Effectiveness of maternal immunization with trivalent inactivated influenza vaccine in pregnant women and their infants.

BACKGROUND: In randomized trials, it has been found that maternal influenza vaccination reduces influenza infections in both women and their infants. However, these trials have been performed in low-resource settings, and evidence from high-resource settings is limited. METHODS: Nested within a register-based cohort of all women giving birth in Denmark between 2010 and 2016 (n = 357 810 births), we conducted two case-control studies using a test-negative design of all pregnant women and their infants, respectively, tested for influenza virus with reverse transcriptase-polymerase chain reaction. Influenza virus-positive cases were matched (1:1) with influenza virus-negative controls for calendar time and (gestational or infant) age at testing. The effectiveness of maternal immunization with trivalent inactivated influenza vaccine was estimated from the odds ratios of vaccination among cases versus controls using logistic regression with adjustment for potential confounders. RESULTS: Among 313 pregnant women positive for influenza virus, 16 (5.1%) were vaccinated; by comparison, 34 (10.9%) pregnant women were vaccinated among 313 matched influenza virus-negative controls. The effectiveness of vaccination against laboratory-confirmed influenza infection in pregnant women was 63.9% [95% confidence interval (CI), 29.1 to 81.6]. Among 460 infants positive for influenza virus, 23 (5.0%) were offspring of women vaccinated during pregnancy; by comparison, 52 (11.3%) infants were the offspring of women vaccinated during pregnancy among 460 matched influenza virus-negative controls. The effectiveness of maternal vaccination against laboratory-confirmed influenza infection in infants younger than 6 months of age was 56.8% (95% CI, 25.0 to 75.1). CONCLUSIONS: Seasonal trivalent inactivated influenza vaccination in pregnancy was associated with a statistically significant reduced risk of laboratory-confirmed influenza infections in pregnant women and their infants in a high-resource setting.

The association between seasonal influenza-like illness cases and foetal death: a time series analysis.

It has been reported that foetal death follows a seasonal pattern. Influenza virus infection has been postulated as one possible contributor to this seasonal variation. This ecological study explored the temporal association between the influenza activity and the frequency of foetal death. Time series analysis was conducted using weekly influenza-like illness consultation proportions from the Danish sentinel surveillance system and weekly proportions of spontaneous abortions and stillbirths from hospital registers from 1994 to 2009. The association was examined in an autoregressive (AR) integrated (I) moving average (MA) model and subsequently analysed with cross-correlation functions. Our findings confirmed the well-known seasonality in influenza, but also seasonality in spontaneous abortion. No clear pattern of seasonality was found for stillbirths, although the analysis exposed dependency between observations. One final AR integrated MA model was identified for the influenza-like illness (ILI) series. We found no statistically significant relationship between weekly influenza-like illness consultation proportions and weekly spontaneous abortion proportions (five lags: P = 0.52; 11 lags: P = 0.91) or weekly stillbirths (five lags: P = 0.93; 11 lags: P = 0.40). Exposure to circulating influenza during pregnancy was not associated with rates of spontaneous abortions or stillbirths. Seasonal variations in spontaneous abortion were confirmed and this phenomenon needs further investigation.

Varicella-zoster immunoglobulin treatment in pregnant women in Denmark from 2005 to 2015: descriptive epidemiology and follow-up.

Primary infection with varicella-zoster virus in pregnancy poses a risk of severe infection and embryopathies. Upon exposure, seronegative women are candidates for varicella-zoster immunoglobulin (VZIG). The aim of this paper was to describe risk factors for VZIG treatment including sources of varicella exposure and to study how many women developed clinical infection and received postpartum vaccination. We identified all pregnant women who received VZIG from December 2005 to March 2015. Additional information was obtained from Danish registers and a follow-up questionnaire. A total of 104 women were included and 88 completed the questionnaire. Significantly more women had 'other country of origin' than Denmark. They were more often second para (57%) and had most commonly been exposed to varicella by their own child (58%). Five women developed clinical varicella infection, and only 26·5% were vaccinated after delivery. The study concludes that few women developed infection after VZIG and none developed pneumonia. General practitioners should be particularly aware of obtaining varicella anamnesis in parous women from non-temperate countries in order to perform selective vaccination prior to pregnancy. In case of varicella exposure during pregnancy in a seronegative woman, postpartum vaccination is crucial.

Improving national surveillance of Lyme neuroborreliosis in Denmark through electronic reporting of specific antibody index testing from 2010 to 2012.

Our aim was to evaluate the results of automated surveillance of Lyme neuroborreliosis (LNB) in Denmark using the national microbiology database (MiBa), and to describe the epidemiology of laboratory-confirmed LNB at a national level. MiBa-based surveillance includes electronic transfer of laboratory results, in contrast to the statutory surveillance based on manually processed notifications. Antibody index (AI) testing is the recommend laboratory test to support the diagnosis of LNB in Denmark. In the period from 2010 to 2012, 217 clinical cases of LNB were notified to the statutory surveillance system, while 533 cases were reported AI positive by the MiBa system. Thirty-five unconfirmed cases (29 AI-negative and 6 not tested) were notified, but not captured by MiBa. Using MiBa, the number of reported cases was increased almost 2.5 times. Furthermore, the reporting was timelier (median lag time: 6 vs 58 days). Average annual incidence of AI-confirmed LNB in Denmark was 3.2/100,000 population and incidences stratified by municipality ranged from none to above 10/100,000. This is the first study reporting nationwide incidence of LNB using objective laboratory criteria. Laboratory-based surveillance with electronic data-transfer was more accurate, complete and timely compared to the surveillance based on manually processed notifications. We propose using AI test results for LNB surveillance instead of clinical reporting.

Burden and characteristics of influenza A and B in Danish intensive care units during the 2009/10 and 2010/11 influenza seasons.

Influenza surveillance in Danish intensive care units (ICUs) was performed during the 2009/10 and 2010/11 influenza seasons to monitor the burden on ICUs. All 44 Danish ICUs reported aggregate data for incidence and point prevalence, and case-based demographical and clinical parameters. Additional data on microbiological testing, vaccination and death were obtained from national registers. Ninety-six patients with influenza A(H1N1)pdm09 were recorded in 2009/10; 106 with influenza A and 42 with influenza B in 2010/11. The mean age of influenza A patients was higher in 2010/11 than in 2009/10, 53 vs. 44 years (P = 0·004). No differences in other demographic and clinical parameters were detected between influenza A and B patients. In conclusion, the number of patients with severe influenza was higher in Denmark during the 2010/11 than the 2009/10 season with a shift towards older age groups in influenza A patients. Influenza B caused severe illness and needs consideration in clinical and public health policy.

European all-cause excess and influenza-attributable mortality in the 2017/18 season: should the burden of influenza B be reconsidered?

OBJECTIVES: Weekly monitoring of European all-cause excess mortality, the EuroMOMO network, observed high excess mortality during the influenza B/Yamagata dominated 2017/18 winter season, especially among elderly. We describe all-cause excess and influenza-attributable mortality during the season 2017/18 in Europe. METHODS: Based on weekly reporting of mortality from 24 European countries or sub-national regions, representing 60% of the European population excluding the Russian and Turkish parts of Europe, we estimated age stratified all-cause excess morality using the EuroMOMO model. In addition, age stratified all-cause influenza-attributable mortality was estimated using the FluMOMO algorithm, incorporating influenza activity based on clinical and virological surveillance data, and adjusting for extreme temperatures. RESULTS: Excess mortality was mainly attributable to influenza activity from December 2017 to April 2018, but also due to exceptionally low temperatures in February-March 2018. The pattern and extent of mortality excess was similar to the previous A(H3N2) dominated seasons, 2014/15 and 2016/17. The 2017/18 overall all-cause influenza-attributable mortality was estimated to be 25.4 (95%CI 25.0-25.8) per 100,000 population; 118.2 (116.4-119.9) for persons aged 65. Extending to the European population this translates into over-all 152,000 deaths. CONCLUSIONS: The high mortality among elderly was unexpected in an influenza B dominated season, which commonly are considered to cause mild illness, mainly among children. Even though A(H3N2) also circulated in the 2017/18 season and may have contributed to the excess mortality among the elderly, the common perception of influenza B only having a modest impact on excess mortality in the older population may need to be reconsidered.

Second-trimester maternal serum alpha-fetoprotein and risk of adverse pregnancy outcome(1).

OBJECTIVE: To determine the risk of adverse pregnancy outcome by maternal serum alpha-fetoprotein (MSAFP) level. METHODS: We followed 77,149 pregnant women and their infants from MSAFP screening in the 15th to 20th week of gestation until 1 year after birth. Information on pregnancy outcome was obtained from national registries. The relative risks (RRs) and 95% confidence intervals (CIs) for adverse pregnancy outcome were estimated according to the level of MSAFP, with adjustment for confounders. RESULTS: A total of 638 pregnancies resulted in spontaneous abortion, 289 in stillbirth, and 437 in infant death. Compared with women with MSAFP levels at 0.75-1.24 multiples of the median (MoM), those with MSAFP levels greater than or equal to 2.5 MoM had an increased risk of spontaneous abortion (RR 12.5; 95% CI 9.7, 16.1), preterm birth (RR 4.8; 95% CI 4.1, 5.5), small for gestational age (RR 2.8; 95% CI 2.4, 3.2), low birth weight (RR 5.8; 95% CI 5.0, 6.6), and infant death (RR 1.9; 95% CI 1.2, 2.8). Women with MSAFP levels below 0.25 MoM had an increased risk of spontaneous abortion (RR 15.1; 95% CI 9.3, 24.8), preterm birth (RR 2.2; 95% CI 1.3, 3.8), and stillbirth (RR 4.0; 95% CI 1.0, 16.0); those with levels less than 0.5 MoM had an increased risk of infant death (RR 1.9; 95% CI 1.2, 3.0). The increased risk of infant death remained after the subtraction of recognized conditions associated with extreme MSAFP values. CONCLUSION: Pregnant women with extreme MSAFP values in the second trimester have an increased risk of fetal and infant deaths. Obstet Gynecol 2001;97:277-82.

[Population screening for HIV in Sisimiut, Greenland]. / Befolkningsscreening for hiv i Sisimiut, Grønland.

INTRODUCTION: In the years 1985-1998, 91 HIV-positive persons were diagnosed in Greenland, resulting in an incidence of HIV infection three times higher in Greenland than in Denmark. Of these cases 25% were diagnosed in Sisimiut, which, however, only comprises 10% of the total population of Greenland. In spite of an active HIV case-tracing programme at the Health Centre, there was a fear of unknown HIV-positives in the town. Therefore, the Health Centre initiated an HIV screening campaign among all adults and school children in the town of Sisimiut and two adjacent settlements. MATERIAL AND METHODS: The screening campaign was carried out in the weeks 46 and 47 in November 1998 by the staff at the Health Centre. All participants filled out a questionnaire concerning demographic variables, and had blood samples drawn. For adults the campaign mainly took place in the community centre and the large work places, and for the children at the schools. Blood samples were tested for antibodies against HIV 1 and 2 at Statens Serum Institut using ELISA tests and confirmatory Western Blot. RESULTS: Of the total population of 4807, 2858 persons took part in the screening campaign (participation rate 59%). Among adults the participation rate was 50%, and for children aged 6-17 years the rate was 86%. Four HIV-positive persons were tested positive. Of these three were already known HIV-positives, and the last person was highly suspect of HIV infection. DISCUSSION: There is no evidence of widespread HIV infection in Sisimiut. No unknown groups of HIV-positive persons were identified. Thus, the intensive case-tracing programme as carried out by the Health Centre seems effective.

Reproductive history and allergic rhinitis among 31145 Danish women.

BACKGROUND AND OBJECTIVE: A successful pregnancy is associated with a strong skewing of the immune system towards a Th2-type immune response. Because such a deviation is also the hallmark of allergic disease, it was investigated whether allergic rhinitis in women was associated with an increased likelihood of becoming pregnant and having a successful outcome of pregnancies. MATERIAL AND METHODS: Information on allergic rhinitis and reproductive history was obtained for 31145 pregnant women who participated in a national birth cohort study in Denmark during September 1997 to March 2000, and for whom complete information on siblings and place of residence and birth was available via the Civil Registration System. Data were analysed using logistic regression. RESULTS: Women who had previously been pregnant (OR = 0.91, 95% CI 0.85-0.98) or who had given birth previously (OR = 0.91, 95% CI 0.85-0.98) were less likely to report allergic rhinitis than others. The number of previous spontaneous abortions, gestational week of the first spontaneous abortion and fertility treatment were not associated with allergic rhinitis. Women who had waited less than a year to become pregnant more often had allergic rhinitis (OR = 1.18, 95% CI 1.06-1.32, P = 0.002) than women who had waited for more than a year. Early age at menarche was associated with an increased likelihood of allergic rhinitis (Ptrend = 0.003). CONCLUSIONS: Our findings did not support the hypothesis that an atopic genotype overall should be associated with an increased likelihood of successful outcome of pregnancies, but it might be associated with a decreased waiting time to pregnancy.

Atopic sensitization among children in an arctic environment.

BACKGROUND: Asthma has been reported to be rare among Inuits, but so far total and specific IgE levels have never been determined in arctic populations. OBJECTIVE: To determine the prevalence of atopy in children living in an arctic environment, and to examine whether atopy and total IgE levels were associated with parental place of birth, as a measure of ethnicity, and travel history. MATERIAL AND METHODS: All schoolchildren in Sisimiut, a community on the West coast of Greenland, were screened for atopy. Blood samples were analysed for total IgE and for specific IgE against inhalant and food allergens. Information on place of birth of children and their parents was obtained from national registries. Information on travel history was obtained from self-administered questionnaires. RESULTS: A total of 1031 schoolchildren aged 5 to 18 years had a blood sample drawn (85% of available children for the study). Of these, 151 (14.6%) children were sensitized to at least one inhalant allergen and 42 (4.1%) to at least one food allergen. Sensitization to grass was most common, whereas sensitization to mugwort, birch, animal-dander and house-dust mite was infrequent. Children whose parents were both born abroad had a higher risk of sensitization to inhalant allergens compared with children born of Greenlandic parents (OR = 8.6, 95% CI 2.8-27.1). Furthermore, children who had been abroad had a higher risk of sensitization towards pollen (OR = 1.6, 95% CI 1.0-2.5) and animal-dander (OR = 2.1, 95% CI 1.0-4.6) after adjustment for confounders. Both atopic and non-atopic children demonstrated high levels of total IgE (medians of 251 and 58 kU/L). CONCLUSIONS: Compared with European findings Greenlandic children have high levels of total IgE but a low prevalence of allergic sensitization towards inhalant allergens. This may be due to a low genetic susceptibility to atopy and less allergen exposure, as well as to living conditions in an arctic environment.