Title page for ETD etd-11172005-120800


Document Type Doctoral Thesis
Author Pavlov, Dobromir Nikolov
URN etd-11172005-120800
Document Title Genomic mutations in oral poliovirus vaccine strains : implications for the eradication of poliovirus
Degree PhD (Medical Virology)
Department Medical Virology
Supervisor
Advisor Name Title
Prof W O K Grabow Co-Supervisor
Dr M M Ehlers Supervisor
Keywords
  • no key words available
Date 2004-10-09
Availability unrestricted
Abstract
Large epidemics of poliomyelitis spread across the world in the first half of the 20th century. However, polio incidence fell rapidly across the world following the introduction of the oral poliovirus vaccine (OPV). Since the introduction of immunisation with OPV, the vaccine had a remarkable track record of success, because the number of wild-type polio cases decreased from 350 000 to 500 and the number of polio endemic countries declined from 125 to 10. Thus, the global eradication of wild-type poliovirus (PV) seems a realistic goal for the foreseeable future.

Despite its many advantages, one disadvantage of the OPV is the potential risk of revertants of the OPV strains, which may cause neurological complications in vaccine recipients and susceptible contacts. Immunocompetent persons excrete OPV strains for a limited period of time. In contrast, immunodeficient people may become chronically infected and excretion times as long as 10 years have been reported. As a consequence, in the last phase of polio eradication this group of people may serve as potential reservoirs for vaccine-derived polioviruses (VDPVs). Two cases of vaccine-associated paralytic poliomyelitis have been reported in human immunodeficiency virus (HIV)-positive children, although, presently there is no evidence for prolonged excretion of PV from patients with HIV and acquired immunodeficiency syndrome (AIDS). Highly evolved VDPVs have been isolated from sewage and river water even in the absence of cases of paralytic poliomyelitis.

This study aimed to investigate the prevalence of PVs in sewage and river water as well as in stool specimens of HIV-positive children (including those with an AIDS indicator condition according to the Centers for Disease Control and Prevention classification). Secondly, the study investigated the occurrence of genomic mutations in these OPV isolates.

A total of 49 PV vaccine strains were isolated from the sewage and river water, and 13 PV vaccine strains were detected in the stools of immunodeficient children. Two of the immunodeficient patients (vaccinated 15 months ago) tested positive for Sabin PVs type 1 and 3. Another immunodeficient patient (vaccinated 42 months ago) tested positive for Sabin PV type 1.

The 5’untranslated and the VP1 regions in the genomes of the OPV isolates were partially sequenced. The majority of the OPV strains detected in the sewage and river water displayed >99% VP1 sequence identity to the original PV vaccine strains and were classified as “OPV-like viruses”. Two OPV isolates were identified as “suspected” VDPVs, since these isolates showed £99% VP1 sequence identity to the PV vaccine strains and had probably replicated in one or more people for 12 to 16 months since the administration of the initiating OPV dose. In contrast, three “suspected” immunodeficient VDPVs were identified in the stools of the immunodeficient children. All of the OPV-like and “suspected” VDPV isolates carried genomic mutations, which had been associated with reversion of the attenuated PV phenotypes to increased neurovirulence.

The identification of OPV-like and “suspected” VDPVs in this study emphasised the fundamental importance regarding the control of health risks constituted by OPV vaccination, particularly with regard to immunodeficient individuals such as HIV-positive children, and the possible role of water in the transmission of potentially hazardous VDPVs. These research findings provided valuable data, concerning prolonged excretion of OPV strains by individuals with secondary immunodeficiency and this could have major implications for strategies aimed for the global post-polio eradication era.

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  08appendix.pdf 200.88 Kb 00:00:55 00:00:28 00:00:25 00:00:12 00:00:01

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