Guillain-Barré syndrome and influenza vaccines: A meta-analysis

Cases of Guillain-Barré syndrome (GBS) have been occasionally associated with influenza vaccines; this possible risk, even if rare, is a matter of much concern. To investigate the strength of this association, a systematic review and a meta-analysis have been conducted; for the purpose, controlled observational studies addressing the risk of GBS associated with different influenza vaccines were sought. We finally selected 39 studies of interest published between 1981 and 2014 (seasonal influenza vaccines, 22; pandemic influenza vaccines, 16; both vaccines simultaneously administered, 1); funnel plot did not identify publication bias. At the association between any influenza vaccine – whether seasonal or pandemic – with GBS, the overall relative risk was 1.41 (95% CI, 1.20–1.66). Pandemic vaccines presented a higher risk (RR = 1.84; 95% CI, 1.36–2.50) compared to seasonal vaccines (RR = 1.22; 95% CI, 1.01–1.48); the latter should be considered as marginally statistically significant. Pandemic adjuvanted vaccines were not found to be related to a higher risk compared to non-adjuvanted vaccines. The results of the present meta-analysis point to a small but statistically significant association between influenza vaccines, particularly the pandemic ones, and GBS, which is consistent with current explanations upon possible mechanisms for this condition to appear.     

Guillain-Barré syndrome

Guillain-Barré syndrome is the most common paralytic illness affecting children and adolescents in countries with established immunization programs. The term is currently used to encompass a group of disorders in which an autoimmune response occurs days or weeks after an antecedent infection or event (e.g., immunization) and results in an acute polyradiculoneuropathy with flaccid weakness, areflexia, and increased cerebrospinal fluid protein. This chapter reviews the epidemiology, clinical presentation, diagnostic criteria, pathogenesis, treatment, and outcome of this condition.     

Guillain-Barré syndrome, greater Paris area

We studied 263 cases of Guillain-Barré syndrome from 1996 to 2001, 40% of which were associated with a known causative agent, mainly Campylobacter jejuni (22%) or cytomegalovirus (15%). The cases with no known agent (60%) peaked in winter, and half were preceded by respiratory infection, influenza-like syndrome, or gastrointestinal illness.     

Guillain-Barré syndrome in Stockholm County, 1973--1991

In order to describe the incidence of Guillain-Barré syndrome (GBS) in Stockholm County (SC) and hospital use by GBS patients, we conducted a retrospective epidemiological study on GBS covering 1973--1991, using the Hospital In-patient Register in SC. There were 556 patients, bona fide residents in the county during the study period, discharged from hospitals with GBS diagnosis. The mean annual incidence, age-adjusted to the European population, was 1.84 (2.15 for males and 1.57 for females) per 100,000 population. The incidence increased with age and showed a bimodal distribution with peaks in the 10--29 and 70--79 age-groups. Annual incidence rates were highest in 1978 and 1983. Neither heterogeneity of annual or monthly rates nor linear trends during the period were found to be significant, except in 1978 for patients below 40 years of age, RR 1.72 (95% CI 1.08--2.71) and in 1983 for patients at ages 40 years and over, RR 1.48 (95% CI 1.02--2.16), when compared with GBS incidences in the same age-groups during the remaining study period. The mean ± SD duration of hospital stay, including long-term care or rehabilitation institutions, for GBS patients, was 86 ± 210 days, with considerably longer duration for the elderly. The rate of hospital use by GBS patients was 162 days per 100,000 inhabitants per year. In accordance with results of prior studies in South-West Stockholm and described GBS epidemics in Sweden, this study supports that an etiologically different subgroup of GBS exists at ages below 40 years, and that relevant but small time-space variations, such as the reported zimeldine epidemic in 1983, resist detection by hospital data analysis of pooled GBS cases. Efficient epidemiological surveillance of GBS may require targeted development of clinicoepidemiological tools.     

An epidemiologic and clinical evaluation of Guillain-Barré syndrome reported in association with the administration of swine influenza vaccines

As a result of a court order, computerized summaries of approximately 1,300 cases reported as Guillain-Barré syndrome by state health departments to the Centers for Disease Control during the intensive national surveillance instituted following the swine influenza vaccination program in 1976-1977 became available for further study. Although the data were not uniformly adequate to confirm the diagnosis of Guillain-Barré syndrome, they were sufficient to enable classification according to extent of motor involvement. Vaccinated cases with "extensive" paresis or paralysis occurred in a characteristic epidemiologic pattern closely approximated by a lognormal curve, suggesting a causal relationship between the disease and the vaccine. Cases with "limited" motor involvement showed no such pattern, suggesting that this group included a substantial proportion of cases which were unrelated to the vaccine. The effect attributed to the vaccine lasted for at least six weeks and possibly for eight weeks but not longer. The relative risk of acquiring "extensive" disease over a six-week period following vaccination ranged from 3.96 to 7.75 depending on the particular baseline estimate of expected normal or endemic incidence that was chosen. Correspondingly, the number of cases that could be attributed to the vaccine over the six-week period ranged from 211 to 246, or very slightly higher over an eight-week period if the lowest baseline estimate was used. The total rate of Guillain-Barré syndrome cases attributed to prior use of the vaccine was 4.9 to 5.9 per million vaccinees.     

A tailored COVID-19 vaccination pathway for children 5–11 years in Victoria,Australia

BackgroundProcedural anxiety was anticipated in children 5–11 years during the COVID-19 vaccine rollout in Victoria, Australia, as children in this age group receive few routine vaccines. Therefore, the Victorian state government designed a tailored, child-friendly vaccine program. This study aimed to assess parental satisfaction with elements of the bespoke vaccination pathway.MethodsThe Victorian government and state-run vaccination hubs in Victoria facilitated an online immunisation plan to help parents identify their child’s support needs, and utilised experienced paediatric staff and additional supports for children with severe needle distress and/or disability. All parents/guardians of children 5–11 years who received a COVID-19 vaccine in a vaccination hub were sent a 16-item feedback survey via text message.ResultsBetween 9 February and 31 May 2022 there were 9203 responses; 865 children (9.4%) had a first language other than English, 499 (5.4%) had a disability or special needs, and 142 (1.5%) were Aboriginal or Torres Strait Islander. Most parents (94.4%; 8687/9203) rated their satisfaction with the program as very good or excellent. The immunisation plan was used by 13.5% (1244/9203) of respondents, with usage more common for Aboriginal or Torres Strait Islander children (26.1%; 23/88) or families with a first language other than English (23.5%; 42/179). The child-friendly staff (88.5%, 255/288) and themed environment (66.3%, 191/288) were the most valued measures for vaccination. Additional support measures were required by 1.6% (150/9203) of children in the general population and 7.9%, (17/261) of children with a disability and/or special needs.ConclusionA tailored COVID-19 vaccination program for children 5–11 years, with additional support for children with severe needle distress and/or disability, had high parental satisfaction. This model could be utilised for COVID-19 vaccination in pre-school children and for routine childhood vaccination programs to provide optimal support to children and their families.     

No significant increase in Guillain-Barré syndrome after COVID-19 vaccination in adults: A vaccine adverse event reporting system study

ObjectiveTo investigate the association between Guillain-Barré syndrome (GBS) and COVID-19 vaccination.BackgroundOn July 13, 2021, the US Food and Drug Administration (FDA) released a new warning that Johnson & Johnson COVID-19 vaccine could increase the risk of developing GBS.MethodsThe reporting rate of adult GBS after COVID-19 vaccination, ascertained with Brighton criteria, was compared with the reporting rate after other vaccinations during the same time period, and also compared with the reporting rate during control periods. Statistical methods such as proportion tests, and Pearson’s chi-squared test were utilized to identify significant relationships. Self-controlled and case centered analyses were conducted. A machine learning model was utilized to identify the factors associated with a worse outcome defined as emergency room (ER) or doctor visits, hospitalizations, and deaths.ResultsThe reporting rate of GBS after COVID-19 vaccination was significantly higher than after influenza and other vaccinations (49.7, 0.19, 0.16 per 10 million, p < 0.0001). However, the reporting rate was within the incidence range of GBS in the general population. Using self-controlled and case centered analyses, there was a significant difference in the reporting rate of GBS after COVID-19 vaccination between the risk period and control period (p < 0.0001). There was an estimated 0.7–1.7 per million excess reports of GBS within 6 weeks of COVID-19 vaccination. Machine learning model demonstrated that female gender and age between 18 and 44 are associated with worse outcome. No association was found between the onset interval of GBS and its prognosis.ConclusionsAlthough the reporting rate of GBS after COVID-19 vaccination was not statistically different than that of the general population, the increased reporting of GBS within the first 6 weeks after COVID-19 vaccination, more so than with other vaccinations, suggests that some cases of GBS are temporally associated with COVID-19 vaccination. However, there is a reduction in the reporting rate of GBS after other vaccines, compared to reporting rates pre-COVID-19, highlighting limitations inherent in any passive surveillance system. These findings warrant continuous analysis of GBS after COVID-19 vaccination. Further improvement of the machine learning model is needed for clinical use.     

Guillain-Barré syndrome in patients treated for Hodgkin disease

INTRODUCTION: A 14-year-old boy treated with Hodgkin's disease developed muscular weakness and pain, hypotonia, abolished deep tendon reflexes. Examination of the cerebrospinal fluid showed albuminocytologic dissociation, the characteristic finding of Guillain-Barré syndrome. After high dose steroid treatment complete recovery occurred. DISCUSSION: Paraneoplastic neuropathies may develop in patients with cancer, Guillain-Barré syndrome occurs in patients with active Hodgkin's disease. CONCLUSIONS: Progressive neurological signs may indicate the presence of a malignancy, or in case of chemotherapy shows the activity of the tumour.     

Incidence of Guillain-Barré syndrome following infection with Campylobacter jejuni

Evidence of recent or ongoing Campylobacter jejuni infection has been found in approximately one out of every four cases of Guillain-Barré syndrome (GBS). It is increasingly accepted that C. jejuni infection is an important causal factor for GBS. However, the likelihood of GBS' occurring following an episode of C. jejuni gastroenteritis has not been measured. The authors measured the incidence of GBS in a large cohort of persons with laboratory-confirmed C. jejuni infection. Cases of C. jejuni infection were derived from the Swedish national laboratory reporting system for the years 1987--1995. Follow-up for GBS was carried out using the Swedish national hospital inpatient register. Nine cases of GBS were detected in the cohort, which comprised 29,563 cases of C. jejuni infection--a rate of 30.4 per 100,000 (95% confidence interval: 13.9, 57.8). This compares with an expected incidence of 0.3 per 100,000 in a 2-month period in the general population. GBS is an important but rare complication of C. jejuni infection. The risk of developing GBS during the 2 months following a symptomatic episode of C. jejuni infection is approximately 100 times higher than the risk in the general population.     

The risk of Guillain-Barré syndrome following infection with Campylobacter jejuni

To estimate the incidence of Guillain-Barré syndrome (GBS) following Campylobacter jejuni infection (CI) we studied three populations where outbreaks of CI had occurred involving an estimated 8000 cases. No case of GBS was detected in the 6 months following the outbreaks in the local populations. The point estimate for the risk of GBS following CI estimated in this study was 0 in 8000 (95% confidence interval 0-3).     

Imminent respiratory insufficiency in children resulting from Guillain-Barré syndrome

Early recognition of Guillain-Barré syndrome (GBS) is crucial to anticipate and adequately respond to possible respiratory insufficiency. Young children with GBS frequently have non-specific complaints and are more difficult to examine, which may cause a significant delay in diagnosing GBS. We present 3 children, all boys, aged 22 months, 7 years and 4 years respectively, with GBS in whom the diagnosis was missed upon admission, resulting in a failure to appreciate the risk of acute respiratory insufficiency. Two children had to undergo emergency intubation, and one of these cases had a fatal outcome. Young children with GBS often present with pain and refusal to walk, or with difficulty swallowing, and are often initially misdiagnosed with e.g. tonsillitis or coxitis. These nonspecific symptoms can be a first sign of a progressive polyradiculoneuropathy and should prompt a full neurological examination and timely referral to a paediatric neurological centre with Intensive Care facilities.     

An infant with pain and meningeal irritation due to Guillain-Barré syndrome

In a five-month-old girl, who for a week had cried and displayed a relapse in the motor development, generalised hypotonia and meningism were found. Eventually, the results of the cerebrospinal fluid analysis and electromyography indicated Guillain-Barré syndrome. She was treated with immunoglobulins and made a quick recovery. Guillain-Barré syndrome is an acute or subacute inflammatory demyelinating polyradiculoneuropathy that can occur at any age. In children, the classic symptoms such as a flaccid paralysis and areflexia are not always predominant. Instead, pain is often the most prominent symptom, along with meningism. These symptoms are often insufficiently recognised in practice and as a result of this, delays in the diagnosis of this potentially life-threatening disease often occur.