Effect of human rhinovirus infection in pediatric patients with influenza-like illness on the 2009 pandemic influenza A（H1N1） virus

Background Some research groups have hypothesized that human rhinoviruses （HRVs） delayed the circulation of the 2009 pandemic influenza A（H1N1） virus （A（H1N1）pdm09） at the beginning of Autumn 2009 in France.This study aimed to evaluate the relationship between HRV and A（H1N1）pdm09 in pediatric patients with influenza-like illness in Beijing,China.Methods A systematic analysis to detect A（H1N1）pdm09 and seasonal influenza A virus （FLU A） was performed on 4 349 clinical samples from pediatric patients with influenza-like illness during the period June 1,2009 to February 28,2010,while a one-step real-time RT-PCR （rRT-PCR） assay was used to detect HRV in 1 146 clinical specimens selected from those 4 349 specimens.Results During the survey period,only one wave of A（H1N1）pdm09 was observed.The percentage of positive cases for A（H1N1）pdm09 increased sharply in September with a peak in November 2009 and then declined in February 2010.Data on the monthly distribution of HRVs indicated that more HRV-positive samples were detected in September （2.2％） and October （3.3％）,revealing that the peak of HRV infection in 2009 was similar to that of other years.Among the 1 146 specimens examined for HRVs,21 （1.8％） were HRV-positive,which was significantly lower than that reported previously in Beijing （15.4％ to 19.2％） （P ＜0.01）.Overall,6 samples were positive for both A（H1N1）pdm09 and HRV,which represented a positive relative frequency of 1.60％ and 2.08％ HRV,considering the A（H1N1）pdm09-positive and-negative specimens,respectively.The odds ratio was 0.87 （95％ CI 0.32; 2.44,P=0.80）.Conclusions HRVs and A （H1N1）pdm09 co-circulated in this Chinese population during September and October 2009,and the HRV epidemic in 2009 did not affect A（H1N1）pdm09 infection rates in Beijing,China as suggested by other studies.However,the presence of A（H1N1）pdm09 might explain the unexpected reduction in the percentage of HRV positive cases during the period studied.

Determination of epidemic parameters from early phase fatality data： A case study of the 2009 A（H1N1） pandemic in Europe

This paper demonstrates that the susceptible-infected-removed （SIR） model applied to the early phase of an epidemic can be used to determine epidemic parameters reliably. As a case study, the SIR model is applied to the fatality data of the 2009 fall wave cycle of the A（H1N1） pandemic in 12 European countries. It is observed that the best estimates of the basic reproduction number R0 and the mean duration of the infection period l/r/ lie on a curve in the scatterplots, indicating the existence of a nearly-invariant quantity which corresponds to the duration of the epidemic. Spline interpolation applied to the early phase of the epidemic, an approximately 10-week period, together with a future control point in the stabilization region, is sufficient to estimate model parameters. The SIR model is run over a wide range of parameters and estimates of R0 in the range 1.2- 2.0 match the values in the literature. The duration of the infection period, 1/η is estimated to be in the range 2.0-7.0 days. Longer infection periods are tied to spatial characteristics of the spread of the epidemic.

Immunogenic and Protective Properties of the First Kazakhstan Vaccine against Pandemic Influenza А(Н1N1) pdm09 in Ferrets

This paper presents the results of a pre-clinical study of the immunogenicity and efficacy of an egg-derived, inactivated, whole-virion adjuvanted vaccine （Refluvac） on ferret models. For this purpose, groups of eight ferrets （6 to 7 months old） were injected with 0.5 mL of vaccine specimens containing 3.75, 7.5 or 15.0 μg of virus hemagglutinin. Administration was intramuscular and given either as a single dose or as two doses 14 days apart. All vaccine specimens manifested immunogenicity in ferrets for single （HI titer, from 51 ± 7 to 160 ± 23） and double （HI titer, from 697± 120 to 829 ± 117） administrations. To assess the protective effects of the vaccine, ferrets from the vaccinated and control groups were infected intranasally with pandemic virus A/California/7/09 （H1N1） pdm09 at a dose of 106 106/0.5 mL. Fourteen days post-infection, the ferrets inoculated with single or double vaccines containing 3.75, 7.5 or 15.0 ~g of hemagglutinin per dose showed no signs of influenza infection, weight loss, or body temperature rise, and no premature deaths occurred. The number of vaccinated ferrets shedding the virus via the upper airway, as well as the amount of virus shed after infection, was significantly reduced in comparison with animals from the control group. Based on our results, we suggest that a single vaccination at a dose of 3.75 or 7.5 μg hemagglutinin be used for Phase I clinical trials.

Close Relationship between the 2009 H1N1 Virus and South Dakota AIV Strains

Although previous publications suggest the 2009 pandemic influenza A (H1N1) virus was reassorted from swine viruses of North America and Eurasia,the immediate ancestry still remains elusive due to the big evolutionary distance between the 2009 H1N1 virus and the previously isolated strains. Since the unveiling of the 2009 H1N1 influenza,great deal of interest has been drawn to influenza,consequently a large number of influenza virus sequences have been deposited into the public sequence databases. Blast analysis demonstrated that the recently submitted 2007 South Dakota avian influenza virus strains and other North American avian strains contained genetic segments very closely related to the 2009 H1N1 virus,which suggests these avian influenza viruses are very close relatives of the 2009 H1N1 virus. Phylogenetic analyses also indicate that the 2009 H1N1 viruses are associated with both avian and swine influenza viruses circulating in North America. Since the migrating wild birds are preferable to pigs as the carrier to spread the influenza viruses across vast distances,it is very likely that birds played an important role in the inter-continental evolution of the 2009 H1N1 virus. It is essential to understand the evolutionary route of the emerging influenza virus in order to find a way to prevent further emerging cases. This study suggests the close relationship between 2009 pandemic virus and the North America avian viruses and underscores enhanced surveillance of influenza in birds for understanding the evolution of the 2009 pandemic influenza.

Natural herbal medicine Lianhuaqingwen capsule anti-influenza A （H1N1） trial： a randomized, double blind, positive controlled clinical trial

Background The 2009 influenza A （H1N1） virus infection is associated with the high risk of severe complications and is spreading more rapidly throughout the world than other reported seasonal influenzas. This study aimed to evaluate the efficacy and safety of the nature herbal medicine Lianhuaqingwen capsule （LHC） in patients infected with influenza A （H1N1） virus. Methods A total of 244 patients aged 16-65 years confirmed with influenza A （H1N1） virus infection by the real time RT-PCR were randomized to one of two treatment groups of 122 patients each. Each group assigned to receive either LHC or Oseltamivir for five days and observation for seven days. The patients were enrolled within 36 hours of illness onset if they had an axillary temperature of ≥37.4℃ and with at least one of the following symptoms： nasal obstruction, runny nose, cough, sore throat, fatigue, headache, myalgia, chills and sweating. The primary end point was the duration of illness. Results Of 244 patients, 240 （98.36%） patients with a median age 21 years completed the study between October 24, 2009 and November 23, 2009. There were no significant overall differences between LHC treated and Oseltamivir treated patients in the median duration of illness （LHC 69 hours vs. Oseltamivir 85 hours P 〉0.05） or the median duration of viral shedding （LHC 103 hours vs. Oseltamivir 96 hours, P 〉0.05）. However, it was worthwhile to note that LHC significantly reduced the severity of illness and the duration of symptoms including fever, cough, sore throat, and fatigue （P〈0.05）. Both study medications were well tolerated. No drug related serious adverse events occurred during the study. Conclusions Compared with Oseltamivir, LHC achieved a similar therapeutic effectiveness reduction of the duration of illness and duration of viral shedding. Therefore, LHC might be an alternative therapeutic measure for influenza A （H1N1） virus infections.

Influence of extreme weather and meteorological anomalies on outbreaks of influenza A (H1N1)

Biological experiments and epidemiological evidence indicate that variations in environment have important effect on the occurrence and transmission of epidemic influenza.It is therefore important to understand the characteristic patterns of transmission for prevention of disease and reduction of disease burden.Based on case records,we analyzed the environmental characteristics including climate variables in Changsha,and then constructed a meteorological anomaly susceptive-infective-removal (SIR) model on the basis of the results of influenza A (H1N1) transmission.The results showed that the outbreak of influenza A (H1N1) in Changsha showed significant correlation with meteorological conditions;the spread of influenza was sensitive to meteorological anomalies,and that the outbreak of influenza A (H1N1) in Changsha was influenced by a combination of absolute humidity anomalous weather conditions,contact rates of the influenza patients and changes in population movements.These findings will provide helpful information regarding prevention strategies under different conditions,a fresh understanding of the emergence and re-emergence of influenza outbreaks,and a new perspective on the transmission dynamics of influenza.

Response of BALB/c mice to a monovalent influenza A （H1N1） 2009 split vaccine

The novel influenza A （H1N1） 2009 virus has emerged to cause the first pandemic of the twenty-first century. Disease outbreaks caused by the influenza A （H 1N 1） virus have prompted concerns about the potential for a pandemic and have driven the development of vaccines against this subtype of influenza A. In this study, we developed a monovalent influenza A （H 1N 1） split vaccine and evaluated its effects in BALB/c mice. Mice were immunized subcutaneously with 2 doses of the vaccine containing hemagglutinin （HA） alone or HA plus an aluminum hydroxide （AI（OH）3） adjuvant. Immunization with varying doses of HA （3.75, 7.5, 15, 30, 45 or 60μg） was performed to induce the production of neutralizing antibodies. The vaccine elicited strong hemagglutination inhibition （HI） and microneutralization, and addition of the adjuvant augmented the antibody response. A preliminary safety evaluation showed that the vaccine was not toxic at large doses （0.5 ml containing 60 μg HA＋600 μg AI（OH）3 or 60 μg HA）. Moreover, the vaccine was found to be safe at a dose of 120 μg HA＋ 1200 μg AI（OH）3 or 120 μg HA in 1.0 ml in rats. In conclusion; the present study provides support for the clinical evaluation of influenza A （H1N1） vaccination as a public health intervention to mitigate a possible pandemic. Additionally, our findings support the further evaluation of the vaccine used in this study in primates or humans.

Comorbid presentation of severe novel influenza A （H1N1） and Evans syndrome： a case report

One 22-month-old boy who was admitted for a fever lasting 6 days as well as a cough and wheezing lasting 2 days was reported. He was diagnosed with influenza A （H1N1, severe type）, severe pneumonia, acute respiratory distress syndrome （ARDS）, Evans syndrome and multiple organ failure. This is the first case of novel influenza A （HIN1） and Evans syndrome. The pathogenesis is still unknown.