Influenza In Infants Research Articles

Influenza and pertussis vaccine coverage in pregnancy in Australia, 2016-2021.

Vaccination in pregnancy is the best strategy to reduce complications from influenza or pertussis infection in infants who are too young to be protected directly from vaccination. Pregnant women are also at risk of influenza complications preventable through antenatal vaccination. Both vaccines are funded under the National Immunisation Program for pregnant women in Australia, but coverage is not routinely reported nationally. We reviewed all reported Australian maternal influenza and pertussis vaccine coverage data for the period 2016-2021, to identify gaps and information needs. Maternal influenza vaccine coverage was suboptimal at < 58% for 2016-2018, with higher coverage of 62-75% reported in two states (Victoria and Western Australia) for 2019-2021. Maternal pertussis vaccine coverage from 2016 was generally higher than for influenza at > 70%, with the highest jurisdictional coverage of 89% reported in Western Australia in 2020. Vaccination rates were often suboptimal among First Nations pregnant women and up to 20% lower than among non-First Nations Australian women; while data were limited, coverage was low among culturally and linguistically diverse women and among women of lower socio-economic status. Jurisdictional perinatal data collections were the best source of information on antenatal vaccine coverage but were only available for a minority of the population; a nationally consistent systematic approach is lacking. Timely and comprehensive data are needed to provide feedback to improve maternal vaccination coverage, particularly among groups with higher risk and/or low uptake, and as new vaccines are recommended, including COVID-19 vaccination.

Efficacy of maternal vaccination during pregnancy against infant respiratory viruses.

Maternal vaccinations were effective in preventing RSV-associated lower respiratory tract infection and influenza in infants. The protection for infants against influenza was highest at 2 months and gradually declined up to 6 months of age. https://bit.ly/3ry3DAH.

Preventing severe influenza in Australian infants: Maternal influenza vaccine effectiveness in the PAEDS-FluCAN networks using the test-negative design

• First multi-state study from Australia on maternal vaccine effectiveness against severe infant influenza. • Influenza vaccination in pregnancy provides greatest protection for infants aged < 2 months. • Despite free availability of the influenza vaccine, uptake in pregnant women remains low.

Risk factors and disease severity in Australian infants aged under 6 months hospitalised with influenza 2011–2019

Infants aged <6months are vulnerable to severe influenza disease and no vaccine is approved for use in this age group. We aimed to describe the epidemiology, risk factors associated with severe outcomes and management of influenza in Australian infants aged <6months. Incident cases aged <6months of laboratory-confirmed influenza were captured through two national active prospective sentinel hospital-based surveillance systems in Australia from 2011 to 2019, inclusive. Demographic and clinical features, disease risk factors and outcomes (intensive care unit (ICU) admission and length of stay) and oseltamivir use were analysed. The proportion of infant influenza hospitalisations and nosocomial cases among all hospitalisations were also reported. Of 680 hospitalised infants aged <6months, 57.9% were male and 14.5% were Indigenous Australian. Median age was 2.6months, 19.2% were born premature and 19.0% had a comorbidity, excluding prematurity. Overall, 77.9% had influenza A. Nosocomial cases accounted for 7.8%. ICU admission occurred in 14.7% and oseltamivir was prescribed for 18.8%. Factors associated with ICU admission included age <1month (adjusted odds ratio (aOR) 3.95, 95% confidence interval (CI): 1.47-10.60), comorbidity (aOR 7.69, 95% CI: 4.04-14.64) and prematurity (aOR 2.60, 95% CI: 1.40-4.81). The proportion of infants with influenza among all infant hospitalisations ranged 1.0-2.6% in the 2019 influenza season. Infants aged <6months, and particularly neonates, experience serious disease from influenza. This data underpins the need for preventative strategies such as maternal immunisation and continued investigation into the possibility of safe and efficacious vaccination prior to 6months of age.

Maternal Vaccination Protects Infants Against Flu and Pertussis

Source: Rowe SL, Leder K, Perrett KP, et al. Maternal vaccination and infant influenza and pertussis. Pediatrics. 2021;148(3): e2021051076; doi.10.1542/peds.2021-051076Investigators from multiple institutions in Australia conducted a population-level inception cohort study to assess the effectiveness of maternal influenza and pertussis vaccination during pregnancy in preventing these diseases in their children during the first 6 months of life. For the study, they abstracted data from the Victorian Perinatal Data Collection (VPDC) on women whose pregnancies ended between September 2015 and December 2017. The VPDC includes information on all live births and stillbirths in Victoria, Australia, including demographic and clinical data related to pregnancy and birth. In addition, whether the mother received influenza and/or pertussis vaccine at any time during pregnancy is recorded. Data from multiple databases were reviewed to identify laboratory-confirmed cases of influenza and pertussis in infants <6 months old during the study period and record ED visits, hospital admissions, and deaths from influenza and pertussis. Information from these databases and VPDC were linked to identify mother-infant dyads.The primary study outcomes were laboratory-confirmed cases of influenza and pertussis in infants born to mothers included in the study, and secondary outcomes included cases of severe disease, defined as ED visit, hospitalization, or death from influenza or pertussis in study infants. Poisson regression was used to calculate the relative risk (RR) for influenza and pertussis in infants of mothers vaccinated during pregnancy vs not vaccinated, after adjusting for multiple confounders. Results were stratified in infants <2 months old, and those 2 to <6 months of age. Vaccine effectiveness (VE) of maternal immunization in preventing childhood illness was estimated as (1-RR) × 100.Data were analyzed on 186,962 mother-infant dyads. Overall, 45.9% of study women were vaccinated against influenza during pregnancy and 68.5% against pertussis. There were 185,404 and 184,194 infants, respectively, included in influenza and pertussis vaccination analyzes. The risk of influenza was significantly reduced in children whose mothers were vaccinated, both among children <2 months old (RR, 0.44; 95% CI, 0.25, 0.77), and in those 2 to <6 months of age (RR, 0.64; 95% CI, 0.42, 0.98), with VE estimated as 56.1% (95% CI, 23.3%, 74.9%) and 35.7% (95% CI, 2.2%, 57.7%), respectively. Maternal vaccination reduced the risk of pertussis in infants <2 months old (RR, 0.20; 95% CI, 0.06, 0.63), with an estimated VE of 80.1% (95% CI, 37.1%, 93.7%), but no significant effect was noted among infants 2 to <6 months old (RR, 0.68; 95% CI, 0.33, 1.39). Maternal pertussis immunization reduced the risk of severe pertussis in infants <2 months old (RR, 0.38; 95% CI, 0.16, 0.94). There were no significant effects from maternal vaccination on severe cases of pertussis in children 2 to <6 months old or on influenza among children <6 months old.The authors conclude that maternal vaccination during pregnancy reduces the risk of influenza and pertussis in infants <2 months old.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The goal of maternal immunization is to provide infants with passive antibodies prior to their first dose of vaccines. In a previous study, Baxter et al1 noted that maternal Tdap during pregnancy significantly reduced pertussis risk during the entire first year of life (See AAP Grand Rounds. 2017;38[2]:15.)1 In the current study, which included infants born at ≥30 weeks’ gestation, this benefit was most notable only in infants <2 months. In contrast, Baxter et al1 enrolled only infants born at ≥37 weeks’ gestation, allowing more time for antibody transfer after maternal Tdap receipt (usually between 27–36 weeks’ gestation).2As demonstrated by the results of the current study, maternal vaccination during pregnancy also reduces the infant’s risk for influenza during the first 6 months of life. Tdap and influenza vaccination rates during pregnancy, however, remain suboptimal.3 To assess influenza and Tdap vaccination coverage among women pregnant during the 2020–21 influenza season, the Centers for Disease Control and Prevention (CDC) conducted a survey during April 2021.4 Among 1,795 survey respondents who were pregnant anytime during October 2020–January 2021, 54.5% reported receiving an influenza vaccine before or during pregnancy. Among 729 respondents, 53.5% reported receiving Tdap during pregnancy. Unfortunately, receipt of both influenza and Tdap vaccines was reported by only 30.7% of women.COVID-19 vaccines also are recommended for all pregnant women.5 Providers need to take every opportunity to recommend these vaccines for their pregnant patients.Vaccination of pregnant women with Tdap, influenza, and COVID-19 vaccines is safe and protects the mother and her young infant.As influenza vaccines are approved only for infants ≥6 months of age, the 6-month duration of immunity conferred by maternal influenza vaccination provides further support for maternal immunization.

Maternal Vaccination and Infant Influenza and Pertussis.

Infant influenza and pertussis disease causes considerable morbidity and mortality worldwide. We examined the effectiveness of maternal influenza and pertussis vaccines in preventing these diseases in infants. This inception cohort study comprised women whose pregnancies ended between September 1, 2015, and December 31, 2017, in Victoria, Australia. Maternal vaccination status was sourced from the Victorian Perinatal Data Collection and linked to 5 data sets to ascertain infant outcomes and vaccination. The primary outcome of interest was laboratory-confirmed influenza or pertussis disease in infants aged <2 months, 2 to <6 months, and <6 months combined. Secondary outcomes included infant hospitalization (emergency presentation or admission) and death. Risk ratios and 95% confidence intervals (CIs) were estimated by Poisson regression. Vaccine effectiveness (VE) was estimated as (1 minus the risk ratio) x 100%. Among 186 962 pregnant women, 85 830 (45.9%) and 128 060 (68.5%) were vaccinated against influenza and pertussis, respectively. There were 175 and 51 infants with laboratory-confirmed influenza and pertussis disease, respectively. Influenza VE was 56.1% (95% CI, 23.3% to 74.9%) for infants aged <2 months and 35.7% (2.2% to 57.7%) for infants aged 2 to <6 months. Pertussis VE was 80.1% (95% CI, 37.1% to 93.7%) for infants aged <2 months and 31.8% (95% CI, -39.1% to 66.6%) for infants aged 2 to <6 months. Our study provides evidence of the direct effectiveness of maternal influenza and pertussis vaccination in preventing these diseases in infants aged <2 months. The findings strengthen the importance of maternal vaccination to prevent these diseases in infants.

Why Does Influenza Hit the Poor More Than the Rich? A 1931 Social Epidemiology Article That Broke New Ground in the History of Confounding, Mediation, and Interaction.

In 1931, Edgar Sydenstricker, the former statistician of the US Public Health Service, challenged the common belief that the 1918 influenza outbreak had affected "the rich and the poor alike." Using data from 112,317 participants in a 1918 US national survey, he observed that, on the contrary, both morbidity and mortality from the flu had been higher among the poor than among the rich. To explain these differences, Sydenstricker stratified the analyses by 2 measures of affluence collected in the survey: "economic status" (from "very poor" to "well-to-do") and household crowding (i.e., number of people per household room). Economic status was associated with influenza attack rates within categories of crowding, but not the opposite, suggesting that characteristics of poverty other than "household congestion" were the culprit of the poor's higher influenza burden. Attack rate ratios for influenza in infants and older adults were greater for the poor or very poor. Sydenstricker reanalyzed an already 12-year-old data set in the context of the Great Depression to build the evidence base relating poverty to ill health. For this purpose he used a stratification approach to assess confounding, mediation, and interaction before the concepts were formally named.

Influenza Illness and Partial Vaccination in the First Two Years of Life.

More information about influenza in low- and middle-income countries could guide the establishment of pediatric influenza vaccine programs. This study (1) characterizes the burden of influenza in infants, and (2) compares signs and symptoms by prior influenza vaccination or influenza illness. Newborns from Managua, Nicaragua, were followed for two years. Data came from primary medical appointments, PCR testing, and parents’ daily symptom diaries. Logistic regression models estimated associations between preceding vaccination or illness and influenza incidence. Linear models compared duration of illness by prior vaccination or influenza illness. Among 833 infants, 31% had PCR-positive influenza, and 28% were vaccinated against influenza. Four (<0.5%) were fully vaccinated. Overall, influenza incidence was 21.0 (95% confidence interval (CI): 18.8, 23.2) per 100 person-years. Incidence was lower among those with prior influenza compared with those without preceding illness or vaccination (OR: 0.64, 95% CI: 0.44, 0.94). Partially vaccinated children had 1 day less fever than those without prior illness or vaccination (p = 0.049). A large proportion of children <2 years in Nicaragua contract influenza. Illness was attenuated for those partially vaccinated. Since few children were fully vaccinated, future studies will need to consider the effectiveness of a two-dose vaccination schedule.

Oseltamivir treatment of influenza A and B infections in infants.

BackgroundOseltamivir treatment is currently the only way of managing influenza in young infants for whom influenza vaccines are not licensed, but little data exist on the effectiveness of the treatment in this age group.MethodsIn a prospective study, we enrolled 431 newborn infants and followed them up for 10 months during their first respiratory season (September 2017‐June 2018). During each respiratory illness, we examined the infants and obtained nasopharyngeal specimens for determination of the viral etiology. Infants with influenza were re‐examined at short intervals, and additional nasopharyngeal specimens were obtained at each visit for measuring the viral load. All infants with symptoms <48 hours received oseltamivir treatment. The parents filled out daily symptom diaries.ResultsAmong 23 infants with influenza A, the mean total duration of illness in oseltamivir recipients was 82.1 hours, compared with 253.5 hours in infants without treatment (P = .0003). For infants with influenza B, the corresponding durations were 110.0 and 173.9 hours, respectively (P = .03). In infants with influenza A, total symptom scores were significantly lower in oseltamivir‐treated infants at all time points between days 3 and 11 after the onset of therapy. In most children with either influenza A or B, viral antigen concentrations declined rapidly within 1‐2 days after the initiation of oseltamivir treatment.ConclusionsOseltamivir treatment of infants with influenza rapidly decreased the viral load in nasopharyngeal secretions and shortened the duration and severity of symptoms. The clinical effectiveness of oseltamivir appeared to be greater against influenza A than against influenza B infections.

Influenza hospitalizations in children under 1 year old in Spain: the importance of maternal immunization

ABSTRACT This study estimates the burden of influenza in infants up to 12 months of age in Spain over 8 seasons (2009/10-2016/17). The survey was conducted by reviewing the Spanish Surveillance System for Hospital Data. Over the eight seasons, 5,618 hospital admissions were recorded for patients younger than 12 months that included codes related to influenza in any diagnostic position (487–488 ICD-9-CM and J9, J10 and J11 CIE 10). In total, 2,363 admissions (42.1%) were female patients whose median age was 3.05 months. Patients younger than 6 months accounted for 3,856 admissions (68.6%). Among them, 59.2% were male, and 40.8% were female (p < .05). Overall, 37.1% (2,084 patients) were younger than 2 months. The hospitalization rate for the entire period studied was 156.09 admissions per 100,000 children under 12 months of age (95% CI: 152.4–160.6). The average duration of hospitalization was 6.6 days (95% CI: 6.4–6.8). Eighteen deaths were recorded for hospitalized patients over the entire period. Of these, 12 patients (66.7%) were younger than 6 months. There is a significant burden of influenza disease in children under 1 year of age in Spain, mainly in children under 6 months of age. Improvements to prevention strategies through increased vaccination coverage in family environments and vaccination strategies involving pregnant woman can contribute decisively and effectively to reducing these hospitalizations.

Global Collaborative Research Informs Wise Use of Tests and Antibiotics for Bronchiolitis.

Bronchiolitis is a lower respiratory viral infection that is a leading cause of hospitalization for infants.1 Organizations around the world have published guidelines for bronchiolitis to address widely varying rates of tests and treatments within their countries.2 Specific recommendations vary, but research consistently shows that many of these interventions are unnecessary and may cause unwarranted cost and the potential for harm because of associated radiation, antibiotic exposure, and other effects. In this issue of Pediatrics, Zipursky et al3 analyze testing protocols at a higher level by comparing trends across countries using a retrospective data set from the Pediatric Emergency Research Network (PERN), which combines 6 multicenter networks including 38 emergency departments from 8 countries in North America, Europe, the United Kingdom, Australia, and New Zealand. Authors of previous analyses addressed respiratory treatments4 and prediction of severe disease,5 but in this study, the investigators focus on antibiotics and laboratory testing. They report that 32.6% of infants received a nonindicated test, with rates varying widely between networks. Antibiotic use was overall low (7.6%) and was associated with ordering a chest radiograph.Retrospective analysis of clinical practice has limitations, in particular for testing and antibiotic use for bronchiolitis. The authors reviewed charts based on diagnosis codes, which may be differentially assigned on the basis of the results of a test. For example, a bronchiolitis diagnosis may change to pneumonia on the basis of a chest radiograph result. Schuh et al6 demonstrated in a prospective cohort that routinely obtaining a radiograph led clinicians to make pneumonia diagnoses that radiology review did not support and to prescribe antibiotics that did not appear to benefit patients. Zipursky et al,3 in their multicenter study, similarly find that radiograph use was associated with antibiotic prescription, and the network in the United Kingdom and Ireland had the lowest rates for both laboratory testing and antibiotic use. Assignment of diagnosis codes may also vary because of different definitions of the condition. In the United Kingdom, the definition of bronchiolitis, as reflected in their national guidelines,7 has consistently included the presence of crackles as a specific sign, whereas in North America, the definition for research studies and clinical guidelines has typically focused on wheeze.8 Perhaps clinicians in the United Kingdom accept the presence of crackles as an expected finding in an infant with bronchiolitis and are less likely to order imaging. Further researchers could look at outcomes to follow the impact of international variation in practice, although quality improvement collaborative networks within the United States have already shown that radiography can be safely reduced for bronchiolitis without negatively impacting outcomes.9Despite these limitations, comparing trends across countries can help us to better evaluate practice and drive further research. In the PERN study, respiratory viral testing led the nonindicated laboratory list in frequency, despite practice guidelines recommending against its routine use, because identifying a specific virus rarely changes management.2 However, evolving recommendations for broad testing and treatment of influenza in febrile infants, which is a rare cause (<2%) in cohort studies of typical bronchiolitis,10 and the now evolving severe acute respiratory syndrome coronavirus 2 pandemic will require these questions to be re-examined. Coronaviruses have always been a cause of bronchiolitis hospitalizations, and the PERN network is currently conducting an international prospective study that will help assess pediatric disease related to the new viral strain.11 Among other tests, Zipursky et al3 also found that urinalysis and urine cultures were obtained at a measurable rate, even in afebrile infants, although recent reviews suggest that urinary tract infection is uncommon in bronchiolitis using updated guidelines for screening.12The PERN collaboration of international networks of pediatric emergency providers is an encouraging sign of potential opportunities to come, for bronchiolitis and other conditions. In addition to studying variation, the ability to leverage large populations across the globe will provide the ability to study evolving conditions, as occurred with the H1N1 influenza virus and now severe acute respiratory syndrome coronavirus 2, as well as uncommon conditions, as is planned with severe asthma.13,14 As clinical practice becomes more standardized within countries because of national guidelines and quality improvement initiatives, such as the Choosing Wisely campaign, the ability to compare across countries is an opportunity to evaluate variation that can lead to innovation.15,16 Building on these research networks to link data to other sources could allow further analysis of the impact of variation across countries, connect these practices to health outcomes, and help us to make the wisest choices as a global pediatric community.

PENGARUH METODE EKSTRAKSI KENCUR (Kaempferia galanga L.) TERHADAP PERTUMBUHAN Staphylococcus aureus

Kaempferia galanga L. or known as Kencur is an herbal plant that is widely used by people with various benefits such as influenza in infants, headaches, sprains, relieving fatigue, inflammation of the stomach, coughing, improving menstruation, inflammation of children's ears, dirty blood, eyes aches, diarrhea, and colds. However, studies that have used Kencur as an antibacterial against Staphylococcus aureus have never been done. Therefore, scientific research is needed to determine the ability of Kencur extract as an antibacterial that inhibits the growth of Staphylococcus aureus. 3 extraction methods were used, with the aim of determining the right method for obtaining Kencur bioactive compounds as antibacterial. The three extraction methods used were the press method, the infusion method, and the maceration method using methanol as a solvent. Each extract obtained from various extraction methods will be tested for antibacterial by observing the growth of Staphylococcus aureus. It was found that with the press method there were no clear zones or growth inhibition zones of Staphylococcus aureus. Using the extract from the infusion method, the same thing is obtained, namely there is no clear zone or growth inhibition zone of Staphylococcus aureus. However, it is different when given an extract from the maceration method using methanol solvent, a 17 mm clear zone is formed but there is no inhibition zone. This can indicate that, methanol extract from Kencur can inhibit the growth of Staphylococcus aureus (17 mm).

Assessment of Effectiveness of Seasonal Influenza Vaccination During Pregnancy in Preventing Influenza Infection in Infants in England, 2013-2014 and 2014-2015.

Maternal influenza vaccination is increasingly recognized to protect infants from influenza infection in their first 6 months. We used the screening method to estimate vaccine effectiveness (VE) against laboratory-confirmed influenza in infants in England, using newly available uptake data from the Clinical Practice Research Datalink pregnancy register, matched on week of birth and region and adjusted for ethnicity. We found VE of 66% (95% confidence interval [CI], 18%-84%) in the 2013-2014 season and 50% (95% CI, 11%-72%) in 2014-2015, with similar VE against influenza-related hospitalization. VE against the dominant circulating influenza strain was higher, at 78% (95% CI, 16%-94%) against H1N1 in 2013-2014, and 60% (95% CI, 16%-81%) against H3N2 in 2014-2015.

Benefit of Inactivated Influenza Vaccine in Infants in Iran: A Community based Randomized Control Trial

Background: Influenza in infants and young children is a major medical problem which causes excess medical visits, antibiotic prescriptions and hospitalization even in otherwise healthy children. Many of the developed countries have recommended influenza vaccination for all children (>6month old), but the economic benefit of this strategy is not clear especially for developing countries. Objectives: To find the difference in the incidence of influenza-like illness (ILI) and economic cost related to it between TIV vaccinated and non-vaccinated infants in Mashhad, Iran. Methods: This was a community randomized controlled trial which was started in November 2005 and ended up at May 2006. Each of the study and control groups were composed of 500 infants between 6 month and 20 months old who were brought for routine vaccination. The study group was given two doses of TIV; the control group received routine care without any extra intervention. Both groups were followed by monthly telephone calls (up to six months after the vaccination) and were asked about signs and symptoms of flu like illnesses and any cost related to them. SPSS 11.5 was used for statistical analysis, P

Changes in trends and impact of testing for influenza in infants with fever

Infants aged <90days who present with fever commonly undergo various invasive procedures due to the risk of bacterial infection in this age group. A great proportion of cases, however, are due to viral infection, including influenza. The aim of this study was therefore to assess the impact of influenza testing in infants <90days with fever, as well as analyze the subject characteristics to identify which infants should be considered for such testing. Clinical characteristics and trends in influenza virus testing and treatment were analyzed among febrile infants <90days who presented to the emergency room and were diagnosed with influenza during 2005-2015. Among 5,347 febrile infants aged <90days, 963 (18%) underwent influenza virus test. A total of 114 (11.8%) were diagnosed with influenza. The positivity rate reached 67% of febrile infants during epidemics. Of them, 83 had a history of family contact. While more than half presented with upper respiratory symptoms, 34% had only fever without respiratory symptoms. A decrease in antibiotic use and admission rates during the study period among infants diagnosed with influenza was seen (P for trend <0.05). During the influenza epidemic season, diagnostic tests for influenza based on a detailed contact history are necessary in assessing the cause of fever. Targeted testing for influenza may lead to a decrease in antibiotic use and admission rates in young infants.

Year-round influenza immunisation during pregnancy in Nepal: a phase 4, randomised, placebo-controlled trial

Influenza immunisation during pregnancy is recommended but not widely implemented in some low-income regions. We assessed the safety and efficacy in mothers and infants of year-round maternal influenza immunisation in Nepal, where influenza viruses circulate throughout the year. In this phase 4, randomised, placebo-controlled trial, we enrolled two consecutive sequential annual cohorts of pregnant women from the Sarlahi district in southern Nepal. We randomised mothers 1:1 to receive seasonally recommended trivalent inactivated influenza vaccine or saline placebo in blocks of eight, stratified by gestational age at enrolment (17-25 weeks vs 26-34 weeks). Women were eligible if they were married, 15-40 years of age, 17-34 weeks' gestation at enrolment, and had not previously received any influenza vaccine that season. We collected serum samples before and after immunisation, and cord blood from a subset of women and infants. Staff masked to allocation made home visits every week from enrolment to 6 months after delivery. Midnasal swabs for respiratory virus PCR testing were collected during maternal acute febrile respiratory infections, and from infants with any respiratory symptom. We assessed vaccine immunogenicity, safety, and three primary outcomes: the incidence of maternal influenza-like illness in pregnancy and 0-180 days postpartum, the incidence of low birthweight (<2500 g), and the incidence of laboratory-confirmed infant influenza disease from 0 to 180 days. This trial is registered with ClinicalTrials.gov, number NCT01034254. From April 25, 2011, to Sept 9, 2013, we enrolled 3693 women in two cohorts of 2090 (1041 assigned to placebo and 1049 to vaccine) and 1603 (805 assigned to placebo and 798 to vaccine), with 3646 liveborn infants (cohort 1, 999 in placebo group and 1010 in vaccine group; cohort 2, 805 in placebo group and 798 in vaccine group). Immunisation reduced maternal febrile influenza-like illness with an overall efficacy of 19% (95% CI 1 to 34) in the combined cohorts; 9% efficacy (-16 to 29) in the first cohort, and 36% efficacy (9 to 55) in the second cohort. For laboratory-confirmed influenza infections in infants aged 0-6 months, immunisation had an overall efficacy for the combined cohorts of 30% (95% CI 5 to 48); in the first cohort, the efficacy was 16% (-19 to 41), and in the second cohort it was 60% (26 to 88). Maternal immunisation reduced the rates of low birthweight by 15% (95% CI 3-25) in both cohorts combined. The rate of small for gestational age infants was not modified by immunisation. The number of adverse events was similar regardless of immunisation status. Miscarriage occurred in three (0·2%) participants in the placebo group versus five (0·3%) in the vaccine group, stillbirth occurred in 31 (1·7%) versus 33 (1·8%), and congenital defects occurred in 18 (1·0%) versus 20 (1·1%). Five women died in the placebo group and three died in the vaccine group. The number of infant deaths at age 0-6 months was similar in each group (50 in the placebo group and 61 in the vaccine group). No serious adverse events were associated with receipt of immunisation. Year-round maternal influenza immunisation significantly reduced maternal influenza-like illness, influenza in infants, and low birthweight over the entire course of the study, indicating the strategy could be useful in subtropical regions. Bill & Melinda Gates Foundation.

PANDEMIC INFLUENZA A (H1N1) PDM 09 IN THE SEASON 2015/2016: ANALYSIS OF FATAL OUTCOMES IN CHILDREN

The analysis of the characteristics of the current influenza A(H1N1) pdm 09 at 624 children in the 2015/2016 season. For severe illness (5%) characterized by short incubation period, lack of initial period, acute or acute onset with rapid development of multiorgan failure, prolonged febrile body temperature (up to 5—6 days or more) in the absence of complications, a prolonged severe intoxication (4—5 days or more), a significant frequency of diarrhea syndrome (10,2%), hemorrhagic syndrome (5.3%), exacerbation of comorbidity (20%), combined with other viral infections — herpes, rotavirus, enterovirus and others (33%). In the clinical analysis of blood — leukopenia (33.9%), leukocytosis (14.5%) with neutrophilic shift (11.3%), neutrophilia (51.6%), monocytosis (45.2%), lymphocytosis (9.7%), thrombocytopenia, anemia, accelerated erythrocyte sedimentation rate moderately; in the biochemical analysis of blood, hypernatremia, increase in the concentration of lactate, hyperfermentemia (ALT, AST, ALP, LDH, CPK), hypoproteinemia, dysproteinemia, increased CRP, increased creatinine and urea, increase of procalcitonin (PCT). In the structure of complications of pneumonia was 6%, stenosing laryngotracheitis — 9.8%, obstructive bronchitis — 14.5%. Two unvaccinated against influenza in infants who become ill during the epidemic period for influenza and SARS from homes with a typical clinical picture, died from severe (toxic) form of pandemic influenza. Pandemic influenza occurred at the background of severe immunosuppression (atrophy of the thymus, depletion of follicles of peripheral organs of immunogenesis — spleen, lymph nodes, tonsils). The main cause of death was the development of multiple organ failure with rapid progressive lesion of the vital organs.

Maternal influenza immunisation in resource-limited settings

Pregnant women and young infants are at high risk of developing severe infl uenza. 1,2 Among infants, those younger than 6 months have the highest risk of developing complications associated with infl uenza; 3 however, antiviral treatments and infl uenza vaccines are not approved in this age group. Given that infl uenza vaccines administered to pregnant women have shown a good safety profi le 4 and effi cacy to prevent infl uenza in infants younger than 6 months, 5,6 maternal immunisation seems to be an important strategy to protect both pregnant women and their infants. WHO targets seasonal infl uenza vaccination of pregnant women as a high priority. 7 Most high-income countries recommend maternal infl uenza immunisation to reduce the burden of infl uenza in the pregnant woman and her infant. 8 However, additional data are needed to support decisions about introduction of infl uenza vaccine in pregnant women in resource-limited settings. The Bill & Melinda Gates Foundation funded three large trials in South Africa, Mali, and Nepal, with the objective of increasing the evidence base for the eff ect of maternal infl uenza immunisation. 9 In The Lancet Infectious Diseases, Milagritos D Tapias and colleagues 10 report results of the trial done in Mali—a poorly-resourced country with high infant and maternal mortality. This is the largest randomised controlled trial evaluating the effi cacy, safety, and immuno genicity of trivalent inactivated infl uenza vaccine administered to third-trimester pregnant women to prevent infl uenza in infants younger than 6 months. 4193 women were immunised: 2018 with tri valent inactivated infl uenza vaccine and 2085 with conjugate quadrivalent meningococcal vaccine. Vaccine effi cacy against fi rst-episode laboratory confi rmed infl uenza in infants (the primary outcome) was 33·1% (95% CI 3·7–53·9) in infants born to women immunised at any time prepartum (intention-to-treat analysis), and 37·3% (7·6–57·8) in those born to women vaccinated at least 14 days prepartum (per-protocol analysis). Among participating women, vaccine effi cacy was 70·3% (95% CI 42·2–85·8) overall, 76·6% (28·4–94·3) in pregnant women, and 70·1% (28·0–89·1) in the post-partum period. There was no benefi cial eff ect of the trivalent inactivated infl uenza vaccine on birthweight. The technical and logistical feasibility of implementation of a new maternal immunisation programme was also shown with a high rate of recruitment among eligible women. Evidence of the effi cacy of maternal infl uenza immunisation to prevent infl uenza in infants in low-income countries from this trial is convincing and in agreement with fi ndings from the two previously reported randomised trials from Bangladesh (63% vaccine effi cacy, 95% CI 5–85) 5 and South Africa (48·8%, 11·6–70·4).

Maternal immunisation with trivalent inactivated influenza vaccine for prevention of influenza in infants in Mali: a prospective, active-controlled, observer-blind, randomised phase 4 trial

SummaryBackgroundDespite the heightened risk of serious influenza during infancy, vaccination is not recommended in infants younger than 6 months. We aimed to assess the safety, immunogenicity, and efficacy of maternal immunisation with trivalent inactivated influenza vaccine for protection of infants against a first episode of laboratory-confirmed influenza.MethodsWe did this prospective, active-controlled, observer-blind, randomised phase 4 trial at six referral centres and community health centres in Bamako, Mali. Third-trimester pregnant women (≥28 weeks' gestation) were randomly assigned (1:1), via a computer-generated, centre-specific list with alternate block sizes of six or 12, to receive either trivalent inactivated influenza vaccine or quadrivalent meningococcal vaccine. Study personnel administering vaccines were not masked to treatment allocation, but allocation was concealed from clinicians, laboratory personnel, and participants. Infants were visited weekly until age 6 months to detect influenza-like illness; laboratory-confirmed influenza diagnosed with RT-PCR. We assessed two coprimary objectives: vaccine efficacy against laboratory-confirmed influenza in infants born to women immunised any time prepartum (intention-to-treat population), and vaccine efficacy in infants born to women immunised at least 14 days prepartum (per-protocol population). The primary outcome was the occurrence of a first case of laboratory-confirmed influenza by age 6 months. This trial is registered with ClinicalTrials.gov, number NCT01430689.FindingsWe did this trial from Sept 12, 2011, to Jan 28, 2014. Between Sept 12, 2011, and April 18, 2013, we randomly assigned 4193 women to receive trivalent inactivated influenza vaccine (n=2108) or quadrivalent meningococcal vaccine (n=2085). There were 4105 livebirths; 1797 (87%) of 2064 infants in the trivalent inactivated influenza vaccine group and 1793 (88%) of 2041 infants in the quadrivalent meningococcal vaccine group were followed up until age 6 months. We recorded 5279 influenza-like illness episodes in 2789 (68%) infants, of which 131 (2%) episodes were laboratory-confirmed influenza. 129 (98%) cases of laboratory-confirmed influenza were first episodes (n=77 in the quadrivalent meningococcal vaccine group vs n=52 in the trivalent inactivated influenza vaccine group). In the intention-to-treat population, overall infant vaccine efficacy was 33·1% (95% CI 3·7–53·9); in the per-protocol population, vaccine efficacy was 37·3% (7·6–57·8). Vaccine efficacy remained robust during the first 4 months of follow-up (67·9% [95% CI 35·1–85·3] by intention to treat and 70·2% [35·7–87·6] by per protocol), before diminishing during the fifth month (57·3% [30·6–74·4] and 60·7 [33·8–77·5], respectively). Adverse event rates in women and infants were similar among groups. Pain at the injection site was more common in women given quadrivalent meningococcal vaccine than in those given trivalent inactivated influenza vaccine (n=253 vs n=132; p<0·0001), although 354 [92%] reactions were mild. Obstetrical and non-obstetrical serious adverse events were reported in 60 (3%) women in the quadrivalent meningococcal vaccine group and 61 (3%) women in the trivalent inactivated influenza vaccine group. Presumed neonatal infection was more common in infants in the trivalent inactivated influenza vaccine group than in those in the quadrivalent meningococcal vaccine group (n=60 vs n=37; p=0·02). No serious adverse events were related to vaccination.InterpretationVaccination of pregnant women with trivalent inactivated influenza vaccine in Mali—a poorly resourced country with high infant mortality—was technically and logistically feasible and protected infants from laboratory-confirmed influenza for 4 months. With adequate financing to procure the vaccine, implementation will parallel the access to antenatal care and immunisation coverage of pregnant women with tetanus toxoid.FundingBill & Melinda Gates Foundation.

Burden of Influenza and Respiratory Syncytial Virus Infection in Pregnant Women and Infants Under 6 Months in Mongolia: A Prospective Cohort Study.

BackgroundPregnant women and infants under 6 months are at risk of influenza-related complications. Limited information exists on their community burden of respiratory viruses.Methods and FindingsThis prospective, observational open cohort study was conducted in Baganuur district, Ulaanbaatar, Mongolia during 2013/14 and 2014/15 influenza seasons. Influenza-like illness (ILI) and severe acute respiratory infection (sARI) were identified by follow-up calls twice a week. For those identified, influenza and respiratory syncytical virus (RSV) were tested by point-of-care test kits. We calculated overall and stratified (by trimester or age group) incidence rates (IR) and used Cox proportional hazard regression for risk factor analyses. Among 1260 unvaccinated pregnant women enrolled, overall IRs for ILI, sARI and influenza A were 11.8 (95% confidence interval (C.I):11.2–12.4), 0.1 (95%C.I:0.0–0.4), and 1.7 (95%C.I:1.5–1.9) per 1,000person-days, respectively. One sARI case was influenza A positive. IRs and adjusted hazard ratios (Adj.HR) for ILI and influenza A were lowest in the third trimester. Those with co-morbidity were 1.4 times more likely to develop ILI [Adj.HR:1.4 (95%C.I:1.1–1.9)]. Among 1304 infants enrolled, overall ILI and sARI IRs were 15.2 (95%C.I:14.5–15.8) and 20.5 (95%C.I:19.7–21.3) per 1,000person-days, respectively. From the tested ILI (77.6%) and sARI (30.6%) cases, the overall positivity rates were 6.3% (influenza A), 1.1% (influenza B) and 9.3% (RSV). Positivity rates of influenza A and RSV tend to increase with age. sARI cases were 1.4 times more likely to be male [Adj.HR:1.4 (95%C.I:1.1–1.8)]. Among all influenza A and RSV positive infants, 11.8% and 68.0% were respectively identified among sARI hospitalized cases.ConclusionWe observed low overall influenza A burden in both groups, though underestimation was likely due to point-of-care tests used. For infants, RSV burden was more significant than influenza A. These findings would be useful for establishing control strategies for both viruses in Mongolia.