The global eradication of poliomyelitis, a goal set by the World Health Assembly in 1988, may likely be achieved within the next five years. Cases of poliomyelitis have decreased dramatically in the last 20 years, from an estimated 350,000 cases in 1988 to under 1300 in 2004 - a greater than 99% reduction. However, the recent discovery of circulating virulent vaccine derived polioviruses (VDPV), capable of causing paralytic poliomyelitis, threatens eradication. In addition, well-known point mutations of the three Sabin serotypes are associated with development of vaccine-associated paralytic poliomyelitis (VAPP). Thus, global cessation of oral polio vaccine (OPV) use as soon as eradication occurs is a high priority. Understanding the dynamics of circulation of OPV, and especially of VDPV and VAPP, and the impact of human immunodeficiency virus (HIV) infection on viral shedding and on the immunogenicity of inactivated polio vaccine (IPV), is critical for the development of post-eradication vaccination policies. Information about the immunogenicity of IPV regimens is important to assess whether IPV can be used to control potential post-eradication outbreaks in areas of high HIV prevalence. There is a lack of critical data, especially among immunodeficient individuals who may shed more VAPP and VDPV for longer periods than those with normal immune function, to evaluate post-eradication vaccination options being considered by the World Health Organization. We propose to provide data, in a timely fashion, to evaluate the shedding and transmission of OPV, VAPP and VDPV by healthy and immunodeficient populations given OPV in a developing country, and to assess the immunogenicity and mucosal immunity of IPV regimens in healthy and immunodeficient infants living in poor sanitary conditions, which may affect IPV immunogenicity. The proposed studies will be carried among HIV- infected and uninfected infants living in Chitungwiza, Zimbabwe, with an HIV seroprevalence of 20%, to address specific gaps in designing polio vaccination strategies for developing areas of the world. Lay description. Paralytic poliomyelitis (polio) may soon be eradicated. However, polio caused by the live polio vaccine can occur and may threaten efforts to eradicated polio. We propose strategies to identify the effect of HIV infection on polio eradication strategies in a developing country and to study the use of a killed polio vaccine in eradication of poliomyelitis worldwide. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI068577-01A1
Application #
7230647
Study Section
AIDS Clinical Studies and Epidemiology Study Section (ACE)
Program Officer
Park, Eun-Chung
Project Start
2007-07-01
Project End
2012-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$513,868
Indirect Cost
Name
Stanford University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
009214214
City
Stanford
State
CA
Country
United States
Zip Code
94305
Holubar, Marisa; Troy, Stephanie B; Nathoo, Kusum et al. (2017) Shedding of Oral Poliovirus Vaccine (OPV) by HIV-Infected and -Uninfected Mothers of OPV-Vaccinated Zimbabwean Infants. J Pediatric Infect Dis Soc 6:105-108
Troy, Stephanie B; Musingwini, Georgina; Halpern, Meira S et al. (2013) Vaccine poliovirus shedding and immune response to oral polio vaccine in HIV-infected and -uninfected Zimbabwean infants. J Infect Dis 208:672-8
Troy, Stephanie B; Rowhani-Rahbar, Ali; Dyner, LauraLe et al. (2012) Hematologic and immunologic parameters in Zimbabwean infants: a case for using local reference intervals to monitor toxicities in clinical trials. J Trop Pediatr 58:59-62