Susceptible individuals usually excrete polioviruses for 2-6 weeks, and occasionally for up to 137 days after they have been immunized with oral poliovirus vaccine (OPV) (1-5). The shed viruses frequently show increased neurovirulence and are often transmitted to close contacts. Patients with B-cell immune deficiency disorders are at increased risk of complications associated with enterovirus infections, including chronic meningoencephalitis, long-term intestinal excretion of the viruses, and vaccine-associated paralytic poliomyelitis (VAPP) (6). Nineteen individuals with excretion of vaccine-derived polioviruses for six or more months have been reported in the literature or to WHO (7-9) (D. Wood, personal communication, 2003). All but three of these individuals are known to have stopped excreting polioviruses or died. Some became paralysed several years after acquiring the intestinal infection (7, 10). Viruses isolated in the stool of vaccinated individuals typically revert to increased neurovirullence, and long-term excretors shed viruses that are often as neurovirulent as wild-type viruses (7, 11-13). Persistent intestinal poliovirus excretors could theoretically reintroduce polioviruses into general circulation if routine immunization of children was stopped after the eradication of wild-type viruses (10-14). We studied people known to have B-cell immune deficiency disorders in four countries in order to estimate the rate of long-term poliovirus excretors in this at-risk population.
Methods Study population United States
Families registered with the immune Deficiency Foundation (www.primaryimmune.org) were sent a letter inviting people 3-35 years of age with common variable immune deficiency (CVID), X-linked agammaglobulinaemia (XLA) or selective immunoglobulin A (IgA) deficiency to participate in the study. Participants who returned a postcard were mailed a consent form, a brief questionnaire, a request for laboratory results validating the diagnosis, and instructions for collecting and shipping a stool specimen. Subsequently, selected immunologists were asked to enroll patients with CVID or XLA who were two or more years of age.
Eligible people were recruited from the immunology clinics at the Hospital Infantil de Mexico "Dr Federico Gomez" and Instituto National de Pediatria.
Participants were recruited from nine referral centres for the treatment of primary immunodeficiencies, and virus cultures were performed at the Enterovirus Laboratory (WHO Regional Reference Laboratory at Instituto Oswaldo Cruz, Rio de Janeiro). The diagnostic criteria for CVID, XLA, and selective IgA deficiency were based on the International Consensus Guidelines for Diagnosis of Primary Immunodeficiencies (15).
Participants with primary immunodeficiency were recruited from patients attending an immunology clinic at the Royal Free Hospital in London.
Consent and Institutional Review Board approvals
Written informed consent was obtained from participants or their legal guardians and assent was obtained from children aged five years or more. These studies were approved by the Joint Committee on Clinical investigation (JCCI) at the Johns Hopkins University School of Medicine or the Committee on Human Research (CHR) at the Johns Hopkins Bloomberg School of Hygiene and Public Health. The study of people in the United States was approved by the Centers for Disease Control and Prevention (CDC; Atlanta, GA) Institutional Review Board, the study in Mexico by Instituto National de Pediatria, and the study in Brazil by the Federal University of Minas Gerais and other participating institutions.
Specimen collection and processing
WHO-recommended kits were used for collection of 5-10g of stool. Protocult ([c] 1990 ABC Medical Enterprises, Rochester, MN) receptacle collection devices were shipped to individuals in the United States. …