One or two doses of hepatitis A vaccine in universal vaccination programs in children in 2020: A systematic review

BackgroundHepatitis A virus (HAV) is a global health concern as outbreaks continue to occur. Since 1999, several countries have introduced universal vaccination (UV) of children against HAV according to approved two-dose schedules. Other countries have implemented one-dose UV programs since 2005; the long-term impact of this schedule is not yet known.MethodsWe conducted a systematic literature search in four electronic databases for data published between January 2000 and July 2019 to assess evidence for one-dose and two-dose UV of children with non-live HAV vaccines and describe their global impact on incidence, mortality, and severity of hepatitis A, vaccine effectiveness, vaccine efficacy, and antibody persistence.ResultsOf 3739 records screened, 33 peer-reviewed articles and one conference abstract were included. Rapid declines in incidence of hepatitis A and related outcomes were observed in all age groups post-introduction of UV programs, which persisted for at least 14 years for two-dose and six years for one-dose programs according to respective study durations. Vaccine effectiveness was ≥95% over 3–5 years for two-dose programs. Vaccine efficacy was >98% over 0.1–7.5 years for one-dose vaccination. Antibody persistence in vaccinated individuals was documented for up to 15 years (≥90%) and ten years (≥74%) for two-dose and one-dose schedules, respectively.ConclusionExperience with two-dose UV of children against HAV is extensive, demonstrating an impact on the incidence of hepatitis A and antibody persistence for at least 15 years in many countries globally. Because evidence is more limited for one-dose UV, we were unable to draw conclusions on immune response persistence beyond ten years or the need for booster doses later in life. Ongoing epidemiological monitoring is essential in countries implementing one-dose UV against HAV. Based on current evidence, two doses of non-live HAV vaccines are needed to ensure long-term protection.     

Twenty-five years of the WHO vaccines prequalification programme (1987–2012): Lessons learned and future perspectives

The World Health Organization (WHO) vaccines prequalification programme was established in 1987. It is a service provided to United Nations procurement agencies to ensure that the vaccines supplied through these agencies are consistently safe and effective under conditions of use in national immunization programmes. This review describes the purpose and aims of the programme, its evolution during 25 years of existence, its added value, and its role in the context of the WHO strategy to ensure the global availability of vaccines of assured quality. The rationale for changes introduced during the implementation of the programme is provided. The paper also discusses the resources involved, both human and financial, its performance, strengths and weaknesses and steps taken to maximize its efficiency. This historical perspective is used to inform proposed future changes to the service.     

Robot-assisted laparoscopic repair of perineal hernia after abdominoperineal resection: A case report and review of the literature

IntroductionPerineal hernia is a protrusion of the pelvic floor containing intra-abdominal viscera. The occurrence of postoperative perineal hernia after abdominoperineal resection (APR) is rare, but reports have indicated a recent increase in occurrence following surgical treatment for rectal cancer. This has been attributed to a shift towards extralevator abdominoperineal resection, together with more frequent and long-term use of neoadjuvant therapy.Presentation of caseHere, we report the case of a patient who underwent APR for cancer. Twenty months postoperative, a perineal hernia was detected. The patient was electively scheduled for surgery. Robot-assisted laparoscopy was performed using the da Vinci Surgical System. The perineal hernia was repaired by primary closure with the placement of Symbotex Composite mesh as reinforcement for the pelvic floor. The surgery was performed without any adverse events, and the patient was discharged the day after surgery. Clinical follow-up proceeded at the designated time intervals without difficulties.DiscussionRecurrence rates of perineal hernia remain high, and surgeons face numerous challenges related to poor view, suturing and mesh placement in the deep pelvis. Numerous approaches have been described, but there is still no consensus as to the optimal repair technique for perineal hernia.ConclusionSymptomatic perineal hernias can feasibly be repaired with robot-assisted laparoscopy. Furthermore, suturing and mesh placement require less effort with the robot approach when compared to the open and laparoscopic approaches. These promising findings are demonstrated in the included video.     

Infant pertussis and maternal immunity: The curious case of Canada

BackgroundThe United Kingdom (UK) and Canada use the same acellular pertussis vaccine and both experienced large pertussis outbreaks in the past, occurring in the 1980s in the UK and 1990s in Canada, yet current epidemiology differs. A national outbreak with infant deaths occurred in the UK in 2012, yet outbreaks remain localized and death from pertussis rare in Canada.AimWe explored whether past outbreaks in children may influence future risk when those children become parents.MethodsWe conducted an ecological within-country birth cohort analysis in women of childbearing age of the relative risk of ever having pertussis infection by two points in time, 2002 and 2012, comparing with 1992 as the baseline. We used notified cases of pertussis in England and Wales and Canada to compare trends in relative risk. We projected forward to 2022 in Canada assuming incidence remained stable.ResultsIn Canada, the cumulative risk of previous pertussis was similar in 2002 and 2012 and, in both periods, was higher than in 1992. In England and Wales, the cumulative risk of pertussis fell stepwise from 1992 to 2012. Projecting forwards, the pattern of risk in Canada becomes similar to England and Wales in 2022.ConclusionsWidespread pertussis outbreaks in children may reduce the risk of pertussis in infants when those children become parents. Further research is needed to determine the mechanism. As birth cohorts that experienced outbreaks grow past childbearing age, pertussis burden in infants in Canada may increase, following trends observed in England and Wales.     

The Use of Cost‐Effectiveness Analysis for Pediatric Immunization in Developing Countries

Context: Developing countries face critical choices for introducing needed, effective, but expensive new vaccines, especially given the accelerated need to decrease the mortality of children under age five and the increased immunization resources available from international donors. Cost‐effectiveness analysis (CEA) is a tool that decision makers can use for efficiently allocating expanding resources. Its use in developing countries, however, lags behind that in industrialized countries. Methods: We explored how CEA could be made more relevant to immunization policymaking in developing countries by identifying the limitations for using CEA in developing countries and the impact of donor funding on the CEA estimation. We conducted a comprehensive literature search using formal search protocols and hand searching indexed and gray literature sources. We then systematically summarized the application of CEA in industrialized and developing countries through thematic analysis, focusing on pediatric immunization and methodological and contextual issues relevant to developing countries. Findings: Industrialized and developing countries use CEA differently. The use of the Disability‐Adjusted Life Year (DALY) outcome measure and an alternative generalized cost‐effectiveness analysis approach is restricted to developing countries. In pediatric CEAs, the paucity of evaluations and the lack of attention to overcoming the methodological limitations pertinent to children's cognitive and development distinctiveness, such as discounting and preference characterization, means that pediatric interventions may be systematically understudied and undervalued. The ability to generate high‐quality CEA evidence in child health is further threatened by an inadequate consideration of the impact of donor funding (such as GAVI immunization funding) on measurement uncertainty and the determination of opportunity cost. Conclusions: Greater attention to pediatric interventions and donor funding in the conduct of CEA could lead to better policies and thus more worthwhile and good‐value programs to benefit children's health in developing countries.     

A perspective for atherosclerosis vaccination: Is there a place for plant-based vaccines?

Alternatives to pharmacological treatments for atherosclerosis are highly desirable in terms of cost and compliance. During the last two decades several vaccination strategies have been reported as an effort to develop immunotherapeutic treatments. This approach consists on eliciting immune responses able to modulate either the atherosclerosis-associated inflammatory processes or the activity of some physiological mechanisms that are up-regulated under this pathologic condition. In particular, the apolipoprotein B100 (ApoB100) and the cholesterilester transferase protein (CETP) have been targeted in these strategies. It is considered that recent progress in the development of experimental models of oral vaccines against atherosclerosis has opened a new avenue in the field: as plant-based vaccines are considered a viable platform for vaccine production and delivery at low costs, they could serve as an oral-delivered therapeutic approach for atherosclerosis in an economical and patient-friendly manner. The rationale of the design, development and evaluation of possible plant-based vaccines against atherosclerosis is discussed in this review. We identify within this approach a significant trend that will positively impact the field of atherosclerosis vaccination.     

A new challenge in forensic toxicology exemplified by a case of murder under the influence of a synthetic cannabinoid – AM-2201

Among new psychoactive substances (NPS) available on the narcotic market, a significant number consists of synthetic cannabinoids commonly known as smokable herbal “spice” and “K2”, and which are legally treated as a legal alternative to marijuana. The dearth of information on the pharmacology of these intoxicants as they are introduced into the market has created the urgent need among healthcare providers for case studies on the substances belonging to this group, both in terms of the consequences of using such intoxicants, and in methods of detection. The subject of the present report is a multi-parameter analysis of a criminal case of an 18-year-old male who was charged with murder of his female relative and attempted murder of two other victims by stabbing. The defendant pleaded guilty, but he claimed that he had been acting without volition, because he was under the influence of the synthetic cannabinoid AM-2201, which had been purchased from a dealer as a 10 g package labelled “Mr Green – No bad trip”. Analytical methods including gas chromatography – electron ionization – quadrupole ion trap mass spectrometry (GC-EI-QIT/MS) and liquid chromatography, electrospray ionization, tandem mass spectrometry (LC-ESI-MS-MS) were developed to determine the presence of AM-2201 in the Mr Green – No Bad Trip, and in the blood of the perpetrator, respectively. Toxicological findings are discussed in the context of psychoactive and adverse physical effects resulting from the presence of AM-2201 in the human body; the observations were also analyzed in conjunction with data from the literature.     

Immunization of newborns with bacterial conjugate vaccines

Bacterial conjugate vaccines are based on the principle of coupling immunogenic bacterial capsular polysaccharides to a carrier protein to facilitate the induction of memory T-cell responses. Following the success of Haemophilus influenzae type b conjugate vaccines in the 1980s, conjugate vaccines for Streptococcus pneumoniae and Neisseria meningitidis infections were developed and proven to be effective in protecting children against invasive disease. In this review, the use of conjugate vaccines in human newborns is discussed. Neonatal Haemophilus influenzae type b and pneumococcal conjugate vaccination schedules have been trialed and proven to be safe, with the majority of studies demonstrating no evidence for the induction of immune tolerance. Whether their neonatal administration also results in an earlier induction of clinical protection in the first 2–3 critical months of life is still to be demonstrated.     

Seasonal variation in rates of emergency room visits and acute admissions following recommended infant vaccinations in Ontario,Canada: A self-controlled case series analysis

ObjectivesTo determine if birth month has an effect on the incidence of adverse events following the 2- and 12-month recommended vaccinations.Study designUsing health administrative databases, we conducted a population-based retrospective cohort study and employed a self-controlled case series analysis approach. We included children born in Ontario, Canada between April 1st 2002 and March 31st 2010 who received the diphtheria, tetanus, pertussis, inactivated poliovirus and Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine recommended at 2 months and/or the measles, mumps, and rubella vaccine recommended at 12 months. We calculated the relative incidence (RI) of hospitalizations and emergency room visits within a pre-specified risk period compared to a control period following vaccination. We measured the effect of birth month using relative incidence ratios (RIRs) to compare the RI for infants born in each month to that for the month having the lowest RI.ResultsFor the 2-month vaccination, we observed the lowest and highest RIs for infants born in October and April, respectively. The RIR (95% CI) for April compared to October was 2.06 (1.59–2.67, p < 0.0001), consistent with a strong seasonal effect. For the 12-month vaccination, November births had the lowest RI, whereas August births had the highest. The RIR (95% CI) for August compared to November was 1.52 (1.30–1.77, p < 0.0001).ConclusionsOur findings suggest a seasonal effect on susceptibility to adverse events following vaccination exists. Further study will be important to elucidate potential biological and/or behavioral explanations for the seasonal effect we observed.