Acute disseminated encephalomyelitis (ADEM) and Guillain-Barré syndrome (GBS) are distinct demyelinating disorders that share an autoimmune pathogenesis and prior history of viral infection or vaccination. Our patient is a 10 years with acute flaccid paralysis, quadriparesis (lower limbs affected more than upper limbs), generalized areflexia and urinary retention. He had difficulty in speech and drooling of saliva. He also presented with raised intracranial pressure with papilledema; then bilateral optic neuritis developed during the later course of illness. Based on the temporal association and exclusion of alternative etiologies, diagnosis of the association between ADEM and GBS was made. Electro-diagnosis (electromyography-nerve conduction velocity) and magnetic resonance imaging study supported our diagnosis. He improved remarkably after treatment with intravenous immunoglobulin and intravenous methylprednisolone.

Two cases of conjugal contact transfer vaccinia are described. Each patient had intimate contact after their respective partners, active-duty military personnel, received the smallpox vaccination.

Three cases of cross-infection after smallpox vaccination are described, in two of which the outcome was fatal. Probably all occurred because simple precautions were not observed at the time of vaccination--for example, exclusion of contraindications and warnings about risks. If those countries still requiring evidence of vaccination for entry were to abolish this rule, however, the risk of cross-infection could be eliminated. Vaccinating a person with contraindications is justified only when exposure to smallpox has occurred.

The antiperoxidative effect of coriander seeds (Coriandrum sativum) was studied in rats administered high fat diet. Significant decrease in the levels of lipid peroxides, free fatty acids and glutathione was observed when compared to control group whereas the activity of antioxidant enzymes showed increase.

We report a child presenting with severe demyelinating myelitis complicated with critical illness polyneuropathy. This previously healthy 8-month-old boy presented with acute superior limb weakness, absent tendon reflexes, and respiratory failure. Spinal magnetic resonance imaging showed an extensive cervical demyelinating lesion. Spinal cord trauma was suspected and high doses of dexamethasone were administered. Electromyography and nerve conduction studies showed absence of compound muscle action potentials and sural nerve sensory action potential, which was suggestive of a severe Guillain-Barré syndrome. However, intravenous immunoglobulins did not induce any improvement. Afterward, sural nerve biopsy showed a mild neuropathy, but muscle biopsy revealed abnormalities compatible with severe critical illness myopathy. After 5 months of evolution without improvement, the patient died following withdrawal of life support therapy. This case highlights the possible occurrence of critical illness polyneuromyopathy when treatment with corticosteroids are used in patients with acute demyelinating myelitis.

BACKGROUND:In addition to antigens, vaccines contain small amounts of preservatives, adjuvants, and residual substances from the manufacturing process. Some parents have concerns about the safety of these ingredients, yet no large epidemiological studies have specifically examined associations between health outcomes and vaccine ingredients, other than thimerosal. This study examined the extent to which the Vaccine Safety Datalink (VSD) could be used to study vaccine ingredient safety in children.

METHODS:Children born 2004-2011 were identified in VSD data. Using immunization records, two cohorts were identified: children who were up-to-date and children who were undervaccinated before age 2 years. A database was also created linking vaccine type and manufacturer with ingredient amounts documented in vaccine package inserts. Thirty-four ingredients in two or more infant vaccines were identified. However, only amounts (in mg) for aluminum were consistently documented and commonly contained in infant vaccines. Analyses compared vaccine aluminum exposure across cohorts and determined the statistical power for studying associations between aluminum exposure and hypothetical vaccine adverse events.

RESULTS:Among 408,608 children, mean cumulative vaccine aluminum exposure increased from 1.11 to 4.00mg between ages 92-730 days. Up-to-date children were exposed to 11-26% more aluminum from vaccines than undervaccinated children. Power analyses demonstrated that safety studies of aluminum could detect relative risks ranging from 1.1 to 5.8 for a range of adverse event incidence.

CONCLUSIONS:The safety of vaccine aluminum exposure can be feasibly studied in the VSD. However, possible biological mechanisms and confounding variables would need to be considered before conducting any studies.

INTRODUCTION:A number of safety signals-complex regional pain syndrome (CRPS), postural orthostatic tachycardia syndrome (POTS), and chronic fatigue syndrome (CFS)-have emerged with human papillomavirus (HPV) vaccines, which share a similar pattern of symptomatology. Previous signal evaluations and epidemiological studies have largely relied on traditional methodologies and signals have been considered individually.

OBJECTIVE:The aim of this study was to explore global reporting patterns for HPV vaccine for subgroups of reports with similar adverse event (AE) profiles.

METHODS:All individual case safety reports (reports) for HPV vaccines in VigiBaseuntil 1 January 2015 were identified. A statistical cluster analysis algorithm was used to identify natural groupings based on AE profiles in a data-driven exploratory analysis. Clinical assessment of the clusters was performed to identify clusters relevant to current safety concerns.

RESULTS:Overall, 54 clusters containing at least five reports were identified. The four largest clusters included 71 % of the analysed HPV reports and described AEs included in the product label. Four smaller clusters were identified to include case reports relevant to ongoing safety concerns (total of 694 cases). In all four of these clusters, the most commonly reported AE terms were headache and dizziness andfatigue or syncope; three of these four AE terms were reported in>50 % of the reports included in the clusters. These clusters had a higher proportion of serious cases compared with HPV reports overall (44-89 % in the clusters compared with 24 %). Furthermore, only a minority of reports included in these clusters included AE terms of diagnoses to explain these symptoms. Using proportional reporting ratios, the combination of headache and dizziness with either fatigue or syncope was found to be more commonly reported in HPV vaccine reports compared with non-HPV vaccine reports for females aged 9-25 years. This disproportionality remained when results were stratified by age and when those countries reporting the signals of CRPS (Japan) and POTS (Denmark) were excluded.

CONCLUSIONS:Cluster analysis reveals additional reports of AEs following HPV vaccination that are serious in nature and describe symptoms that overlap those reported in cases from the recent safety signals (POTS, CRPS, and CFS), but which do not report explicit diagnoses. While the causal association between HPV vaccination and these AEs remains uncertain, more extensive analyses of spontaneous reports can better identify the relevant case series for thorough signal evaluation.

INTRODUCTION: Although the hepatitis B vaccination tolerance is generally good, adverse effects, which are specially neurologic and cutaneous, have been observed and some cases of induced diseases with immunological disorders have been reported.

CASE REPORT: A 6 year-old boy presented a cutaneous lupus erythematosus and a severe buccal aphthosis following hepatitis B vaccination. There was no clinical or biological symptom of systemic lupus erythematosus nor of Behçet's disease. Under chloroquine therapy, the cutaneous manifestations of lupus erythematosus disappeared quickly and those of buccal aphthosis improved.

DISCUSSION: Hepatitis B vaccination side effects are probably in relation with a specific or non specific stimulation of the immune system. In our case, cellular immunity is perhaps involved through the HBs antigen. Considering the rarity of these side effects, an individual predisposition seems very likely.

BACKGROUND:Pneumococcal polysaccharide vaccine (PPV) is used in children at high risk of IPD. PPV is generally not considered to induce immunologic memory, whereas pneumococcal conjugate vaccines (PCVs) elicit protective antibody responses in infants and induce immunologic memory. Little is known about the characteristics of immune responses to PCV in children who previously received PCV and PPV in series.

OBJECTIVE:To characterize immune responses to 13-valent pneumococcal CRM197 conjugate vaccine (PCV13; serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) in children vaccinated in infancy with 9-valent pneumococcal-meningococcal C-CRM197 conjugate combination vaccine (PCV9-MnCC), followed by a toddler dose of PCV9-MnCC or 23-valent pneumococcal polysaccharide vaccine (PPV23).

METHODS:Children (n=89) who received PCV9-MnCC in infancy and PPV23 or PCV9-MnCC at age 12 months in a previous (2002-2003) study were vaccinated at age 7.5 years with PCV13; groups PPV23/PCV13 (n=50) and PCV9/PCV13 (n=39). Immunoglobulin (Ig)G antibodies, avidity, and opsonophagocytic activity (OPA) were measured before and at 1 and 4 weeks postvaccination.

RESULTS:One week postvaccination, IgG levels increased significantly for all serotypes in both groups, and>97% of vaccinees achieved IgG≥0.35μg/ml 4 weeks after PCV13 vaccination. The PCV9/PCV13 group had higher IgG responses compared with the PPV23/PCV13 group. The upper limits of the 95% confidence intervals of the PPV23/PCV13:PCV9/PCV13 IgG geometric mean concentration ratios were<1.0 for serotypes 1, 4, 5, 9V, 18C, and 23F at 1 week. OPA and avidity results supported these findings.

CONCLUSIONS:PPV23 vaccination of toddlers may compromise subsequent responses to pneumococcal conjugate vaccines. The clinical relevance of this finding is unclear.

A number of dermatoses have been reported to appear in close temporal or spatial relationship to the intramuscular injection of vaccines. We describe two young children who had morphea consistent with the deep morphea type (morphea profunda) that appeared at the site of a previous vaccination. Trauma has been implicated as an important trigger of morphea, both in children and in adults. Furthermore, vaccines might induce an immune response, which could lead to morphea in predisposed individuals.

Routine childhood vaccination against measles, mumps and rubella has virtually abolished virus-related morbidity and mortality. Notwithstanding this, we describe here devastating neurological complications associated with the detection of live-attenuated mumps virus Jeryl Lynn (MuV) in the brain of a child who had undergone successful allogeneic transplantation for severe combined immunodeficiency (SCID). This is the first confirmed report of MuVassociated with chronic encephalitis and highlights the need to exclude immunodeficient individuals from immunisation with live-attenuated vaccines. The diagnosis was only possible by deep sequencing of the brain biopsy. Sequence comparison of the vaccine batch to the MuVisolated from brain identified biased hypermutation, particularly in the matrix gene, similar to those found in measles from cases of SSPE. The findings provide unique insights into the pathogenesis of paramyxovirus brain infections.

Intramuscular vaccination may lead to loss of subcutaneous fat resulting in skin depression at the site of injection. We report for the first time a delayed lipoatrophy after with AS03-adjuvanted influenza A (H1N1) 2009 vaccine. Inadequate administration into the adipose tissue may be causative. During next pandemic, education to optimal intramuscular administration and prolonged monitoring of adverse effects could be proposed.

BACKGROUND:Anthrax is an acute infectious disease caused by the spore-forming bacterium Bacillus anthracis. Due to the current world threat of unpredictable biological terrorism, the Department of Defense has mandated the systematic vaccination of all US military personnel against this warfare agent. Many may experience al mild flu-like illness and soreness at the injection site, but systemic reactions are rare.

CASE REPORT:We report a delayed and potentially serious life-threatening adverse reaction to anthrax vaccine. A previously healthy 34-year-old male was transported to the emergency department with dyspnea, diaphoresis, pallor, and urticarial wheals on his face, arms, and torso after the administration of the third dose of anthrax vaccine. All symptoms resolved after pharmacological intervention and the patient was discharged. Pharmaco-epidemiological data indicate that 30% of anthrax vaccine recipients experience mild local reactions. With large numbers of military personnel being vaccinated, emergency physicians may encounter more vaccine-related adverse reactions.

INTRODUCTION:Primary prevention by prophylactic vaccination against the major cause of cervical cancer, the carcinogenic human papillomavirus (HPV) types 16 and 18, is now available worldwide. Postlicensure adverse neurological effects have been described. The studies realized after the license are descriptive and limited by the difficulty to obtain the information, despite most of the statistical indexes show that the adverse effects by the vaccine of the HPV are not upper compared with other vaccines, the substimation must be considered.

CASE REPORTS:We describe the cases of four young women that developed demyelinating disease after the vaccination of the HPV, with a rank of time between the administration of the dose and the development of the clinical of seven days to a month, with similar symptoms with the successive doses. We have described six episodes coinciding after the vaccination.

CONCLUSIONS:Have been described seizures, autoimmune disorders such as Guillain-Barre syndrome, transverse myelitis, or motor neuron disease, probably adverse effects following immunization by HPV vaccine. So we suggest that vaccine may trigger an immunological mechanism leading to demyelinating events, perhaps in predisposed young.

The Hepatitis B vaccine is highly effective for the prevention of hepatitis B (HBV) infection. We report the development of chronic HBV infection (Genotype F) in a vaccinated immunocompetent individual with an anti-HBsAb of 35 mIU/mL post completion of vaccine series. HBV vaccine is based on recombinant proteins of genotype-A and D (predominant genotypes in Europe). It may not be as effective for the prevention of more genetically diverse viruses such as genotype F (predominant genotype in Central and South America). Healthcare providers and patients should be aware that the HB vaccine does not confer 100% protection against HBV infection, even in the setting of protective antibody levels. Partners of individuals infected with non-A or -D genotypes should be advised to consider additional precautions to prevent transmission even in the setting protective antibody levels. Surveillance of circulating HBV genotypes should be undertaken to inform public health policy in relation to prevention of HB in high-risk groups such as men who have sex with men.

Case Report:  A 54-year-old man was admitted to the hospital with diabetic ketosis due to hyperglycemia. He had been in good health without history of hyperglycemia. Seven days before admission, he received influenza vaccination. Four days after vaccination, he had general fatigue, thirst and polyuria withoutflu-like symptom. On admission, he showed body weight loss for a couple of days, blood glucose was 29.0mmol/l and HbA1c 40 mmol/mol (5.9%). Fasting and 2h- C Peptide immunoreactivity values were<0.0333nmol/L and 0.0999nmol/L, respectively. GAD Ab and IA-2 Ab were negative, so no autoimmunity seemed to participate in the etiology. HLA genotypes were consistent with susceptibility to fulminant type 1 diabetes. Taken together, he was diagnosed as fulminant type 1 diabetes. In addition, ELISPOT assay also showed no association with T cell-mediated autoimmunity.

Conclusion:  This is the first description of fulminant type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway.

A 1-year-old boy was vaccinated with the Oka strain of varicella just prior to the discovery of a tumor that required intensive antitumor therapy. Three months later he developed herpes zoster, which developed into chronic verrucous lesions that were refractory to treatment with acyclovir and which subsequently disseminated. DNA from a biopsy specimen of a chronic herpes-zoster lesion indicated that the Oka vaccine strain of the the virus caused this severe complication. Analysis of this viral DNA demonstrated a mutation in the viral thymidine kinase gene. Plasmids containing this altered gene were unable to produce functional thymidine kinase in an in vitro translation system. The presence of this mutation would explain the clinical resistance to acyclovir. This is the first report of Oka-strain varicella virus causing severe disease after reactivation and of resistance to acyclovir during an infection caused by this virus.

A 26-year-old woman developed significant unilateral anterior cervical and supraclavicular lymphadenopathy 3 days after receiving her first dose (of a total of three doses) of human papilloma virus (HPV) vaccine. She had no history of lymphadenopathy after other previous immunizations, and had received no vaccines other than HPV at that time. The left-sided lymphadenopathy developed after she was vaccinated in the left deltoid muscle. The spatial and temporal relationships between the appearance of the lymphadenopathy and receipt of the vaccine in the absence of other causal agents strongly suggest that the HPV vaccine was the causal agent. Use of the Naranjo adverse drug reaction probability scale indicated that the HPV vaccine was a probable (score of 6) cause of the patient's adverse reaction. The patient received her second dose of the HPV vaccine 2 months later without further lymphadenopathy. To prevent unnecessary lymph node biopsies and patient concern, clinicians should be aware that lymphadenopathy may occur after HPV vaccination.

CONTEXT:To protect troops against the use of anthrax as a biological weapon, the US Department of Defense began an anthrax vaccination program in 1998. 14 years after the inception of the vaccination program, there is no evidence suggesting vaccination against anthrax carries long-term health risks for Active Duty Soldiers.

OBJECTIVE:To investigate the association between Anthrax Vaccine Adsorbed (AVA) received while on Active Duty and subsequent disability determined by the Veterans Benefits Administration.

DESIGN, SETTING AND PARTICIPANTS:Case-control study nested in the cohort of all Active Duty personnel known to have separated from the US Army between December 1, 1997 and December 31, 2005. Cases were≥10% disabled, determined either by the Army prior to separation (N=5846) or by the Veterans Benefits Administration (VBA) after separation (N=148,934). Controls (N=937,705) separated from the Army without disability, and were not receiving pensions from the VBA as of April 2007. Data were from the Total Army Injury and Health Outcomes Database and the VBA Compensation and Pension and Benefits database.

MAIN OUTCOMES:Disability status (yes/no); for primary disability, percent disabled (≥10%, 20%,>20%) and type of disability.

RESULTS:Vaccination against anthrax was four times more likely among disabled Veterans with hostile fire pay records (HFP, a surrogate for deployment). Vaccinated Soldiers with HFP had lower odds of disability separation from the Army 0.89 (0.80, 0.98); there was no association between vaccine and receiving Army disability benefits among those without HFP (OR=1.05, CI: 0.96, 1.14). Vaccination was negatively associated with receiving VA disability benefits for those with HFP (OR=0.66, CI: 0.65, 0.67), but there was little or no association between vaccine and receipt of VA disability benefits for those without HFP (OR=0.95, CI: 0.93, 0.97).

CONCLUSIONS:Risk of disability separation from the Army and receipt of disability compensation from the VA were not increased in association with prior exposure to AVA. This study provides evidence that vaccination against anthrax is not associated with long term disability.

Despite being more than ten years since its introduction, global acceptance to the human papillomavirus (HPV) vaccine is still low. The immunogenetic background of the host, and HPV antigen recognition, are important in natural HPV infection, and should be taken into account in the understanding of adverse autoimmune reactions by the HPV vaccine in certain groups. There is no doubt of the benefit of vaccines in the reduction of the incidence of infectious diseases, and in the case of HPV, the prevention of persistent infection that would lead to cervical cancer. Side-effects, however, should be closely monitored and reported without any bias, to ensure that the benefits of vaccines outweigh the risks of adverse reactions. In this article we bring the attention on certain adverse effects of the vaccine against HPV that have not been well studied as they are not well defined. We also compare the different approaches on HPV vaccine policies regarding its adverse reactions in countries like Japan and Colombia, vs. the recommendations issued by the WHO.