Immunogenicity and tolerability of a quadrivalent meningococcal glycoconjugate vaccine in children 2–10 years of age

Meningococcal disease incidence is highest in infants, but a significant burden of disease also occurs in children. In this Phase II, single-centre US study, 619 healthy children (2–10 years of age) received one dose of an investigational quadrivalent meningococcal CRM₁₉₇-conjugated vaccine (MenACWY-CRM) or a licensed quadrivalent meningococcal polysaccharide vaccine (MPSV4). Immunogenicity was assessed using the serum bactericidal assay with human complement (hSBA) at 1 and 12 months post-vaccination. Local and systemic reactions were recorded for 7 days, all adverse events (AEs) for 1 month, and medically significant and serious AEs (SAEs) for 12 months post-vaccination. For all four serogroups, more MenACWY-CRM recipients achieved an hSBA titre ≥1:4 at 1 month post-vaccination (A: 82%; C: 83%; W-135: 95%; Y: 91%) compared with the group that received MPSV4 (A: 45%; C: 66%; W-135: 71%; Y: 61%); this difference persisted through to 12 months post-vaccination. Both vaccines were well tolerated. In children 2–10 years of age, MenACWY-CRM induced a higher immune response than that of MPSV4, and was well tolerated.     

Per- and polyfluoroalkyl substances in sera from children 3 to 11 years of age participating in the National Health and Nutrition Examination Survey 2013–2014

Several per- and polyfluoroalkyl substances (PFAS) have been measured in U.S. National Health and Nutrition Examination Survey (NHANES) participants 12 years of age and older since 1999–2000, but PFAS data using NHANES individual samples among children younger than 12 years do not exist. To obtain the first nationally representative PFAS exposure data in U.S. children, we quantified serum concentrations of 14 PFAS including perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA), in a nationally representative subsample of 639 3–11 year old participants in NHANES 2013–2014. We used on-line solid-phase extraction coupled to isotope dilution-high performance liquid chromatography-tandem mass spectrometry; limits of detection were 0.1 ng/mL for all analytes. We calculated geometric mean concentrations, determined weighted Pearson correlations, and used linear regression to evaluate associations of sex, age (3–5 vs 6–11 years), race/ethnicity (Hispanic vs non-Hispanic), household income, and body mass index with concentrations of PFAS detected in more than 60% of participants. We detected PFOS, PFOA, PFHxS, and PFNA in all children at concentrations similar to those of NHANES 2013–2014 adolescents and adults, suggesting prevalent exposure to these PFAS or their precursors among U.S. 3–11 year old children, most of whom were born after the phase out of PFOS in the United States in 2002. PFAS concentration differences by sex, race/ethnicity, and age suggest lifestyle differences that may impact exposure, and highlight the importance of identifying exposure sources and of studying the environmental fate and transport of PFAS.     

Anti-pertussis antibody kinetics following DTaP-IPV booster vaccination in Norwegian children 7–8 years of age

At the age of 7–8 years a booster of diphtheria, tetanus, acellular pertussis and polio vaccine is recommended for children in Norway. In this cross-sectional study we have analysed the antibody levels against pertussis vaccine antigens in sera from 498 children aged 6–12 years. The purposes of this study were to investigate the duration of the booster response against the pertussis vaccine antigens pertussis toxin (PT) and filamentous haemagglutinin (FHA); to determine the presence of high levels of pertussis antibodies in absence of recent vaccination; and to analyse how booster immunisation may interfere with the serological pertussis diagnostics. Prior to the booster the IgG antibody levels against PT revealed a geometric mean of 7.3 IU/ml. After the booster the geometric mean peak anti-PT IgG response reached to 45.6 IU/ml, followed by a steady decline in antibody levels over the next few years. The IgG anti-FHA levels followed the anti-PT IgG profiles. Three years after the booster the geometric mean IgG levels were only slightly above pre-booster levels. Prior to the booster 44% of the sera contained ≤5 IU/ml of anti-PT IgG compared to18% 3 years after and 30% 4 years after the booster. When recently vaccinated children were excluded, 6.2% of the children had anti-PT IgG levels above 50 IU/ml which may indicate pertussis infection within the last 2 years. This study indicates that the currently used acellular pertussis vaccines induce moderate immune responses to the pertussis antigens and that the antibodies wane within few years after the booster. This lack of sustained immune response may partly be responsible for the increased number of pertussis cases observed in this age group during the last years.     

Rotavirus hospitalizations among children <5 years of age—Tajikistan, 2013–2014

BackgroundIn January 2015, Tajikistan introduced the monovalent rotavirus vaccine into the national immunization program. Our objective was to estimate pre-vaccine burden of rotavirus-associated hospitalizations in children <5 years of age in Tajikistan.MethodsDuring January 2013–December 2014, active surveillance for acute gastroenteritis (AGE)-associated hospitalizations in children <5 years of age was conducted by sentinel surveillance site staff. Patients’ demographic and clinical data were summarized and a stool sample was collected. An Enzyme Linked Immunosorbent Assay was used for diagnosis of rotavirus infection and subset of the specimens was sent for polymerase chain reaction (PCR) genotyping.ResultsOf 2860 eligible children enrolled and tested, 1207 (42%) were positive for rotavirus. An increase in the number and proportion of rotavirus cases attributed to rotavirus season, with positivity rates >40%, was annually observed during June–September.The median age of rotavirus patients was 9 months and 939/1207 (78%) rotavirus patients were aged 6–23 months. Most (1097/1203; 91%) rotavirus patients were treated with intravenous fluids. G1P[8] was the predominant genotype during both years of surveillance, accounting for 133/222 (60%) of genotyped cases.ConclusionRotavirus is a major cause of hospitalization due to severe AGE in children <5 years of age in Tajikistan, accounting for >40% of cases. Continued, enhanced rotavirus surveillance may allow documentation of changes in rotavirus disease burden following vaccine introduction and assessment of vaccine effectiveness.     

Use of tetanus-diphtheria (Td) vaccine in children 4–7 years of age: World Health Organization consultation of experts

For lifetime protection against diphtheria and tetanus, the World Health Organization (WHO) recommends six doses of diphtheria and tetanus containing vaccines. Td (reduced diphtheria toxoid, ≥2–5 IU) vaccines are currently licensed for ages 7 years and older, but use of Td vaccine for ages 4 years and older would have advantages for immunization programs in many low- and middle-income countries. For this reason, WHO convened an expert consultation to review the currently available evidence for the use of Td vaccine from 4 to 7 years of age which concluded: (1) no relevant biological difference in immune response in the relevant age group compared with children over 7 years of age; (2) adequate seroprotection in several studies with Td vaccine in the 4–7 age group and many studies using combination vaccines; (3) durable and protective response of at least 9–11 years duration in several longitudinal and modelling studies, (4) less reactogenicity compared with use of full-dose diphtheria vaccine, potentially improving the vaccination experience; and (5) adequate control of diphtheria in several countries using Td-containing combination vaccines in 4–7 year old children. On this basis, the experts concluded that from a programmatic perspective, Td vaccine given in ages 4–7 years, as a second booster dose in a six-dose series, would provide adequate protection against diphtheria and tetanus and recommended steps to include this change in age extension listed in the package insert.     

Rotavirus diarrhoea hospitalizations among children under 5 years of age in Nigeria, 2011–2016

BackgroundThe high burden of rotavirus acute gastroenteritis (AGE) is well documented among children under 5 years of age, with the majority of mortality occurring in developing countries. Nigeria ranked second worldwide in the number of rotavirus deaths in 2013. As Nigeria plans to introduce rotavirus vaccine soon, a pre-vaccine documentation of rotavirus disease burden is necessary to determine vaccine impact.MethodsRoutine rotavirus surveillance was conducted during 2011–2016 in 3 sentinel sites in Nigeria using the standard WHO protocol. Children under 5 years of age hospitalized for acute gastroenteritis were enrolled and demographic, clinical and outcome data were collected. A stool sample was subsequently obtained and tested for human rotavirus antigen using the Enzyme-linked immunosorbent assay (ELISA).Results2694 children with acute gastroenteritis were enrolled during January 2011 to December 2016; of these, 1242 (46%) tested positive for rotavirus. Among the rotavirus positive cases, 66% and 94% were younger than 12 months and 24 months respectively. Marked peaks in rotavirus positivity were seen in January of each year. Vomiting, and use of oral and intravenous fluids occurred more often in rotavirus positive cases as compared to rotavirus negative cases.ConclusionThe high prevalence of rotavirus disease highlights the need for urgent introduction of rotavirus vaccine in Nigeria. Additionally, this study provides pre-vaccine introduction disease-burden data that will serve as a baseline for rotavirus vaccine impact-assessment once vaccine has been introduced in the national immunization program.     

Early life factors and being overweight at 4 years of age among children in Malmö, Sweden

Background  

Rising rates of obesity and overweight is an increasing public health problem all over the world. Recent research has shown the importance of early life factors in the development of child overweight. However, to the best of our knowledge there are no studies investigating the potential synergistic effect of early life factors and presence of parental overweight on the development of child overweight.     

Predictors of influenza vaccination in the U.S. among children 9–13 years of age

Background and objectivesU.S. estimates of seasonal influenza (flu) vaccine uptake in 2014–2015 were 62% for 5–12 year olds, dropping to 47% for 13–17 year olds. The Healthy People 2020 goal for these age groups is 80%. It is important to understand factors associated with influenza vaccination, especially for those ages where rates begin to decline. The objective of this study was to identify factors associated with influenza vaccination acceptance in 9–13 year old children.MethodsAn online U.S. survey of mothers of children aged 9–13 assessed children's influenza vaccine uptake in the previous season, healthcare utilization, sociodemographics, and vaccine attitudes. Multivariable logistic regression identified independent predictors of influenza vaccine status.ResultsThere were 2363 respondents (Mean age = 38 years old). Referent children were 57% female and 66% non-minority race/ethnicity with a mean age of 10.6 years. By maternal report, 59% of children had received an influenza vaccine in the previous season. Predictors of influenza vaccine uptake included a recommendation or strong recommendation from a health care provider, seeing a health care provider in the past year, positive attitudes regarding the influenza vaccine, and being a minority race. Child gender, age, insurance coverage, and whether the child had a regular healthcare provider were not associated with influenza vaccine uptake (p = n.s.).ConclusionsThis sample reported overall rates of influenza vaccine uptake similar to national surveillance data, but still lower than national goals. Provider recommendations along with health attitudes and seeing a health care provider were associated with vaccine uptake. Promising interventions may include more directive physician messaging for influenza vaccine uptake in youth, encouraging more regular well-child visits during the adolescent years, and promoting influenza vaccination at alternative sites.     

Parental practices for prevention of home poisoning in children 1-6 years of age

On the basis of calls to the US poison control centers, each year more than 1 million children less than 5 years of age experience potentially toxic ingestions. Several prevention efforts and interventions have been tried to protect young children from poisonings occurring in their homes. The purpose of this study was to determine practices of parents and caregivers of children 1–6 years of age about home poisoning prevention. Seventy-six participants answered an anonymous survey. Caregivers demonstrated poor knowledge about the home poisoning prevention strategies. Only 20% of the participants knew the telephone number of the poison control center and 49% had it near the telephone in case of an emergency. This lack of knowledge was not related to gender, educational level, or occupation. Primary care physicians need to reinforce the orientation about poisoning prevention techniques to all caregivers in order to prevent accidental poisonings in small children.     

Safety and immunogenicity of a measles–mumps–rubella–varicella vaccine given as a second dose in children up to six years of age

Two doses of measles–mumps–rubella vaccine (MMR) are widely recommended and consideration is being given to a similar schedule for varicella vaccine. A combined measles–mumps–rubella–varicella vaccine (MMRV) could be considered for this second dose in children previously vaccinated separately with MMR and varicella vaccines. Healthy children (N = 390) aged 15–75 months (median 54 months) previously immunized with MMR and varicella vaccines were randomly allocated to receive MMRV or separate injections of MMR and varicella vaccines. Before administration of study vaccines, seropositivity rates were 96.4% for measles, 94.3% for mumps, 99.5% for rubella, and 97.9% for varicella. Post-immunization, seropositivity rates were 99.5% for measles and mumps and 100% for rubella and varicella in the MMR + varicella group and 100% for all four antigens in the MMRV group; a 26.2- and 27.2-fold increase in varicella titer was observed in the MMR + varicella vaccine and MMRV groups, respectively. Except for more frequent pain in the MMRV group (33.3% vs. 23.7%, p = 0.043), there were no differences in the incidence of local and solicited symptoms between groups. In children primed with MMR and varicella vaccine, MMRV had non-inferior immunogenicity and similar safety profiles as a second dose of licensed MMR and varicella vaccine administered concomitantly.     

Rotavirus diarrhea in hospitalized children under 5 years of age in Vientiane,Lao PDR, 2009–2015

BackgroundDiarrhea is a leading cause of death in children <5 years worldwide, causing an estimated 215,000 deaths in 2013. This evaluation tracks the epidemiologic patterns and most common rotavirus genotypes among hospitalized children in this age group with acute gastroenteritis in Lao PDR.MethodsChildren <5 years in a central tertiary hospital in the capital city were prospectively enrolled into the surveillance platform during January 2009—December 2015. We collected information regarding clinical characteristics of enrolled children. Stool samples were obtained within 24 h of hospital admission and tested for rotavirus using rotavirus antigen detection enzyme immunoassay. Samples were sent to the regional reference laboratories in Australia and South Korea for genotyping. Bivariate analyses compared demographic and clinical characteristics between rotavirus positive and negative children using Chi-square statistical testing. Seasonality of rotavirus and annual genotype distribution are also described.ResultsWe enrolled 1853 children <5 years with acute gastroenteritis during the surveillance period and collected 1772 fecal specimens, 982 (55%) of which tested positive for rotavirus. A higher proportion of rotavirus acute gastroenteritis was observed among children 12–23 months of age as compared to rotavirus negative children in the same age group, 41% vs 36%. Eighty-six percent of rotavirus positive children experienced vomiting, as compared to 65% of rotavirus negative children. Eighty-five percent (n = 830/982) of rotavirus positive specimens occurred during the dry season (January-April). The most common genotypes identified were G1, G2, G3 and P8 and P4. The most prevalent combined genotype differed annually during the surveillance period.ConclusionSurveillance continues to be important in documenting the burden of rotavirus in children <5 years in Lao PDR as well as providing a baseline for determining the impact of rotavirus vaccine once it is introduced into Lao PDR’s national immunization schedule.     

Nutritional status of school children aged 6–10 years in United Arab Emirates: Comparison with children from different ethnic origins

A field survey was conducted to study the nutritional status of UAE children in selected Emirates in United Arab Emirates (UAE) as compared to others of different ethnic groups and from different countries. Anthropometric data (weight and height) were collected on 1447 children aged 6–10 years from the UAE National population and from Egyptian, Jordanian, Sudanese, and Omani children living in the same country. The indices studied were weight for age, height for age, and weight for height. The cut‐off points used to indicate mild and moderate malnutrition were taken as values below ‐1 SD and ‐2 SD respectively of a reference population. The United States National Center for Health Statistics (NCHS) standards were used.

Results showed that children of UAE Nationals suffered from both stunting and wasting in the four Emirates studied with the highest prevalence in the Emirate of Ajman. Comparisons of anthropometric data for UAE children with those from other nationalities living in UAE, showed that ethnic origin affected the centile and Z‐score distribution of anthropometric indices. A higher percentage of Omani and UAE Nationals fell in the lower centile and Z‐score ranges as compared to children from other ethnic backgrounds. Within the UAE the observed overall levels of malnutrition could be attributed to noneconomic socio‐cultural factors which may also constitute important determinants explaining the differences in nutritional status between UAE Nationals and the other ethnic groups studied. Further studies are needed in order to identify the underlying nutritional and health factors which led to the observed pattern of growth.     

Incidence and epidemiology of intussusception among children under 2 years of age in Chenzhou and Kaifeng,China, 2009–2013

IntroductionIn China, rotavirus is the leading cause of diarrhea hospitalizations among children aged <5 years. A locally manufactured rotavirus vaccine is available for private market use, but little is known about its coverage. Given the impending availability of newer rotavirus vaccines, we evaluated intussusception rates among children aged <2 years to better understand intussusception epidemiology for future vaccine safety monitoring.MethodsWe conducted a retrospective review at 4 hospitals in Chenzhou City of Hunan Province and Kaifeng City of Henan Province. We identified intussusception cases admitted during 2009–2013 by reviewing medical records with the ICD-10 discharge code for intussusception and extracting demographic and clinical information from the electronic clinical record systems.ResultsDuring 2009–2013, 1715 intussusception hospitalizations among 1,487,215 children aged <2 years occurred in both cities. The average annual intussusception hospitalization incidence was 112.9 per 100,000 children aged <2 years (181.8 per 100,000 children <1 year; 56 per 100,000 children 1 to <2 years). Intussusception incidence was low among infants aged <3 months and peaked at age 6–8 months. No clear seasonality was observed. Ultrasound was used to diagnose 95.9% of cases. Enema reduction was performed in 80% cases; 25% of cases in Chenzhou and 16% in Kaifeng required surgical intervention. No deaths were reported. The median time between symptom onset and admission was 1 day.ConclusionsThis study provides information on intussusception incidence and epidemiology in two cities of China during 2009–2013. Monitoring intussusception rates in this population will be important in the post-rotavirus vaccine era.     

Vaccination status of children aged 1–4 years in Afghanistan and associated factors, 2015

BackgroundChildhood mortality in Afghanistan fell by half between 1990 and 2015, due in part to the government’s commitment to improving pediatric immunization services. Although progress has been made, immunization coverage has nonetheless remained low with only 65% of children receiving the third dose of Diphtheria-Pertussis-Tetanus (DPT3) based on WHO estimates. This study aims to calculate the proportion of Afghan children aged 1–4 years who were fully vaccinated, under-vaccinated, or non-vaccinated with government-recommended Expanded Program on Immunization vaccines and identify predictors related to the family’s sociodemographic status and maternal autonomy.MethodsData from the 2015 Afghanistan Demographic and Health Survey was used to calculate the proportion of children who were fully vaccinated (i.e. received all recommended vaccines), under-vaccinated (i.e. received some, but not all), and non-vaccinated (i.e. did not receive any vaccines) according to WHO guidelines. A multivariable multinomial logistic regression model generated odds ratios for under-vaccination and non-vaccination versus full vaccination, and examined associations between independent factors and full vaccination status.ResultsWe found 40.6% of Afghan children age 1–4 were fully vaccinated, 42.4% under-vaccinated, and 17% non-vaccinated. Large disparities characterized immunization coverage among provinces and between urban and rural regions. Birthing in a government institution (vs. non-institutional setting), a higher number of antenatal care visits, and a visit to a health facility in the past 12 months were all associated with increased odds of full immunization. Factors related to maternal autonomy including maternal decision-making and maternal attitudes towards beating were also significantly associated with vaccination status.ConclusionApproximately 60% of children in Afghanistan are under-vaccinated or non-vaccinated, leaving millions of children unnecessarily at risk for vaccine-preventable diseases. Engagement with community and religious leaders to create programs that increase women’s autonomy and expand access to institutional delivery could lead to downstream increases in childhood vaccination coverage.