OBJECTIVES:To describe the epidemiology of pertussis, and to identify changes in the source of pertussis in infants 6 months of age and under, during the 2008-2012 epidemic in south metropolitan Perth.

DESIGN AND SETTING:Analysis of all pertussis cases notified to the South Metropolitan Population Health Unit and recorded on the Western Australian Notifiable Infectious Disease Database over the study period. Information on the source of pertussis was obtained from enhanced surveillance data.

RESULTS:Notification rates were highest in the 5-9 years age group, followed by the 0-4 years and 10-14 years age groups. There was a significant increase in the proportion of known sources who were siblings from the early epidemic period of 2008-2010, compared with the peak epidemic period of 2011-2012 (14.3% versus 51.4%, p = 0.002). The majority of sibling sources were fully vaccinated children aged 2 and 3 years.

CONCLUSIONS:The incidence of pertussis was highest in children aged 12 years and under in this epidemic. At its peak, siblings were the most important sources of pertussis in infants 6 months and younger, particularly fully vaccinated children aged 2 and 3 years. Waning immunity before the booster at 4 years may leave this age group susceptible to infection. Even if cocooning programs could achieve full vaccination coverage of parents and ensure all siblings were fully vaccinated according to national schedules, waning immunity in siblings could provide a means for ongoing transmission to infants. Recent evidence suggests that maternal antenatal vaccination would significantly reduce the risk of pertussis in infants 3 months of age and under.

Involvement of the central nervous system is common in measles, but rare in rubella. However, rubella virus (RV) can cause a variety of central nervous system syndromes, including meningitis, encephalitis, Guillain-Barré syndrome and sub acute sclerosing panencephalitis. We report the occurrence of one fatal case of the encephalitis associated with measles-rubella (MR) vaccine during an immunization campaign in São Paulo, Brazil. A 31 year-old-man, previously in good health, was admitted at emergency room, withconfusion, agitation, inability to stand and hold his head up. Ten days prior to admission, he was vaccinated with combined MR vaccine (Serum Institute of India) and three days later he developed 'flu-like' illness with fever, myalgia and headache. Results of clinical and laboratory exams were consistent with a pattern of viral encephalitis. During hospitalization, his condition deteriorated rapidly with tetraplegia and progression to coma. On the 3rd day of hospitalization he died. Histopathology confirmed encephalitis and immunohistochemistry was positive for RV on brain tissue. RV was alsodetected by qPCR and virus isolation in cerebrospinal fluid, brain and other clinical samples. The sequence obtained from the isolated virus was identical to that of the RA 27/3 vaccine strain.

A recent report shows a correlation of the historical use of thimerosal in therapeutic immunizations with the subsequent development of autism; however, this association remains controversial. Autism occurs approximately four times more frequently in males compared to females; thus, studies of thimerosal toxicity should take into consideration gender-selective effects. The present study was originally undertaken to determine the maximum tolerated dose (MTD) of thimersosal in male and female CD1 mice. However, during the limited MTD studies, it became apparent that thimerosal has a differential MTD that depends on whether the mouse is male or female. At doses of 38.4-76.8mg/kg using 10% DMSO as diluent, seven of seven male mice compared to zero of seven female mice tested succumbed to thimerosal. Although the thimerosal levels used were very high, as we were originally only trying to determine MTD, it was completely unexpected to observe a difference of the MTD between male and female mice. Thus, our studies, although not directly addressing the controversy surrounding thimerosal and autism, and still preliminary due to small numbers of mice examined, provide, nevertheless, the first report of gender-selective toxicity of thimerosal and indicate that any future studies of thimerosal toxicity should take into consideration gender-specific differences.

OBJECTIVE:General practitioners (GPs) play a crucial role in human papillomavirus (HPV) vaccine acceptance in France. We sought to study: (1) GPs' perceptions of its risks and efficacy and their recommendation behavior; (2) the relative importance of factors associated with the frequency of their recommendations.

METHODS:Cross-sectional observational study in 2014 nested in a national panel of 1712 randomly selected GPs in private practice in France (response rate: 92.4%). We used model averaging to analyze the associations of self-reported frequency of GPs' HPV vaccine recommendations with their perception of its risk-benefit balance and their opinions about the utility of vaccines in general.

RESULTS:Overall, 72% of participants reported frequently recommending HPV vaccination; 60% considered that not enough is known about its risks. The model averaging showed that the factors most associated with infrequent recommendation of this vaccine by GPs were: unfavorable perceptions of its risk-benefit balance (OR=0.13; 95%CI=0.09-0.21; partial R(2)=0.10), a decision not to vaccinate one's own daughter(s) with this vaccine (OR=0.13; 95%CI=0.07-0.24; partial R(2)=0.05), and doubts about vaccine utility in general (OR=0.78; 95%CI=0.71-0.86; partial R(2)=0.03).

CONCLUSION:Although nearly three-quarters of French GPs frequently recommended the HPV vaccine, our findings indicate that a substantial percentage of them are hesitant about it. Doubts about its risks and efficacy strongly influence their recommendation behavior. More research is warranted to help design and evaluate tailored tools and multicomponent intervention strategies to address physician's hesitancy about this vaccine.

Varicella virus vaccine strain Oka (V-Oka) has in rare cases caused zoster in vaccinated people. Despite broad usage of V-Oka, little is known about varicella-zoster virus genomic sequence variation of strains in vaccine and isolates from patients with vaccine adverse events. Direct sequencing of 20 regions of V-Oka-GSK was compared to the sequences of the original V-Oka-Biken, GlaxoSmithKline Oka vaccine (V-Oka-GSK), and Oka-parental (P-Oka) strains. We analyzed single nucleotide polymorphisms (SNP) differentiating the Oka parental and Oka vaccine strains identified in open reading frames (ORFs) 6, 9A, 10, 21, 31, 39, 50, 51, 52, 54, 55, and 59 and eight base substitutions within ORF 62. Sixteen of these SNP impose an amino acid change in the corresponding gene product. The genotypic analysis revealed that (i) both V-Oka-GSK and V-Oka-Biken comprise mixtures of strains represented in variable proportion from lot to lot; (ii) V-Oka-GSK/zoster isolated from the zoster patient had six wild-type SNP in ORF 9A, 10, 21, 52, 55, and 62 (mutation 108838); (iii) none of the six revertant SNP would reliably discriminate Oka vaccine from the wild type; and (iv) the genomic variation found in V-Oka/zoster might be associated with changes in the biological behavior of the virus. Further studies will be needed to identify potential virulence factors in variant vaccine strains.

The use of vaccines including aluminum (Al)-based adjuvants is widespread among small ruminants and other animals. They are associated with the appearance of transient injection site nodules corresponding to granulomas. This study aims to characterize the morphology of these granulomas, to understand the role of the Al adjuvant in their genesis, and to establish the presence of the metal in regional lymph nodes. A total of 84 male neutered lambs were selected and divided into 3 treatment groups of 28 animals each: (1) vaccine (containing Al-based adjuvant), (2) adjuvant-only, and (3) control. A total of 19 subcutaneous injections were performed in a time frame of 15 months. Granulomas and regional lymph nodes were evaluated by clinicopathological means. All of the vaccine and 92.3% of the adjuvant-only lambs presented injection-site granulomas; the granulomas were more numerous in the group administered the vaccine. Bacterial culture in granulomas was always negative. Histologically, granulomas in the vaccine group presented a higher degree of severity. Al was specifically identified by lumogallion staining in granulomas and lymph nodes. Al median content was significantly higher ( P<.001) in the lymph nodes of the vaccine group (82.65μg/g) compared with both adjuvant-only (2.53 μg/g) and control groups (0.96 μg/g). Scanning transmission electron microscopy demonstrated aggregates of Al within macrophages in vaccine and adjuvant-only groups. In these two groups, Al-based adjuvants induce persistent, sterile, subcutaneous granulomas with macrophage-driven translocation of Al to regional lymph nodes. Local translocation of Al may induce further accumulation in distant tissues and be related to the appearance of systemic signs.

A 17 year-old woman developed progressive quadriparesis with bilateral facial diplegia after immunization with recombinant hepatitis B vaccine 3 days prior. Cerebrospinal fluid analysis revealed acellular fluid with high protein level. The electrodiagnosis was compatible with demyelinating polyneuropathy. Other potential causes of Guillain-Barre' syndrome (GBS) were ruled out. Her motor power gradually improved and returned to normal later. The temporal relationship between GBS and vaccination was suggestive of a vaccine-induced cause. Mechanisms of this very rare complication are proposed with a literature review.

Using data from Vaccine Adverse Event Reporting System, we identified 69 reports of Guillain-Barré Syndrome (GBS) after Gardasil vaccination that occurred in the United States between 2006 and 2009. The onset of symptoms was within 6 weeks after vaccination in 70% of the patients in whom the date of vaccination was known. The estimated weekly reporting rate of post-Gardasil GBS within the first 6 weeks (6.6 per 10,000,000) was higher than that of the general population, and higher than post-Menactra and post-influenza vaccinations. Further prospective active surveillance for accurate ascertainment and identification of high-risk groups of GBS after Gardasil vaccination is warranted.

Guillain-Barré syndrome is a rare neurological disease of progressive installation, usually following a previous acute infectious state, has a rare incidence, especially in pregnancy, and can induce major complications and high mortality risk. Its occurrence, after immunization to influenza during the last trimester pregnancy, has not been reported before. We presented a case of a 36-year-old pregnant woman that was immunized to H1N1 in the last trimester; 10 days later she developed shoulder and lumbar spine's pain, limbs weakness and facial paralysis with unfavorable clinical evolution and was submittedto intensive therapy care. We described clinical and obstetrical approach, pointing out peculiarities involved in this pathology in pregnancy.

OBJECTIVE:To report a case of Guillain-Barré syndrome (GBS) following a dose of influenza A (H1N1) vaccine (Arepanrix).

CASE SUMMARY:An 11-year-old boy was admitted to the hospital after presenting with facial diplegia; abdominal, forehead, and thigh pain; and acute cervical pain. He had received the Arepanrix H1N1 subcutaneous vaccine 13 days before symptom onset. The neurologic examination also revealed a symmetric bilateral paralysis of the VIIth cranial nerve and intense pain, proximal weakness of the shoulder girdles and pelvis, and preserved deep tendon reflexes. Cerebrospinal fluid analysis revealed an albuminocytologic dissociation. Therefore, a diagnosis of atypical GBS following vaccination against HINI influenza was made.

DISCUSSION:Based on the clinical evaluation, laboratory test results, neurologic features, and the exclusion of alternative diagnoses, the Naranjo probability scale revealed a probable relationship between the clinical manifestations of GBS and the vaccine against influenza A (H1N1) received by the patient. This is the first published case for the 2009 influenza pandemic in children.

CONCLUSIONS:While recent studies have found inconclusive results on the association between influenza vaccine and GBS, all suspected cases should be published for further evaluation.

A 52-year-old woman developed Guillain-Barré syndrome 10 weeks after immunization with recombinant hepatitis B vaccine. Common infectious causes of GBS were ruled out. The temporal relationship between GBS and hepatitis B virus (HBV) vaccination was suggestive of a vaccine-induced cause. The possible mechanisms of this very, rare complication are discussed.

Invasive Haemophilus influenzae type b (Hib) disease decreased dramatically after the introduction of conjugate vaccine in routine immunization schedules. We report a case of a fifteen-months-old girl, previously healthy and vaccinated, admitted in the emergency room with fever and vomiting. She was irritable and the Brudzinski's sign was positive. The cerebrospinal fluid (CSF) analysis showed pleocytosis and high protein level. Empiric intravenous antibiotics (ceftriaxone and vancomycin) were administered for suspected bacterial meningitis during 10 days. Serotyping of the Haemophilus influenzae strain found in CSF revealed a serotype b. After one year of follow-up no Hib meningitis sequelae were noted. Despite vaccination compliance and absence of risk factors, invasive Hib disease can occur due to vaccine failure. Efforts to keep the low incidence of invasive Hib disease should be directed to the maintenance of high vaccination coverage rates, combined with the notification and surveillance strategies already implemented in each country.

We present two cases of bacterial meningitis caused by Haemophilus influenzae type b (Hib) which developed a few days after conjugate Hib vaccination. This phenomenon of postimmunization provocative time period is reviewed and discussed. These cases serve as a reminder to clinicians of the risk, albeit rare, of invasive Hib disease in the short period after successful immunization.

The etiology of dermatomyositis is unknown, but immune mechanisms play an important role. Several dermatological manifestations have been reported among carriers of hepatitis B surface antigen, and after vaccination with the HBV vaccine. Almost all the skin reactions described were peculiar skin eruptions suggestive of an immune complex reaction. Some authors described the occurrence of dermatomyositis after BCG and influenza vaccination. We report a case of a 6-year-old child, who was vaccinated for hepatitis B virus and developed a flu-like disease accompanied by a skin rash, which had the typical features of dermatomyositis. The association of vaccination with autoimmunity is discussed.

OBJECTIVE:To investigate the relationship between hepatitis B (HB) vaccination and a first central nervous system (CNS) demyelinating event in adults.

METHODS:In 1998, we conducted a multicentre, hospital-based case-control study which enrolled 402 cases of first CNS demyelinating event occurring between 1994 and 1995 and 722 controls matched for centre, age, sex and date of admission. An independent expert committee validated the diagnoses of cases and controls. Data on vaccinations were obtained from a standardized phone interview. Forty percent of eligible cases and 50% of eligible controls could not be localized or were excluded because they did not satisfy inclusion or matching criteria.

RESULTS:Conditional logistic regression performed on 236 and 355 matched controls showed that adjusted odds ratios for the first CNS demyelinating event within 2 months following an injection of HB vaccine were 1.8 [95% confidence interval (CI), 0.7-4.6] in the whole group and 1.4 (95% CI, 0.4-4.5) in the subgroup of cases (n = 152) and controls (n = 253) referring to vaccination certificates during the phone interview. Restricting the analyses to the cases with definite or probable multiple sclerosis, these odds ratios were 2.0 (95% CI, 0.8-5.4) and 1.6 (95% CI, 0.4-5.6), respectively. Odds ratios tend towards 1 for a longer interval between HB vaccine and demyelinating event.

CONCLUSIONS:This study was sufficiently powerful to rule out a strong association between HB vaccine exposure and a subsequent demyelinating event. However, it could not provide a clear indication of a moderately increased risk of a CNS demyelinating event shortly after HB vaccination in adults.

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We present four incidental cases that developed partial myelitis following the administration of hepatitis B vaccine in 1998. The first two cases, a 33-year-old man and a 42-year-old woman developed progressive sensory symptoms without motor involvement within 4 weeks following the vaccination. Their magnetic resonance imaging (MRI) disclosed similar lesions consistent with myelitis at their cervical spinal cord. A comparable inflammatory lesion was seen at the T9-T10 levels of the spinal cord in the third case, who was a 40-year-old woman presenting with numbness in her legs and urinary retention following the vaccination. The fourth case who was a 42-year-old woman, presented with sensory symptoms in her left extremities, which developed 3 months after the vaccination. Her MRI showed a hyperintense lesion at C6. She also had two tiny lesions in her cranial MRI. In all cases, there was no history of preceding infections and no clinical evidence suggestive of any other disorders that may cause myelopathy. All patients recovered completely within 3 months with the exception of the third patient who developed new neurological symptoms after 12 months. Similar clinical and imaging presentation of myelitis following hepatitis B vaccination within a 1 year period with no other demonstrable clinical and laboratory evidence for any other disorder raise the probability of a causal link between these two events.

Herpes zoster complicated by meningitis has been mainly reported in immunocompromised patients after reactivation of wild-type varicella-zoster virus. We present one of the first cases of aseptic meningitis after herpes zoster caused by reactivation of vaccine-type varicella-zoster virus in an immunocompetent child. We also highlight the increasing role of both wild-type and vaccine strains of varicella-zoster virus as a cause of viral meningoencephalitis and the use of appropriate laboratory tools to rapidly and accurately identify the virus in order to provide prompt patient care and management.

A healthy 5 year old girl developed herpes zoster in the dermatome supplied by the ophthalmic branch of the fifth cranial nerve 40 months after varicella vaccination. She was admitted to our hospital because of high fever and painful vesicular lesions over the left side of her forehead. She was treated successfully with systemic and topical acyclovir without developing herpetic keratoconjunctivitis. Our acute and convalescent phase evaluations showed that non-specific cellular and humoral immunity was normal. This is the fourth case of herpes zoster developing in an immunocompetent child following vaccination. Unlike the previously reported cases, our patient required hospitalization mainly to prevent ocular involvement. The issue concerning whether the universal introduction of varicella vaccination of normal children will reduce the incidence of the subsequent occurrence of herpes zoster must await further studies involving longer follow-up periods.

PURPOSE:In this study, the case of a healthy pediatric patient who presented with herpes zoster (HZ) stromal keratitis after vaccination with live attenuated varicella vaccine (Varivax) and subsequent booster is described.

METHOD:This is a retrospective case review.

RESULTS:A 6-year-old girl with no medical history presented with HZ ophthalmicus and stromal keratitis. She had received the original Varivax vaccine at 1 year of age and a booster 1 year before presentation. Topical prednisolone acetate was started with subsequent improvement in inflammation and visual acuity. However, the patient was unable to be completely tapered off the steroids because of reactivation.

CONCLUSIONS:HZ ophthalmicus with stromal keratitis is a rare but potentially damaging manifestation of the varicella zoster virus in the pediatric population. Long-term data regarding reactivation rates in the post-vaccination era are still limited. Close follow-up is needed to ensure resolution of the infiltrates, and reactivation may require long-term steroid therapy.