Hospitalization due to varicella in the Netherlands

<p>Abstract</p> <p>Background</p> <p>In the Netherlands, incidence of physician's consultations and hospitalizations for varicella is low compared to other countries. Better knowledge about the severity of varicella among Dutch hospitalized patients is needed. Therefore, a medical record research was conducted among hospitalized patients with diagnosis varicella.</p> <p>Methods</p> <p>Hospital admissions due to varicella in 2003-2006 were obtained from the National Medical Register. Retrospectively, additional data were retrieved from the medical record of patients hospitalized with varicella in 23 Dutch hospitals using a standardized form. Analyses were performed using descriptive statistics.</p> <p>Results</p> <p>The study population (N = 296) was representative for all varicella admissions in the Netherlands (N = 1,658) regarding age, sex, duration of admission and type of diagnosis. Complications were recorded in 76% of the patients (37% had at least one relatively severe complication). Bacterial super infections of skin lesions (28%), (imminent) dehydration (19%), febrile convulsions (7%), pneumonia (7%) and gastroenteritis (7%) were most frequently reported. No varicella-related death occurred within the study population and 3% of the patients had serious rest symptoms.</p> <p>Conclusions</p> <p>It is not likely that the severity of varicella among hospitalized patients in the Netherlands differs from other countries. A considerable part of the varicella complications among hospitalized patients was rather moderate and can be treated effectively, although in a third of the hospitalized cases with complications, severe complications occurred. These data are relevant in the decision-making process regarding whether or not to introduce routine varicella vaccination in the Netherlands.</p

Effectiveness of the DTPa-HBV-IPV/Hib vaccine against invasive Haemophilus influenzae type b disease in the Netherlands (2003–16) : a case-control study

Background: In 2016, an increase in invasive Haemophilus influenzae serotype b (Hib) disease was reported in the Netherlands in children younger than 5 years, which coincided with the introduction of the hexavalent diphtheria, tetanus, and acellular pertussis-hepatitis B virus-inactivated polio virus/Hib vaccine (DTPa-HBV-IPV/Hib) from 2011 onwards. We aimed to estimate the effectiveness of the hexavalent vaccine to assess whether this increase could be explained by decreasing effectiveness. Methods: We did a case-control study in the Netherlands. We selected patients with a Hib infection (cases) by use of the surveillance records of the Netherlands Reference Laboratory for Bacterial Meningitis (Amsterdam). Cases with a Hib infection that began from Jan 1, 2003, to Dec 31, 2016, and who were younger than age 5 years were included. Ten controls from the national vaccination register (Praeventis) were selected for each case, matched by date of birth. Vaccination status was ascertained by use of Praeventis, which details the vaccination records of children living in the Netherlands. The last recorded vaccine dose was used to classify the child as having received the hexavalent DTPa-HBV-IPV/Hib vaccine or a pentavalent vaccine (which excludes the hepatitis B virus component) or another vaccine. We estimated the effectiveness of these vaccines by use of conditional logistic regression. Findings: We included 159 (94%) of 170 cases reported and 1590 matched controls, who had a median age of 1·5 years (IQR 0·8–2·9). The remaining 11 cases could not be cross-matched with vaccination records from Praeventis. 91 (57%) of 159 cases had been vaccinated, compared with 1408 (89%) of 1590 controls. The overall vaccine effectiveness was 92·8% (95% CI 88·7–95·4), with no differences between the year of disease onset (p=0·9670). There were no differences conferred by type of vaccine given: vaccine effectiveness of the pentavalent and other vaccines was 91·8% (95% CI 86·1–95·1) versus 94·0% (89·0–96·8) for the hexavalent vaccine (OR 0·72, 95% CI 0·36–1·45; p=0·3591). Vaccine effectiveness was highest in children aged 1–2 years at disease onset (97·1–99·0%) and was lowest in children aged 3–4 years at disease onset (60·7–82·3%; p=0·0008). Interpretation: Our results support the current vaccination programme, since Hib vaccine effectiveness has not decreased over time or by the introduction of the hexavalent DTPa-HBV-IPV/Hib vaccine. Vaccine effectiveness was high but waned with age. Alternative explanations for the increase in Hib disease therefore need to be assessed. Funding: Dutch Ministry of Health, Welfare and Sports

Effectiveness of the DTPa-HBV-IPV/Hib vaccine against invasive Haemophilus influenzae type b disease in the Netherlands (2003-16): a case-control study.

In 2016, an increase in invasive Haemophilus influenzae serotype b (Hib) disease was reported in the Netherlands in children younger than 5 years, which coincided with the introduction of the hexavalent diphtheria, tetanus, and acellular pertussis-hepatitis B virus-inactivated polio virus/Hib vaccine (DTPa-HBV-IPV/Hib) from 2011 onwards. We aimed to estimate the effectiveness of the hexavalent vaccine to assess whether this increase could be explained by decreasing effectiveness

Pneumococcal conjugate vaccines for preventing acute otitis media in children

BACKGROUND: Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post-PCV era report a shift in causative otopathogens towards non-vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, and 2014. The review title was changed (to include the population, i.e. children) for this update. OBJECTIVES: To assess the effect of PCVs in preventing AOM in children up to 12 years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, Web of Science, and trials registers (ClinicalTrials.gov and WHO ICTRP) to 29 March 2019. SELECTION CRITERIA: Randomised controlled trials of PCV versus placebo or control vaccine. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. The primary outcomes were frequency of all-cause AOM and adverse effects. Secondary outcomes included frequency of pneumococcal AOM and frequency of recurrent AOM (defined as three or more AOM episodes in six months or four or more in one year). We used GRADE to assess the quality of the evidence. MAIN RESULTS: We included 14 publications of 11 trials (60,733 children, range 74 to 37,868 per trial) of 7- to 11-valent PCVs versus control vaccines (meningococcus type C vaccine in three trials, and hepatitis A or B vaccine in eight trials). We included two additional trials for this update. We did not find any relevant trials with the newer 13-valent PCV. Most studies were funded by pharmaceutical companies. Overall, risk of bias was low. In seven trials (59,415 children) PCVs were administered in early infancy, while four trials (1318 children) included children aged one year and over who were either healthy or had a history of respiratory illness. There was considerable clinical heterogeneity across studies, therefore we did not perform meta-analyses.Adverse eventsNine trials reported on adverse effects (77,389 children; high-quality evidence). Mild local reactions and fever were common in both groups, and occurred more frequently in PCV than in control vaccine groups: redness ( 2.5 cm), swelling (> 2.5 cm), and fever (> 39 °C) occurred less frequently (0% to 0.9%, 0.1% to 1.3%, and 0.4% to 2.5%, respectively in children receiving PCV) and did not differ significantly between PCV and control vaccine groups. Pain or tenderness, or both was reported more frequently in PCV than in control vaccine groups: 3% to 38% versus 0% to 8%. Serious adverse events judged causally related to vaccination were rare and did not differ significantly between groups, and no fatal serious adverse event judged causally related to vaccination was reported.PCV administered in early infancyPCV7The effect of a licenced 7-valent PCV with CRM197 as carrier protein (CRM197-PCV7) on all-cause AOM varied from -5% (95% confidence interval (CI) -25% to 12%) relative risk reduction (RRR) in high-risk infants (1 trial; 944 children; moderate-quality evidence) to 6% (95% CI -4% to 16%; 1 trial; 1662 children) and 6% (95% CI 4% to 9%; 1 trial; 37,868 children) RRR in low-risk infants (high-quality evidence). PCV7 with the outer membrane protein complex of Neisseria meningitidis serogroup B as carrier protein (OMPC-PCV7), was not associated with a reduction in all-cause AOM (RRR -1%, 95% CI -12% to 10%; 1 trial; 1666 children; high-quality evidence).CRM197-PCV7 and OMPC-PCV7 were associated with 20% (95% CI 7% to 31%) and 25% (95% CI 11% to 37%) RRR in pneumococcal AOM, respectively (2 trials; 3328 children; high-quality evidence) and CRM197-PCV7 with 9% (95% CI -12% to 27%) to 10% (95% CI 7% to 13%) RRR in recurrent AOM (2 trials; 39,530 children; high-quality evidence).PHiD-CV10/11The effect of a licenced 10-valent PCV conjugated to protein D, a surface lipoprotein of Haemophilus influenzae, (PHiD-CV10) on all-cause AOM varied from 6% (95% CI -6% to 17%; 1 trial; 5095 children) to 15% (95% CI -1% to 28%; 1 trial; 7359 children) RRR in healthy infants (moderate-quality evidence). PHiD-CV11 was associated with 34% (95% CI 21% to 44%) RRR in all-cause AOM (1 trial; 4968 children; high-quality evidence).PHiD-CV10 and PHiD-CV11 were associated with 53% (95% CI 16% to 74%) and 52% (95% CI 37% to 63%) RRR in pneumococcal AOM (2 trials; 12,327 children; high-quality evidence) and PHiD-CV11 with 56% (95% CI -2% to 80%) RRR in recurrent AOM (1 trial; 4968 children; moderate-quality evidence).PCV administered at later agePCV7We found no evidence of a beneficial effect on all-cause AOM of administering CRM197-PCV7 in children aged 1 to 7 years with a history of respiratory illness or frequent AOM (2 trials; 457 children; high-quality evidence) and CRM197-PCV7 combined with a trivalent influenza vaccine in children aged 18 to 72 months with a history of respiratory tract infections (1 trial; 597 children; high-quality evidence).CRM197-PCV9In 1 trial including 264 healthy day-care attendees aged 1 to 3 years, CRM197-PCV9 was associated with 17% (95% CI -2% to 33%) RRR in parent-reported all-cause OM (low-quality evidence). AUTHORS' CONCLUSIONS: Administration of the licenced CRM197-PCV7 and PHiD-CV10 during early infancy is associated with large relative risk reductions in pneumococcal AOM. However, the effects of these vaccines on all-cause AOM is far more uncertain. We found no evidence of a beneficial effect on all-cause AOM of administering PCVs in high-risk infants, after early infancy (i.e. in children one year and above), and in older children with a history of respiratory illness. Compared to control vaccines, PCVs were associated with an increase in mild local reactions (redness, swelling), fever, and pain and/or tenderness. We found no evidence of a difference in more severe local reactions, fever, or serious adverse events judged causally related to vaccination

Association of serotype with risk of death due to pneumococcal pneumonia: a meta-analysis.

BACKGROUND: The 92 capsular serotypes of Streptococcus pneumoniae differ greatly in nasopharyngeal carriage prevalence, invasiveness, and disease incidence. There has been some debate, though, regarding whether serotype independently affects the outcome of invasive pneumococcal disease (IPD). Published studies have shown variable results with regard to case-fatality ratios for specific serotypes and the role of host factors in affecting these relationships. We evaluated whether risk of death due to IPD is a stable serotype-associated property across studies and then compared the pooled effect estimates with epidemiologic and biological correlates. METHODS: We performed a systematic review and meta-analysis of serotype-specific disease outcomes for patients with pneumonia and meningitis. Study-specific estimates of risk of death (risk ratio [RR]) were pooled from 9 studies that provided serotype-specific data on pneumonia and meningitis using a random-effects method with serotype 14 as the reference. Pooled RRs were compared with RRs from adults with low comorbidity scores to evaluate potential confounding by host factors. RESULTS: Significant differences were found in the RR estimates among serotypes in patients with bacteremic pneumonia. Overall, serotypes 1, 7F, and 8 were associated with decreased RRs, and serotypes 3, 6A, 6B, 9N, and 19F were associated with increased RRs. Outcomes among meningitis patients did not differ significantly among serotypes. Serotypes with increased RRs had a high carriage prevalence, had low invasiveness, and were more heavily encapsulated in vitro. CONCLUSIONS: These results suggest that IPD outcome, like other epidemiologic measures, is a stable serotype-associated property

Otitis media and its consequences: beyond the earache

An international group of multidisciplinary experts on middle-ear and paediatric infections met to explore where consensus exists on the management of acute otitis media. After informal discussions among several specialists of paediatric infectious disease, the group was expanded to include a larger spectrum of professionals with complementary expertise in middle-ear disease. Acute otitis media is a very common bacterial infection in children worldwide, leading to excessive antibiotic consumption in children in most countries and to a substantial burden of deafness and suppurative complications in developing countries. The group attempted to move beyond the existing controversies surrounding guidelines on acute otitis media, and to propose to clinicians and public health officials their views on the actions needed to be taken to reduce the disease burden caused by acute otitis media and the microbial antibiotic resistance from the resulting Use of antibiotics. Definition of acute otitis media and diagnostic accuracy are crucial steps to identify children who will potentially benefit from treatment with antibiotics and to eliminate unnecessary prescribing. Although the group agreed that antibiotics are distributed indiscriminately, even to children who do not seem to have the disease, no consensus could be reached on whether antibiotics should be given to all appropriately diagnosed children, reflecting the wide range of practices and lack of convincing evidence from observational studies. The major unanimous concern was an urgent need to reduce unnecessary prescribing of antibiotics to prevent further increases in antibiotic resistance. Prevention of acute otitis media with existing and future viral and bacterial vaccines seems the most promising approach to affect disease burden and consequences, both in developed and developing countries

A novel method to standardise serum IgA measurements shows an increased prevalence of IgA deficiency in young children with recurrent respiratory tract infections.

We developed reference values for IgA for seven age groups and five different laboratory assays. Using these reference values, IgA measurements from 417 cases and 224 controls were standardised to compare groups. In children aged 2 years and older, IgA deficiency was observed in 2.9% (7/242) of cases and 0% (0/189) of controls (P = 0.02)

It Takes Two to Tango: Combining Conventional Culture With Molecular Diagnostics Enhances Accuracy of Streptococcus pneumoniae Detection and Pneumococcal Serogroup/Serotype Determination in Carriage

BACKGROUND: The specificity of molecular methods for the detection of Streptococcus pneumoniae carriage is under debate. We propose a procedure for carriage surveillance and vaccine impact studies that increases the accuracy of molecular detection of live pneumococci in polymicrobial respiratory samples. METHODS: Culture and qPCR methods were applied to detect pneumococcus and pneumococcal serotypes in 1,549 nasopharyngeal samples collected in the Netherlands (n = 972) and England (n = 577) from 946 toddlers and 603 adults, and in paired oropharyngeal samples collected exclusively from 319 Dutch adults. Samples with no live pneumococci isolated at primary diagnostic culture yet generating signal specific for pneumococcus in qPCRs were re-examined with a second, qPCR-guided culture. Optimal Cq cut-offs for positivity in qPCRs were determined via receiver operating characteristic (ROC) curve analysis using isolation of live pneumococci from the primary and qPCR-guided cultures as reference. RESULTS: Detection of pneumococcus and pneumococcal serotypes with qPCRs in cultured (culture-enriched) nasopharyngeal samples exhibited near-perfect agreement with conventional culture (Cohen’s kappa: 0.95). Molecular methods displayed increased sensitivity of detection for multiple serotype carriage, and implementation of qPCR-guided culturing significantly increased the proportion of nasopharyngeal and oropharyngeal samples from which live pneumococcus was recovered (p < 0.0001). For paired nasopharyngeal and oropharyngeal samples from adults none of the methods applied to a single sample type exhibited good agreement with results for primary and qPCR-guided nasopharyngeal and oropharyngeal cultures combined (Cohens kappa; 0.13–0.55). However, molecular detection of pneumococcus displayed increased sensitivity with culture-enriched oropharyngeal samples when compared with either nasopharyngeal or oropharyngeal primary cultures (p < 0.05). CONCLUSION: The accuracy of pneumococcal carriage surveillance can be greatly improved by complementing conventional culture with qPCR and vice versa, by using results of conventional and qPCR-guided cultures to interpret qPCR data. The specificity of molecular methods for the detection of live pneumococci can be enhanced by incorporating statistical procedures based on ROC curve analysis. The procedure we propose for future carriage surveillance and vaccine impact studies improves detection of pneumococcal carriage in adults in particular and enhances the specificity of serotype carriage detection