Title page for ETD etd-07122012-161159


Document Type Doctoral Thesis
Author Gumede-Moeletsi, Heronyma Nelisiwe
Email nicksyg@nicd.ac.za
URN etd-07122012-161159
Document Title Molecular characterisation of wild and Sabin-like polioviruses circulating in Africa after 2000
Degree PhD
Department Medical Virology
Supervisor
Advisor Name Title
Dr M Pallansch Committee Co-Chair
Prof B Schoub Committee Co-Chair
Prof M Venter Supervisor
Keywords
  • Sabin-like polioviruses
  • moleculars
  • poliomyelitis
  • South Africa
Date 2012-04-13
Availability restricted
Abstract
Polioviruses have been around for a long time in man's history. Before the development of killed and live virus vaccines in the 1960's, poliomyelitis was a serious problem in public health. Since then paralytic poliomyelitis remains a threat in certain underdeveloped countries but has been considered a conquered disease in the developed world.

The molecular epidemiology of wild-type 1 polioviruses (WPV1) isolated in Angola in 2005, the Democratic Republic of the Congo (DRC) in 2006-2008 and Namibia in 2006 were investigated by sequence analysis of the complete VP1 gene of all isolates. All outbreak viruses clustered with the Indian type 1 genotype (SOAS) which was unique to India circulating endemically in the Uttar Pradesh (UP) and Bihar provinces in Northern India. Epidemiological and virological analyses suggested that the Namibia outbreak virus had been circulating without detection for at least one year in Angola.

Four cases of acute flaccid paralysis (AFP) occurred in children in Madagascar in 2005. Molecular analysis confirmed cVDPV type 2 and 3 in affected patients. The first case, occurred in Toliara II district, on 09 April 2005. The last two cases were in the Toliara I and Beloha districts and paralysis onset on 26 June and 13 July 2005 respectively. Partial genomic sequencing of the poliovirus isolates revealed considerable divergence from the prototype Sabin strain in all cases. This is the second time that type 2 cVDPV is associated with an outbreak of AFP in Madagascar, and to our knowledge the first time that a type 3 cVDPV is identified in Madagascar.

A total of fifty-six children with AFP were found to excrete VDPVs of serotype 2 in the DRC between 2005 and 2010. These viruses represent at least three emergences and at least two outbreaks. Partial genomic sequencing of the poliovirus isolates revealed considerable nucleotide sequence divergence of between 1.1% to 2o/o from the prototype Sabin strain in the VP1 region of the viral genome. This was the first time that a type 2 cVDPV outbreak was detected in the DRC.

In total, 89 viral isolates obtained from Ethiopia during 2007 to 2010 and partial sequencing analysis confirmed that 13 isolates were VDPV's. Seven AFP cases were type 3, 4 AFP cases were type 2 and 2 contacts for type 3. Partial genomic sequencing of the poliovirus isolates revealed considerable divergence from the prototype Sabin strain in all cases.

Finally, cases of AFP where only Sabin-like viruses were identified were investigated in South Africa with 11 possible VAPP cases identified with recombinant events in the 30 region and also revealing a mutation that restore the original stem-loop structure in the internal ribosomal entry site (IRES) in the 5' Non-Translated Region (NTR).

In this study, the molecular epidemiology of poliovirus outbreaks that occurred in Angola, Namibia, and the DRC is described that were associated with wild polio 1 and 3. Investigation of Sabin-like vaccine strains in the DRC, Madagascar and Ethiopia identified vaccine-derived polioviruses in AFP cases as well as possible vaccineassociated paralytic poliovirus in South Africa.

Copyright 2012, University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria

Please cite as follows:

Gumede-Moeletsi, HN 2012, Molecular characterisation of wild and Sabin-like polioviruses circulating in Africa after 2000, PhD thesis, University of Pretoria, Pretoria, viewed yymmdd < http://upetd.up.ac.za/thesis/available/etd-07122012-161159 / >

D12/4/225/gm
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