Patients with Primary Immunodeficiencies Are a Reservoir of Poliovirus and a Risk to Polio Eradication

Abstract

Immunodeficiency-associated vaccine-derived polioviruses (iVDPVs) have been isolated from primary immunodeficiency (PID) patients exposed to oral poliovirus vaccine (OPV). Patients may excrete poliovirus strains for months or years; the excreted viruses are frequently highly divergent from the parental OPV and have been shown to be as neurovirulent as wild virus. Thus, these patients represent a potential reservoir for transmission of neurovirulent polioviruses in the post-eradication era. In support of WHO recommendations to better estimate the prevalence of poliovirus excreters among PIDs and characterize genetic evolution of these strains, 635 patients including 570 with primary antibody deficiencies and 65 combined immunodeficiencies were studied from 13 OPV-using countries. Two stool samples were collected over 4 days, tested for enterovirus, and the poliovirus positive samples were sequenced. Thirteen patients (2%) excreted polioviruses, most for less than 2 months following identification of infection. Five (0.8%) were classified as iVDPVs (only in combined immunodeficiencies and mostly poliovirus serotype 2). Non-polio enteroviruses were detected in 30 patients (4.7%). Patients with combined immunodeficiencies had increased risk of delayed poliovirus clearance compared to primary antibody deficiencies. Usually, iVDPV was detected in subjects with combined immunodeficiencies in a short period of time after OPV exposure, most for less than 6 months. Surveillance for poliovirus excretion among PID patients should be reinforced until polio eradication is certified and the use of OPV is stopped. Survival rates among PID patients are improving in lower and middle income countries, and iVDPV excreters are identified more frequently. Antivirals or enhanced immunotherapies presently in development represent the only potential means to manage the treatment of prolonged excreters and the risk they present to the polio endgame.

Iterative Excretion of Human Cosaviruses from Different Genotypes Associated with Combined Immunodeficiency Disorder

“…The affected T-cell and B-cell responses expose the patient to repeated microbial infections with severe gastroenteritis and pneumonias. These clinical features may include meningitis [24]. The patient studied here was previously reported with high susceptibility to enterovirus infections; he was sequentially infected by 6 different enterovirus serotypes from October 2010 to November 2012 [23].…”

Assuring immune globulin potency in a world of changing pathogen challenges

“…Use of IG to prevent poliovirus‐induced paralysis fell out of favor due to contradictory results of clinical trials and the advent of efficacious vaccines . Then and now, patients with PI who contract vaccine‐derived or wild‐type poliovirus are prone to persistent excretion that may last for years, even when regular IG treatment is given . Affected patients most often have common variable immunodeficiency or severe combined immunodeficiency .…”

“…[23][24][25] Affected patients most often have common variable immunodeficiency or severe combined immunodeficiency. 23 As case reports attest, IG treatment does not reliably eliminate enteric poliovirus excretion and it is not known whether or how much poliovirus antibody in IG might prevent spread to the central nervous system. At the workshop, McKinlay reported that trials with a single antiviral treatment did not eliminate prolonged poliovirus excretion in patients with PI and that new studies are planned using dual antiviral therapy.…”

Perceived health of patients with common variable immunodeficiency – a cluster analysis

“…CVID is a heterogeneous disease, which is associated with recurrent and severe infections and characterized by deficiencies in antibody production. Previous studies have shown that there are subgroups of patients with CVID with respect to their genotype, B cell or T cell profiles and clinical phenotypes [10][11][12][13][14][15][16]. Most CVID patients receive immunoglobulin (Ig)G substitution, which has a significant impact on health-related quality of life [8,9].…”

“…Most CVID patients receive immunoglobulin (Ig)G substitution, which has a significant impact on health-related quality of life [8,9]. Previous studies have shown that there are subgroups of patients with CVID with respect to their genotype, B cell or T cell profiles and clinical phenotypes [10][11][12][13][14][15][16]. However, very few studies analyzing the heterogeneity of CVID go beyond biomedical perspectives and focus on the psychosocial aspects of the disease including perceived health.…”