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Background: Venous thromboembolism (VTE)-including deep vein thrombosis, pulmonary embolism, and cerebral venous sinus thrombosis (CVST)-may occur early after vaccination against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We sought to describe the site, clinical characteristics, and outcomes of VTE after vaccination against SARS-CoV-2., Methods: In a prospective study using the Registro Informatizado de Enfermedad TromboEmbólica (RIETE) platform, patients with VTE 4-30 days after vaccination against SARS-CoV-2 (1 February 2021 through 30 April 2021) were included. VTE patients recruited from the same centers into RIETE in the same months in 2018-2019 were selected as the reference group. All-cause mortality and major bleeding were the main study outcomes., Results: As of 30 April 2020, 102 patients with post-vaccination VTEs had been identified (28 after adenovirus-based vaccination [ChAdOx1 nCov-19; AstraZeneca] and 74 after mRNA-based vaccination [mRNA-1273; Moderna, and BNT162b2; Pfizer]). Compared with 911 historical controls, patients with VTE after adenovirus-based vaccination more frequently had CVST (10.7% vs. 0.4%, p < 0.001) or thrombosis at multiple sites (17.9% vs. 1.3%, p < 0.001), more frequently had thrombocytopenia (40.7% vs. 14.7%, p < 0.001), and had higher 14-day mortality (14.3% vs. 0.7%; odds ratio [OR]: 25.1; 95% confidence interval [CI]: 6.7-94.9) and major bleeding rates (10.3% vs. 1.0%, OR: 12.03, 95% CI: 3.07-47.13). The site of thrombosis, accompanying thrombocytopenia, and 14-day mortality rates were not significantly different for patients with VTE after mRNA-based vaccination, compared with historical controls., Conclusions: Compared with historical controls, VTE after adenovirus-based vaccination against SARS-CoV-2 is accompanied by thrombocytopenia, occurs in unusual sites, and is associated with worse clinical outcomes.

Background and Aims: Symptomatic or asymptomatic COVID-19 infection has been reported in vaccination. In the current article, we try to elucidate various causes behind COVID-19 infection and mortality following COVID-19 vaccination and suggest possible strategies to counteract this threat., Methods: We carried out a comprehensive review of the literature using suitable keywords such as 'COVID-19', 'Pandemics', 'Vaccines', 'Mortality', 'deaths', 'infections', and 'India' on the search engines of PubMed, SCOPUS, Google Scholar, and ResearchGate in from January to May 2021. Epidemiology, risk factors, Adverse Events Following Immunization (AEFI) and mortality after COVID-19 vaccination were assessed., Results: A number of factors have been associated with symptomatic or asymptomatic COVID-19 infection reported after vaccination. A high viral load, comorbidities, mutant strains, Variants of Concern (VOC) leading to Vaccine escape and casual attitude towards COVID Appropriate Behaviors appear to be the most important factors for infection and deaths after COVID-19 vaccination., Conclusions: COVID-19 Infection and mortality after COVID-19 vaccination are of great concern. Application of COVID Appropriate Behaviour (CAB) before and after vaccination is essential for the population. Effective Vaccines against mutant strains and enhanced vaccination drive are key strategies to avoid this quintessential threat. Early medical intervention in high-risk groups can prevent overall mortality., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article.

A higher risk of death from coronavirus disease 19 has been shown for patients with solid cancers or haematological malignancies (HM). Thanks to the accelerated development of anti-SARS-SoV-2 vaccines in less than a year since the start of the global pandemic, patients with cancer were quickly prioritised in early 2021 for vaccination, however dependent on the very unequal availability at the global level. Impaired immunogenicity of SARS-CoV-2 mRNA vaccines in immunocompromised patients was rapidly reported as early as April 2021, although the vaccination fortunately appears to be generally effective without increasing the spacing. Worryingly, the humoral response of the SARS-CoV-2 vaccination is, however, considered insufficient in patients followed for HM, in particular when they are on anti-CD20 treatment. Thus, improving vaccination coverage by strengthening immune stimulation should be evaluated in patients under active treatment against cancer. Here, we discuss three different approaches: a third dose of early vaccine (repeated immune stimulation), heterologous prime-boost vaccination (multimodal immune stimulation) and a double-dose strategy (maximisation of immune response). Dedicated therapeutic trials, currently almost non-existent, seem rapidly necessary., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Pneumococcal (PC) vaccination is recommended for patients with chronic lymphocytic leukemia (CLL). However, response to vaccines has been investigated in a small series of CLL patients. We analyzed the antibody response and outcomes of 112 CLL patients who received the 13-valent pneumococcal conjugate vaccine (PCV13). An immune response was defined by a twofold increase in the PC-IgG levels assessed by ELISA. The median age of patients was 68 years, 23.2% showed IgG levels ≤ 400 mg/L, 6.3% progressive disease, 52% unmutated IGHV. Twenty-two (19.6%) patients were treatment-naïve and 90 (80.4%) previously treated (40.2% front-line chemoimmunotherapy; ibrutinib first/advanced-line, 9.8%/21.4%; idelalisib advanced-line, 8.9%). Nine (8%) patients developed an immune response, eight treatment-naive, and one on front-line ibrutinib. No responses were observed in patients previously treated with chemoimmunotherapy. Age ≥ 60 years (p = 0.007), IgG levels < 400 mg/L (p < 0.0001), prior treatment (p < 0.0001), and signs of disease progression (p = 0.04) were associated with a lower response rate. Pneumonia-free survival was significantly shorter in patients with clinical signs of progressive disease (HR, 8.39), prior pneumonia (HR, 7.03), and TP53 disruption (HR, 2.91). In conclusion, our results suggest that vaccination should be offered at diagnosis to CLL patients with early stage and stable disease who have better resources for an effective immune response.

Background: Safety of pentavalent (DTwP-HBV-Hib) vaccine has been a public concern in India and other countries. This study attempted to document the association of serious adverse events following immunization (AEFI, including hospitalizations and deaths of all causes) with the 3 doses of pentavalent and oral poliovirus (OPV) vaccines., Methods: A cohort of 30,688 infants in 2 south Indian districts were enrolled and followed-up between October 2014 and May 2016, following their first vaccination with DTwP-HBV-Hib and OPV at public health facilities. During weekly follow-ups, by telephone or home visits, the serious AEFIs (hospitalizations and deaths) occurring any time after each vaccination until 4 weeks after third dose were documented. The incidence risk ratios (IRRs) of serious AEFIs in the first (days 0-6) and fourth weeks (days 21-27) after the vaccine doses were compared using the poisson regression analysis., Results: Of the 30,688 infants enrolled, 30,208 received their third doses of vaccines. During the 4-week periods following each vaccination, there were 365 hospitalizations and 17 deaths. Adjusted incidence risk ratio of 3 doses combined for post-vaccination serious AEFIs during the first week compared with fourth week was 0.8 [95% confidence interval: 0.6-1.0]., Conclusions: There was no increased risk of a serious AEFIs during the first week after any of the 3 doses of pentavalent and OPV vaccination compared with the fourth week. In the absence of any temporal clustering, mortality and hospitalization rates observed in vaccinated infants probably reflects the natural occurrence of such events.

IntroductionIt is unclear whether high-dose influenza vaccine (HD) is more effective at reducing mortality among seniors.AimThis study aimed to evaluate the relative vaccine effectiveness (rVE) of HD. MethodsWe linked electronic medical record databases in the Veterans Health Administration (VHA) and Medicare administrative files to examine the rVE of HD vs standard-dose influenza vaccines (SD) in preventing influenza/pneumonia-associated and cardiorespiratory mortality among VHA-enrolled veterans 65 years or older during the 2012/13, 2013/14 and 2014/15 influenza seasons. A multivariable Cox proportional hazards model was performed on matched recipients of HD vs SD, based on vaccination time, location, age, sex, ethnicity and VHA priority level. ResultsAmong 569,552 person-seasons of observation, 207,574 (36%) were HD recipients and 361,978 (64%) were SD recipients, predominantly male (99%) and white (82%). Pooling findings from all three seasons, the adjusted rVE estimate of HD vs SD during the high influenza periods was 42% (95% confidence interval (CI): 24-59) against influenza/pneumonia-associated mortality and 27% (95% CI: 23-32) against cardiorespiratory mortality. Residual confounding was evident in both early and late influenza periods despite matching and multivariable adjustment. Excluding individuals with high 1-year predicted mortality at baseline reduced the residual confounding and yielded rVE of 36% (95% CI: 10-62) and 25% (95% CI: 12-38) against influenza/pneumonia-associated and cardiorespiratory mortality, respectively. These were confirmed by results from two-stage residual inclusion estimations.DiscussionThe HD was associated with a lower risk of influenza/pneumonia-associated and cardiorespiratory death in men during the high influenza period.

Objectives: To study a potential positive association (referred to as 'a match') between the need for health service (expressed by a mortality risk score) and observed health service utilisation among healthy Danish under-fives. Further, municipal differences in the match were examined to motivate focused comparisons between the organisation of regional health services., Design: Register-based national cohort study., Participants: The population of 1,246,599 Danish children born 1997-2016 who survived until date of first discharge to the home after birth without a diagnosis of severe chronic disease., Main Outcome Measures: Hazard ratios (HR) for a doubling of the mortality rate were calculated for the following health services: total contacts, inpatient contacts (admission > 1 day), outpatient contacts, general practitioner contacts, specialist contacts, medication use, and vaccinations., Results: The use of total contacts, inpatient contacts (> 1 day) and general practitioner contacts as well as medication matched with the mortality risk score, HRs between 1.027 (1.026 to 1.028) and 1.111 (1.108 to 1.113), whereas outpatient and specialist contacts as well as vaccinations did not, HRs between 0.913 (0.912 to 0.915) and 0.991 (0.991 to 0.991). There were some remarkable differences among the 98 Danish municipalities., Conclusions: We found some match between need and use for total contacts, inpatient contacts (> 1 day), contacts with general practitioner, and medication use although the associations were relatively weak. For outpatient and specialist contacts, the mismatch may be related to services not addressing potentially fatal disease whereas for vaccination there was a small mismatch. Our results indicate local discrepancies in diagnosis, and a low adjusted utilisation of hospital admissions in Aarhus compared to the other three major cities in Denmark suggests that a comparison of the organisation of services could be useful., Competing Interests: The authors have declared that no competing interests exist.

Background: Serious adverse reactions after immunization are rare but do occur. In very rare instances, cases with fatal outcome have been reported. These reports can have a huge impact and even more so when due to an immunization error. The aim of this study is to systematically review immunization errors with fatal outcomes in EudraVigilance., Methods: This was a case-series analysis of Individual Case Safety Reports (ICSRs) reporting immunization errors and a fatal outcome. To determine the level of certainty of a causal association between the immunization errors and fatal outcomes two independent reviewers assessed all ICSRs using the WHO tool "Causality assessment of an Adverse Event Following Immunization (AEFI)". In accordance with the tool, the ICSRs were classified as consistent, indeterminate, inconsistent/coincidental, or unclassifiable. In addition, we estimated the contribution of reported errors to the fatal outcomes as large, moderate, small, none, or unclassifiable using a classification developed for this study., Results: A total of 154 ICSRs met the inclusion criteria. Vaccines reported most frequently were pneumococcal (33), rabies (27) and influenza vaccines (24). Most frequently reported errors were non-compliance with recommended schedules of immunization (63). The most frequently reported vaccine-error combination was rabies vaccines and non-compliance with a recommended schedule of immunization (23). Twelve cases were classified as consistent with causal association and had a large error contribution. These cases concerned a cluster of six cases reporting incorrect handling of multi-dose vials containing measles vaccine and six cases reporting administration of live-attenuated vaccines to immunocompromised patients., Discussion: In this study, we showed that fatal outcomes following immunization errors are very rare. Four key issues were the importance of: (1) quality control of multi-dose vaccines, (2) screening patients for immunocompromising factors, (3) education on the importance of adherence, and (4) measures to improve distinction between vaccines and medicines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Vaccination continues to be the single most important and successful public health intervention, due to its prevention of morbidity and mortality from prevalent infectious diseases. Severe immunologically mediated reactions are rare and less common with the vaccine than the true infection. However, these events can cause public fearfulness and loss of confidence in the safety of vaccination. In this paper, we perform a systematic literature search and narrative review of immune-mediated vaccine adverse events and their known and proposed mechanisms, and outline directions for future research. Improving our knowledge base of severe immunologically mediated vaccine reactions and their management drives better vaccine safety and efficacy outcomes., (© 2019 The British Pharmacological Society.)

Immunization is one of the greatest public health achievements of the 20 th century. Vaccines have enabled the eradication of deadly diseases and decreased the morbidity and mortality associated with various infections. Most vaccines are safe to administer and cause only minor side effects. Although very rare, various glomerular diseases and acute kidney injury have been reported following immunization with certain vaccines including influenza, pneumococcal, and hepatitis B vaccines. This review summarizes these rare renal complications that have been published in the literature. Physicians and other health-care providers administrating vaccines should be aware of these very rare but possible renal side effects., Competing Interests: None

Objective: To analyze the characterisitics of the death cases suspected to be related to vaccination in Fujian Province from 2012 to 2017. Methods: A total of 33 death cases information which was suspected to be related to the vaccinations from 2012 to 2017 were extracted from Chinese Adverse Events Following Immunization Information System (AEFI). The autopsy reports and the conclusions made by AEFI investigation diagnosis expert committee were collected at the same time. The inoculation data were obtained through the Fujian province Immunization Program Information System. The AEFI incidence, rare vaccine reaction incidences and mortality rates following immunization were figured out to analyze the characterisitics of the death cases associated with vaccination. Results: The age of deuths cases was from 26 days to 52 months. Among 33 cases, 23 were males, and 8 were due to vaccine-related reaction, and the others were due to coincidental events. The number of rare vaccine reaction cases from 2012 to 2017 were 2,3,6,8,7 and 7, respectively. The highest AEFI incidence was measles and rubella combined attenuated live vaccine [38.88 (95 %CI : 36.85-40.91)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [2.01 (95 %CI : 1.73-2.30)/100 000 dose]. The highest rare vaccine reaction incidence was measles and rubella combined attenuated live vaccine [15.04 (95 %CI : 13.78-16.30)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [0.38 (95 %CI : 0.25-0.50)/100 000]. The highest mortality rate was inactivated poliomyelitis vaccine [0.26 (95 %CI : 0.04-0.54)/100 000 doses], and the lowest mortality rate was measles, mumps and rubella combined attenuated live vaccine [0.01 (95 %CI : 0.00-0.08)/100 000 doses]. The Spearman correlation analysis showed that there were correlations between AEFI incidence and rare vaccine reaction incidence ( r= 0.64, P= 0.048), there were no correlations between AEFI incidence and mortality rate ( r= -0.34, P= 0.329), and there were no correlations between rare vaccine reaction incidence and mortality rate ( r= -0.25, P= 0.484). Conclusion: Neither AEFI incidence nor rare vaccine reaction incidence was correlation with mortality rate. The main causes of death following vaccination were coincidental events.

Introduction: Influenza epidemics are of higher risk at the extremes of life and in people with comorbidities. Effective -vaccination prevents the occurrence of serious cases and decreases mortality., Objective: To describe deaths from influenza with a history of timely vaccination, from the 2010 to the 2018 season in Mexico., Method: Cross-sectional, descriptive study where the Influenza Epidemiological Surveillance System database was used., Results: From 2010 to 2018, 65 vaccinated individuals died from influenza, from which 55% of cases (n = 36) were due to type A (H1N1), 51% (n = 33) were females, median age was 57 years, 21 % (n = 14) did not meet the operational definition of influenza-like illness or severe acute respiratory infection, 83% (n = 54) had at least one comorbidity, with the most common being diabetes mellitus and hypertension (32% each); 55% (n = 36) of deaths received antiviral treatment and only 8% (n = 5) had no comorbidities and received treatment with oseltamivir., Conclusions: Deaths from influenza with timely vaccination represent a very low percentage of the totality. Vaccination against influenza has been a specific prevention strategy that decreases disease burden., (Copyright: © 2019 Permanyer.)

Background: Measles vaccine (MV) may protect against non-measles mortality. We tested whether survival depended on age of measles vaccination., Methods: Bandim Health Project follows children under 5 years of age through a Health and Demographic Surveillance System in rural Guinea-Bissau. Children aged 6-36 months with a vaccination card inspected were followed to the next visit or for a maximum of 6 months. In Cox proportional-hazards models adjusted for age and village cluster, we compared the survival of children vaccinated with MV early (< 9 months), as recommended (9-11 months) or late (> 12+ months) with the survival of measles-unvaccinated children. Among measles-vaccinated children, we modelled the effect of age at measles vaccination linearly to assess mortality changes per month increase in vaccination age., Results: From 1999 to 2006, 14,813 children (31,725 observations) were included. Children vaccinated with MV had a Hazard Ratio (HR) of 0.76 (95% CI: 0.63-0.91) compared with measles-unvaccinated children; censoring measles deaths did not change the results (HR = 0.79 (0.65-0.95)). For early MV the HR was 0.68 (0.53-0.87), for MV as recommended the HR was 0.77 (0.62-0.96) and for late MV the HR was 0.86 (0.67-1.11). Limiting the analysis to measles-vaccinated children, age at measles vaccination was associated with a 2.6% (0.4-5.1%) increase in mortality per month increase in vaccination age., Conclusion: Early MV was associated with a large survival advantage. The current policy to increase vaccination age, when measles control improves, may not optimize the impact of MV on child survival.

There have been a number of spontaneous reports of sudden unexpected death soon after the administration of Infanrix hexa (combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis and Haemophilus influenza type B vaccine). The manufacturer, GlaxoSmithKline (GSK), submits confidential periodic safety update reports (PSURs) on Infanrix hexa to the European Medicines Agency (EMA). The latest is the PSUR 19. Each PSUR contains an analysis of observed/expected sudden deaths, which shows that the number of observed deaths soon after immunisation is lower than that expected by chance. This commentary focuses on that aspect of the PSUR which has a bearing on policy decisions. We analysed the data provided in the PSURs. It is apparent that the deaths acknowledged in the PSUR 16 were deleted from the PSUR 19. The number of observed deaths soon after vaccination among children older than one year was significantly higher than that expected by chance once the deleted deaths were restored and included in the analysis. The manufacturer must explain the figures that have been submitted to the regulatory authorities. The procedures undertaken by the EMA to evaluate the manufacturer's claims in the PSUR need to be reviewed. The Drugs Controller General of India nearly automatically accepts drugs and vaccines approved by the EMA. There is a need to reappraise the reliance on due diligence by the EMA.

Splenectomy is a well-recognised risk factor for life-threatening overwhelming post-splenectomy infection (OPSI). To prevent OPSI, immunisations against encapsulated bacteria (S. pneumoniae, N. meningitidis, H. influenzae) and influenza virus are recommended. However, there is still a lack of uniformity and poor compliance with these recommendations. Following a local physicians' awareness campaign regarding the importance of vaccine prophylaxis of splenectomised patients, we aimed to register vaccination coverage, mortality and infection rates in all patients who underwent splenectomy at our hospital, over a six-year time span. Reasons for splenectomy, patients' compliance with vaccinations, mortality and infectious events were recorded. The reasons for splenectomy in the 216 identified patients (mean age 58.2 ± 14; M:F ratio 1.4:1) were haematologic disorders (38.8%), solid tumours (28.7%), traumatic rupture (22.7%) and other causes (9.7%). A total of 146 patients (67.6%) received at least one of the four vaccines. Overall, the mortality rate was significantly greater in unvaccinated compared to vaccinated patients (p < 0.001), although after the adjustment for the cause of splenectomy the statistical significance was lost (p = 0.085) due to the burden of solid tumour-related mortality. Among the 21 reported cases of OPSI, eight were fatal and five were potentially vaccine-preventable. Our results show that two-thirds of splenectomised patients comply with vaccine prophylaxis. Future interventional studies or ad hoc registries might overcome barriers to vaccination or intentional non-compliance.

Background: Ten years ago, we formulated two hypotheses about whole-cell diphtheria-tetanus-pertussis (DTP) vaccination: first, when given after BCG, DTP increases mortality in girls and, second, following DTP there is an increase in the female/male mortality rate ratio (MRR). A recent review by WHO found no convincing evidence that DTP increases mortality in females., Methods: We used previous DTP reviews as well as the recent WHO review for assessing the hypotheses. As pre-specified we excluded studies with survival or frailty bias; if children had received BCG and DTP simultaneously; and if the children had received neonatal vitamin A., Results: In seven studies of BCG-vaccinated children, DTP vaccination was associated with a 2.54 (95% CI 1.68-3.86) increase in mortality in girls (with no increase in boys [ratio 0.96, 0.55-1.68]). In 10 studies of BCG-vaccinated children, the female-to-male mortality ratio was 2.45 (1.48-4.06) times higher after DTP than before DTP. In 15 studies of children who had received DTP after previous BCG vaccination, mortality was 1.53 (1.21-1.93) times higher in girls than boys. The findings were similar in studies conducted before and after formulation of the hypotheses., Conclusions: The two hypotheses were confirmed in the studies that fulfilled pre-specified criteria., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

We report on the case of fatal "purpura fulminans" caused by Neisseria meningitidis W135 that occurred in a young French soldier vaccinated a few months earlier with the tetravalent conjugate vaccine ACYW135. Biological investigations revealed adequate titers of postvaccination antibodies against serogroups A, C, and W135 and led to the post-mortem diagnosis of a complete C7 complement deficiency. Late complement component deficiency is a well-known risk factor of meningococcal diseases, but usually exposes to recurrent mild infections, whereas severe invasive meningococcal diseases are more likely to occur among properdin-deficient patients. Awareness of the potentially life-threatening nature of late complement component deficiency should lead to improved diagnosis among young people, especially when past medical history reveals recurrent mild infections., (Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.)

Background: World Health Organization recently reviewed the possible nonspecific effects of diphtheria-tetanus-pertussis (DTP) vaccine. The results were considered inconsistent though most studies suggested deleterious effects. We examined whether inconsistencies in results reflected differences in effect of DTP or differences in the methodology used in different studies., Methods: If children remain unvaccinated because they are frail or if children (including dead ones) with no information on vaccination status are classified as "unvaccinated," the mortality rate becomes unnaturally high among "unvaccinated" controls. To measure this bias, we defined the "bias index" as the mortality rate ratio (MRR) between unvaccinated and vaccinated children., Results: Five studies had frail or poorly defined control groups and survival bias, the bias index being 2.0-8.0; in these studies DTP was associated with an MRR of 0.39 (0.18-0.83). Eight studies determined "unvaccinated" by vaccination card and the bias index was 0.5-1.7; in these studies DTP was associated with an MRR of 2.00 (1.50-2.67)., Conclusion: The observed inconsistencies in results were because of methodologic differences between studies. Bias does not seem to explain why DTP is associated with higher mortality.

Purpose: To assess those published cases of yellow fever (YF) vaccine-associated viscerotropic disease that meet the Brighton Collaboration criteria and to assess the safety of YF vaccine with respect to viscerotropic disease., Literature Search: Ten electronic databases were searched with no restriction of date or language and reference lists of retrieved articles., Methods: All abstracts and titles were independently read by two reviewers and data independently entered by two reviewers., Results: All serious adverse events that met the Brighton Classification criteria were associated with first YF vaccinations. Sixty-two published cases (35 died) met the Brighton Collaboration viscerotropic criteria, with 32 from the US, six from Brazil, five from Peru, three from Spain, two from the People's Republic of China, one each from Argentina, Australia, Belgium, Ecuador, France, Germany, Ireland, New Zealand, Portugal, and the UK, and four with no country stated. Two cases met both the viscerotropic and YF vaccine-associated neurologic disease criteria. Seventy cases proposed by authors as viscerotropic disease did not meet any Brighton Collaboration viscerotropic level of diagnostic certainty or any YF vaccine-associated viscerotropic disease causality criteria (37 died)., Conclusion: Viscerotropic disease is rare in the published literature and in pharmacovigilance databases. All published cases were from developing countries. Because the symptoms are usually very severe and life threatening, it is unlikely that cases would not come to medical attention (but might not be published). Because viscerotropic disease has a highly predictable pathologic course, it is likely that viscerotropic disease post-YF vaccine occurs in low-income countries with the same incidence as in developing countries. YF vaccine is a very safe vaccine that likely confers lifelong immunity., Competing Interests: The author reports no conflicts of interest in this work.

Background: Diphtheria-tetanus-pertussis (DTP) may be associated with increased female mortality; the effect of co-administration with BCG is not known., Methods: Between 1989 and 1997, we examined female and male mortality rates in rural Senegal where 7824 infants received the first dose of DTP and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine., Results: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person-years, but mortality increased with subsequent doses of DTP-IPV to 45/1000 person-years. Among boys, BCG and DTP-IPV1 simultaneously reduced mortality from 72/1000 person-years to 60/1000 person-years and mortality decreased further with subsequent doses of DTP-IPV to 34/1000 person-years. In age-adjusted analyses, female-male mortality rate ratios were 0.83(95% CI 0.50-1.40) among unvaccinated children and 0.58 (95% CI 0.35-0.96) among children vaccinated simultaneously with BCG and DTP-IPV1, but increased to 1.17 (95% CI 0.67-2.03) after DTP-IPV2, and 1.63 (95% CI 0.86-3.10) after DTP-IPV3. Difference in vaccination coverage could not explain these sex-differential patterns; girls had significantly better weight-for-age than boys so nutritional status did not explain the increase in female mortality after DTP-IPV3., Conclusions: Whereas BCG co-administered with DTP-IPV was associated with lower female than male mortality, subsequent DTP-IPV vaccinations were associated with an increase in female mortality relative to male mortality., (© The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: This study evaluates the potential association of vaccination and death in the Vaccine Safety Datalink (VSD)., Methods: The study cohort included individuals ages 9 to 26 years with deaths between January 1, 2005, and December 31, 2011. We implemented a case-centered method to estimate a relative risk (RR) for death in days 0 to 30 after vaccination.Deaths due to external causes (accidents, homicides, and suicides) were excluded from the primary analysis. In a secondary analysis, we included all deaths regardless of cause. A team of physicians reviewed available medical records and coroner's reports to confirm cause of death and assess the causal relationship between death and vaccination., Results: Of the 1100 deaths identified during the study period, 76 (7%) occurred 0 to 30 days after vaccination. The relative risks for deaths after any vaccination and influenza vaccination were significantly lower for deaths due to nonexternal causes (RR 0.57, 95% confidence interval [CI] 0.38-0.83, and RR 0.44, 95% CI 0.24-0.80, respectively) and deaths due to all causes (RR 0.72, 95% CI 0.56-0.91, and RR 0.44, 95% CI 0.28-0.65). No other individual vaccines were significantly associated with death. Among deaths reviewed, 1 cause of death was unknown, 25 deaths were due to nonexternal causes, and 34 deaths were due to external causes. The causality assessment found no evidence of a causal association between vaccination and death., Conclusions: Risk of death was not increased during the 30 days after vaccination, and no deaths were found to be causally associated with vaccination., (Copyright © 2016 by the American Academy of Pediatrics.)

Background: Invasive meningococcal disease (IMD) is a major cause of bacterial meningitides and septicaemia. This study shows the results of the laboratory-based surveillance of IMD in Belgium over the period 1997-2012., Methods: The results are based on microbiological and molecular laboratory surveillance of 2997 clinical isolates of N. meningitides received by the Belgian Meningococcal Reference Centre (BMRC) over the period 1997-2012., Results: Serogroup B has always been a major cause of meningococcal disease in Belgium, with P3.4 as most frequent serotype till 2008, while an increase in non-serotypable strains has been observed in the last few years. Clonal complexes cc-41/44 and cc-269 are most frequently observed in serogroup B strains. In the late nineties, the incidence of serogroup C disease increased considerably and peaked in 2001, mainly associated with phenotypes C:2a:P1.5,2, C:2a:P1.5 and C:2a:P1.2 (ST-11/ET-37 clonal complex). The introduction of the meningococcal C conjugate vaccine has been followed by an 88% significant decrease in serogroup C disease from 2001 to 2004 nationally, yet sharper in Flanders (92%) compared to Wallonia (77%). Since 2008 a difference in incidence of serogroup C was observed in Flanders (0-0.1/100,000) versus Wallonia (0.1-0.3/100,000)., Conclusion: This study showed the change in epidemiology and strain population over a 16 years period spanning an exhaustive vaccination campaign and highlights the influence of regional vaccination policies with different cohorts sizes on short and long-term IMD incidences.

Background: Influenza is a significant cause of morbidity and mortality in older adults. High-dose (HD) trivalent inactivated vaccine has increased immunogenicity in older adults compared with standard-dose (SD) vaccine. We assessed the relative effectiveness of HD influenza vaccination (vs SD influenza vaccination)., Methods: We conducted a retrospective cohort study among patients who receive primary care at Veteran Health Administration (VHA) medical centers, and who received influenza vaccine in the 2010-2011 influenza season. The primary outcome was hospitalization for influenza or pneumonia. We also conducted an analysis in subgroups defined by age., Results: We evaluated 25 714 patients who received HD vaccine and 139 511 who received SD vaccine in 23 VHA medical centers. The rate of hospitalization for influenza or pneumonia was 0.3% in both groups in the influenza season. After accounting for patient characteristics in propensity-adjusted analyses, the risk of hospitalization for influenza or pneumonia was not significantly lower among patients receiving HD vaccine vs those receiving SD vaccine (risk ratio, 0.98; 95% confidence interval, .68-1.40). In the subgroup of patients ≥85 years of age, receiving HD (compared with SD) vaccine was associated with lower rates of hospitalization for influenza or pneumonia., Conclusions: HD vaccine was not found to be more effective than SD vaccine in protecting against hospitalization for influenza or pneumonia; however, we found a protective effect in the oldest subgroup of patients. Additional studies are needed to evaluate the effectiveness of HD vaccine., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

We propose a method to analyse the 2009 outbreak in the region of Botucatu in the state of São Paulo (SP), Brazil, when 28 yellow fever (YF) cases were confirmed, including 11 deaths. At the time of the outbreak, the Secretary of Health of the State of São Paulo vaccinated one million people, causing the death of five individuals, an unprecedented number of YF vaccine-induced fatalities. We apply a mathematical model described previously to optimise the proportion of people who should be vaccinated to minimise the total number of deaths. The model was used to calculate the optimum proportion that should be vaccinated in the remaining, vaccine-free regions of SP, considering the risk of vaccine-induced fatalities and the risk of YF outbreaks in these regions.

Background: The World Health Organization recommends vitamin A supplementation (VAS) at routine vaccination contacts after 6 months of age based on the assumption that it reduces mortality by 24%. The policy has never been evaluated in randomized controlled trials for its effect on overall mortality. We conducted a randomized double-blind trial to evaluate the effect of VAS with vaccines., Methods: We randomized children aged 6 to 23 months 1:1 to VAS (100000 IU if aged 6-11 months, 200000 IU if aged 12-23 months) or placebo at vaccination contacts in Guinea-Bissau. Mortality rates were compared in Cox proportional-hazards models overall, and by gender and vaccine., Results: Between August 2007 and November 2010, 7587 children were enrolled. Within 6 months of follow-up 80 nonaccident deaths occurred (VAS: 38; placebo: 42). The mortality rate ratio (MRR) comparing VAS versus placebo recipients was 0.91 (95% confidence interval 0.59-1.41) and differed significantly between boys (MRR 1.92 [0.98-3.75]) and girls (MRR 0.45 [0.24-0.87]) (P = .003 for interaction between VAS and gender). At enrollment, 42% (3161/7587) received live measles vaccine, 29% (2154/7587) received inactivated diphtheria-tetanus-pertussis-containing vaccines, and 21% (1610/7587) received both live and inactivated vaccines. The effect of VAS did not differ by vaccine group., Conclusions: This is the first randomized controlled trial to assess the effect of the policy on overall mortality. VAS had no overall effect, but the effect differed significantly by gender. More trials to ensure an optimal evidence-based vitamin A policy are warranted., (Copyright © 2014 by the American Academy of Pediatrics.)

Objective: To test the hypothesis that a gender differential exists in the effect on child mortality of BCG, DTP, measles vaccine as administered under programme conditions in Ballabgarh HDSS area., Methods: All live births in 28 villages of Ballabgarh block in North India from 2006 to 2011 were followed until 31 December 2011 or 36 months of age whichever was earlier. The period of analysis was divided into four time periods based on eligibility for vaccines under the national immunisation schedule (BCG for tuberculosis, primary and booster doses of diphtheria-tetanus-pertussis and measles). Cox proportional hazards regression was used to assess the association between sex and risk of mortality by vaccination status using age as the timescale in survival analysis and adjusting for wealth index, access to health care, the presence of a health facility in the village, parental education, type of family, birth order of the child and year of birth., Results: 702 deaths (332 boys and 370 girls) occurred among 12,142 children in the cohort in the 3 years of follow-up giving a cumulative mortality rate of 57.5 per 1000 live births with 35% excess girl child mortality. Age at vaccination for the four vaccines did not differ by sex. There was significant excess mortality among girls after immunisation with DTP, for both primary (HR 1.65; 95% CI:1.17-2.32) and DTPb (2.21; 1.24-3.93) vaccinations. No significant excess morality among girls was noted after exposure to BCG 1.06 (0.67-1.67) or measles 1.34 (0.85-2.12) vaccine., Conclusion: This study supports the contention that DTP vaccination is partially responsible for higher mortality among girls in this study population., (© 2013 John Wiley & Sons Ltd.)

Objectives: Estimates of treatment effectiveness in epidemiologic studies using large observational health care databases may be biased owing to inaccurate or incomplete information on important confounders. Study methods that collect and incorporate more comprehensive confounder data on a validation cohort may reduce confounding bias., Study Design and Setting: We applied two such methods, namely imputation and reweighting, to Group Health administrative data (full sample) supplemented by more detailed confounder data from the Adult Changes in Thought study (validation sample). We used influenza vaccination effectiveness (with an unexposed comparator group) as an example and evaluated each method's ability to reduce bias using the control time period before influenza circulation., Results: Both methods reduced, but did not completely eliminate, the bias compared with traditional effectiveness estimates that do not use the validation sample confounders., Conclusion: Although these results support the use of validation sampling methods to improve the accuracy of comparative effectiveness findings from health care database studies, they also illustrate that the success of such methods depends on many factors, including the ability to measure important confounders in a representative and large enough validation sample, the comparability of the full sample and validation sample, and the accuracy with which the data can be imputed or reweighted using the additional validation sample information., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Children with sickle cell disease (SCD) are susceptible to recurrent infections, which are often life threatening and necessitate frequent vaccinations. Given the altered baseline immunity and proinflammatory state associated with SCD, we sought to determine the relative safety and efficacy of vaccination in transgenic SCD mice., Methods: Eight-week-old SCD mice were vaccinated with ovalbumin and aluminum hydroxide weekly for 3 wk by the intraperitoneal or intramuscular route. One week after the third vaccination, serum cytokines/chemokines, immunoglobulins, and bronchoalveolar lavage fluid cytokines were measured., Results: Only SCD mice were prone to mortality associated with vaccination, as 40% of the animals died after the intraperitoneal vaccinations and 50% died after the intramuscular vaccinations. Serum IgG2b and IgM were significantly lower in SCD mice than in C57BL/6 mice after vaccination, but ovalbumin-specific IgE was significantly higher. Serum interleukin (IL)-1α, IL-2, IL-5, macrophage inflammatory protein 1α, and granulocyte macrophage-colony stimulating factor were significantly lower in SCD mice than in C57BL/6 mice after vaccination, whereas bronchoalveolar lavage fluid IL-1β and IL-6 were increased., Conclusion: Mice with SCD appear to have a dysregulated immune response to vaccination. Thus, the relative safety and immunogenicity of vaccination should be studied in greater detail in the context of SCD.

Background: The increasing life expectancy in most European countries has resulted in growth of the population 50 and older. This population is more susceptible to infectious diseases because of immunosenescence, co-morbidity and general frailty. Thus, to promote healthy aging, vaccination against vaccine-preventable-diseases could be one strategy. In addition to its possible individual benefits, vaccination may also yield social benefits, such as a lower overall cost of healthcare. Most European countries, however, offer only influenza vaccine although vaccines for pneumococcal disease, herpes zoster, pertussis, and hepatitis A are also available. Our aim is to review the knowledge of these vaccines for persons aged 50 and older and explore the arguments for expanding current vaccination programmes beyond just influenza., Methods: The evaluation model of Kimman et al. was used to assess herpes zoster, pneumococcal disease, pertussis and hepatitis A in terms of four domains: pathogen, vaccine, disease outcomes and cost-effectiveness. The sources were Dutch surveillance systems, seroprevalence studies and the international literature., Results: Herpes zoster, pneumococcal disease and pertussis are prevalent among persons aged 50 and older. Vaccines vary in effectiveness and have mild and self-limiting side effects. Vaccination against pneumococcal disease and pertussis causes adaptation of the responsible pathogen. For pertussis and hepatitis A, the vaccine is not registered specifically for the elderly population. Vaccination against herpes zoster and pertussis could improve quality of life, while vaccination against pneumococcal disease and hepatitis A prevents mortality. However, only vaccination against herpes zoster and pneumococcal disease appear to be cost-effective., Conclusions: Vaccination can improve the health of the elderly population. As our review shows, however, the data are too incomplete to accurately judge its potential impact. More research is needed to determine how vaccination can most effectively improve the health of the growing population 50 years and older.

Objective: To compare mortality rates due to respiratory diseases among elderly individuals residing in the Federal District of Brasília, Brazil, prior to and after the implementation of a national influenza vaccination campaign., Methods: This was an ecological time series analysis. Data regarding the population of individuals who were over 60 years of age between 1996 and 2009 were obtained from official databases. The variables of interest were the crude mortality rate (CMR), the mortality rate due to the respiratory disease (MRRD), and the proportional mortality ratio (PMR) for respiratory diseases. We performed a qualitative analysis of the data for the period prior to and after the implementation of the vaccination campaign (1996-1999 and 2000-2009, respectively)., Results: The CMR increased with advancing age. Over the course of the study period, we observed reductions in the CMR in all of the age brackets studied, particularly among those aged 80 years or older. Reductions in the MRRD were also found in all of the age groups, especially in those aged 80 years or older. In addition, there was a decrease in the PMR for respiratory diseases in all age groups throughout the study period. The most pronounced decrease in the PMR for respiratory diseases in the > 70 year age bracket occurred in 2000 (immediately following the implementation of the national vaccination campaign); in 2001, that rate increased in all age groups, despite the greater adherence to the vaccination campaign in comparison with that recorded for 2000., Conclusions: Influenza vaccination appears to have a positive impact on the prevention of mortality due to respiratory diseases, particularly in the population aged 70 or over.

Background: WHO recommends oral polio vaccine at birth (OPV0) in polio endemic countries. During a period without OPV in Guinea-Bissau in 2004, we observed that not receiving OPV0 was associated with significantly decreased mortality in boys and better immune response to BCG vaccination. In 2007, whilst conducting a trial of BCG and vitamin A supplementation (VAS) at birth to low birthweight (LBW) children, OPV was again lacking for a short period. We used this natural experiment to test the previous observations., Methods: In the trial LBW infants were randomised to early or delayed BCG and VAS or placebo at birth. We noted whether the children received OPV0 or not. We compared children who received No OPV0 with those who received OPV0 in the 2 months before and the 2 months after the period without OPV. Mortality was compared in Cox regression models providing adjusted hazard ratios (aHR); the immune response to BCG was assessed in Poisson models providing adjusted prevalence ratios (aPR)., Results: Ninety-nine children received No OPV0 and were compared with 243 children who received OPV0. No OPV0 was associated with insignificantly higher mortality during the first year of life, the aHR being 1.83 (95% CI: 0.93-3.61). The effect was similar in boys and girls. Overall, there was no significant association between No OPV0 and having a positive PPD response (aPR=1.33 (0.64-2.78)) or a scar (aPR=1.02 (0.93-1.11)) after BCG vaccination, though No OPV0 boys were more likely to develop a scar (aPR: 1.10 (1.01-1.20))., Conclusions: The findings did not support our previous observation that not receiving OPV0 was associated with reduced mortality in boys. The findings weakly supported that OPV0 leads to a dampened response to simultaneously administered BCG vaccine in boys., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

In this study, the Vaccine Adverse Event Reporting System (VAERS) database, 1990-2010, was investigated; cases that specified either hospitalization or death were identified among 38,801 reports of infants. Based on the types of vaccines reported, the actual number of vaccine doses administered, from 1 to 8, was summed for each case. Linear regression analysis of hospitalization rates as a function of (a) the number of reported vaccine doses and (b) patient age yielded a linear relationship with r(2) = 0.91 and r(2) = 0.95, respectively. The hospitalization rate increased linearly from 11.0% (107 of 969) for 2 doses to 23.5% (661 of 2817) for 8 doses and decreased linearly from 20.1% (154 of 765) for children aged <0.1 year to 10.7% (86 of 801) for children aged 0.9 year. The rate ratio (RR) of the mortality rate for 5-8 vaccine doses to 1-4 vaccine doses is 1.5 (95% confidence interval (CI), 1.4-1.7), indicating a statistically significant increase from 3.6% (95% CI, 3.2-3.9%) deaths associated with 1-4 vaccine doses to 5.5% (95% CI, 5.2-5.7%) associated with 5-8 vaccine doses. The male-to-female mortality RR was 1.4 (95% CI, 1.3-1.5). Our findings show a positive correlation between the number of vaccine doses administered and the percentage of hospitalizations and deaths. Since vaccines are given to millions of infants annually, it is imperative that health authorities have scientific data from synergistic toxicity studies on all combinations of vaccines that infants might receive. Finding ways to increase vaccine safety should be the highest priority.

Background: The status of immunocompromised patients is well recognized in end stage renal disease (ESRD). As described recently, this acquired immune dysfunction in the uremic milieu may be one of the main pathogenic factors for mortality in ESRD. The aim of this study was to determine the relationship between the immune response following a hepatitis B vaccination (HBV vaccination) and the survival of maintenance dialysis patients., Methods: A total of 156 patients (103 on hemodialysis and 53 on continuous ambulatory peritoneal dialysis) were recruited. After receiving a full dose of the HBV vaccination, all patients were followed up for to 5 years to evaluate the association of patient survival, cause of mortality, and immune response., Results: The response rate to the hepatitis B vaccination was 70.5%. There was no significant association between the immune response and the 5-year survival rate (p =0.600) or between the post-vaccination anti-HBs titers and the 5-year survival rate (p = 0.201). The logistic prediction model with the coefficient as non-response following HBV vaccination, diabetes mellitus, old age, and low albumin level could significantly predict infection-cause mortality (sensitivity = 0.842, specificity = 0.937)., Conclusion: There was no significant association between the immune response to HBV vaccination and the 5-year survival rate. However, non-response following HBV vaccination might be associated with infection-cause mortality in dialysis patients.

Objective: To analyse the data reported by the national surveillance system of Brazil, including data on diarrhoea mortality and hospital admissions before and after rotavirus vaccine introduction, and evaluate the impact of its widespread use under operational conditions., Method: Retrospective analysis of routinely collected data was reported by several surveillance systems of Brazil, comprising an 8-year period of all diarrhoea-related hospitalisations and deaths in children <5 years old (2002-2009). Linear regressions were used to compare trends of diarrhoea hospitalisations and deaths before and after vaccine introduction (2002-2005 vs. 2006-2009)., Results: There was a long-term reduction in hospitalisations that preceded the introduction of the vaccine. This reduction was more marked in <1-year-old than in 1- to 4-year-old children. All-cause diarrhoea hospitalisations decreased further after vaccine introduction and the decrease was larger in <1-year-old (-35.6%) than in 1- to 4-year-old children (-12.3%). The number of deaths was decreasing before vaccine introduction, and the decrease also accelerated after vaccine introduction, with deaths halving in <1-year-old and decreasing by 32.9% in 1- to 4-year-old children. The linear relationships between hospitalisations and deaths were statistically different before and after vaccine introduction., Conclusions: The data demonstrate a decreasing trend in all-cause diarrhoea-related hospitalisations and deaths in children <5 years of age. These reductions were steeper between 2006 and 2009, highlighting the potential beneficial effect of the rotavirus vaccine associated with all-cause diarrhoeal disease., (© 2011 Blackwell Publishing Ltd.)

Background: The risk of immediate adverse events due to the inflammation created by a vaccine is a potential concern for pediatric vaccine programs., Methods: We analyzed data on children born between March 2006 and March 2009 in the province of Ontario. Using the self-controlled case series design, we examined the risk of the combined endpoint of emergency room visit and hospital admission in the immediate 3 days post vaccination to a control period 9-18 days after vaccination. We examined the end points of emergency room visits, hospital admissions and death separately as secondary outcomes., Results: We examined 969,519 separate vaccination events. The relative incidence of our combined end point was 0.85 (0.80-0.90) for vaccination at age 2 months, 0.74 (0.69-0.79) at age 4 months and 0.68 (0.63-0.72) at age 6 months. The relative incidence was reduced for the individual endpoints of emergency room visits, admissions and death. There were 5 or fewer deaths in the risk interval of all 969,519 vaccination events. In a post hoc analysis we observed a large reduction in events in the immediate 3 days prior to vaccination suggesting a large healthy vaccinee effect., Conclusion: There was no increased incidence of the combined end point of emergency room visits and hospitalizations in the 3-day period immediately following vaccination, nor for individual endpoints or death. The health vaccinee effect could create the perception of worsening health following vaccines in the absence of any vaccine adverse effect and could also mask an effect in the immediate post-vaccination period., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background: Improving child survival through various health interventions has been one of the main preoccupations of public health programs in developing nations. However, efforts to understand the child death determinants and determine whether the health interventions are really contributing to the reduction of mortality were not satisfactory. The purpose of this study is to identify determinants and causes of child mortality., Methods: The study was conducted in the town of Jimma, Ethiopia, using a case control study design. Cases were identified through enumeration of all children and deaths prior to interview of the study subjects. Controls were under five children of the same age (+/-2 months) residing in the nearest household. Data was entered into EPI -info 6.4 software and analyzed using SPSS., Results: Seventy four cases and 222 controls were included in the study. The study found that children who never breast fed [OR = 13.74, 95%CI (3.34, 56.42]] and children with mothers having more than five children [OR = 3.34, 95%CI (1.27, 8.76)] were more likely to die than their counterparts. Vaccination reduced the risk of death [OR=.26, 95%CI (0.10, 0.67) significantly. Pneumonia was the most common immediate cause of death [29.7% (95% CI (19.66, 41.48)] followed by acute diarrhea and malaria each contributing for 23% [95%CI (13.99, 34.21)] of deaths., Conclusion: Immunization, breastfeeding and low parity mothers were independently found to be protective from childhood death. Strengthening the child survival initiatives, namely universal child immunization, family planning and breast feeding - is strongly recommended.

Background: The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy., Methodology/principal Findings: The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999-2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1-23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0-1, 0-7, and 0-14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0-7 and 0-14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined., Conclusions: The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age.

Background: The historical Japanese influenza vaccination program targeted at schoolchildren provides a unique opportunity to evaluate the indirect benefits of vaccinating high-transmitter groups to mitigate disease burden among seniors. Here we characterize the indirect mortality benefits of vaccinating schoolchildren based on data from Japan and the US., Methods: We compared age-specific influenza-related excess mortality rates in Japanese seniors aged ≥65 years during the schoolchildren vaccination program (1978-1994) and after the program was discontinued (1995-2006). Indirect vaccine benefits were adjusted for demographic changes, socioeconomics and dominant influenza subtype; US mortality data were used as a control., Results: We estimate that the schoolchildren vaccination program conferred a 36% adjusted mortality reduction among Japanese seniors (95%CI: 17-51%), corresponding to ∼1,000 senior deaths averted by vaccination annually (95%CI: 400-1,800). In contrast, influenza-related mortality did not change among US seniors, despite increasing vaccine coverage in this population., Conclusions: The Japanese schoolchildren vaccination program was associated with substantial indirect mortality benefits in seniors.

Objective: To evaluate the safety of vaccine by analyzing the death cases after vaccination., Methods: To collect and analyze infomation of death cases related after vaccination in Shanghai during 2006-2008., Results: In the 6 death cases reported after vaccination, 1 case was rare serious adverse events following immunization (AEFI), respiratory and circulatory failure caused by allergic disease. Other 5 cases were not related to vaccination., Conclusions: Coincidental event is common type in death after vaccination. Monitoring adverse events following immunization is the key measure to deal with the death cases following immunization.

It is widely believed that influenza (flu) vaccination of the elderly reduces all-cause mortality, yet randomized trials for assessing vaccine effectiveness are not feasible and the observational research has been controversial. Efforts to differentiate vaccine effectiveness from selection bias have been problematic. The authors examined mortality before, during, and after 9 flu seasons in relation to time-varying vaccination status in an elderly California population in which 115,823 deaths occurred from 1996 to 2005, including 20,484 deaths during laboratory-defined flu seasons. Vaccine coverage averaged 63%; excess mortality when the flu virus was circulating averaged 7.8%. In analyses that omitted weeks when flu circulated, the odds ratio measuring the vaccination-mortality association increased monotonically from 0.34 early in November to 0.56 in January, 0.67 in April, and 0.76 in August. This reflects the trajectory of selection effects in the absence of flu. In analyses that included weeks with flu and adjustment for selection effects, flu season multiplied the odds ratio by 0.954. The corresponding vaccine effectiveness estimate was 4.6% (95% confidence interval: 0.7, 8.3). To differentiate vaccine effects from selection bias, the authors used logistic regression with a novel case-centered specification that may be useful in other population-based studies when the exposure-outcome association varies markedly over time.