable RNA for at least two weeks.
They noted that "because all of our patients received oseltamivir treatment, we could not determine the actual effect of the antiviral therapy on infection caused by the novel pandemic virus."
NIH Reports Rapid Development of Drug-Resistant H1N1
Government researchers have reported the first two cases of drug-resistant strains of the H1N1 influenza virus. Both immunocompromised patients became infected with the virus in 2009; they developed drug-resistant strains after less than two weeks on therapy, according to the report from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. This information comes on the heels of new reports warning that H1N1 influenza is still a serious threat in certain areas.
The two patients developed resistance to the key influenza drug oseltamivir (Tamiflu®), and one also demonstrated clinical resistance to intravenous peramivir - an antiviral agent now in experimental testing.
Both patients had immune limitations due to blood stem cell transplants that occurred several years previously, and both recovered from their influenza infections. "While the emergence of drug-resistant influenza virus is not in itself surprising, these cases demonstrate that resistant strains can emerge after only a brief period of drug therapy," said NIAID Director Anthony S. Fauci, MD. "We have a limited number of drugs available for treating influenza and these findings provide additional urgency to efforts to develop antivirals that attack influenza virus in novel ways."
At the end of March, influenza activity, still almost all attributed to the pandemic 2009 H1N1 strain, was at its lowest level since the official start of the season at the end of August, the CDC reported.
For the week ending March 27, 1.6% of outpatient visits were for flu-like illness, which was below the baseline level (2.3%), researchers from the CDC's National Center for Immunization and Respiratory Diseases reported in the April 16 issue of Morbidity and Mortality Weekly Report.
During the flu season, that rate exceeded baseline levels for 18 weeks, with a peak of 7.7% in the week ending October 24.
Yet, despite the ongoing overall decline in influenza activity and deaths, some areas of the country, particularly the Southeast, continue to have sustained transmission.
Alabama, Georgia, Mississippi, and South Carolina continue to report elevated levels of influenza activity, flu-related hospitalizations, and higher-than-baseline levels of influenza-like illness. Flu-related deaths are still being reported.
That highlights "the need to maintain public health surveillance and continue to offer 2009 H1N1 vaccine," the authors wrote.
The CDC researchers analyzed the characteristics of the current ongoing flu season through March 27.
Unlike in previous seasons, the prevalence of influenza-like illness peaked in late October rather than in February.
In addition, as this and numerous other epidemiological reports have confirmed, younger individuals have been disproportionately affected, with the highest hospitalization rate found in children 4 years and younger (6.6 per 10,000 population) and generally declining with age.
Of 422,648 specimens tested by World Health Organization and National Respiratory and Enteric Virus Surveillance System collaborating laboratories in the U.S., 21.1% were positive for influenza.
Of those, 99.7% were influenza A, and nearly all of those with known subtypes were the pandemic strain.
The seasonal strains that were isolated were similar to those recommended by the WHO and the FDA for inclusion in the 2010-2011 trivalent influenza vaccine along with the pandemic strain. The three strains are A/Perth/16/2009 (H3N2), B/Brisbane/60/2008 (B), and A/California/07/2009 (H1N1).
Some rare cases of resistance to oseltamivir (Tamiflu) have been identified, but all isolated viruses have been susceptible to zanamivir (Relenza).
Some other findings of the current analysis:
Through March 27, there 41,689 hospitalizations and 2,096 deaths attributed to laboratory-confirmed influenza reported to the CDC.
For the week ending March 27, pneumonia or influenza was reported as an underlying or contributing cause of death for 7.9% of patients, slightly above the week-specific epidemic threshold of 7.8%, but lower than the previous seven weeks.
Influenza-related death rates since the end of August have been highest among those ages 50 to 64 (1.56 per 100,000 population) and lowest in childern (0.43 per 100,000 for those 4 and younger and 0.36 per 100,000 for those ages 5 to 18).
There have been 269 pediatric deaths attributed to laboratory-confirmed influenza; 81% were confirmed to be from the pandemic H1N1 strain and 18% were from an unsubtyped influenza A, likely to be the pandemic strain.
More than two-thirds (69%) of the pediatric deaths occurred in children with underlying health conditions that increased the risk of complications
AP – A man wearing a mask looks on while people wait in line to get a vaccine against swine flu in Bucharest, …
Fri Jan 8, 12:17 pm ET
ATLANTA –Swine flu infectionscontinue to drop and only one state — Alabama — was reporting widespread cases last week.
Four states had widespread cases the previous week. The number has been dropping since late October, when nearly all states had widespread flu reports.
TheCenters for Disease Control and Preventionalso reported Friday that there are no signs of seasonal flu right now, only the swine variety. But CDC officials noted there is still more flu around than normally seen at this time of year, and illnesses could increase as kids return to school after the holiday break.
How Virulent Is the 2009 Influenza A H1N1 (Swine Flu) Virus?
We might have better T cell responses against H1N1 than we thought.
New pandemic strains of influenza virus typically are more virulent than those that have been circulating longer, presumably because they present novel antigens to hosts. In this new study, researchers showed that 2009 influenza A H1N1 virus does not contain many surface antigens that have been presented to B cells by other viral strains. This conclusion is consistent with previous findings that few people who were born after 1957 have neutralizing antibodies to 2009 H1N1 and that H1N1 infection has been more problematic among younger people. Neutralizing antibodies typically recognize viral surface antigens.
However, the current pandemic H1N1 virus thus far has not proved to be as virulent as was feared initially. The researchers found that, compared with B cells, T cells (particularly CD8+ cells) are much more likely to recognize 2009 H1N1 virus — especially nonsurface antigens. Whereas the surface antigens of 2009 H1N1 are quite novel, the internal antigens are less novel. Although T cell responses to influenza virus might not affect transmissibility of the virus, they likely will affect virulence.
Comment: 2009 H1N1 virus is more virulent than seasonal flu viruses in laboratory animals with no previous influenza immunity. This report suggests, however, that internal antigens of 2009 H1N1 are less novel than its surface antigens and elicit a vigorous T cell response that diminishes severity of infection. Alternatively, the H1N1 pandemic, which began in March 2009, might have been relatively benign until now simply because temperatures have been relatively warm. Flu viruses love cold dry air, and winter weather will be here soon.
State Report Cards Show Shortcomings in Preparedness
Although states have made substantial progress in preparing for public health emergencies, the H1N1 pandemic has revealed remaining deficiencies, according to a new report.
Of 10 key indicators of preparedness, 20 states achieved six or fewer; the worst performer, Montana, fulfilled only three, according to an assessment by the Trust for America's Health (TFAH) and the Robert Wood Johnson Foundation.
There were seven states -- Arkansas, Delaware, New York, North Carolina, Oklahoma, Texas, and Vermont -- tied for the highest score of nine out of 10.
The unexpected emergence of pandemic H1N1 coupled with shrinking state budgets in a crumbling economy exposed problems with the public health infrastructure, including a lack of real-time coordinated disease surveillance and laboratory testing, outdated vaccine production techniques, limited hospital surge capacity, and a smaller public health workforce, the report stated.
It urged increases in funding for preparedness and efforts to solidify the public health infrastructure, even in the face of waning H1N1 activity.
"As the second wave of H1N1 starts to dissipate, it doesn't mean we can let down our defenses," said Richard Hamburg, deputy director of TFAH, in a statement. "In fact, it's time to double down and provide a sustained investment in the underlying infrastructure, so we will be prepared for the next emergency and the one after that."
The 10 indicators and how states performed in 2009:
Antiviral stockpiling: 13 states purchased less than half of their share of federally subsidized antivirals to stockpile for an influenza pandemic.
Hospital preparedness/hospital bed availability reporting: 10 states and the District of Columbia report weekly data for at least 50% of the hospitals within their jurisdiction to the National Hospital Available Beds for Emergencies and Disasters System, which is required by the Department of Health and Human Service's Assistant Secretary for Preparedness and Response.
Lab pickup and delivery services for public health laboratories: 13 states do not have the capacity for timely transportation of samples around the clock to an appropriate public health Laboratory Response Network reference lab.
Surge workforce capacity in public health laboratories: 12 states and the District of Columbia do not have enough staff to work five 12-hour days for six to eight weeks in response to an infectious disease outbreak.
Biosurveillance: six states do not have a disease surveillance system compatible with the CDC's National Electronic Disease Surveillance System.
Food safety: 14 states were not able to identify the pathogen responsible for reported foodborne disease outbreaks at a rate that met or exceeded the national average of 46%.
Medical Reserve Corps readiness: nine states do not meet criteria for readiness, which include the presence of a state coordinator, compliance with the National Incident Management System guidelines, and integration with the state Emergency System for Advance Registration of Volunteer Health Professionals.
Community resiliency as it pertains to children and preparedness: 20 states and the District of Columbia require all licensed childcare facilities to have a multihazard written evacuation and relocation plan.
Legal preparedness: 19 states have not adopted entity emergency liability protections or have made no formal determination under existing law.
Public health funding commitment: 27 states cut funding for public health from budgets from 2007-2008 to 2008-2009.
The report authors recommended that funding be restored for emergency preparedness -- federal preparedness funds have dropped by 27% since 2005 -- to help address remaining deficiencies.
They also recommended:
Improvements in surge capacity
Increased accountability and transparency of public health agencies, which should include a publicly available H1N1 after-action report
Improvements in community preparedness, including additional measures to reach out quickly to high-risk populations and to address disparities based on income or race
Development of full legal preparedness for public health emergencies at the state level, including liability protections for healthcare workers and mandates that insurance companies cover vaccines
New York's governor has asked providers to make the H1N1 vaccine available to all living there, rather than limiting access to a subset of high-risk groups. The governor said that this is a particularly good time for state residents to get the vaccine, especially since many are traveling for the holiday.
To date, the state has received more than 5 million H1N1 doses, and this week it will get an additional 500,000 doses. Now, the federal government is predicting that growing amounts of the vaccine will be available in coming weeks.
Until now, the vaccine has been distributed only to children over the age of 6 months, healthcare workers and those with conditions that otherwise would weaken them, such as diabetes and asthma.
To date, the H1N1 flu has killed about 10,000 U.S. residents, including 1,100 children and 7,500 younger adults, according to CDC.
Rice, BCM team finds weakness in H1N1’s method for evading detection by the immune system
The H1N1 influenza virus has been keeping a secret that may be the key to defeating it and other flu viruses as well.
Researchers at Rice University and Baylor College of Medicine (BCM) have found what they believe is a weakness in H1N1’s method for evading detection by the immune system.
Comparing its genetic sequences going all the way back to the virus’s first known appearance in the deadly “Spanish flu” outbreak of 1918, they discovered a previously unrealized role of receptor-binding residues in host evasion, which effectively becomes a bottleneck that keeps the virus in check.
Rice’s Jianpeng Ma and graduate student Jun Shen and BCM’s Qinghua Wang compared the sequences of more than 300 strains of H1N1 to track its evolution; they reported their results in a recent online edition of the scientific journal PLoS ONE.
The researchers were looking in particular at hemagglutinin (HA), the protein “hook” that allows the virus to attach itself to and infect host cells. It’s long been known that five regions of H1N1’s HA serve as antigenic sites, the protein fragments that trigger the body’s immune system. These antigenic sites, first mapped in 1981, shuffle their amino-acid sequences in the endless cat-and-mouse game that viruses play to survive.
The researchers discovered several key residues involved in both antigenic sites and the receptor-binding site, the part of the protein that attaches to a cell and allows the virus to invade.
The common belief has been that the receptor binding could not change. “The site is known, but no one thought it was involved in the immune system. In order to recognize the receptor, that particular region has to be robust,” Ma said. “But it turns out this region is not only variable, but also interacts with the immune system.”
For a virus to evade antibodies, all five antigenic sites would have to disguise themselves by mutating. The new finding led the researchers to believe the receptor-binding residues would also have to mutate, but not so much that the binding no longer works. “If the binding is abolished, the virus dies,” said Ma, a Rice professor in bioengineering with a joint appointment at BCM.
Such dual-function residues are a likely bottleneck for the virus, he said, because they’re under the tightest restrictions. Thus, they could be easier to track over time and may chart a path to predict future mutations that will aid in vaccine design.
“It becomes a weak link and provides us with a window into the virus that we can monitor,” Ma said. “The virus’s bottleneck is our opportunity.”
Wang, an assistant professor of biochemistry and molecular biology at BCM who has long studied the structure and function of HA, has been involved in the project since it began and is now working to verify the results in vitro. She hopes confirming the computations will lead to more efficiency in creating vaccines not only for H1N1 but also for other strains of the flu.
“An underlying implication is that this may not be restricted to H1N1,” Wang said. “It may apply to other influenza viruses as well. If studying viral evolution can help predict what will cause a severe problem in humans, you can actually pre-stock vaccines, which will save time.”
H1N1 Influenza Adopted Novel Strategy to Move from Birds to Humans
The 2009 H1N1 influenza virus used a new strategy to cross from birds into humans, a warning that it has more than one trick up its sleeve to jump the species barrier and become virulent.
In a report in the journal Proceedings of the National Academy of Sciences, University of California, Berkeley, researchers show that the H1N1, or swine flu, virus adopted a new mutation in one of its genes distinct from the mutations found in previous flu viruses, including those responsible for the Spanish influenza pandemic of 1918, the "Asian" flu pandemic in 1957 and the "Hong Kong" pandemic of 1968.
Previous influenza strains that crossed from birds into people had a specific point mutation in the bird virus's polymerase gene that allowed the protein to operate efficiently inside humans as well. The polymerase transcribes the virus's RNA, allowing the host to express viral genes, and also copies the viral genome, needed to make new viruses.
The 2009 H1N1 virus retains the bird version of the polymerase, but has a second mutation that seems to suppress the ability of human cells to prevent the bird polymerase from working.
"We were quite shocked when we looked at the swine flu virus, which was clearly replicating in people and other mammalian systems, yet had a polymerase that looked like it was derived from a bird virus, which should not function too well in a human cell type," said UC Berkeley post-doctoral fellow Andrew Mehle of the Department of Molecular and Cell Biology. "The other mutation within the polymerase seems to compensate and allow the enzyme to function."
The researchers also discovered another strategy -- one not yet adopted by any known flu virus -- by which influenza virus can increase its virulence even more. When a particular human subunit is substituted for one of the three protein subunits that make up the bird polymerase, the new combination makes the polymerase more efficient in human cells.
"This is an extremely rare mutation and a rare combination, which suggests that there may be other ways that haven't emerged yet that these viruses are going to continue to evolve," said Jennifer Doudna, UC Berkeley professor of molecular and cell biology and an investigator in the Howard Hughes Medical Institute.
"As mechanistic biologists, we are hoping that by understanding how the virus works at the molecular level, we will be able to predict with more accuracy how it will evolve."
She suggested that those monitoring influenza outbreaks around the world in search of new variants be on the lookout for this recombination of polymerase subunits, which could herald an uptick in swine flu virulence. The findings also could help scientists develop better antiviral treatments, Mehle and Doudna said.
"The more we can understand the biochemistry and the particular structure of these polymerase complexes, the better we can make rational decisions about drug development," Mehle said.
H1N1, which appeared on the scene earlier this year, was dubbed swine flu because it emerged from pigs, in which human, bird and pig influenza viruses mixed, swapped genes and gave rise to a variant that could infect human cells and reproduce.
While mutations in the surface protein hemagglutinin -- indicated by the H in H1N1 -- are key to allowing the virus to enter human cells, mutations in the polymerase enzyme are key to the virus's ability to replicate inside human cells. All previous flu strains that entered and were transmitted in humans had a single mutation in the second subunit of the bird polymerase gene, which apparently allowed the enzyme to operate in human cells.
Last year, Mehle and Doudna showed that human cells apparently prevent the three subunits of bird virus polymerases from assembling into a functioning enzyme. A single amino acid switch at position 627 on the second subunit of the polymerase overcomes that inhibition and allows the virus to replicate. Apparently, Mehle said, when the amino acid glutamic acid -- typical of most bird virus polymerases -- is changed to a lysine, typical of human polymerases, the surface charge of the subunit changes from acidic (negatively charged) to basic (positively charged) and allows assembly of the subunits. Previous studies in mammals have shown that a lysine in that position enhances polymerase activity, increases viral replication and transmission, and in some cases, is associated with increased pathogenicity and death.
In their new study, Mehle and Doudna found that H1N1 has two rare mutations in the second subunit: a serine at position 590 and an arginine at position 591. This combination, which is most common in pigs, apparently has the same effect on surface charge as the mutation at position 627, allowing the polymerase complex to form and function in human cells.
Mehle noted that, in addition to such point mutations, flu viruses also mix and match the three subunits. Both the 1957 and 1968 viruses had polymerases composed of a first subunit from a bird and the other two subunits from humans. H1N1 has a human-like first subunit, while the second and third are bird-like -- hence the need for a mutation in the second subunit to make it more human-like.
To see which other combinations might make H1N1 more virulent, they mixed human, avian and pig subunits in culture, replicating the pig "mixing vessel," Mehle said. Several combinations with a human third subunit increased the activity of the polymerase enzyme when other mutations were not present in the second subunit. Viruses with this alteration are now being tested in human cell culture to see if they are more virulent.
"In addition to having individual amino acid changes affecting the ability of the virus to transmit across species and be more pathogenic, we need to think about these entire gene segments being exchanged back and forth," said Doudna, who also is a faculty affiliate of the California Institute for Quantitative Biosciences (QB3). "Those will affect the outcome of disease."
"We are very hopeful that the kind of basic science that we are doing here will have an impact on human health, either at the level of diagnostics or thinking forward to development of antiviral therapeutics," she added.
Mehle and Doudna continue to explore the polymerase to discover what in human cells prevents the assembly of the bird polymerase, and to determine the three-dimensional structure of the enzyme and its three subunits.
Opening and Mixing Tamiflu® Capsules with Liquids if Child Cannot Swallow Capsules
December 1, 2009 4:00 PM ET
Is there a shortage of oral suspension (liquid) Tamiflu®?
The Food and Drug Administration (FDA) and the maker of Tamiflu® (Roche) have said that available supplies of liquid Tamiflu® for children are limited.
What is being done about this?
A pharmacist can make a Tamiflu® suspension (liquid) using available Tamiflu® adult capsules, which are not in short supply. CDC has alerted pharmacists about this option and provided instructions on how to prepare a suspension using adult capsules. Some pharmacies, including some chains, can do this already, others are not yet prepared. Children’s doses of Tamiflu® are also available in capsules.
What can I do if my child cannot swallow capsules?
If your doctor prescribes Tamiflu® capsules for your child and your child cannot swallow capsules, the prescribed capsules may be opened, mixed with a thick sweetened liquid, and given that way.
What liquids can I use?
A thick sweetened liquid, such as regular or sugar-free chocolate syrup, that masks the flavor of the medicine can be mixed with the contents of the Tamiflu® capsule. You don’t have to use chocolate syrup but thick, sweet liquids work best at covering up the taste of the medicine. The child should consume the liquid mixture entirely.
If my child can’t swallow capsules, how do I open Tamiflu® capsules and mix the medicine?
Pour a small amount (about a spoonful) of the thick sweetened liquid into a cup or bowl. Carefully open the Tamiflu capsule prescribed by your doctor and pour out all of the powder inside the capsule and mix it into the liquid. The exact amount of liquid used doesn’t matter, as long as the powder inside the capsule is mixed in well. All of the medicine may not dissolve, just be sure it is all well mixed. Use only the prescribed dose.
What will I need to do this?
You will need
The prescribed Tamiflu® capsule
A small bowl or cup
A spoon
A spoonful of a thick sweetened liquid, such as regular or sugar-free chocolate syrup
How do I mix the ingredients?
Pour a small amount (about a spoonful) of the thick sweetened liquid into a cup or bowl.
Holding one capsule over the bowl, carefully pull the capsule open and pour the complete contents of the capsule into the bowl.
Stir the mixture and give the entire dose to the child with a spoon.
Should my child take all of the mixture??
Yes, make sure your child takes all of the medicine mixture.
have said that available supplies of liquid Tamiflu® for children are limited.