Paralytic poliomyelitis caused by a vaccine-derived polio virus in an antibody-deficient Argentinean child

Abstract

We describe a case of poliomyelitis in a 3-year-old Argentinean boy with X-linked hypogammaglobulinemia. The child had no history of polio vaccination, but a poliovirus isolated from a stool sample had 97.2% genetic similarity to the Sabin 1 vaccine strain. According to the WHO definition, this is the first case reported of a vaccine-derived poliovirus infection (iVDPV) recorded in continental Latin America. The use of live oral polio vaccine (OPV) in the polio eradication initiative has led to elimination of indigenous wild polio and certification of the Americas as polio-free in September 1994. 1 An important feature of polioviruses including the Sabin strains in OPV is their continued genetic variation through mutation and recombination. Selective pressures in the human intestine can cause partial reversion of the attenuated OPV strains to neurovirulence, resulting in vaccine-associated paralytic poliomyelitis (VAPP), 2 which is clinically identical with the paralysis caused by wild virus, affecting both vaccine recipients and their contacts. Risk of VAPP is highest after the first dose of OPV, estimated as 1 case per 750 000 children vaccinated, and 3000 times higher in immunocompromised persons. Only OPV causes VAPP, the only indigenous form of polio in those countries that have eradicated wild poliovirus. 3, 4 A major challenge for the polio eradication “endgame” strategy is the recent characterization of vaccine-derived polio viruses (VDPV), defined by the WHO as a Sabin vaccine virus that shows >1% drift in the VP1 region of the genome. 5 Both types of VDPV, those circulating in the population (cVDPV) and those from immunodeficient long term excretors (iVDPV), may acquire both the neurovirulence and the transmission characteristics of wild-type strains, leading to polio outbreaks. In this communication we present one case of paralytic polio caused by an iVDPV in a primary antibody-deficient child and the implications for the polio eradication endgame strategy. Case report. The patient is a boy born in 1995 from consanguineous parents living in the rural area of the city of San Pedro, in the province of Buenos Aires, a community with low socioeconomic status and poor hygiene conditions including lack of drinking water. The child had no history of medical problems, and his vaccination history consisted of only one dose of Calmette-Guérin bacillus at birth. He had not traveled out of his village and was not thought to have been in contact with persons recently vaccinated with OPV. At 3 years of age, in September 1998, he was hospitalized because of fever lasting for 24 h, associated with progressive asymmetric flaccid paralysis. Medical examination found Stage 1 malnutrition and decreased muscular tone in both legs and left arm, involving both proximal and distal muscles. Tendon reflexes were decreased in the right arm and absent in the left arm and both legs. No sensory loss was noted. Lumbar puncture revealed pleocytosis (82 cells/mm3) and elevated protein concentration (1.49 g/l). The glucose value was normal. He had a marked deficiency in immunoglobulins: 3.23 g/l for IgG (normal range, 8.2 to 13.2 g/l); 0.15 g/l for IgM (normal, 0.65 to 1.01 g/l); and 0.07 g/l for IgA (normal, 0.57 to 1.33 g/l). Salivary IgA was undetectable. T cell subsets were determined with flux cytometry. CD3 and CD8 populations were in the normal range, but in peripheral blood a small decrease was noted for the CD4 subset (29%; normal range, 36 to 46%) as well as for the CD19 subset (2%; normal range of 7 to 23%). X-linked hypogammaglobulinemia was diagnosed, and the child was given monthly therapy with iv gamma-globulin. Laboratory studies. Stool specimens obtained at the acute phase of the paralysis were inoculated into human rhabodomyosarcoma cells and transgenic mouse cell lines expressing the human poliovirus surface receptor (LB20), the WHO procedure for isolation and identification of polioviruses and also tested for enterovirus using a reverse transcription-nested PCR technique. Stool samples positive by viral isolation were investigated with the use of poliovirus-specific neutralizing antisera (CDC, Atlanta, GA) and with the Lim-Benyesh Melnick pool specific for polio and nonpolio enteroviruses and by PCR for pan-enterovirus and pan-polio Sabin 1, 2 and 3. The first stool sample yielded a poliovirus type 1, the major capsid protein (VP1) of which showed 97.2% genetic similarity to Sabin 1 vaccine strain, thus representing a VDPV by the WHO definition. All other stool samples were negative for poliovirus isolation. Three years later only nonpolio enteroviruses were isolated from four stool samples obtained 1 to 3 months apart during 1 year. At this time clinical assessment for residual neurologic deficit sequelae found hypotrophy of the left arm and both legs with skeletal deformities, without sensory loss. Electromyography confirmed the damage to the dorsal root ganglia. Discussion. The present case differs from “cl