Effect of time at temperature on wild poliovirus titers in stool specimens

AbstractBackgroundThe effect of transport temperature on the viability of poliovirus in stool specimens from paralyzed cases has not been tested. Quality assurance of programmatic indicators will be necessary in the final phase of polio eradication.ObjectiveTo estimate the effect of time at elevated temperatures on wild poliovirus titers in stool specimens.MethodsWe exposed aliquots of pooled wild poliovirus type 1 specimens to elevated temperatures (27°C, 31°C, and 35°C) for varying time periods up to 14 days. We determined the virus titer of these aliquots and created decay curves at each temperature to estimate the relationship between time at temperature and virus titer.ResultsWe found significantly different slopes of decay at each temperature. The negative slopes increased as the temperature increased.ConclusionsWhile poliovirus in stool remains relatively stable at moderately elevated temperature, transport at higher temperatures could impact sample integrity and virus isolation results

The potential impact of expanding target age groups for polio immunization campaigns

Background: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission. Methods: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent. Results: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas. Conclusions: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases

Characterization of poliovirus variants selected for resistance to the antiviral compound V-073

V-073, a small-molecule capsid inhibitor originally developed for nonpolio enterovirus indications is considerably more potent against polioviruses. All poliovirus isolates tested to date (n = 45), including wild, vaccine, vaccine-derived, and laboratory strains, are susceptible to the antiviral capsid inhibitor V-073. We grew poliovirus in the presence of V-073 to allow for the identification of variants with reduced susceptibility to the drug. Sequence analysis of 160 independent resistant variants (80 isolates of poliovirus type 1,40 isolates each of types 2 and 3) established that V-073 resistance involved a single amino acid change in either of two virus capsid proteins, VP1 (67 of 160 [42%]) or VP3 (93 of 160 [58%]). In resistant variants with a VP1 change, the majority (53 of 67 [79%]) exhibited a substitution of isoleucine at position 194 (equivalent position 192 in type 3) with either methionine or phenylalanine. Of those with a VP3 change, alanine at position 24 was replaced with valine in all variants (n = 93). The resistance phenotype was relatively stable upon passage of viruses in cell culture in the absence of drug. Single-step growth studies showed no substantial differences between drug-resistant variants and the virus stocks from which they were derived, while the resistant viruses were generally more thermally labile than the corresponding drug-susceptible parental viruses. These studies provide a foundation from which to build a greater understanding of resistance to antiviral compound V-073

Poliovirus vaccine shedding among persons with HIV in Abidjan, Cote d’Ivoire

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 enrolled-315 during the 8-12 months after an OPV campaign held in 2001 and 104 during the 7-13 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

Molecular identification and characterization of two proposed new enterovirus serotypes, EV74 and EV75

Fil: Oberste, M. Steven. Centers for Disease Control and Prevention. Respiratory and Enteric Viruses Branch; Estados Unidos.Fil: Michele, Suzanne M. Centers for Disease Control and Prevention. Respiratory and Enteric Viruses Branch; Estados Unidos.Fil: Maher, Kaija. Centers for Disease Control and Prevention. Respiratory and Enteric Viruses Branch; Estados Unidos.Fil: Schnurr, David. California Department of Health Services. Viral and Rickettsial Disease Laboratory; Estados Unidos.Fil: Cisterna, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Junttila, Nina. Swedish Institute for Disease Control. Department of Virology; Suecia.Fil: Uddin, Moyez. Institute of Public Health; Bangladesh.Fil: Chomel, Jean-Jacques. Centre National de Référence des Entérovirus; Francia.Fil: Lau, Chi-Shan. Queen Mary Hospital. Department of Health; China.Fil: Ridha, Walid. National Polio Laboratory; Irak.Fil: Al-Busaidy, Suleiman. Ministry of Health. Department of Laboratories; Oman.Fil: Norder, Helene. Swedish Institute for Disease Control. Department of Virology; Suecia.Fil: Magnius, Lars O. Swedish Institute for Disease Control. Department of Virology; Suecia.Fil: Pallansch, Mark A. Centers for Disease Control and Prevention. Respiratory and Enteric Viruses Branch; Estados Unidos.Sequencing of the gene that encodes the capsid protein VP1 has been used as a surrogate for antigenic typing in order to distinguish enterovirus serotypes; three new serotypes were identified recently by this method. In this study, 14 enterovirus isolates from six countries were characterized as members of two new types within the species Human enterovirus B, based on sequencing of the complete capsid-encoding (P1) region. Isolates within each of these two types differed significantly from one another and from all other known enterovirus serotypes on the basis of sequences that encode either VP1 alone or the entire P1 region. Members of each type were greater than or equal to 77(.)2% identical to one another (89(.)5% amino acid identity) in VP1, but members of the two different types differed from one another and from other enteroviruses by greater than or equal to 31% in nucleotide sequence (25% amino acid sequence difference), indicating that the two groups represent separate new candidate enterovirus types. The complete P1 sequences differed from those of all other enterovirus serotypes by greater than or equal to 31% (26% amino acid sequence difference), but were highly conserved within a serotype (< 8% amino acid sequence difference). Phylogenetic analyses demonstrated that isolates of the same serotype were monophyletic in both VP1 and the capsid as a whole, as shown previously for other enterovirus serotypes. This paper proposes that these 14 isolates should be classified as members of two new human enterovirus types, enteroviruses 74 and 75 (EV74 and EV75)

Diversity of picornaviruses in rural Bolivia

Fil: Nix, W Allan. Centers for Disease Control and Prevention; Estados Unidos.Fil: Khetsuriani, Nino. Centers for Disease Control and Prevention; Estados Unidos.Fil: Peñaranda, Silvia. Centers for Disease Control and Prevention; Estados Unidos.Fil: Maher, Kaija. Centers for Disease Control and Prevention; Estados Unidos.Fil: Venczel, Linda. Centers for Disease Control and Prevention; Estados Unidos.Fil: Cselkó, Zsuzsa. Centers for Disease Control and Prevention; Estados Unidos.Fil: Freire, Maria Cecilia. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Cisterna, Daniel. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Lema, Cristina L. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas; Argentina.Fil: Rosales, Patricia. Ministry of Health and Sports; Bolivia.Fil: Rodríguez, Jacqueline R. Pediatric Hospital San Antonio de Los Sauces; Bolivia.Fil: Rodríguez, Wilma. Ministry of Health and Sports; Bolivia.Fil: Halkyer, Percy. Pan-American Health Organization; Bolivia.Fil: Ronveaux, Olivier. Pan-American Health Organization; Bolivia.Fil: Pallansch, Mark A. Centers for Disease Control and Prevention; Estados Unidos.Fil: Oberste, M Steven. Centers for Disease Control and Prevention; Estados Unidos.The family Picornaviridae is a large and diverse group of viruses that infect humans and animals. Picornaviruses are among the most common infections of humans and cause a wide spectrum of acute human disease. This study began as an investigation of acute flaccid paralysis (AFP) in a small area of eastern Bolivia, where surveillance had identified a persistently high AFP rate in children. Stools were collected and diagnostic studies ruled out poliovirus. We tested stool specimens from 51 AFP cases and 34 healthy household or community contacts collected during 2002-2003 using real-time and semi-nested reverse transcription polymerase chain reaction assays for enterovirus, parechovirus, cardiovirus, kobuvirus, salivirus and cosavirus. Anecdotal reports suggested a temporal association with neurological disease in domestic pigs, so six porcine stools were also collected and tested with the same set of assays, with the addition of an assay for porcine teschovirus. A total of 126 picornaviruses were detected in 73 of 85 human individuals, consisting of 53 different picornavirus types encompassing five genera (all except Kobuvirus). All six porcine stools contained porcine and/or human picornaviruses. No single virus, or combination of viruses, specifically correlated with AFP; however, the study revealed a surprising complexity of enteric picornaviruses in a single community

The potential impact of expanding target age groups for polio immunization campaigns

BACKGROUND: Global efforts to eradicate wild polioviruses (WPVs) continue to face challenges due to uninterrupted endemic WPV transmission in three countries and importation-related outbreaks into previously polio-free countries. We explore the potential role of including older children and adults in supplemental immunization activities (SIAs) to more rapidly increase population immunity and prevent or stop transmission. METHODS: We use a differential equation-based dynamic poliovirus transmission model to analyze the epidemiological impact and vaccine resource implications of expanding target age groups in SIAs. We explore the use of older age groups in SIAs for three situations: alternative responses to the 2010 outbreak in Tajikistan, retrospective examination of elimination in two high-risk states in northern India, and prospective and retrospective strategies to accelerate elimination in endemic northwestern Nigeria. Our model recognizes the ability of individuals with waned mucosal immunity (i.e., immunity from a historical live poliovirus infection) to become re-infected and contribute to transmission to a limited extent. RESULTS: SIAs involving expanded age groups reduce overall caseloads, decrease transmission, and generally lead to a small reduction in the time to achieve WPV elimination. Analysis of preventive expanded age group SIAs in Tajikistan or prior to type-specific surges in incidence in high-risk areas of India and Nigeria showed the greatest potential benefits of expanded age groups. Analysis of expanded age group SIAs in outbreak situations or to accelerate the interruption of endemic transmission showed relatively less benefit, largely due to the circulation of WPV reaching individuals sooner or more effectively than the SIAs. The India and Nigeria results depend strongly on how well SIAs involving expanded age groups reach relatively isolated subpopulations that sustain clusters of susceptible children, which we assume play a key role in persistent endemic WPV transmission in these areas. CONCLUSIONS: This study suggests the need to carefully consider the epidemiological situation in the context of decisions to use expanded age group SIAs. Subpopulations of susceptible individuals may independently sustain transmission, which will reduce the overall benefits associated with using expanded age group SIAs to increase population immunity to a sufficiently high level to stop transmission and reduce the incidence of paralytic cases

Outbreak of Type 2 Vaccine-Derived Poliovirus in Nigeria: Emergence and Widespread Circulation in an Underimmunized Population

Wild poliovirus has remained endemic in northern Nigeria because of low coverage achieved in the routine immunization program and in supplementary immunization activities (SIAs). An outbreak of infection involving 315 cases of type 2 circulating vaccine-derived poliovirus (cVDPV2; >1% divergent from Sabin 2) occurred during July 2005–June 2010, a period when 23 of 34 SIAs used monovalent or bivalent oral poliovirus vaccine (OPV) lacking Sabin 2. In addition, 21 “pre-VDPV2” (0.5%–1.0% divergent) cases occurred during this period. Both cVDPV and pre-VDPV cases were clinically indistinguishable from cases due to wild poliovirus. The monthly incidence of cases increased sharply in early 2009, as more children aged without trivalent OPV SIAs. Cumulative state incidence of pre-VDPV2/cVDPV2 was correlated with low childhood immunization against poliovirus type 2 assessed by various means. Strengthened routine immunization programs in countries with suboptimal coverage and balanced use of OPV formulations in SIAs are necessary to minimize risks of VDPV emergence and circulation