Prevalence of vaccine-derived polioviruses in stools of immunodeficient children in South Africa

Abstract

Aims: The aim of the study was to determine the prevalence of vaccine-derived polioviruses (VDPVs) in stool specimens of immunodeficient patients such as HIV-positive children (including those with an AIDS indicator condition, according to the Centres for Disease Control and Prevention classification) by applying various molecular techniques. Methods and Results: A total of 164 stool samples from HIV-positive children and 23 stool samples from healthy immunocompetent children (the control group) were analysed during 2003 and 2004. By applying a reverse transcription polymerase chain reaction (RT-PCR) in combination with a nested PCR, a total of 54 enteroviruses were detected in the stool specimens of the immunodeficient children. The use of restriction enzymes and a Sabin specific RT-triplex PCR confirmed the presence of 13 polioviruses (PVs), such as seven Sabin PV type 1, four Sabin PV type 3 and two Sabin PV type 2 isolates. The 5¢untranslated region and the VP1 capsid-encoding protein of the 13 PVs and the three PVs from the stools of the immunocompetent children were partially sequenced and their genetic relatedness was deduced from the constructed phylogenetic trees. The majority of the PVs isolated from the stools of the immunodeficient children (10 of 13 isolates) were classified as 'oral poliovirus vaccine (OPV)-like viruses', as these isolates had close sequence relationships (>99% in VP1 nucleotide sequences) to the original Sabin PV vaccine strains. Three PVs showed £99% VP1 sequence identity to the Sabin PV vaccine strains and were classified as 'suspected' immunodeficient VDPVs (iVDPVs). All of the OPV-like isolates and the 'suspected' iVDPVs carried mutations at specific positions in their partially sequenced regions, which have been associated with reversion of the attenuated Sabin PV vaccine strains to increased neurovirulence. Conclusions: Thus, this study adds further evidence to the observation that immunodeficient individuals may excrete OPV strains with potential neurovirulent phenotypes. Significance and Impact of the Study: Prolonged excretion of PVs by immunodeficient individuals is of major concern, because continued replication of PVs in the human gut could result in the reversion of these viruses to greater neurovirulence. When exposed to OPV, immunodeficient patients may become chronically infected, spreading potentially neurovirulent VDPVs for many months or years to close contacts and children who are no longer being vaccinated after termination of OPV vaccination in the near future.

Sabin and wild type polioviruses from children who presented with acute flaccid paralysis in Nigeria

“…Thus, in Nigeria, as in other parts of the world, the only current exposure to poliovirus type 2 is from use of the live, attenuated oral polio vaccine (OPV). Likewise in a study by Pavlov et al 32 ., the majority of the polioviruses isolated from the stools of the immunodeficient children (10 of 13 isolates) were classified as 'oral poliovirus vaccine (OPV)-like viruses'. The finding in this study deviates from that of Grassly et al 16 .,who reported that wild-type poliovirus serotypes 1 and 3 were isolated from the stool samples of 103 (0.74%) and 104 (0.74%) healthy contacts, respectively.…”

Vaccine Poliovirus Shedding and Immune Response to Oral Polio Vaccine in HIV-Infected and -Uninfected Zimbabwean Infants

“…A cross-sectional study in Guatemala examined the stools of 94 HIV-infected children (median age, 3.6 years) who had not received OPV for at least 6 months along with 101 HIV-infected adults and also found no detectable poliovirus [16]. In contrast, a cross-sectional study in South Africa examined 164 stool samples from hospitalized HIV-infected children and found 13 containing OPV-derived strains, 5 from children who had not received OPV for >6 months [17,18]. However, when these polioviruses were sequenced, only 2 of the 5 viruses showed the degree of divergence expected had these children been excreting the virus continuously since their last vaccination.…”

“…OPV is given to children regardless of HIV status at 3, 4, 5, and 18 months of age per the Zimbabwean vaccination schedule. During the study period, supplementary vaccination campaigns providing additional OPV doses were held [6][7][8][9][10][11][12][13][14][15][16][17][18] Enrollment occurred between September 2008 and December 2010 at 2 community clinics in Chitungwiza. Initial inclusion criteria included age between 2 and 4 months, a birth mother with known HIV status, and plans to receive OPV according to the national schedule.…”

“…Two prospective studies did not show vaccine poliovirus shedding beyond 6 months, but they were small, and 1 had very low retention rates [14,15]. Of 2 cross-sectional studies, 1 detected no poliovirus in stool samples from 94 HIV-infected Guatemalan children 6 months to ≥10 years after their last OPV dose, but the other did detect VDPV in the stools of hospitalized HIV-infected South African children [16][17][18]. However, as a cross-sectional study, it is unclear whether these isolates were cVDPV acquired in the community or iVDPV from chronic infection in the individual children.…”

Immunogenicity and safety of an acellular pertussis, diphtheria, tetanus, inactivated poliovirus, Hib-conjugate combined vaccine (PentaximTM) and monovalent hepatitis B vaccine at 6, 10 and 14 months of age in infants in South Africa

“…25 Routine primary vaccination with aP vaccines, including Pentaxim™, resulted in a marked decrease in pertussis incidence, with protection remaining high for 5 -7 years after the third dose. 28 As South Africa was close to certification as polio free at the time of the study (its last case of polio caused by a wild-type polio virus occurred in 1989 29 ), omission of the OPV birth dose posed no risk to participants and did not pose ethical problems. Combined vaccines that include IPV are available in the South African National Immunisation Programme and the seroprotection achieved against all three poliovirus types in our study provides additional evidence for the immunogenicity of the IPV antigens included in the combination vaccine at 6, 10 and 14 weeks of age.…”