Impact of the 13-valent pneumococcal conjugate vaccine (pcv13) on invasive pneumococcal disease and carriage in Alaska

BackgroundAlaska Native (AN) children have experienced high rates of invasive pneumococcal disease (IPD). In March 2010, PCV13 was introduced statewide in Alaska. We evaluated the impact of PCV13 on IPD in children and adults, 45 months after introduction.MethodsPneumococcal sterile site isolates, reported through state-wide surveillance, were serotyped using standard methods. We defined a pre-PCV13 time period 2005–2008 and post-PCV13 time period April 2010–December 2013; excluding Jan 2009–March 2010 because PCV13 was introduced pre-licensure in one high-risk region in 2009.ResultsAmong Alaska children <5 years, PCV13 serotypes comprised 65% of IPD in the pre-PCV13 period and 26% in the PCV13 period. Among all Alaska children <5 years, IPD rates decreased from 60.9 (pre) to 25.4 (post) per 100,000/year (P<0.001); PCV13 serotype IPD decreased from 37.7 to 6.4 (P<0.001). Among AN children <5 years, IPD rates decreased from 149.2 to 60.8 (P<0.001); PCV13 serotype IPD decreased from 87.0 to 17.4 (P<0.001); non-PCV13 serotype IPD did not change significantly. Among persons 5–17 and ≥45 years, the post-vaccine IPD rate was similar to the baseline period, but declined in persons 18–44 years (39%, P < 0.001); this decline was similar in AN and non-AN persons (38%, P = 0.016, 43%, P = 0.014, respectively).ConclusionsForty-five months after PCV13 introduction, overall IPD and PCV13-serotype IPD rates had decreased 58% and 83%, respectively, in Alaska children <5 years of age when compared with 2005–2008. We observed evidence of indirect effect among adults with a 39% reduction in IPD among persons 18–44 years.     

Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized,double-blind,placebo-controlled trial

BackgroundA randomized, double-blind, placebo-controlled multicenter trial was conducted in healthy Chinese infants to assess the efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RotaTeq™, RV5) against rotavirus gastroenteritis (RVGE).Methods4040 participants aged 6–12 weeks were enrolled and randomly assigned to either 3 oral doses of RV5 (n = 2020) or placebo (n = 2020), administered ∼4 weeks apart. The participants also received OPV and DTaP in a concomitant or staggered fashion. The primary objective was to evaluate vaccine efficacy (VE) against naturally-occurring RVGE at least 14 days following the third dose. Key secondary objectives included: VE against naturally-occurring severe RVGE and VE against severe and any-severity RVGE caused by rotavirus serotypes contained in the vaccine, occurring at least 14 days after the third dose. All adverse events (AEs) were collected for 30 days following each dose. Serious AEs (SAEs) and intussusception cases were collected during the entire study. (ClinicalTrials.gov registry: NCT02062385).ResultsVE against RVGE of any-severity caused by any serotype was 69.3% (95% CI: 54.5, 79.7). The secondary efficacy analysis showed an efficacy of: 78.9% (95% CI: 59.1, 90.1) against severe RVGE caused by any serotype; 69.9% (95% CI: 55.2, 80.3) and 78.9% (95% CI: 59.1, 90.1) against any-severity and severe RVGE caused by serotypes contained in the vaccine, respectively. Within 30 days following any vaccination, 53.5% (1079/2015) and 53.3% (1077/2019) of participants reported at least one AE, and 5.8% (116/2015) and 5.7% (116/2019) reported SAEs in the vaccine and placebo groups, respectively. No SAEs were considered vaccine-related in recipients of RV5. Two intussusception cases were reported in recipients of RV5 who recovered after receiving treatment. Neither was considered vaccine-related.ConclusionsIn Chinese infants, RV5 was efficacious against any-severity and severe RVGE caused by any serotype and generally well-tolerated with respect to AEs.     

Impact of rotavirus vaccine on all-cause diarrhea and rotavirus hospitalizations in Madagascar

BackgroundRotavirus vaccine was introduced into the Extended Program on Immunization in Madagascar in May 2014. We analyzed trends in prevalence of all cause diarrhea and rotavirus hospitalization in children <5 years of age before and after vaccine introduction and assessed trend of circulating rotavirus genotypes at Centre Hospitalier Universitaire Mère Enfant Tsaralalàna (CHU MET).MethodsFrom January 2010 to December 2016, we reviewed the admission logbook to observe the rate of hospitalization caused by gastroenteritis among 19619 children <5 years of age admitted at the hospital. In June 2013–December 2016, active rotavirus surveillance was also conducted at CHUMET with support from WHO. Rotavirus antigen was detected by EIA from stool specimen of children who are eligible for rotavirus gastroenteritis surveillance at sentinel site laboratory and rotavirus positive specimens were further genotyped at Regional Reference Laboratory by RT-PCR.ResultsDiarrhea hospitalizations decreased after rotavirus vaccine introduction. The median proportion of annual hospitalizations due to diarrhea was 26% (range: 31–22%) before vaccine introduction; the proportion was 25% the year of vaccine introduction, 17% in 2015 and 16% in 2016. Rotavirus positivity paralleled patterns observed in diarrhea. Before vaccine introduction, 56% of stool specimens tested positive for rotavirus; the percent positive was 13% in 2015, 12% in 2016. Diverse genotypes were detected in the pre-vaccine period; the most common were G3P[8] (n = 53; 66%), G2P[4] (n = 12; 15%), and G1P[8] (n = 11; 14%). 6 distinct genotypes were found in 2015; the most common genotype was G2P[4] (n = 10; 67%), the remaining, 5, G12[P8], G3[P8], G1G3[P4], G3G12[P4][P8] and G1G3[NT] had one positive specimen each.ConclusionsFollowing rotavirus vaccine introduction all-cause diarrhea and rotavirus-specific hospitalizations declined dramatically. The most common genotypes detected in the pre-vaccine period were G3P[8] and G2P[4] in 2015, the post vaccine period.     

Temporal association of rotavirus vaccination and genotype circulation in South Africa: Observations from 2002 to 2014

BackgroundRotavirus vaccination has reduced diarrhoeal morbidity and mortality globally. The monovalent rotavirus vaccine was introduced into the public immunization program in South Africa (SA) in 2009 and led to approximately 50% reduction in rotavirus hospitalization in young children. The aim of this study was to investigate the rotavirus genotype distribution in SA before and after vaccine introduction.Materials and methodsIn addition to pre-vaccine era surveillance conducted from 2002 to 2008 at Dr George Mukhari Hospital (DGM), rotavirus surveillance among children <5 years hospitalized for acute diarrhoea was established at seven sentinel sites in SA from April 2009 to December 2014. Stool specimens were screened by enzyme immunoassay and rotavirus positive specimens genotyped using standardised methods.ResultsAt DGM, there was a significant decrease in G1 strains from pre-vaccine introduction (34%; 479/1418; 2002–2009) compared to post-vaccine introduction (22%; 37/170; 2010–2014; p for trend <.001). Similarly, there was a significant increase in non-G1P[8] strains at this site (p for trend <.001). In expanded sentinel surveillance, when adjusted for age and site, the odds of rotavirus detection in hospitalized children with diarrhoea declined significantly from 2009 (46%; 423/917) to 2014 (22%; 205/939; p < .001). The odds of G1 detection declined significantly from 2009 (53%; 224/421) to 2010–2011 (26%; 183/703; aOR = 0.5; p < .001) and 2012–2014 (9%; 80/905; aOR = 0.1; p < .001). Non-G1P[8] strains showed a significant increase from 2009 (33%; 139/421) to 2012–2014 (52%; 473/905; aOR = 2.5; p < .001).ConclusionsRotavirus vaccination of children was associated with temporal changes in circulating genotypes. Despite these temporal changes in circulating genotypes, the overall reduction in rotavirus disease in South Africa remains significant.     

Impact of rotavirus vaccination on diarrhea-related hospitalizations in São Paulo State,Brazil

IntroductionFollowing introduction of routine infant rotavirus vaccination, severe diarrhea hospitalization rates declined among children aged <5 years throughout Brazil. Ensuring equity of rotavirus vaccine impact is important in countries that self-finance immunization programs. The objective of this study was to examine rotavirus vaccine impact on diarrhea admission rates among children aged <5 years in Brazil's public health system, according to area-based measures of human development in the state of São Paulo, Brazil.MethodsEcological analysis of public health system hospitalization rates for acute gastroenteritis among children aged <5 years in the state of São Paulo, Brazil, according to five categories of municipal development based on a modified Human Development Index for municipalities. Acute gastroenteritis hospitalization rates among children aged <5 years after national rotavirus vaccine introduction (2008–2011) were compared to rates in pre-vaccine years (2000–2005) to calculate percent decline in rates (1 − rate ratio) and 95% confidence intervals (CI) for each municipal development category. Direct hospitalization costs during the two periods were compared.ResultsAnnual rates declined by 40% (95% CI, 39–42%) from 631 diarrhea hospitalizations per 100,000 person years pre-rotavirus vaccination to 377 per 100,000 post-vaccination among children aged <5 years and 50% (95% CI, 48–52%) from 1009 to 505 per 100,000 among infants. Highest rates were observed in least developed municipalities. Significant declines of 26–52% among children <5 years and 41–63% among infants were observed in all categories of municipal development. Lower diarrhea hospitalization rates resulted in annual savings of approximately 2 million USD for the state of São Paulo. Savings in direct hospitalization costs benefitted municipalities in all five categories.ConclusionThe introduction of rotavirus vaccination was associated with substantial reductions of diarrhea-related admissions at all levels of municipal development in São Paulo State, Brazil.     

Impact of a publicly funded monovalent rotavirus vaccination program in the Province of Quebec (Canada)

In November 2011, the province of Quebec, Canada implemented a publicly funded rotavirus (RV) vaccination program using the monovalent RV vaccine (RV1). To assess its impact, trends in passive RV laboratory detection and Emergency Department (ED) visits for gastroenteritis (GE) at two pediatric centers were evaluated.MethodsRV tests performed were extracted from the virology laboratory databases and ED visits for GE between July 1, 2006 and June 30, 2013, from the ED databases of The Montreal Children's Hospital (MCH) and Centre Hospitalier Universitaire de Sherbrooke (CHUS). The percent positive RV tests over time and season duration were assessed using 5-week moving averages. We defined season start and end as the first two and the last two consecutive weeks where the percent positive RV tests were ≥10%, respectively.ResultsComparing the pre- and post-vaccination program periods, a decrease in the proportion of positive RV tests was seen: 15.9% vs. 5.1% (p < 0.001). Pre-vaccination program, RV seasons started between December and February, peaked in March or April and ended in May. In 2011–2012, the season started in March, peaked in April, and ended in May. In 2012–2013, the season lasted 3 weeks in May. ED visits for GE decreased post-introduction of the RV1 program: from 4.8% to 3.4% in 2011–2012, and 4.2% in 2012–13 (p < 0.001). In children <2 years of age, ED GE visits decreased from 7.5% to 4.8% in 2011–2012, and 5.2% in 2012–2013 (p < 0.001). Admissions for GE also decreased significantly from 0.41% of all ED visits to 0.14% in 2011–2012 and 0.22% in 2012–2013 (p < 0.005).ConclusionImplementation of a publicly funded RV vaccination program had a major impact on the epidemiology of RV infections in Quebec: RV seasons have started later and been of shorter duration, peak positives were fewer, and ED visits for GE decreased.     

Trends in mortality burden of hepatocellular carcinoma,cirrhosis, and fulminant hepatitis before and after roll-out of the first pilot vaccination program against hepatitis B in Peru: An analysis of death certificate data

The first pilot vaccination program against hepatitis B in Peru was implemented in the hyperendemic Abancay province in 1991. To assess the impact of vaccination on mortality rates of hepatitis B-related hepatocellular carcinoma (HCC), cirrhosis, and fulminant hepatitis, we compared mortality trends before (1960–1990) and after (1991–2012) roll-out of the vaccination program, using death certificate data from the Municipalidad Provincial de Abancay. Our results showed that, following program roll-out, the overall mortality rates (per 100,000 population) decreased from 9.20 to 3.30 for HCC (95% CI, 1.28–10.48%; P < 0.014), from 16.0 to 6.3 for cirrhosis (95% CI, 3.20–16.10%; P < 0.004), and from 34.80 to 1.28 for fulminant hepatitis (95% CI, 16.70–50.30%; P < 0.001). The absolute number of deaths attributable to cirrhosis (10 [8.80%] vs. 0.0%; P < 0.001) and fulminant hepatitis (83 [40.0%] vs. 5 [19.20%]; P < 0.026) decreased in 5–14-year-old children following vaccination. These findings showed reduced mortality rates of hepatitis B-related liver diseases, particularly cirrhosis and fulminant hepatitis in children under 15 years, following implementation of the vaccination program against hepatitis B.     

Impact of PCV7/PCV13 introduction on invasive pneumococcal disease (IPD) in young children: Comparison between meningitis and non-meningitis IPD

BackgroundThe worldwide introduction of pneumococcal conjugate vaccines (PCV) into National Immunization Programs resulted in rapid and substantial reduction of invasive pneumococcal disease (IPD) rates in children. However, the reduction of meningitis vs. non-meningitis IPD (nm-IPD) was not yet fully elucidated. We compared 7-valent and 13-valent PCV (PCV7 and PCV13) impact on pneumococcal-meningitis vs. nm-IPD in Israeli children <5 years.MethodsWe conducted an ongoing nationwide, prospective, population-based, active surveillance. PCV7 and PCV13 were implemented in Israel in July 2009 and November 2010, respectively. All pneumococcal isolates (blood and/or CSF) from IPD episodes in children <5 years from July 2000 through June 2015 were included. Extrapolation for missing serotypes (34.7% of all isolates) was conducted.Results4163 IPD cases were identified; 3739 nm-IPD (89.8%) and 424 meningitis (10.2%). During the pre-PCV period (2000–2008), children <12 months constituted 52.1% and 33.7% of meningitis and nm-IPD, respectively (p < 0.001). The respective proportions of non-PCV13 serotypes (non-VT) were 18.2% vs. 10.1%, (p < 0.001).Comparing the last study year (2014–2015) to the mean of pre-PCV period, meningitis incidence in children <5 years decreased non-significantly by 27%, while nm-IPD decreased significantly by 69%. Dynamic rates of meningitis and nm-IPD caused by PCV13 serotypes were similar, with 93% and 95% overall reductions, respectively. However, non-VT increased in meningitis relatively to nm-IPD, mainly in children <24 months. Serotype 12F rose sharply and significantly since 2009–2010 through 2014–2015 (28.6% of all non-VT meningitis in children <24 m).ConclusionsThe overall impact of PCV7/PCV13 in children <5 years in Israel was less prominent in meningitis than in nm-IPD. This could be attributed to the younger age of children with meningitis and differences in causative serotypes between the two groups, as the decline of the incidence of meningitis and nm-IPD caused by vaccine-serotypes is similar. Continuous monitoring of meningitis and nm-IPD is warranted.     

Decline of rotavirus-coded hospitalizations in children under 5 years: A report from Japan where rotavirus vaccines are self-financed

ObjectivesTo estimate the trend in incidence of rotavirus gastroenteritis (RVGE) hospitalization among children aged <5 years in Japan during pre- and post-vaccine periods (2009–2011 and 2012–2015).Study designThis retrospective observational study used a health insurance claims database (constructed by Japan Medical Data Center Co., Ltd.). Rotavirus vaccine became commercially available in 2011. We analyzed data of all children aged <5 years between January 2009 and December 2015. We estimated the incidence rate (IR) of RVGE hospitalization per 1000 person-years from 2009 to 2015 and incidence rate ratio (IRR) of post-vaccine years compared with the averaged pre-vaccine years. IRs and IRRs were also estimated by age group. Primary analysis was limited to the rotavirus season (January to June) of each year.ResultsThe IR was 6.3–9.3 in pre-vaccine years, 2.3 in 2014, and 3.0 in 2015; the decline was estimated to be 71% in 2014 and 61% in 2015 (p < 0.01). By age group, reduction in hospitalizations began in 2013 among children <1 year old, followed by children aged 1 to <5 years in 2014. In the 2014 season, a 65% reduction in RVGE hospitalization was observed in children aged 36 to <60 months, although this age group was unlikely to be vaccinated.ConclusionsA substantial decline of RVGE hospitalization in 2014 and its persistence was observed among children aged <5 years in Japan after introduction of rotavirus vaccine, although not included in the national immunization program. Indirect effects of rotavirus vaccination were suggested in the 2014 season.     

Release from drinking-age restrictions is associated with increases in alcohol-related motor vehicle collisions among young drivers in Canada

BackgroundAlcohol-related motor vehicle collisions (MVCs) are a key concern in current international debates about the effectiveness of minimum legal drinking age (MLDA) laws, but the majority of this literature is based on natural experiments involving MLDA changes occurring 2–4 decades ago.MethodsA regression-discontinuity approach was used to estimate the relation between Canadian drinking-age laws and population-based alcohol-related MVCs (n = 50,233) among drivers aged 15–23 years in Canada.ResultsIn comparison to male drivers slightly younger than the MLDA, those just older had immediate and abrupt increases in alcohol-related MVCs of 40.6% (95% CI 25.1%–56.6%; P < 0.001) in Ontario; 90.2% (95% CI 7.3%–171.2%; P = 0.033) in Manitoba; 21.6% (95% CI 8.5%–35.0%; P = 0.001) in British Columbia; and 27.3% (95% CI 10.9%–44.5%; P = 0.001) in Alberta; but also an unexpected significant decrease in the Northwest Territories of − 102.2% (95% CI − 120.7%–74.9%; P < 0.001). For females, release from MLDA restrictions was associated with increases in alcohol-related MVCs in Ontario [34.2% (95% CI 0.9%–68.0%; P = 0.044)] and Alberta [82.2% (95% CI 41.1%–125.1%; P < 0.001)]. Nationally, in comparison to male drivers slightly younger than the legislated MLDA, male drivers just older had significant increases immediately following the MLDA in alcohol-related severe MVCs [27.0% (95% CI 12.6%–41.7%, P < 0.001)] and alcohol-related fatal MVCs [53.4% (95% CI 2.4%–102.9%, P = 0.04)].ConclusionsRelease from Canadian drinking-age restrictions appears to be associated with immediate increases in alcohol-related fatal and non-fatal MVCs, especially among male drivers.     

The nucleotide changes within HBV core promoter/precore during the first 12 weeks of nucleos(t)ide treatment might be associated with a better virological response

ObjectivesWe aimed to study the dynamic changes of hepatitis B virus (HBV) core promoter/precore (CP/preC) sequences during antiviral treatment and their associations with virological responses.Materials and methodsThe baseline and 12-week CP/preC sequences (nts 1655–2014) were obtained from 52 chronic hepatitis B patients with positive hepatitis B e antigen (HBeAg), who received a 104-week lamivudine and adefovir dipivoxil combination therapy. The mutations within the CP/preC were analyzed against genotype specific reference sequences. The nucleotide change rates in individuals during therapy were analyzed in a pairwise comparison manner.ResultsThere was no significant difference of the mutation rate at each nucleotide site between baseline and week 12 of treatment (P > 0.05). The mutation rates of A1762T/G1764A and G1896A were found to decrease from 46.2% (24/52) at baseline to 36.5% (19/52) at week 12 (P = 0.426) and from 28.8% (15/52) to 21.2% (11/52) (P = 0.497), respectively. The nucleotide change rates varied from 0.0% - 7.8% in individuals [0.0% in Group 1 (N = 26); 0.3% - 7.8% in Group 2 (N = 26)] during the first 12-week treatment. HBV DNA levels in Group 2 were significantly lower than those in Group 1 throughout therapy (P < 0.01) (e.g., 1.5 ± 1.3 log₁₀ IU/ml vs. 2.6 ± 1.0 log₁₀ IU/ml at week 104, P = 0.001). At week 104 the rates of HBV DNA undetectable and HBeAg loss in Group 2 were significantly higher than those in Group 1 (P < 0.05). Along with the increased nucleotide change rates, the rate of HBV DNA undetectable at week 104 tended to increase (odds ratio = 0.323, 95% confidence interval = 0.138–0.758, P < 0.001).ConclusionOur findings suggested that the nucleotide changes within HBV CP/preC region during the first 12-week treatment might be associated with a better virological response.     

Low intake of vitamin A–rich foods among children,aged 12–35 months,in India: association with malnutrition,anemia, and missed child survival interventions

ObjectiveTo determine whether children in India who have a low intake of vitamin A–rich foods are at higher risk of malnutrition, anemia, and not receiving child health interventions.MethodsWe analyzed data from the India National Family Health Survey, 2005–2006.ResultsOf 17 847 children (41.9%), aged 12–35 months, 7020 did not receive vitamin A–rich foods, based on 24-h recall. The prevalence of stunting, severe stunting, underweight, and severe underweight among children who did and did not receive vitamin A–rich foods was, respectively, 52.5% versus 59.0%, 26.7% versus 32.9%, 43.8% versus 48.5%, and 17.9% versus 21.6% (all P < 0.0001). Children who did not receive vitamin A–rich foods were more likely to be anemic, not have completed childhood immunizations, and not to have received vitamin A supplementation in the previous 6 mo (all P < 0.0001). Maternal education of ≥10, 7–9, and 1–6 y, respectively, compared with no formal education was associated with the child receiving vitamin A–rich foods (odds ratio 1.41, 95% confidence interval 1.20–1,67, P < 0.0001; odds ratio 1.20, 95% confidence interval 1.04–1.37, P = 0.01; odds ratio 1.16, 95% confidence interval 1.02–1.32, P = 0.02) in a multivariate logistic regression model adjusting for maternal age, household size, socioeconomic status, and location.ConclusionChildren who did not receive vitamin A–rich foods were more likely to be malnourished and to have missed basic child health interventions, including vitamin A supplementation. Children were more likely to receive vitamin A–rich foods if their mothers had previously achieved higher primary or secondary education levels.     

Haemophilus influenzae type b carriage and burden of its related diseases in Chinese children: Systematic review and meta-analysis

BackgroundHaemophilus influenzae type b (Hib) is an important cause of invasive bacterial disease in children worldwide. The limited awareness of disease burden is a major barrier to the introduction of Hib vaccine into China’s National Immunization Program. Therefore, we conducted a systematic review and meta-analysis to estimate carriage of Hib and burden of its related diseases in Chinese children.MethodsWe systematically searched Pubmed, Web of Science, Ovid, Chinese National Knowledge Infrastructure (CNKI), and Wanfang databases for studies published up to December 31, 2016, reporting Hib carriage and burden of Hib diseases among children in Mainland China. Pooled estimates were obtained using random-effects models.ResultsWe included 27 studies with 15783 children across 14 provinces. The pooled carriage of Hib was 5.87% (95% CI 3.42–8.33) for healthy children. The pooled proportion of disease due to Hib were 4.06% (95% CI 3.29–4.83) for acute lower respiratory tract infection (ALRI) and 27.32% (95% CI 0.41–54.24) for bacterial meningitis. The proportion of ALRI caused by Hib was higher in northern China than that in the south. Significant heterogeneity was noted across and within regions (P < 0.001). After the induction of Hib vaccine, meta-regression showed that carriage of Hib changed little (P = 0.725), but the proportion of ALRI caused by Hib in children decreased (P < 0.001).ConclusionsHib carriage persists at low levels among children in China. The proportion of ALRI due to Hib infection decreased with year. Incorporation of Hib vaccine into the National Immunization Program could reduce the burden of Hib disease in China.     

The impact of 10-valent and 13-valent pneumococcal conjugate vaccines on hospitalization for pneumonia in children: A systematic review and meta-analysis

BackgroundThis systematic review and meta-analysis aimed at summarizing available data on the impact of PCV10 and PCV13 in reducing the incidence of CAP hospitalizations in children aged <5 years.MethodsA systematic search of the literature was conducted. We included time-series analyses and before-after studies, reporting the incidence of hospitalization for pneumonia in the periods before and after the introduction of PCV10 or PCV13 into the immunization program. Pooled estimates of Incidence Rate Ratio (IRR) were calculated by using a random-effects meta-analytic model. Results were stratified according to age-groups (<24 months and 24–59 months) and case definitions of pneumonia (clinically and radiologically confirmed pneumonia).ResultsA total of 1533 potentially relevant articles were identified. Of these, 12 articles were included in the analysis. In children aged <24 months, the meta-analysis showed a reduction of 17% (95%CI: 11–22%, p-value < 0.001) an of 31% (95%CI: 26–35%, p-value < 0.001) in the hospitalization rates respectively for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs.In children aged 24–59 months, the meta-analysis showed a reduction of 9% (95%CI: 5–14%, p-value < 0.001) and of 24% (95%CI: 12–33%, p-value < 0.001) in the hospitalization rates for clinically and radiologically confirmed pneumonia, respectively, after the introduction of the novel PCVs.High heterogeneity was detected among studies evaluating the hospitalization rate for clinically and radiologically confirmed pneumonia.ConclusionsThe results of this study revealed a significant impact of PCV10 and PCV13 in reducing the hospitalizations for pneumonia, particularly in children aged <24 months and for radiologically confirmed disease. Further appropriately designed studies, comparing the impact of PCV10 and PCV13, are needed in order to obtain solid data on which to establish future immunization strategies.     

Adiposity is not beneficial to bone mineral density in 0–5 year old Chinese children: The Jiangsu bone health study

ObjectiveData on obesity in relation to bone mineral density(BMD) in infants and preschool children were sparse in China. The objective of this study was to examine the associations between body mass index (BMI) and BMD.Subjects and methodsThis was a large population-based multicenter study in which the representative children aged 0–5 years were recruited from 13 Children’s Health Care Centers by a stratified cluster random-sampling method in Jiangsu Province, China. BMD was measured by using quantitative ultrasound. The association of BMD with BMI and obesity were evaluated using multiple linear regression and logistic regression analysis taking into account the effects of confounders. The relations between age, weight, height, BMI and BMD were analyzed by using Pearson’s correlation and further tested using partial correlation in the additive model.ResultsA total of 5,289 children (2786 boys and 2503 girls) were recruited. The BMD was positively linear relation with age, length/height, and was inversely linear relation with BMI (r = 0.711, P < 0.001; r = 0.727, P < 0.001; r = −0.318, P < 0.001, respectively). The BMD gradually increased when the weight was in the range within 21.2 kg, but started to gain slowlyand even decreased when the weight was over 21.2 kg. After adjusting for confounders, compared with control group, children with obesityhad higher odds of low BMD (OR 95%CI: 2.73 (1.57, 4.76), P < 0.001), the speed of sound (SOS)value in children with obesity was lower 47.45 (β = −47.45, 95%CI = −85.07, −9.83, P = 0.013).ConclusionsAdiposity was not advantageous for bone mineral density in 0-5-year-old Chinese children.     

Effects of rotavirus vaccine on all-cause acute gastroenteritis and rotavirus hospitalizations in Israel: A nationwide analysis

BackgroundIn December 2010, the pentavalent rotavirus vaccine (RotaTeq) was added to the national immunization program in Israel. The study aim was to examine national reductions in all-cause acute gastroenteritis (AGE) and rotavirus gastroenteritis (RVGE) hospitalizations among children aged 0–59 months following the introduction of universal rotavirus immunization in Israel.MethodsWe extracted data from the Israel National Hospital Discharge Database. Hospitalization rates were calculated by dividing the annual number of all-cause AGE and RVGE hospitalizations by the number of children aged 0–59 months residing Israel. To assess rate reductions, we compared the mean hospitalization rate for the pre-vaccine years (2002–2008) with that for the universal vaccination years (2011–2017). Interrupted time-series analyses were undertaken. During 2008–2010 rotavirus vaccines were partially available.ResultsA total of 131,116 AGE hospitalizations were reported, of which 13,111 (10.0%) were coded as RVGE hospitalizations. The average annual all-cause AGE hospitalization rate during the pre-vaccine period was 147.9 (95% CI 146.7–149.0) per 10,000 children aged 0–59 months, and declined by 38.7–53.0% during the universal vaccination years. The average annual pre-vaccine RVGE hospitalization rate was 16.9 (95% CI 16.5–17.3) per 10,000 children, and declined by 89.1% during 2016–2017.Findings from interrupted time-series analyses showed significant impact of introducing universal rotavirus immunization on the declines of all-cause AGE and RVGE hospitalizations rates. A multivariable Autoregressive Integrated Moving Average model showed that the variable “immunization period” was a significant predictor of RVGE hospitalizations (t = 7.3, p < 0.001) for the universal vaccination years.The declines in hospitalizations rates of all-cause AGE were lower among Arab children compared to Jewish children, but the declines in RVGE rates were similar between the groups.ConclusionsNational hospitalization data demonstrated substantial and consistent reductions in all-cause AGE and RVGE hospitalizations following the implementation of universal rotavirus vaccination program.     

Comparative incidence dynamics and serotypes of meningitis,bacteremic pneumonia and other-IPD in young children in the PCV era: Insights from Israeli surveillance studies

IntroductionWidespread introduction of pneumococcal conjugated vaccines (PCVs) impacted on invasive pneumococcal disease (IPD). However, IPD reduction may not be similar in all outcomes within IPD.We assessed PCV7/PCV13 impact on pneumococcal meningitis, bacteremic pneumonia (BP) and other (non-meningitis, non-pneumonia) IPD episodes in children <5 years in Israel.MethodsA prospective, population-based, active nationwide surveillance.All pneumococcal invasive episodes with positive blood/CSF cultures, July 2000 through June 2016, were included. Three sub-periods were defined: pre-PCV (2000–2008), PCV7 (2009–2011) and PCV13 (2014–2016). Incidence rate ratios (IRRs) were calculated.ResultsOverall, 4321 episodes were recorded; 456 (10.6%) meningitis, 1478 (34.2%) pneumonia and 2387 (55.2%) other-IPD.In the pre-PCV period, proportion of serotypes in PCV13, but not in PCV7 (mainly serotypes 1, 5 and 19A) was higher in BP (43.3%) compared with other-IPD episodes (32.8%, p < 0.001) and similar to that of meningitis (37.6%, p = 0.1). The proportion of episodes in children <12 months was higher in meningitis (52.1%) compared with pneumonia (23.2%) and other-IPD episodes (39.5%; p < 0.001 for both).The declines of the 3 entities were not similar; Meningitis rate non-significantly declined by 24% (IRR = 0.76; 95% CI 0.57–1.01), while BP and other-IPD rates significantly declined by 57% and 70%, respectively. In contrast to other entities, BP did not decline significantly after PCV7 introduction but started to decline only after PCV13 introduction.Rates of meningitis, pneumonia and other-IPD caused by PCV13-serotypes (VT13) substantially declined by 88%, 95% and 97%, respectively, comparing PCV13 and the pre-PCV periods. However, diseases caused by non-VT13 increased by 256%, 302% in meningitis and pneumonia, respectively, but only 116% in other-IPD.ConclusionsFollowing PCV7/PCV13 introduction, rates of episodes caused by VT13 were substantially reduced in all 3 groups. However, differences in age distribution, serotype replacement and specific serotype decrease suggest different pathogenesis and host susceptibility between the 3 entities.     

Overweight and obesity in Eastern Morocco: Prevalence and associated risk factors among high school students

BackgroundOverweight and obesity in children and adolescents have become a major public health problem affecting most countries worldwide. The purpose of the study was to assess the prevalence and risk factors of overweight and obesity among public high school students in Eastern Morocco.MethodsA cross-sectional survey was conducted between February and May 2014 among a sample of 2271 students (1086 girls and 1185 boys). References from the International Obesity Task Force (IOTF) were used to determine the prevalence of overweight and obesity.ResultsThe prevalence of overweight and obesity reached 12.2% (14.2% in girls vs 10.4% in boys, P < 0.01) and 3.0% (3.1% in girls vs 2.8% in boys), respectively. Risk factors associated with overweight and obesity were urban residence (OR = 1.76; [1.18–2.63]; P < 0.01), father's income ≥ 5000 MAD (OR = 1.32; [1.02–1.70]; P < 0.05), father's overweight (including obesity) (OR = 1.87; [1.38–2.54]; P < 0.001) and female sex (OR = 1.31; [1.02–1.68]; P < 0.05).ConclusionThe prevalence of overweight/obesity has reached an alarming rate among high school students in the Eastern region of Morocco. The findings of the present study suggest an urgent need to set up a strategy to prevent and combat this epidemic.     

A 13-year survey of pneumococcal nasopharyngeal carriage in children with acute otitis media following PCV7 and PCV13 implementation

BackgroundThis nasopharyngeal (NP) carriage surveillance study was requested by the European Agency for the Evaluation of Medicinal Products as a post-licensing commitment to determine whether the use of the pneumococcal conjugate vaccines (PCVs) including 7 then 13 valents (introduced in 2001 and 2010, respectively) caused a shift in the distribution of Streptococcus pneumoniae serotypes in children with acute otitis media and modified the resistance of this bacterial species to antibiotics.MethodsBetween 2001 and 2014, 121 pediatricians obtained nasopharyngeal swabs from children with acute otitis media aged 6–24 months. The swabs were analyzed by the French National Reference Centre for Pneumococci. Demographics, medical history and physical examination findings were recorded.ResultsOver the 13 years, among the 7991 enrolled patients, the proportion of PCV-vaccinated children (≥1 dose) increased (54.3–99.7%, p < 0.001). Overall, pneumococcal carriage was reduced from 71.2% to 56.2% from 2001 to 2014 (p < 0.001) and carriage of PCV7 serotypes (STs) from 44.5% to 1.2% (p < 0.001). The carriage of 6 additional STs plus 6C increased from 17.2% to 24.3% from 2001 to 2010 (p < 0.001) and decreased after PCV13 implementation (21.4–3.5%, p < 0.001). The proportion of ST 19A carriage increased from 8.6% to 15.8% from 2001 to 2010 (p < 0.001) and decreased to 1.2% in 2014. After PCV13 implementation, the most frequently carried non-PCV13 STs were ST 15B/C, 11A, 15A, and 35B. Penicillin non-susceptible pneumococcal strains decreased from 67.1% in 2001 to 33.1% in 2014 (p < 0.001).ConclusionsBy the number of patients enrolled and the duration, this study is the largest performed to date. It allows to demonstrate a strong impact of PCVs and to describe the complex dynamics of pneumococcal carriage during AOM. As pneumococcal carriage decreased during AOM, a reduction in the incidence of pneumococcal AOM could be expected.     

Evaluating the effectiveness of the universal immunization program against varicella in Japanese children

ObjectiveMatched case control study was conducted to elucidate the effectiveness of the Oka/Biken vaccine immediately after implementation of the universal immunization program in Japan.MethodsCases were laboratory confirmed varicella patient under 15 years of age diagnosed at 14 designated pediatric clinics between September 2015 and September 2016. Controls were selected from patients who visited the same practice for different reasons as the varicella case within 2 weeks. Swab samples were collected from varicella suspected patients and molecular diagnostic assays were used to confirm varicella cases. Matched odds ratio were used to calculate vaccine effectiveness (VE).ResultsVaricella zoster virus DNA was detected in 183 (81.3%) of 225 suspected cases. One sample was excluded because it was positive for the Oka vaccine strain (182/225, 80.9%). Three hundred twenty-three control subjects were enrolled. The effectiveness of 1 dose of the Oka/Biken vaccine compared with no vaccine was 76.7% (95% confidence interval [CI]: 58.6–86.9%; P < 0.001). The effectiveness of 2 doses of the Oka/Biken vaccine was 94.2% (95% CI: 85.7–97.6%; P < 0.001). After adjusting for potential confounding effects, the adjusted VE of 1 and 2 doses of varicella vaccine were 76.9% (95% CI: 58.1–87.3%; P < 0.001) and 94.7% (95% CI: 86.0–98.0%; P < 0.001), respectively.ConclusionsVE of one dose of Oka/Biken varicella vaccine was insufficient to control varicella. Therefore, two doses of Oka/Biken varicella vaccine is significant for controlling varicella in Japan.