Age: 1.8
Sex: U
Vaccine: PNC13
Symptoms: Lethargy, Meningitis pneumococcal, Pleocytosis, Pyrexia, Speech disorder developmental
Clinical narrative: The initial case was missing the following minimum criteria: no identifiable patient. Upon receipt of follow up information on 07Nov2016, this case now contains all required information to be considered valid. This is a literature spontaneous report. This is first of 7 reports and this case refers to Case 1: 21 month-old patient. Fourteen cases of pneumococcal meningitis and twelve cases of invasive pneumococcal disease (IPD) not including meningitis were identified. Between Jan2004 and Dec2012 there were 0 to 2 cases of pneumococcal meningitis each year. In contrast, the authors identified 7 cases of pneumococcal meningitis presenting in children aged 5 months to 6 years between Jul2013 and Dec2014. The duration of symptoms prior to presentation ranged from 2 to 5 days (mean 3.4 days). CSF analysis was remarkable for very modest pleocytosis observed in all but 1 child. Six children had a positive CSF Gram stain for Gram-positive diplococci with cultures positive for S pneumoniae. The 6-year-old child who was moribund on presentation had a positive blood culture and brain imaging, which showed meningeal enhancement and herniation. All 5 surviving children with meningitis experienced severe hearing loss and developmental impairment. In addition, 2 children developed seizures, 2 developed hemolytic uremic syndrome, 1 developed hydrocephalus requiring a shunt, 2 had transient cranial nerve palsy, 1 suffered persistent palsy of cranial nerve II, and 2 children died. Two patients completed immunization with pneumococcal 13-val conj vac (dipht CRM197 protein) and both were infected with nonvaccine serotype 23B. Two children were partially immunized with pneumococcal 13-val conj vac (dipht CRM197 protein) and both were infected with nonvaccine strains (22F, 15B). Three infections resulted from serotypes contained within pneumococcal 13-val conj vac (dipht CRM197 protein): A 5-month-old infant who received 2 doses of pneumococcal 13-val conj vac (dipht CRM197 protein) and a 6-year old with an unknown immunization history were both infected with serotype 19A, and an unimmunized toddler was infected with serotype 18C. Immunological studies performed on the 5-month-old showed normal immunoglobulins and total hemolytic complement. The patient had no known conditions such as asplenia or sickle cell anemia that would predispose to a pneumococcal infection. Discussion: The authors reported a cluster of cases of pneumococcal meningitis in young infants and children in the pneumococcal 13-val conj vac (dipht CRM197 protein)  era associated with a very high degree of morbidity and mortality. All patients in this cluster experienced neurologic sequelae in contrast to rates of 40% to 63% reported in the recent literature. There were several possible explanations for the poor outcomes in these cases. The decreasing incidence of meningitis in general may lower practitioners' suspicion for bacterial meningitis, which may lead to delayed diagnosis. The modest pleocytosis observed in 5 patients may reflect a less robust inflammatory reaction which in turn may be associated with fewer early symptoms, also leading to delayed diagnosis. The main limitation to this brief report was that it was not population-based, and the authors were thus not able to comment on incidence rates. Accordingly, the high degree of observed morbidity and mortality, in addition to the clustering of cases, may simply be a chance event. Nonetheless, it was alarming that 7 of 14 cases occurring during a 10-year period were observed during 17 months. A 21 month-old patient received immunization with three single doses of pneumococcal 13-val conj vac (dipht CRM197 protein) on unknown dates. On an unspecified date, the patient presented symptoms of fever, lethargy, low tone, unilateral esotropia, was hospitalized and diagnosed with pneumococcal meningitis. The duration of symptoms before diagnosis was 3 days. Laboratory data includes: blood culture positive; CSF Results: Nucleated Cells (/uL): 196; Protein (mg/dl) 130; Glucose (mg/dL): less than 1, Serotype: 22 F. Complications observed in hospital included: ataxia, transient cranial nerve VI palsy, poor feeding. Duration of Follow-up After Admission: 14 months. The patient had the following subacute sequelae: bilateral hearing loss and cochlear implant, autism spectrum disorder, language delays, and hypotonia. Outcome was unknown. Pfizer is a marketing authorization holder of pneumococcal 13-val conj vac (dipht CRM197 protein) in the reporter's country. This may be a duplicate report if another marketing authorization holder of pneumococcal 13-val conj vac (dipht CRM197 protein) has submitted the same report to the regulatory authorities.; Sender's Comments: Serotype 22 F is not contained in pneumococcal 13-val conj vac (dipht CRM197 protein), therefore a lack of efficacy in this patient can be excluded. The Company considers the pneumococcal meningitis and its reported complications not related to pneumococcal 13-val conj vac (dipht CRM197 protein). The impact of this report on the benefit/risk profile of the Pfizer product is evaluated as part of Pfizer procedures for safety evaluation, including the review and analysis of aggregate data for adverse events. Any safety concern identified as part of this review, as well as any appropriate action in response, will be promptly notified to Regulatory Authorities, Ethics Committees and Investigators, as appropriate. Linked Report(s): US-PFIZER INC-2016518575 Different patient/event, same drug; US-PFIZER INC-2016518576 Different patient/event, same drug; US-PFIZER INC-2016518578 Different patient/event, same drug; US-PFIZER INC-2016518579 Different patient/event, same drug; US-PFIZER INC-2016518580 Different patient/event, same drug.