Nucleotide variation in Sabin type 3 poliovirus from an Albanian infant with agammaglobulinemia and vaccine associated poliomyelitis.
Vaccine-associated paralytic poliomyelitis (VAPP) and immunodeficient long-term polio excretors constitute a significant public health burden and are a major concern for the WHO global polio eradication endgame.



Poliovirus type 3 characterized as Sabin-like was isolated from a 5-month-old Albanian child with X-linked agammaglobulinemia and VAPP after oral polio vaccine administration. Diagnostic workup and treatment were performed in Italy. Poliovirus replicated in the gut for 7 months. The 5' non coding region (NCR), VP1, VP3 capsid proteins and the 3D polymerase genomic regions of sequential isolates were sequenced. Increasing accumulation of nucleotide mutations in the VP1 region was detected over time, reaching 1.0 % of genome variation with respect to the Sabin reference strain, which is the threshold that defines a vaccine-derived poliovirus (VDPV). We identified mutations in the 5'NCR and VP3 regions that are associated with reversion to neurovirulence. Despite this, all isolates were characterized as Sabin-like. Several amino acid mutations were identified in the VP1 region, probably involved in growth adaptation and viral persistence in the human gut. Intertypic recombination with Sabin type 2 polio in the 3D polymerase region, possibly associated with increased virus transmissibility, was found in all isolates. Gamma-globulin replacement therapy led to viral clearance and neurological improvement, preventing the occurrence of persistent immunodeficiency-related VDPV.



This is the first case of VAPP in an immunodeficient child detected in Albania through the Acute Flaccid Paralysis surveillance system and the first investigated case of vaccine associated poliomyelitis in Italy since the introduction of an all-Salk schedule in 2002. We discuss over the biological and clinical implications in the context of the Global Polio Eradication Program and emphasize on the importance of the Acute Flaccid Paralysis surveillance.
Department of Pediatrics, University of Pavia, Policlinico San Matteo IRCCS Foundation, Pavia, Italy. thomas.foiadelli@gmail.com.
Thomas
T
Foiadelli
Department of Pediatrics, University of Pavia, Policlinico San Matteo IRCCS Foundation, Pavia, Italy.
Salvatore
S
Savasta
National Center for Immunobiologicals Control and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Andrea
A
Battistone
Control of Communicable Disease Department, Institute of Public Health, Tirana, Albania.
Majlinda
M
Kota
Department of Pediatrics, University of Pavia, Policlinico San Matteo IRCCS Foundation, Pavia, Italy.
Carolina
C
Passera
National Center for Immunobiologicals Control and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Stefano
S
Fiore
Control of Communicable Disease Department, Institute of Public Health, Tirana, Albania.
Silvia
S
Bino
National Center for Immunobiologicals Control and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Concetta
C
Amato
National Neurological Institute IRCCS Foundation C. Mondino, Pavia, Italy.
Alessandro
A
Lozza
Department of Pediatrics, University of Pavia, Policlinico San Matteo IRCCS Foundation, Pavia, Italy.
Gian Luigi
GL
Marseglia
National Center for Immunobiologicals Control and Evaluation, Istituto Superiore di Sanità, Rome, Italy.
Lucia
L
Fiore
D000361:Agammaglobulinemia / Q000150:complications*; D000415:Albania; D036022:Capsid Proteins / Q000235:genetics*; D004576:Electromyography; D040181:Genetic Diseases, X-Linked / Q000150:complications*; D006801:Humans; D007223:Infant; D007558:Italy; D008297:Male; D009154:Mutation; D009431:Neural Conduction; D011051:Poliomyelitis / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control / Q000821:virology; D017955:Poliovirus / Q000235:genetics*; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects*; D012367:RNA, Viral / Q000235:genetics*; D017423:Sequence Analysis, RNA
D036022:Capsid Proteins; D011055:Poliovirus Vaccine, Oral; D012367:RNA, Viral
Acute flaccid paralysis; Oral polio vaccine; Poliovirus; Vaccine-associated paralytic poliomyelitis; Vaccine-derived poliovirus; X-linked agammaglobulinemia