Does Simultaneous Administration of Bivalent (Types 1 and 3) Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine Induce Mucosal Cross-immunity to Poliovirus Type 2?

Background: Inactivated poliovirus vaccine (IPV) alone does not induce mucosal immunity. However, it was hypothesized that administration of IPV together with bivalent (types 1+3) oral poliovirus vaccine (bOPV) may stimulate mucosal cross-immunity to poliovirus type 2 (PV2). Methods: Cuban infants were randomized to receive either one dose of IPV (Arm A); one dose of IPV with bOPV (Arm B) at about 6 months of age or no vaccine (Arm C). Subjects were challenged with one dose of trivalent OPV (tOPV); they were about 7 months old in arms A and B, and about 3 months old in arm C at a time of the tOPV challenge. Sera were collected before vaccination and 30 days after tOPV challenge and tested for presence of poliovirus neutralizing antibodies; stool samples were collected at days 0, 7, 14, 21 and 49 post-challenge and tested for presence of poliovirus. Results: We enrolled 333 children. Excretion of PV2 following tOPV challenge was highest on day 7 (75 [CI 95% = 65-82%], 68 [CI 95% = 58-75%] and 73 [CI 95% = 63-80%] for study arms A, B, and C respectively); excretion decreased with every subsequent stool sampling; no significant differences either in proportion of PV2 excretion or in its duration were observed between study arms. Conclusions: There was no reduction in excretion of PV2 after tOPV challenge in children who had received IPV with bOPV when compared to those who had received IPV alone or no vaccine. Polio eradication program cannot assume any PV2 mucosal response with the current polio immunization schedule. Clinical Trials Registration: The trial was registered with the Australian New Zealand Clinical Trials Registry and allocated trial number ACTRN12616000169448.

Occurrence of enterovirus RNA in serum of children with newly diagnosed type 1 diabetes and islet cell autoantibody-positive subjects in a population with a low incidence of type 1 diabetes.

BACKGROUND: The penetrance of type 1 diabetes mellitus (T1DM) in a genetically susceptible population is largely determined by environmental influences amongst which the human enteroviruses are prominent putative factors. AIM/HYPOTHESIS: The aim of this study was to determine the occurrence of enterovirus RNA in serum of children with type 1 diabetes at onset and ICA-positive subjects in a population with low incidence of type 1 diabetes and high circulation of enteroviruses. SUBJECTS AND METHODS: Serum samples were collected from children with newly diagnosed type 1 diabetes (n = 34); islet autoantibody-positive (n = 32) and -negative (n = 31) first-degree relatives of type 1 diabetic patients; and control subjects (n = 194). Enteroviral RNA was assessed using a highly sensitive reverse transcriptase-polymerase chain reaction method. RESULTS: The frequency of positive signals corresponding to enteroviral sequence amplifications were higher in newly diagnosed T1DM children (9/34, 26.5%) and islet autoantibody-positive first-degree relatives (5/32, 15.6%) than in their corresponding matched controls (2/68, 2.9%, p = 0.0007 and 0/64, 0.0%, p = 0.0033, respectively). The presence of enteroviral RNA appeared to be associated with severe diabetic ketoacidosis at onset (pH < 7.1, p = 0.0328) and high ICA titres ( > or = 20 JDF units, p < 0.05). CONCLUSIONS: Despite there is a high circulation of enteroviruses and a low type 1 diabetes incidence in the Cuban population, the presence of enteroviral RNA is associated with type 1 diabetes and beta-cell autoimmunity and is similar to European countries in which this scenario is reversed.