Investigations of clinical isolations of oral poliovirus vaccine strains between 2000 and 2005 in southern Taiwan

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Abstract

Background

In Taiwan, trivalent oral poliovirus vaccine (tOPV) is in the routine immunization schedule, but its association with illnesses had not been examined.

Objectives

To investigate clinical presentations and viral characteristics of patients with poliovirus isolates.

Study design

Clinical data, vaccination records and viral sequences were retrospectively analyzed for patients from whom polioviruses were isolated during 2000–2005.

Results

OPV-like strains were the only pathogen identified in 208 children who were diagnosed with lower respiratory tract infection (24.5%), acute gastroenteritis (16.8%) or upper respiratory tract infection (10.6%). Timing of poliovirus isolation relative to the tOPV vaccination was unusual in 59 patients, including 6 before any dose and 53 more than 10 weeks after the 3rd or later dose of tOPV. Sequence analyses of the VP1, 2C and 3C/D regions for 19 poliovirus isolates revealed that 4 had previously reported neurovirulence reversions, 1 had intertypic recombination, and 6 had both. No patient had neurological complications, but 3 died of myocarditis, including 2 with recombinant strains and 1 who never received OPV.

Conclusion

This study describes the isolation of OPV-like strains from patients with a variety of illnesses, raising concerns about their pathogenic potential in an area where tOPV is routinely administered. The detection of genetic variations among OPV-like strains warrants continuing surveillance for these variants in patients with severe illnesses besides neurological complications.

Introduction

Live-attenuated oral poliovirus vaccine (OPV) has played an important role in the eradication of wild-type polioviruses in many parts of the world since the 1960s.1, 2 OPV replicates in the gastrointestinal (G.I.) tract after vaccination and can infect unvaccinated hosts. This increases the population immunity in areas with suboptimal vaccine coverage.1, 2 Vaccinees can shed viruses up to 4 months or longer; this period can be decades if recipients are immunodeficient.3, 4, 5 The excreted viruses may rarely revert to neurovirulent strains and produce vaccine-associated paralytic poliomyelitis (VAPP) in the recipients and their contacts.1, 5 Sequential infections and outbreaks caused by vaccine-derived polioviruses (VDPV) have been reported where immunization rates were not high.6

The poliovirus contains a 7.5 kb single-stranded RNA genome that has a high rate of genetic evolution through nucleotide substitutions and recombination with other polioviruses or human enteroviruses C (HEV-C).7, 8 The nucleotide substitution rate is around 1% per year in the VP1 gene. Sequence divergence in VP1 from Sabin strains is used by the World Health Organization (WHO) to categorize isolates into: (1) <1%, OPV-like; (2) 1–15%, VDPVs; and (3) >15%, wild-type.1, 9, 10 Recombination can occur early and frequently in OPV recipients.11 Previous studies showed that recombinant strains were mostly OPV-like isolates, but also could be VDPVs or cause VAPP.12, 13, 14, 15, 16 Recombinants containing HEV-C sequences have been isolated from cases of acute flaccid paralysis (AFP).16, 17, 18, 19

As the goal of global eradication of poliomyelitis approaches, the occurrence of diseases related to OPV and genetic variability of Sabin strains from clinical cases should be investigated. By linking laboratory data and vaccination records and further reviewing of patients’ charts from hospitals, we examined these issues in southern Taiwan during 2000–2005.

Section snippets

Surveillance system and patient source

The Centers for Disease Control (CDC), Taiwan since 1999 has maintained a laboratory-based infectious disease surveillance program that utilizes over 750 sentinel physicians to identify and collect specimens from patients with flu-like syndromes, hand–foot–mouth disease, herpangina or acute gastroenteritis.20, 21 Depending on patients’ initial symptoms, throat swab, rectal swab, nasopharyngeal aspirate, cerebrospinal fluid or other specimens were collected.21 Comprehensive bacterial and viral

Patient series

Among 12,236 enteroviruses isolated in the surveillance during 2000–2005, 1.5% was polioviruses.21 All polioviruses were confirmed as OPV-like, except VDPVs from an immunodeficiency patient in northern Taiwan that was reported elsewhere and not included here.29 Higher percentages of polioviruses, 3.8% in 2001 and 1.6% in 2002 were noticed, as compared to 0.84–0.88% in 2000 and 2003–2005 (p < 0.05). This increased detection of OPV in 2001–2002 prompted us to investigate the extent of illnesses

Discussion

This is the first clinical and virologic investigation in Taiwan of a large series of children with poliovirus isolation. OPV-like strains were the only pathogen found in 208 immunocompetent patients with LRI, AGE, and even fatal myocarditis. In 53 patients that had received at least 3 doses of tOPV, the time of poliovirus isolation was >10 weeks after the vaccination, suggesting that they likely were re-infected from the environment. Similarly, 6 patients acquired Sabin strains from the

Acknowledgements

The study was supported by the intramural funding of the National Health Research Institutes, Taiwan. Authors wish to thank members of “Virology Reference Laboratories Network” and “Sentinel Physician Surveillance of Infectious Diseases” by Centers for Disease Control, Taiwan.

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    Chia-Yu Chi and Fan-Chen Tseng contributed equally to this work.

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