Maldonado Epi Group  

Research on Oral Poliovirus Vaccines

The poliomyelitis eradication goal - set by the World Health Assembly in 1988 may be achieved within the next decade.  The program  is based on massive global vaccination campaigns using oral polio vaccine (OPV). Cases of poliomyelitis have decreased dramatically from an estimated 350,000 cases in 1988 to less than 649 cases in 2011. However, OPV itself can cause disease. OPV can mutate into vaccine-derived poliovirus (VDPV) with prolonged replication, which have caused 18 separated outbreaks and are just as virulent as wild poliovirus. OPV can also quickly acquire well-known point mutations that are associated with the development of vaccine-associated paralytic poliomyelitis (VAPP), usually in infants after their first dose of OPV.  Thus continued OPV use may jeopardize poliomyelitis eradication.

We are interested in the following areas:

  1. OPV and HIV:

Studies had shown that individuals with humoral immunodeficiencies may shed OPV for years.  Infants with perinatal human immunodeficiency virus (HIV) infection may have humoral as well as cellular immunodeficiencies, which might result in prolonged OPV replication. Zimbabwe, where OPV is given routinely to all infants and antenatal HIV prevalence is 16%, provides a natural setting to study the effect of perinatal HIV infection on OPV shedding, mutation, and transmission. Our cross-sectional study found that pediatric HIV infection is associated with a poor serologic response to OPV. The ongoing study funded by NIH was conducted in and around Chitungwiza, Zimbabwe. The stool, blood and health information were serially collected from 421 HIV positive and HIV negative infants during and after OPV administration through 24 months of age. We are investigating the determinants of OPV shedding in infants perinatally infected with HIV and their household contacts.

  1. OPV and IPV:

Inactivated polio vaccine (IPV) does not have the potential to cause poliomyelitis because it is a killed virus vaccine. It is not entirely clear how IPV administration impacts OPV circulation in both the environment and vaccinated population. Children previously vaccinated with IPV are known to shed OPV for a longer period of time after an OPV challenge than children previously vaccinated with OPV.  Mexico switched to a primary IPV regimen in 2007, but still gives OPV during semiannual national immunization days (NIDs). With its unique vaccination practices, Mexico is an ideal setting to study the duration of OPV circulation in a population now vaccinated with IPV. Our cross-sectional study found that OPV circulation continues for at least 13 weeks after a NID. The ongoing study funded by WHO was conducted in municipalities near Orizaba, Mexico from August 2010 to July 2011. Monthly stool was collected from 72 children and 144 household contacts. Monthly sewage was also collected from 4 arroyos draining the municipalities. We are investigating OPV circulation and mutation after NID in sewage and stool, as well as OPV transmission in household contacts of vaccinees after NID.

Polio Research Photos

Selected publications:

  1. Real-Time PCR Analysis of Sewage Samples to Determine Oral Polio Vaccine Circulation Duration and Mutation after Mexican National Immunization Weeks Stephanie B. Troy, Leticia Ferreyra-Reyes, Sergio Canizales-Quintero, ChunHong Huang, Yu-Jin Lee, Renata Báez-Saldaña,Elizabeth Ferreira-Guerrero, Lourdes García-García, Yvonne Maldonado, MD
    Journal of the Pediatric Infectious Diseases Society, accepted
  2. Immunologic response to oral polio vaccine in human immunodeficiency virus-infected and uninfected Zimbabwean children.

    Gnanashanmugam D, Troy SB, Musingwini G, Huang C, Halpern MS, Stranix-Chibanda L, Shetty AK, Kouiavskaia D, Nathoo K, Chumakov K, Maldonado YA.
    Pediatr Infect Dis J. 2012 Feb; 31(2):176-80.

  3. Intradermal fractional dose inactivated polio vaccine: a review of the literature.Nelson KS, Janssen JM, Troy SB, Maldonado Y.
    Vaccine. 2012 Jan 5; 30(2):121-5. Epub 2011 Nov 17. Review.
  4. Hematologic and immunologic parameters in zimbabwean infants: a case for using local reference intervals to monitor toxicities in clinical trials.

    Troy SB, Rowhani-Rahbar A, Dyner L, Musingwini G, Shetty AK, Woelk G, Stranix-Chibanda L, Nathoo K, Maldonado YA.
    J Trop Pediatr. 2012 Feb; 58(1):59-62. Epub 2011 Apr 18.

  5. Use of a novel real-time PCR assay to detect oral polio vaccine shedding and reversion in stool and sewage samples after a mexican national immunization day.

    Troy SB, Ferreyra-Reyes L, Huang C, Mahmud N, Lee YJ, Canizales-Quintero S, Flaster H, Báez-Saldaña R, García-García L, Maldonado Y.
    J Clin Microbiol. 2011 May; 49(5):1777-83. Epub 2011 Mar 16.

  6. Impact of fetal and neonatal viral (and parasitic) infections on later development and disease outcome.

    Maldonado YA.
    Nestle Nutr Workshop Ser Pediatr Program. 2008; 61:225-42.  Review.

  7. Shedding and reversion of oral polio vaccine type 3 in Mexican vaccinees: comparison of mutant analysis by PCR and enzyme cleavage to a real-time PCR assay.

    Gnanashanmugam D, Falkovitz-Halpern MS, Dodge A, Fang M, Wong LJ, Esparza M, Hammon R, Rivas-Merelles EE, Santos JI, Maldonado Y.
    J Clin Microbiol. 2007 Aug; 45(8):2419-25. Epub 2007 Jun 20.

 


More Information

For more information about the Poliovirus Research, please contact Dr. Yvonne (Bonnie) Maldonado at (650)723-5682.

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