Prolonged Replication of a Type 1 Vaccine-Derived Poliovirus in an Immunodeficient Patient

Abstract

VP1 sequences were determined for poliovirus type 1 isolates obtained over a 189-day period from a poliomyelitis patient with common variable immunodeficiency syndrome (a defect in antibody formation). The isolate from the first sample, taken 11 days after onset of paralysis, contained two poliovirus populations, differing from the Sabin 1 vaccine strain by ∼10%, differing from diverse type 1 wild polioviruses by 19 to 24%, and differing from each other by 5.5% of nucleotides. Specimens taken after day 11 appeared to contain only one major poliovirus population. Evolution of VP1 sequences at synonymous third-codon positions occurred at an overall rate of ∼3.4% per year over the 189-day period. Assuming this rate to be constant throughout the period of infection, the infection was calculated to have started ∼9.3 years earlier. This estimate is about the time (6.9 years earlier) the patient received his last oral poliovirus vaccine dose, approximately 2 years before the diagnosis of immunodeficiency. These findings may have important implications for the strategy to eliminate poliovirus immunization after global polio eradication.

Feasibility of Quantitative Environmental Surveillance in Poliovirus Eradication Strategies

“…The vaccination coverage rate in these areas varies from less than 25% up to 85% and higher than the national vaccination coverage of at least 95% in the Netherlands. Vulnerable groups within a population such as vaccinated-but-immunodeficient individuals may contribute to poliovirus circulation because of prolonged shedding (20,21,28). Silent transmission may be missed by types of surveillance other than environmental surveillance, such as AFP or enterovirus diagnostics.…”

“…However, infected individuals, whether they are with or without symptoms, will shed high levels of poliovirus in their feces for several weeks, and these viruses will subsequently end up in the environment (3). In fact, in immune-deficient patients a prolonged poliovirus excretion is frequently seen, which can continue for years (20). The consequence is that these poliovirus strains can cause frequent new infections when susceptible individuals come in contact with these strains.…”

Rhinovirus Genome Variation during Chronic Upper and Lower Respiratory Tract Infections

“…While the evolution of rhinoviruses has been well characterized at the serotype or species level [13,28,29,30,31,32], little is known about the diversity generated during the course of a natural human infection. Several studies have investigated the genomic variability of enteroviruses and vaccine-derived polioviruses during chronic infections in immunocompromised patients, but there is no such report for rhinoviruses [33,34,35,36].…”

Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis

“…VDPVs of the first type cause outbreaks of paralytic poliomyelitis in inadequately immunized communities and are indistinguishable from wild polioviruses in their pathogenic properties. iVDPVs emerge in OPV-vaccinated individuals with primary B-cell immunodeficiencies and can establish chronic infection and be excreted into the environment for several years (20,24). Besides the immediate danger to the chronic carriers (some of the patients eventually become paralyzed by the continuously evolving poliovirus), the presence of chronic excretors poses a serious challenge to the polio eradication campaign, providing an ample source of virulent polioviruses in the environment, making it impossible to halt immunization against poliomyelitis (12).…”