Poliovirus vaccine strains detected in stool specimens of immunodeficient children in South Africa

Abstract

After exposure to the oral poliovirus vaccine (OPV), immunocompetent persons excrete poliovirus (PV) vaccine strains for a limited period. In contrast, immunodeficient individuals remain sometimes chronically infected, and in some cases, PV excretion times as long as 10 years have been reported. During prolonged replication in the human intestine, the PV vaccine strain almost invariably reverts its attenuated character and acquires neurovirulent properties (vaccine-derived PVs, or VDPVs), which resemble wild-type PV strains. The aim of this study was to determine the occurrence of OPV strains in stools of immunodeficient children from a selected area in South Africa, as a first step toward future research on the prevalence and potential health impact of VDPVs. In a period of 1 year, a total of 164 stool samples of HIV-positive children aged 4 months to 8 years were studied for the excretion of OPV strains. In addition, 23 stool samples from healthy immunocompetent children were analyzed after receiving their OPV immunization. By applying a reverse transcription-polymerase chain reaction in combination with a nested PCR, a total of 54 enteroviruses (EVs) were detected in the stool specimens of the immunodeficient children. Using restriction enzyme analysis, 13 PVs were distinguished from 41 nonpolio EVs (NPEVs). A Sabin-specific RT-triplex PCR confirmed the presence of 7 Sabin PV type 1, 4 Sabin PV type 3, and 2 Sabin PV type 2 isolates. The majority of the NPEV group was made up of 7 coxsackievirus B3 (CBV3), 6 echovirus 11 (ECV11), 5 ECV9, and 3 coxsackievirus A6 (CAV6) isolates. According to the results, two of the immunodeficient patients (P023 and P140) who had received their last OPV immunization more than 15 months before (vaccinated at 14 weeks of age) tested positive for Sabin PVs types 3 and 1, respectively. A 5-year-old immunodeficient patient (P052) who had received her last OPV immunization more than 42 months before (vaccinated at 18 months of age) tested positive for Sabin PV type 1. These results suggested that immunodeficient patients vaccinated with OPV might excrete potentially pathogenic VDPVs for a prolonged period. These VDPVs may circulate in the community, resulting in possible infections in the unvaccinated population. Therefore, the information obtained in this study would be essential for strategies aimed at the protection of both immunodeficient as well as immunocompetent individuals against complications of vaccination with OPV. Article Outline

Interference of Vaccine Derived Polio Viruses with Diagnosis of Enteroviral Diseases in Neonatal Period

“…In South Africa 30% of stool samples from healthy (vaccinated) children (0-18 month) tested positive for polioviruses. Polio virus excretion generally stopped by the end of the second week after each vaccination [11]. In Bangladesh 17.6% of the stool samples from infants were positive for polioviruses up to 25 days after vaccination [12].…”

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.…”

The Role of Prolonged Viral Gastrointestinal Infections in the Development of Immunodeficiency-Related Enteropathy

“…Several studies have investigated the duration of enterovirus excretion, most notably poliovirus. Vaccination program strategies have eradicated polio in several continents [66]; although due to the use of live oral poliovirus vaccine, and the fact that sporadic immunocompromised patients fail to clear the infection and thus become chronic excretors, vaccine-derived poliovirus (VDPV) still circulates in the population [67][68][69]. VDPV may be excreted up to 4-8 weeks by a large proportion of susceptible healthy individuals [65,70]; one healthy infant excreted VDPV for 10 months [71].…”