Clinical-epidemiological profile of deaths from influenza with a history of timely vaccination, Mexico 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.

[Analysis on death from adverse event following immunization surveillance system of Shandong Province during 2011-2016].

Objective: To analyze the occurrence and death of Adverse Event Following Immunization (AEFI) in Shandong province. Methods: Collecting the information of AEFI cases from 2011 to 2016, which were reported through the National AEFI Management System in Shandong province up to January 15, 2017. The autopsy reports of death following immunization were issued by the qualified institutions. The inoculation data from 2011 to 2016 was obtained through Immunization Information Management System of Shandong province. Chi-square test was used to compare the incidence rate of AEFI and mortality related to immunization among different time and age groups. Results: A total of 189 864 512 doses of vaccine were administered in Shandong province during 2011-2016, the total number of AEFI cases was 89 973 and the incidence rate of AEFI was 473.88/1 000 000. The number of death cases was 52 and the mortality rate was 0.27/1 000 000. The incidence rate of AEFI from 2011 to 2016 respectively was 273.63/1 000 000, 405.22/1 000 000, 479.88/1 000 000, 545.13/1 000 000, 500.66/1 000 000, and 627.09/1 000 000 (P<0.001), respectively. The mortality rate from 2011 to 2016 was 0.17/1 000 000, 0.16/1 000 000, 0.25/1 000 000, 0.39/1 000 000, 0.26/1 000 000, and 0.40/1 000 000 (P=0.285), respectively.The mortality rates of HepB, BCG and IPV were the top three. There was statistical significance of the mortality rate among different month-old children (P<0.001). The highest mortality rate was<2 month-old (1.09/1 000 000), and the next was 4-5 month-old (0.54/1 000 000), and the lowest was ≥10 month-old (0.06/1 000 000). The mortality rate of spring (from February to April), summer (from May to July), autumn (from August to October) and winter (from November to January of next year) was 0.41/1 000 000, 0.16/1 000 000, 0.08/1 000 000 and 0.48/1 000 000 (P<0.001), respectively. Among 52 death cases, 26 cases were anatomized, including 3 rare vaccine reaction following immunization and 23 coincidental events; 26 cases were not anatomized, including 17 coincidental events and 9 unknown causes. Conclusion: The AEFI mortality rate of<2 month-old, spring and winter, and the second dose was higher than else, which was similar to normal child mortality. Immunization did not increase the risk of death, and the most deaths following immunization were coincidental events.

Survival of rabid rabbits after intrathecal immunization.

Rabies is a fatal zoonotic disease for which no effective treatment measures are currently available. Rabies virus (RABV) has anti-apoptotic and anti-inflammatory properties that suppress nerve cell damage and inflammation in the CNS. These features imply that the elimination of RABV from the CNS by appropriate treatment could lead to complete recovery from rabies. Ten rabbits showing neuromuscular symptoms of rabies after subcutaneous (SC) immunization using commercially available vaccine containing inactivated whole RABV particles and subsequent fixed RABV (CVS strain) inoculation into hind limb muscles were allocated into three groups. Three rabbits received no further treatment (the SC group), three rabbits received three additional SC immunizations using the same vaccine, and four rabbits received three intrathecal (IT) immunizations, in which the vaccine was inoculated directly into the cerebrospinal fluid (the SC/IT group). An additional three naïve rabbits were inoculated intramuscularly with RABV and not vaccinated. The rabbits exhibited neuromuscular symptoms of rabies within 4-8 days post-inoculation (dpi) of RABV. All of the rabbits died within 8-12 dpi with the exception of one rabbit in the SC group and all four rabbits in SC/IT group, which recovered and started to respond to external stimuli at 11-18 dpi and survived until the end of the experimental period. RABV was eliminated from the CNS of the surviving rabbits. We report here a possible, although still incomplete, therapy for rabies using IT immunization. Our protocol may rescue the life of rabid patients and prompt the future development of novel therapies against rabies.

Sudden death in the first 2 years of life following immunization in the Republic of Korea.

BACKGROUND: Because the peak age for incidence of sudden deaths in infancy temporally coincides with the age of infant primary immunization, some have raised the question as to whether immunization is a risk factor for sudden death in infancy. Recent occurrence of two sudden deaths in infants in Korea has renewed concerns about the causal association between immunization and sudden deaths in infants. METHODS: We carried out a retrospective review of data from the Korea Centers for Disease Control and Prevention Adverse Events Following Immunization Surveillance System and Vaccine Compensation programs. RESULTS: From 1994 to 2011, a total of 45 cases of sudden deaths in the first 2 years of life following immunization were reported in Korea. The causes of death were classified as follows: infectious diseases (n= 13); accidental injuries (n= 7); congenital abnormalities (n= 2); and malignancy (n= 1). Of 20 sudden deaths in infancy, nine deaths met Brighton Collaboration case definition level I and II, and therefore were classified as possible sudden infant death syndrome cases. Hepatitis B vaccine (n= 13) was the most frequent vaccine with temporal association with sudden deaths in the first 2 years of life. CONCLUSION: Few sudden deaths in the first 2 years of life following immunization have been reported, despite the use of universal immunization in Korea. The majority of deaths in infancy did not meet case definition for sudden infant death syndrome. Encouraging investigators to perform thorough investigation, including postmortem autopsy and death scene examination, may promote data comparability and provide guidance on decision-making in the vaccine-safety monitoring and response system in Korea.

Comparative efficacy of immunization with inactivated whole tachyzoites versus a tachyzoite-bradyzoite mixture against neosporosis in mice.

The worldwide economic impact of Neospora caninum infection has caused the development of effective vaccines to become one of the main goals in the field of neosporosis research. In this study, the protection conferred by antigens from inactivated whole tachyzoites (TZ) and a tachyzoite-bradyzoite mixture (TZ-BZ) of N. caninum (Nc-Spain7 isolate) incorporated into a water-in-oil emulsion (W/O) and aluminium hydroxide-ginseng extract (Al/G) was evaluated in mouse models of congenital and cerebral N. caninum infection. Immunization with TZ-BZ induced congenital and cerebral neosporosis exacerbation that was mainly characterized by reduced neonatal median survival time and increased parasite presence in adult mouse brains. The immune response of mice immunized with TZ-BZ was characterized by an increase in IFN-γ expression prior to challenge and an increase in IL-4 expression accompanied with significantly higher levels of antibodies against 2 recombinant bradyzoite-specific proteins (rNcSAG4 and rNcBSR4) after challenge. Immunization with TZ in W/O significantly reduced neonatal mortality, vertical transmission as well as parasite presence in adult mouse brains and induced a strong humoral immune response. The current study demonstrates the critical role of stage-specific antigens and adjuvants on the development of effective inactivated vaccines for the prevention of N. caninum infection.

Epidemiological studies of the 'non-specific effects' of vaccines: I--data collection in observational studies.

Routine vaccination programmes have led to substantial declines in the incidence of most of the target diseases. In these circumstances, vaccine effects beyond those on the target diseases may become evident. Several studies have suggested that certain vaccines may influence mortality in low income settings in ways that cannot be attributed to effects on target diseases. Trials of such 'non-specific' effects are difficult if not impossible to organise; and observational studies of them are prone to serious confounding, because those who do or do not receive vaccines are likely to differ in many ways, some of which relate to their subsequent risk of early death, independent of vaccination. They are also prone to other biases, including the selective loss of vaccination records for children who die. We review these potential sources of bias and suggest what and how data may be collected to optimise the validity of such studies.

Deaths reported to national surveillance for adverse events following immunization in China, 2010-2015.

BACKGROUND: The national Adverse Events Following Immunization (AEFI) surveillance system in China (CNAEFIS) has collected AEFI reports -including deaths following all vaccines used in China since 2008. AIMS: To review reports of AEFI-associated death cases from 2010 to 2015 to assess potential vaccine safety issues. METHODS: Descriptive analysis of epidemiologic characteristic of AEFI-associated death cases and standard causality assessment for reported causes of deaths. To estimate the risk of death after vaccination, we used population data, administered doses and live births to calculate denominators. RESULTS: During 2010-2015, 753 deaths were reported to CNAEFIS from mainland China. Highest numbers were reported in 2013 and 2014 when reporting peak of AEFI-associated deaths occurred after media reports concerning "death following Hepatitis B vaccination" in China. About 95% of deaths were in children <5 years of age and males accounted for 60%. Most common vaccines associated with reports of fatal AEFIs were vaccines in national immunization schedule. In causality assessment, 120 (16.0%) deaths were classified as vaccine-associated reactions such as anaphylactic reactions and disseminated BCG infections; 594 (78.9%) deaths were identified as coincidental events. The main causes of death were asphyxia, and Sudden Infant Death Syndrome. The overall estimated AEFI-associated death rates were: 0.26 per million vaccination doses administered and 0.09 per million population. The neonatal AEFI death rate was 0.77 per million live births. CONCLUSIONS: These data provide reassuring information about the small risk of death following immunization. They also illustrate sensitivity of passive reporting to public information and that peaks in serious AEFI reports should be interpreted with caution. Continuous monitoring and scientific causality assessment for serious AEFIs, including AEFI-associated deaths is imperative to ensure public confidence in the immunization program.

Patterns of childhood immunization and all-cause mortality.

BACKGROUND: Evidence supports the safety of the recommended childhood immunization schedule as a whole. However, additional research is warranted as parents' refusing or delaying vaccinations has increased in recent years. All-cause mortality has been identified as a priority outcome to study in the context of the recommended immunization schedule. METHODS: We included children born January 1, 2004 through December 31, 2009, enrolled in the Vaccine Safety Datalink (VSD) from birth through 18 months of age. We examined vaccination patterns during the first 18 months of life among 8 vaccines, and identified deaths occurring between 19 and 48 months of age. We excluded children with complex chronic conditions, contraindications to vaccination, and deaths due to injuries, congenital anomalies, or diseases with onset prior to 19 months of age. We calculated mortality rates among children with different patterns of immunization, and incidence rate ratios (IRR) using the Cox proportional hazards model for children vaccinated according to the schedule versus undervaccinated children, adjusting for outpatient healthcare utilization, influenza vaccination, sex, and VSD site. RESULTS: Among 312,388 children in the study, 199,661 (64%) were vaccinated according to the schedule, and 112,727 (36%) were delayed or not vaccinated for at least one vaccine dose. Of 18 deaths eligible for analysis, 11 occurred in children following the schedule (2.28 per 100,000 person-years), and seven occurred in undervaccinated children (2.57 per 100,000 person-years). Mortality rates among children following the schedule were not significantly different from those of undervaccinated children when excluding deaths with unknown causes (IRR = 1.29, 95% CI = 0.33-4.99), as well as when including deaths with unknown causes (IRR = 0.84, 95% CI = 0.32-2.99). CONCLUSION: Although there were few deaths, our results do not indicate a difference in risk of all-cause mortality among fully vaccinated versus undervaccinated children. Our findings support the safety of the currently recommended immunization schedule with regard to all-cause mortality.

Randomized Trials Comparing Inactivated Vaccine After Medium- or High-titer Measles Vaccine With Standard Titer Measles Vaccine After Inactivated Vaccine: A Meta-analysis.

BACKGROUND: Observational studies have suggested that girls have higher mortality if their most recent immunization is an inactivated vaccine rather than a live vaccine. We therefore reanalyzed 5 randomized trials of early measles vaccine (MV) in which it was possible to compare an inactivated vaccines [after medium-titer MV (MTMV) or high-titer MV (HTMV)] and a live standard titer MV (after an initial inactivated vaccine). METHODS: The trials were conducted in Sudan, Senegal, The Gambia and Guinea-Bissau. The intervention group received live MTMV or HTMV from 4 to 5 months and then an inactivated vaccine from 9 to 10 months of age; the control children received inactivated vaccine/placebo from 4 to 5 months and standard titer MV from 9 to 10 months of age. We compared mortality from 9 months until end of study at 3 to 5 years of age for children who received inactivated vaccine (after MTMV or HTMV) and standard titer MV (after inactivated vaccine), respectively. The original datasets were analyzed using a Cox proportional hazards model stratified by trial. RESULTS: The mortality rate ratio (MRR) was 1.38 (95% confidence interval: 1.05-1.83) after an inactivated vaccine (after MTMV or HTMV) compared with a standard titer MV (after inactivated vaccine). Girls had a MRR of 1.89 (1.27-2.80), whereas there was no effect for boys, the sex-differential effect being significant (P = 0.02). Excluding measles cases did not alter these conclusions, the MRR after inactivated vaccines (after MTMV or HTMV) being 1.40 (1.06-1.86) higher overall and 1.92 (1.29-2.86) for girls. Control for variations in national immunization schedules for other vaccines did not modify these results. CONCLUSIONS: After 9 months of age, all children had been immunized against measles, and mortality in girls was higher when they had received inactivated vaccines (after MTMV or HTMV) rather than live standard titer MV (after an inactivated vaccine).

The heterologous (non-specific) effects of vaccines: implications for policy in high-mortality countries.

There are important interactions between vaccines, and between vaccines and unrelated (heterologous) infections. In high-mortality regions, until the next vaccine is given, live vaccines such as bacillus Calmette-Guérin (BCG) and measles vaccines reduce mortality from infections such as pneumonia and sepsis. However, non-live vaccines such as diphtheria, tetanus and whole-cell pertussis vaccine (DTP) may increase mortality from infections other than diphtheria, tetanus and pertussis. All-cause mortality might be reduced if an extra dose of Edmonston-Zagreb measles vaccine were given at 20 weeks of age, 4-6 weeks after the third dose of DTP, with no subsequent doses of DTP in girls, and no vitamin A in girls or boys before the second dose of measles vaccine at 9 months of age. Policy should change to increase the proportion of babies given BCG and oral polio vaccine at birth, and should recognize the important differences between BCG, DTP and measles vaccines produced by different manufacturers.

Clinical-epidemiological profile of deaths from influenza with a history of timely vaccination, Mexico 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.

[Review of the sudden death and death following immunization of influenza vaccine].

To evaluate the safety of influenza Type A (H1N1) vaccine by review the incidence, epidemiology characteristics of sudden death and the deaths related with immunization, especially focus on the sudden deaths after immunization of influenza Type A (H1N1) vaccine. Preliminary showed that those deaths reported as adverse events following immunization did not associated with the vaccine. Vaccination campaign according to the national immunization strategy should be carried out and appropriately respond to the emergency events should be strenghtened.

Infant mortality.

Infant mortality continues to be a major public health issue in the United States. Although some preventive strategies for neonatal mortality are emerging for congenital malformations, notably neural tube defects, the prevention of preterm deliveries among disadvantaged populations remains elusive, suggesting the need for different approaches to women's health needs. Despite the lack of success in preventing preterm birth, neonatal mortality rates continued to decline substantially, a decline attributed to improvements in neonatal intensive care associated with surfactant use. The increasing survival of very preterm infants continues to raise questions about their longer term outcomes especially with several recent studies on difficulties in school, and about the need for postdischarge developmental interventions. Attempts to decrease postneonatal mortality received marked attention with the recommendations for specific positioning to prevent sudden infant death syndrome and heightened attention to increased immunization completion rates. The dismal ranking of the United States in infant mortality rates among industrialized countries, however, continues to present a social policy challenge.