Poliovirus Vaccine Shedding among Persons with HIV in Abidjan, Cote d'Ivoire
Global Immunization Division, National Immunization Program
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
Enterovirus Laboratory, Institute Pasteur
Projet RetrovirusCote d'Ivoire, Abidjan, Cote d'Ivoire
Expanded Programme on Immunization, Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland
Background.
As polio eradication nears, the development of immunization policies for an era without the disease has become increasingly important. Outbreaks due to circulating vaccine-derived poliovirus (VDPV) and rare cases of immunodeficient persons with prolonged VDPV shedding lend to the growing consensus that oral poliovirus vaccine (OPV) use should be discontinued as soon after polio eradication as possible. The present study was conducted to assess whether persons infected with human immunodeficiency virus (HIV) experience prolonged VDPV shedding and serve as a source of reintroduction of virus into the population.
Methods.
Adults infected with HIV had specimens tested (1) 8 months after a mass OPV campaign, to determine whether poliovirus related to OPV administered during the campaign was present (i.e., prolonged excretion), and (2) starting 7 weeks after a subsequent campaign, to determine whether poliovirus could be detected after the height of OPV exposure.
Results.
A total of 419 participants were enrolled315 during the 812 months after an OPV campaign held in 2001 and 104 during the 713 weeks after a 2002 campaign. No poliovirus was isolated from any participants.
Conclusions.
It appears unlikely that adults infected with HIV experience prolonged vaccine virus shedding, and, therefore, they probably represent a minimal risk of reintroducing vaccine virus into the population after poliovirus has been eradicated. Since adopting the initiative to eradicate polio globally in 1988, 3 World Health Organization regions (American, Western Pacific, and European) have been certified as polio free, and the number of polio-endemic countries has decreased from 125 in 1988 to 6 in 2003 [1, 2]. As a polio-free world approaches, developing polio immunization policies after eradication has become increasingly relevant, especially in light of risks associated with the use of oral poliovirus vaccine (OPV). In addition to vaccine-associated paralytic polio (VAPP), there are risks of circulating vaccine-derived poliovirus (cVDPV), which can maintain person-to-person transmission and cause paralytic disease, and immunodeficiency-related VDPV (iVDPV), which is associated with prolonged infection and shedding of mutant poliovirus vaccine strains among persons with primary immune deficiencies. The polio eradication program depends on OPV to interrupt the final chains of poliovirus transmission; however, these discoveries lend to the growing consensus that OPV use should be discontinued as soon after polio eradication as possible. Much work is under way to develop a safe and efficient approach for accomplishing this objective globally.
Genetically, VDPVs are defined as having >1% sequence difference from the Sabin vaccine virus [3]. The first polio outbreak caused by cVDPVs was detected on the island of Hispaniola in 2000; it resulted in the paralysis of 21 children and clearly demonstrated for the first time the potential for vaccine strains to circulate and cause paralytic disease [4]. Subsequent cVDPV outbreaks were detected in the Philippines in 2001 (3 cases), Madagascar in 2002 (4 cases), and, through retrospective analysis, Egypt in 19881993 (30 cases) [57]. Absence of wild poliovirus of the same serotype and low vaccination coverage were associated with the outbreaks; however, it is not clear whether low population immunity alone is sufficient for the emergence of cVDPVs [8]. A complementary explanation is that only after essential mutations for virulence and transmissibility are acquired within an individual (i.e., an immunodeficient individual) are vaccine viruses able to circulate and cause disease in the population.
Shedding of iVDPVs for a duration of at least 6 months has been identified in 19 patients with B cell immune deficiency disorders from 7 different countries [917]. Some of these patients have shed virus for >10 years, and some have developed paralytic polio, demonstrating that prolonged replication even within a single individual increases the virulence of these vaccine-related viruses. There has been no evidence of paralytic disease resulting from secondary exposure to iVDPVs; however, since most contacts of these individuals are immune, the significance of this observation is uncertain. Studies designed to search for more patients with prolonged shedding of vaccine virus show that these cases are rare [16, 18]. One study has reported that a healthy child possibly shed vaccine virus for 6 months; however, this finding is not definitive, because serial sampling did not cover the entire 6-month period, and the child's mother was HIV infected [19].
VAPP is the rare occurrence of paralytic polio among OPV recipients or contacts of recipients, which occurs an estimated rate of 1 case per
Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
Enterovirus Laboratory, Institute Pasteur
Projet RetrovirusCote d'Ivoire, Abidjan, Cote d'Ivoire
Expanded Programme on Immunization, Department of Immunization, Vaccines and Biologicals, World Health Organization, Geneva, Switzerland
Background.
As polio eradication nears, the development of immunization policies for an era without the disease has become increasingly important. Outbreaks due to circulating vaccine-derived poliovirus (VDPV) and rare cases of immunodeficient persons with prolonged VDPV shedding lend to the growing consensus that oral poliovirus vaccine (OPV) use should be discontinued as soon after polio eradication as possible. The present study was conducted to assess whether persons infected with human immunodeficiency virus (HIV) experience prolonged VDPV shedding and serve as a source of reintroduction of virus into the population.
Methods.
Adults infected with HIV had specimens tested (1) 8 months after a mass OPV campaign, to determine whether poliovirus related to OPV administered during the campaign was present (i.e., prolonged excretion), and (2) starting 7 weeks after a subsequent campaign, to determine whether poliovirus could be detected after the height of OPV exposure.
Results.
A total of 419 participants were enrolled315 during the 812 months after an OPV campaign held in 2001 and 104 during the 713 weeks after a 2002 campaign. No poliovirus was isolated from any participants.
Conclusions.
It appears unlikely that adults infected with HIV experience prolonged vaccine virus shedding, and, therefore, they probably represent a minimal risk of reintroducing vaccine virus into the population after poliovirus has been eradicated. Since adopting the initiative to eradicate polio globally in 1988, 3 World Health Organization regions (American, Western Pacific, and European) have been certified as polio free, and the number of polio-endemic countries has decreased from 125 in 1988 to 6 in 2003 [1, 2]. As a polio-free world approaches, developing polio immunization policies after eradication has become increasingly relevant, especially in light of risks associated with the use of oral poliovirus vaccine (OPV). In addition to vaccine-associated paralytic polio (VAPP), there are risks of circulating vaccine-derived poliovirus (cVDPV), which can maintain person-to-person transmission and cause paralytic disease, and immunodeficiency-related VDPV (iVDPV), which is associated with prolonged infection and shedding of mutant poliovirus vaccine strains among persons with primary immune deficiencies. The polio eradication program depends on OPV to interrupt the final chains of poliovirus transmission; however, these discoveries lend to the growing consensus that OPV use should be discontinued as soon after polio eradication as possible. Much work is under way to develop a safe and efficient approach for accomplishing this objective globally.
Genetically, VDPVs are defined as having >1% sequence difference from the Sabin vaccine virus [3]. The first polio outbreak caused by cVDPVs was detected on the island of Hispaniola in 2000; it resulted in the paralysis of 21 children and clearly demonstrated for the first time the potential for vaccine strains to circulate and cause paralytic disease [4]. Subsequent cVDPV outbreaks were detected in the Philippines in 2001 (3 cases), Madagascar in 2002 (4 cases), and, through retrospective analysis, Egypt in 19881993 (30 cases) [57]. Absence of wild poliovirus of the same serotype and low vaccination coverage were associated with the outbreaks; however, it is not clear whether low population immunity alone is sufficient for the emergence of cVDPVs [8]. A complementary explanation is that only after essential mutations for virulence and transmissibility are acquired within an individual (i.e., an immunodeficient individual) are vaccine viruses able to circulate and cause disease in the population.
Shedding of iVDPVs for a duration of at least 6 months has been identified in 19 patients with B cell immune deficiency disorders from 7 different countries [917]. Some of these patients have shed virus for >10 years, and some have developed paralytic polio, demonstrating that prolonged replication even within a single individual increases the virulence of these vaccine-related viruses. There has been no evidence of paralytic disease resulting from secondary exposure to iVDPVs; however, since most contacts of these individuals are immune, the significance of this observation is uncertain. Studies designed to search for more patients with prolonged shedding of vaccine virus show that these cases are rare [16, 18]. One study has reported that a healthy child possibly shed vaccine virus for 6 months; however, this finding is not definitive, because serial sampling did not cover the entire 6-month period, and the child's mother was HIV infected [19].
VAPP is the rare occurrence of paralytic polio among OPV recipients or contacts of recipients, which occurs an estimated rate of 1 case per