Age: 0.33
Sex: F
Vaccine: HIBV, MEN, MMR, PNC13, UNK, UNK, VARCEL
Symptoms: Lymphocyte percentage decreased, Mean cell haemoglobin concentration normal, Mean cell haemoglobin normal, Mean cell volume normal, Mean platelet volume normal
Clinical narrative: Tonsillitis; This 15-month-old female subject was enrolled in a blinded study. The subject received the 4th dose of Bexsero vs Placebo co-administered with PCV and routine vaccines (intramuscular) on 28th June 2019. The subject received the 3rd dose of DTPa-HBV-IPV (intramuscular) on 28th December 2018, for prophylaxis. The subject received the 2nd dose of Rotarix lyophilized formulation (oral) on 2nd November 2018, for prophylaxis. The subject received the 3rd dose of Hiberix (intramuscular) on 28th December 2018, for prophylaxis. The subject received the 1st dose of M-M-R II (subcutaneous) on 28th June 2019, for prophylaxis. The subject received the 1st dose of Varivax (subcutaneous) on 28th June 2019, for prophylaxis. The subject received the 5th dose of Prevnar 13 (intramuscular) on 28th June 2019, for prophylaxis.   Co-suspect products included dtpa-hbv-ipv vaccine pre-filled syringe device injection syringe for prophylaxis and rotavirus vaccine oral applicator device (Rotarix Oral Applicator Device) oral applicator for prophylaxis.   On 27th October 2019, 121 days after receiving Bexsero vs Placebo co-administered with PCV and routine vaccines, M-M-R II, Varivax and Prevnar 13, 303 days after receiving DTPa-HBV-IPV and Hiberix and 359 days after receiving Rotarix lyophilized formulation, the subject developed moderate - grade 2 tonsillitis. Serious criteria included hospitalization. The subject was treated with amoxicillin + clavulanic acid (Augmentin), ampicillin-Sulbactam, lidocaine Cream, vancomycin, ceftriaxone sodium (Ceftrixone), ibuprofen, paracetamol (Tylenol) and cefdinir. The outcome of tonsillitis was recovered/resolved on 5th November 2019.   The investigator considered that there was no reasonable possibility that the tonsillitis may have been caused by Bexsero vs Placebo co-administered with PCV and routine vaccines, DTPa-HBV-IPV, Rotarix lyophilized formulation, Hiberix, M-M-R II, Varivax and Prevnar 13.   Relevant Tests: On 31 Oct 2019 Mucous present (reference range none/hpf) and Chest x-ray Peripronchial cuffing is present, suggestive of underlying reactive airway disease vs viral illness. On 01Nov2019 CF Soft Tissue Neck with Contrast = Enlarged palatine tonsils and adenoids bilaterally consistent with history of tonsillitis. No evidence of focal abscess. Mildy enlarged cervical lymph nodes bilaterally, likely reactive. Heterogeneous groundglass opacity in left upper lobe raising question of early pneumonia vs atelectasis related to airways disease. On 01Nov2019 Lab results and fever were SUGGESTIVE of a serious bacterial infection. Therefore, additional tests were done. Spinal fluid was normal and meningitis was NOT confirmed.   Diagnostic results (unless otherwise stated, normal values were not provided): On 31st October 2019, Alanine aminotransferase result was 24 u/L (normal low: 24.00, normal high: 59.00), Anion gap result was 9 mmol/L (normal low: 7, normal high: 15), Aspartate aminotransferase result was 39 u/L (normal low: 16.00, normal high: 57.00), Band neutrophil percentage result was 19 % (normal low: 0.00, normal high: 4.00), Blood albumin result was 3.6 g/dL (normal low: 3.50, normal high: 4.70), Blood alkaline phosphatase result was 400 u/L (normal low: 185.00, normal high: 383.00), Blood bilirubin result was 0.10 mg/dL (normal low: 0.20, normal high: 1.30), Blood calcium result was 9.4 mg/dL (normal low: 9.00, normal high: 11.00), Blood chloride result was 106 mmol/L (normal low: 98.00, normal high: 107.00), Blood creatinine result was 0.26 mg/dL (normal low: 0.20, normal high: 0.80), Blood culture result was no growth, Blood glucose result was 134, Blood glucose result was 149 mg/dL (normal low: 60, normal high: 100), Blood potassium result was 3.9 mmol/L (normal low: 3.50, normal high: 5.50), Blood sodium result was 137 mmol/L (normal low: 135.00, normal high: 144.00), Blood urea result was 10 mg/dL (normal low: 6.00, normal high: 17.00), C-reactive protein result was 138.20 mg/L (normal low: 0.00, normal high: 10.00), CSF cell count result was 5,2, CSF culture result was no growth, CSF glucose result was (Spinal fluid) 70 mg/dL (normal low: 40, normal high: 70), CSF lymphocyte count result was 80, 100 % (normal low: 40.0, normal high: 80.0), CSF protein result was (Spinal fluid) 18.0 mg/dL (normal low: 12.0, normal high: 60.0), CSF red blood cell count result was 85.21 /uL (normal high: less than equal to 2), CSF white blood cell count result was 5, 2 /uL (normal high: less than equal to 5), Carbon dioxide result was 22 mmol/L (normal low: 22.00, normal high: 32.00), Chest X-ray result was see text, Culture urine result was no growth, Enterovirus test result was not detected, Haematocrit result was 32.4 % (normal low: 33.00, normal high: 45.00), Haemoglobin result was 10.9 g/dL (normal low: 10.50, normal high: 13.50), Influenza A virus test result was negative, Influenza B virus test result was negative, Lumbar puncture result was negative for meningitis, fluid clear, Lymphocyte percentage result was 16 % (normal low: 15.00, normal high: 70.00), Mean cell haemoglobin result was 29.5 pg (normal low: 23.00, normal high: 31.00), Mean cell haemoglobin concentration result was 33.6 g/dL (normal low: 31.00, normal high: 37.00), Mean cell volume result was 87.6 fL (normal low: 75.00, normal high: 86.00), Mean platelet volume result was 9.4 fL (normal low: 8.60, normal high: 13.00), Monocyte percentage result was 14 % (normal low: 0.00, normal high: 10.00) and Monocyte percentage result was 20/Macrophages % (normal low: 15.0, normal high: 45.0). On 31st October 2019, Neutrophil count result was 15.90 x10e3/mcL (normal low: 1.50, normal high: 7.50), Neutrophil count result was 51 % (normal low: 15.00, normal high: 70.00), Platelet count result was 292 x10e3/mcL (normal low: 150.00, normal high: 420.00), Procalcitonin result was 3.31 ng/mL (normal high: less than 0.05), Protein total result was 6.3 g/dL (normal low: 6.00, normal high: 7.80), Red blood cell count result was 3.70 x10E6/mcL (normal low: 3.50, normal high: 5.50), Red blood cells urine result was 0-2 /HPF (normal low: 0, normal high: 2), Red cell distribution width result was 12.5 % (normal low: 11.00, normal high: 16.00), Streptococcus test result was Negative, Urinary sediment present result was 0-5 /HPF (normal low: 0, normal high: 5), White blood cell count result was 22.71 x10e3/mcL (normal low: 5.00, normal high: 16.00), White blood cells urine result was 0-2 /HPF (normal low: 0, normal high: 5) and pH urine result was 6.0 (normal low: 5.00, normal high: 8.50). On 1st November 2019, Adenovirus test result was detected. On 2nd November 2019, Blood glucose result was 85, C-reactive protein result was 80.9 mg/L (normal low: 0.00, normal high: 10.00), Haematocrit result was 33.1 % (normal low: 33.00, normal high: 45.00), Haemoglobin result was 10.4 g/dL (normal low: 10.50, normal high: 13.50), Mean cell haemoglobin result was 29.1 pg (normal low: 23.00, normal high: 31.00), Mean cell haemoglobin concentration result was 31.4 g/dL (normal low: 31.00, normal high: 37.00), Mean cell volume result was 92.5 fL (normal low: 75.00, normal high: 86.00), Mean platelet volume result was 9.2 fL (normal low: 8.60, normal high: 13.00), Platelet count result was 286 x10e3/mcL (normal low: 150.00, normal high: 420.00), Red blood cell count result was 3.58 x10E6/mcL (normal low: 3.50, normal high: 5.50), Red cell distribution width result was 13.2 % (normal low: 11.00, normal high: 16.00) and White blood cell count result was 12.67 x10e3/mcL (normal low: 5.00, normal high: 16.00).  GSK Receipt Date - 08-NOV-2019  10/27:subject is taken to Urgent Care for cough and congestion lasting almost 1 month. Dx= acute suppurative otitis media. Antibiotic started. 10/30: subject is seen by PI/PCP for fever despite being on antibiotic, Tylenol and ibuprofen for 3 days. Dx Tonsilitis. 10/31: subject is taken to ER for fever of 104F. She has become increasingly fussy and unable to console, has decreased p.o intake, tachycardia and increasing fever over the past 2 days. Lab results and escalating fever are suggestive of a serious bacterial infection, source is uncertain. Labs show leukocytosis with bandemia and elevated CRP. Chest X-Ray did not reveal source of infection and urinalysis was clean. Ceftrixone and Vancomycin started for suspected bacterial meningitis. Parents are agreeable to proceed with Lumbar puncture negative for meningitis. Due to the lab results and fever concern, subject is transferred to the Hospital. Hospitalist concludes that the source of fever is likely Para pharyngeal due to the evidence of tonsillitis and persistent fever due to oral antibiotic could be due to inadequate coverage of cefdinir. Subject put on clear liquid diet and continued medications. Additional tests were done. Spinal fluid was normal and meningitis was NOT confirmed  11/2: Discharge dx fever in pediatric patient and tonsillitis. Condition at discharge was stable. Prescriptions include amoxicillin clavulanate for 4 days. Instructed to follow up with PCP within 7 days. No follow up labs recommended.  11/8: Hospital follow up with PI/PCP. Subject is alert and eating better, no fever. Instructions to stop antibiotics and to discuss possible tonsillectomy in the near future scheduled for 12/5/19.  11/14: Study Coordinator contact LAR/Mom who states that subject has fully recovered. She estimated the date of recovery for 11/5. No more wheezing or fever.  Follow up information received on 11-Mar-2025 End of study Unblinding completed.; Sender's Comments: A case of tonsillitis, 121 days after receiving 4th dose of Bexsero vs Placebo co-administered with PCV and routine vaccines, 1st dose of M-M-R II  and Varivax and 5th dose of Prevnar 13, 303 days after receiving 3rd dose of DTPa-HBV-IPV vaccine with  DTPa-HBV-IPV vaccine pre-filled syringe device injection syringe and Hiberix and 359 days after receiving 2nd dose of Rotarix lyophilized formulation with Rotarix Oral Applicator Device, in a 15-month -old female subject. Report is inconsistent with causal relation to the vaccine product, considering implausible time to onset and and absence of biological plausibility . US-GLAXOSMITHKLINE-US2020119049: