Despite Safe and Effective Vaccine, Measles Cases and Deaths Increased Worldwide From 2021 to 2022.

This Medical News story discusses the latest data on measles cases, deaths, and vaccination coverage worldwide.

Venous Thrombosis within 30 Days after Vaccination against SARS-CoV-2 in a Multinational Venous Thromboembolism Registry.

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.

Current perspectives for SARS-CoV-2 vaccination efficacy improvement in patients with active treatment against cancer.

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.

Elucidating causes of COVID-19 infection and related deaths after vaccination.

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.

Response to the conjugate pneumococcal vaccine (PCV13) in patients with chronic lymphocytic leukemia (CLL).

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.

High-dose influenza vaccination and mortality among predominantly male, white, senior veterans, United States, 2012/13 to 2014/15.

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.

The match between need and use of health services among healthy under-fives in Denmark: A register-based national cohort study.

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.

A Prospective Cohort Study on the Safety of Infant Pentavalent (DTwP-HBV-Hib) and Oral Polio Vaccines in Two South Indian Districts.

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.

Fatal outcomes following immunization errors as reported to the EudraVigilance: A case series.

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.

Perfil clínico-epidemiológico de las defunciones por influenza con antecedente de vacunación oportuna, México 2010-2018.

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.

INTRODUCCIÓN: Las epidemias de influenza son de mayor riesgo en los extremos de la vida y en personas con comorbilidades. La vacunación efectiva previene la aparición de casos graves y disminuye la mortalidad. OBJETIVO: Describir las defunciones por influenza en México con antecedente de vacunación oportuna, de 2010 a 2018. MÉTODO: Estudio transversal descriptivo en el que se utilizó la base de datos del Sistema de Vigilancia Epidemiológica de Influenza. RESULTADOS: De 2010 a 2018 fallecieron por influenza 65 personas con vacunación, 55 % (n = 36) de las cuales por tipo A (H1N1), 51 % (n = 33) del sexo femenino, la mediana de edad fue de 57 años, 21 % (n = 14) no cumplía la definición operacional de enfermedad tipo influenza o infección respiratoria aguda grave, 83 % (n = 54) tenía al menos una comorbilidad; las comorbilidades más frecuentes fueron diabetes mellitus e hipertensión arterial (32 % cada una); 55 % (n = 36) recibió tratamiento antiviral y solo 8 % (n = 5) no presentaba comorbilidades y tenía tratamiento con oseltamivir. CONCLUSIONES: Las defunciones por influenza con vacunación oportuna representan un porcentaje muy bajo del total. La vacunación contra influenza ha sido una estrategia de prevención específica que disminuye la carga de la enfermedad.

Vaccine-associated kidney diseases: A narrative review of the literature.

Immunization is one of the greatest public health achievements of the 20th 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.

Immune-mediated adverse reactions to vaccines.

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.

[Analysis on the characteristics of suspected vaccine-related deaths in Fujian Province, 2012-2017].

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.

Is early measles vaccination associated with stronger survival benefits than later measles vaccination?

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.

Infanrix hexa and sudden death: a review of the periodic safety update reports submitted to the European Medicines Agency.

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.

Vaccination coverage and mortality after splenectomy: results from an Italian single-centre study.

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.

Is diphtheria-tetanus-pertussis (DTP) associated with increased female mortality? A meta-analysis testing the hypotheses of sex-differential non-specific effects of DTP vaccine.

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.