Prolonged Excretion of Poliovirus among Individuals with Primary Immunodeficiency Disorder: An Analysis of the World Health Organization Registry

Abstract

Individuals with primary immunodeficiency disorder may excrete poliovirus for extended periods and will constitute the only remaining reservoir of virus after eradication and withdrawal of oral poliovirus vaccine. Here, we analyzed the epidemiology of prolonged and chronic immunodeficiency-related vaccine-derived poliovirus cases in a registry maintained by the World Health Organization, to identify risk factors and determine the length of excretion. Between 1962 and 2016, there were 101 cases, with 94/101 (93%) prolonged excretors and 7/101 (7%) chronic excretors. We documented an increase in incidence in recent decades, with a shift toward middle-income countries, and a predominance of poliovirus type 2 in 73/101 (72%) cases. The median length of excretion was 1.3 years (95% confidence interval: 1.0, 1.4) and 90% of individuals stopped excreting after 3.7 years. Common variable immunodeficiency syndrome and residence in high-income countries were risk factors for long-term excretion. The changing epidemiology of cases, manifested by the greater incidence in recent decades and a shift to from high- to middle-income countries, highlights the expanding risk of poliovirus transmission after oral poliovirus vaccine cessation. To better quantify and reduce this risk, more sensitive surveillance and effective antiviral therapies are needed.

Keywords: immunodeficiency-related vaccine-derived poliovirus; oral poliovirus vaccine; polio eradication; primary immunodeficiency; vaccine-derived poliovirus.

Figure 1

Year of detection of 101 reported chronic and prolonged immunodeficiency-related vaccine-derived poliovirus cases from 1962 to 2016, by income classification of country of residence: low income (n = 1), lower-middle income (n = 24), upper-middle income (n = 47), and high-income (n = 29). Income classification based on 2016 World Bank Classification.

Figure 2

Geographic location of 101 reported chronic and prolonged immunodeficiency-related vaccine-derived poliovirus cases, 1962–2016. Shown by serotype of virus in most recent specimen available: 1 (n = 15), 2 (n = 68), 3 (n = 13), 1 + 2 (n = 2), and 2 + 3 (n = 3).

Figure 3

Kaplan–Meier curves for the length of poliovirus excretion in reported chronic and prolonged immunodeficiency-related vaccine-derived poliovirus cases, 1962–2016. (A) For all reported cases (n = 101, dotted lines: 95% Confidence Limits). (B) Comparison by income classification of country of residence: low income (n = 1), lower-middle income (n = 24), upper-middle income (n = 47), and high-income (n = 29). Two-tailed P < 0.001 for log-rank test for equality of Kaplan–Meier curves. (C) Comparison by primary immunodeficiency disorder: antibody disorders (n = 31), CVID (n = 21), SCID and other combined humoral T-cell deficiencies (n = 27), and other disorders (n = 13). Two-tailed P < 0.001 for log-rank test for equality of Kaplan–Meier curves. Abbreviation: CVID, common variable immunodeficiency disorder; SCID, severe combined immunodeficiency disorder.