Henrietta Hall

Maternal Influenza Vaccination and Effect on Influenza Virus Infection in Young Infants

OBJECTIVE To assess the effect of seasonal influenza vaccination during pregnancy on laboratory-confirmed influenza in infants to 6 months of age. DESIGN Nonrandomized, prospective, observational cohort study. SETTING Navajo and White Mountain Apache Indian reservations, including 6 hospitals on the Navajo reservation and 1 on the White Mountain Apache reservation. PARTICIPANTS A total of 1169 mother-infant pairs with mothers who delivered an infant during 1 of 3 influenza seasons. MAIN EXPOSURE Maternal seasonal influenza vaccination. MAIN OUTCOME MEASURES In infants, laboratory-confirmed influenza, influenza-like illness (ILI), ILI hospitalization, and influenza hemagglutinin inhibition antibody titers. RESULTS A total of 1160 mother-infant pairs had serum collected and were included in the analysis. Among infants, 193 (17%) had an ILI hospitalization, 412 (36%) had only an ILI outpatient visit, and 555 (48%) had no ILI episodes. The ILI incidence rate was 7.2 and 6.7 per 1000 person-days for infants born to unvaccinated and vaccinated women, respectively. There was a 41% reduction in the risk of laboratory-confirmed influenza virus infection (relative risk, 0.59; 95% confidence interval, 0.37-0.93) and a 39% reduction in the risk of ILI hospitalization (relative risk, 0.61; 95% confidence interval, 0.45-0.84) for infants born to influenza-vaccinated women compared with infants born to unvaccinated mothers. Infants born to influenza-vaccinated women had significantly higher hemagglutinin inhibition antibody titers at birth and at 2 to 3 months of age than infants of unvaccinated mothers for all 8 influenza virus strains investigated. CONCLUSIONS Maternal influenza vaccination was significantly associated with reduced risk of influenza virus infection and hospitalization for an ILI up to 6 months of age and increased influenza antibody titers in infants through 2 to 3 months of age.

Isolation and Characterization of Avian Influenza Viruses, Including Highly Pathogenic H5N1, from Poultry in Live Bird Markets in Hanoi, Vietnam, in 2001

ABSTRACT Since 1997, outbreaks of highly pathogenic (HP) H5N1 and circulation of H9N2 viruses among domestic poultry in Asia have posed a threat to public health. To better understand the extent of transmission of avian influenza viruses (AIV) to humans in Asia, we conducted a cross-sectional virologic study in live bird markets (LBM) in Hanoi, Vietnam, in October 2001. Specimens from 189 birds and 18 environmental samples were collected at 10 LBM. Four influenza A viruses of the H4N6 (n = 1), H5N2 (n = 1), and H9N3 (n = 2) subtypes were isolated from healthy ducks for an isolation frequency of over 30% from this species. Two H5N1 viruses were isolated from healthy geese. The hemagglutinin (HA) genes of these H5N1 viruses possessed multiple basic amino acid motifs at the cleavage site, were HP for experimentally infected chickens, and were thus characterized as HP AIV. These HA genes shared high amino acid identities with genes of other H5N1 viruses isolated in Asia during this period, but they were genetically distinct from those of H5N1 viruses isolated from poultry and humans in Vietnam during the early 2004 outbreaks. These viruses were not highly virulent for experimentally infected ducks, mice, or ferrets. These results establish that HP H5N1 viruses with properties similar to viruses isolated in Hong Kong and mainland China circulated in Vietnam as early as 2001, suggest a common source for H5N1 viruses circulating in these Asian countries, and provide a framework to better understand the recent widespread emergence of HP H5N1 viruses in Asia.

Intercontinental Circulation of Human Influenza A(H1N2) Reassortant Viruses during the 2001–2002 Influenza Season

Reassortant influenza A viruses bearing the H1 subtype of hemagglutinin (HA) and the N2 subtype of neuraminidase (NA) were isolated from humans in the United States, Canada, Singapore, Malaysia, India, Oman, Egypt, and several countries in Europe during the 2001-2002 influenza season. The HAs of these H1N2 viruses were similar to that of the A/New Caledonia/20/99(H1N1) vaccine strain both antigenically and genetically, and the NAs were antigenically and genetically related to those of recent human H3N2 reference strains, such as A/Moscow/10/99(H3N2). All 6 internal genes of the H1N2 reassortants examined originated from an H3N2 virus. This article documents the first widespread circulation of H1N2 reassortants on 4 continents. The current influenza vaccine is expected to provide good protection against H1N2 viruses, because it contains the A/New Caledonia/20/99(H1N1) and A/Moscow/10/99(H3N2)-like viruses, which have H1 and N2 antigens that are similar to those of recent H1N2 viruses.

Comparison of 10 influenza A (H1N1 and H3N2) haemagglutinin sequences obtained directly from clinical specimens to those of MDCK cell- and egg-grown viruses

PCR was used to amplify and sequence the complete HA1 region of the haemagglutinin (HA)-encoding genes of 10 clinical isolates of influenza virus of the H1N1 or H3N2 subtypes. These sequences were compared to those obtained from viruses isolated from the same specimens after passage in eggs and MDCK cells. Amino acid substitutions in the egg-derived HA sequences were found in nine out of the 10 specimens analysed, whereas seven out of eight of the MDCK-derived HA sequences were identical to those in the corresponding original specimens. Changes in the H1 HA occurred at residues 77a, 196 (also found in the corresponding HA from the MDCK isolate), 225, 226 and 227; changes in the H3 HA occurred at residues 137, 156, 186, 248 and 276. In addition, we have shown that an amino acid change at residue 145 in the HA of the H3 subtype that was previously demonstrated to be egg-selected is now present in circulating strains.

Infection of a child in Hong Kong by an influenza A H3N2 virus closely related to viruses circulating in European pigs

Influenza virus A/Hong Kong/1774/99, isolated from a young child with mild influenza, was shown to be similar in its antigenic and genetic characteristics to H3N2 viruses circulating in pigs in Europe during the 1990s and in particular to be closely related to viruses isolated from two children in the Netherlands in 1993. Similar viruses had previously not been identified outside Europe. Although there is little evidence as to how the child contracted the infection, it appears likely that pigs in southern China were the source of infection. Characteristics shared with the European swine viruses include resistance to the anti-influenza drugs amantadine and rimantadine. Thus not only does this incident once again highlight the potential of pigs as a source of novel human influenza viruses, but also indicates the potential for emergence of amantadine-resistant human viruses.

Risk of breast cancer in young women in relation to body size and weight gain in adolescence and early adulthood.

SummaryFindings have been inconsistent on effects of adolescent body size and adult weight gain on risk of breast cancer in young women. These relations were examined in a population-based case control study of 1590 women less than 45 years of age newly diagnosed with breast cancer during 1990–1992 in three areas of the US and an age-matched control group of 1390 women. Height and weight were measured at interview and participants asked to recall information about earlier body size. Logistic regression was used to estimate the relative risk of breast cancer adjusted for other risk factors. Women who were either much heavier or lighter than average in adolescence or at age 20 were at reduced risk. Weight gain after age 20 resulted in reduced risk, but the effect was confined to early-stage and, more specifically, lower grade breast cancer. Neither the risk reduction nor the variation by breast cancer stage or grade was explained by the method of cancer detection or by prior mammography history. These findings suggest that relations between breast cancer risk in young women and body weight at different ages is complex and that the risk reduction with adult weight gain is confined to less aggressive cancers.

Transmission of influenza A viruses between pigs and people, Iowa, 2002-2004.

Please cite this paper as: Terebuh et al. (2010) Transmission of influenza A viruses between pigs and people, Iowa, 2002–2004. Influenza and Other Respiratory Viruses 4(6), 387–396.

Influenza A and B infection in children in urban slum, Bangladesh.

To the Editor: Influenza A and B viruses are associated with seasonal epidemics (1). Influenza is increasingly recognized as a cause of severe respiratory disease among healthy children in industrialized countries (2–4). However, little information is available from developing countries (5). We assessed the contribution of influenza and other respiratory viruses to febrile respiratory illness among children enrolled at the ICDDR,B Kamalapur surveillance and intervention site (6) in an urban slum in Dhaka, Bangladesh. This study was reviewed and approved by the Research Review and Ethical Review Committees of ICDDR,B and the Institutional Review Board of the Centers for Disease Control and Prevention (CDC) (Atlanta, GA, USA). Surveillance in Kamalapur has been described (6,7). Briefly, the site is divided into 7 geographic strata and subdivided into geographic clusters of 50–100 households. Eighty-six clusters were randomly selected and 5,000 households within those clusters were enrolled after written consent was obtained. Prospective fever surveillance methodology has been described (7). To evaluate viral causes of febrile respiratory illness, paired (acute- and convalescent-phase) serum specimens were retrospectively selected from the surveillance period of December 6, 2000 to December 5, 2001, from patients with documented fever >38.5°C, a cough for >1 day but <4 days, and age <13 years, and who were negative for antibodies to dengue by immunoglobulin M (IgM) antibody-capture ELISA. Sera were tested by hemagglutination inhibition (HI) for influenza A (H1N1 and H3N2) virus and B virus, and by ELISA for respiratory syncytial virus, parainfluenza virus types 1, 2, and 3, adenovirus, and human metapneumovirus at CDC by using standard methods (8). Acute infection was defined as IgM in serum sample or a >4-fold increase in IgG titer between acute- and convalescent-phase serum samples for noninfluenza viruses or a >4-fold increase in HI titer for influenza viruses. Statistical analysis was performed by using Stata Statistical Software Release 8.2, 2003 (Stata Corporation, College Station, TX, USA). Continuous variables were compared by using analysis of variance. Univariate categorical analysis was conducted by using 2 × 2 tables to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Multivariate analysis was conducted by using stepwise forward logistic regression and all covariates significant with a 5% precision in univariate analysis. We adjusted the model for clustering (multiple observations per patient) and tested for goodness of fit. Of 889 patients who came to the ICDDR, B Kamalpur field clinic with fever during the surveillance period, 198 (22%) met inclusion criteria for retrospective sampling. Of these, 128 had adequate paired serum specimens for influenza testing. Only 107 (83.6%) pairs had sufficient serum remaining for testing for other viruses. Of 128 children, 21 (16%) had acute influenza infections; 2 of these children had both influenza A and B. Overall, 10 influenza A (8 H1N1 and 2 H3N2) and 13 influenza B infections were detected (Table). Other respiratory virus infections were detected in 33 children and accounted for 35 noninfluenza virus infections (Table). One child was coinfected with both influenza A (H3N2) virus and HMPV. Seven (70%) of 10 influenza A cases occurred during April–June (pre-monsoon period), and 10 (77%) influenza B cases occurred during July–September (monsoon period). Table Virus infections detected by serologic analysis in children <13 years of age, December 2000–December 2001, Dhaka, Bangladesh* Data for 107 serum pairs tested for both influenza and other viruses indicated that influenza-infected children were older than children without influenza (OR 3.1, 95% CI 1.1–9.3). Multivariate analysis indicated that only reported body pain was more common in influenza patients than in others (OR 3.3, 95% CI 1.5–7.1). Three influenza-infected children had clinical pneumonia (tachypnea defined by the World Health Organization) with crepitations. We confirmed that influenza A and B were common causes of febrile illness among children in Dhaka. Because these infections were identified in 1 of 6 dengue-negative febrile children tested for influenza, these infections may play a substantial role in respiratory diseases in these children. Our study confirms findings of a previous hospital study (9) but provides additional information for nonhospitalized febrile children. Acute infections coincided with the warm pre-monsoon and monsoon periods. Our study had several limitations. First, the surveillance system was not originally designed to identify influenza and relied on fever for specimen collection. Our retrospective selection criteria reflected the classic initial manifestations of influenza (1,4), and thus could have missed nonfebrile cases. Second, the study was not designed to reflect age distribution of children with respiratory infection, but rather those with fever and who had adequate amounts of available sera. This feature potentially biases toward older children. Third, data describe only 1 year, and patterns of illness may differ in other years. Fourth, acute infection was determined by serologic analysis. Previous studies in Bangladesh reported nutrition-related impaired immune responsiveness (10). Thus, some influenza-infected children who showed a nondetectable immune response may not have been included. These findings indicate that influenza and other respiratory viruses contribute to pediatric febrile illness in urban Bangladesh. They also justify prospective surveillance to better define epidemiology and clinical findings associated with these viruses.

Pathogenesis of and immunity to a new influenza A (H5N1) virus isolated from duck meat

Abstract The outbreak of avian influenza H5N1 in Hong Kong in 1997 raised concerns about the potential for the H5 subtype to cause a human pandemic. In 2001 a new H5N1 virus, A/Duck Meat/Anyang/AVL-1/2001 (A/Dkmt), was isolated from imported duck meat in Korea. The pathogenesis of this virus was investigated in mice. A/Dkmt virus had low infectivity but was lethal for mice at high doses, and at lethal doses, the virus replicated in the brains of infected mice. A/Dkmt virus cross-reacted poorly with ferret antisera raised against human H5N1 viruses, but prior infection with A/Dkmt virus protected mice from death after secondary infection with human H5N1 virus.