Monitoring For Rotavirus Serotypes In The Americas. Jon Gentsch

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1 Monitoring For Rotavirus Serotypes In The Americas Jon Gentsch Centers for Disease Control and Prevention, Atlanta, USA * The findings and conclusions in this presentation are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention (CDC). PAHO/WHO Collaborating Center for Rotavirus and Other Viral Agents of Gastroenteritis

2 Introduction Rationale for rotavirus strain surveillance Introduction to serotypes Surveillance in the Americas Conclusions and future directions

3 Rotavirus Strain Surveillance in Vaccine Era Vaccine Research Impact of vaccines on strain prevalence and evolution Will immune selection over time result in emergence of strains that escape protection? Vaccine stability Reversion to virulence Transmission, gastroenteritis in unvaccinated Reassortment with wild-type rotavirus Virus Evolution origin of new strains through reassortment Role of animal rotaviruses genetic variation in RV genes

4 Rotavirus Serotype Classification RNA Segment Protein VP1 VP2 VP3 VP4 NSP1 VP6 NSP2 NSP3 VP7 NSP4 NSP5 VP2 VP4 Neutralization antigen VP6 Subgroup antigen VP7 Neutralization antigen Subcore Provided by MK Estes P type G type

5 Methods: Processing Stool Samples for Strain Surveillance Rotavirus Detection (e.g., IDEIA (Oxoid [Ely]) Genotype positives using hemi-nested RT-PCR VP4 gene fragment (P) RT-PCR PCR P[11] P[6] P[8] P[9] P[4] P[10] P types VP7 gene fragment (G) PCR G9 G2 RT-PCR G4 G3 G types Identify genotypes by electrophoresis

6 Human Rotavirus Serotypes and Genotypes Four historically common strains globally (>30 yrs) P[8],2 or P[6],2 or P[4],2 or P[9],2 1.2% Unusual 7.5% Rare 0.5% P[8]G9 emerged since 1995 Emerged since 2000 P[8],G9 21.5% P[8],G4 6.6% P[8],G3 7.5% P[4],G2 11.8% P[8], 43.5% Data of K Banyai, PG types

7 Uncommon rotavirus genotypes: >20 G types, >30 P types and ~80 G-P combinations in humans Adapted from Kirkwood et al

8 Rotavirus Serotypes: Lessons learned from surveillance Only few globally common strains Periodic emerging strains Huge diversity Large temporal and geographic variation

9 Surveillance in the United States National Rotavirus Strain Surveillance System (NRSSS) New Vaccine Surveillance Network (NVSN) PAHO/WHO Collaborating Center for Rotavirus and Other Viral Agents of Gastroenteritis

10 National Rotavirus Strain Surveillance System (United States, ) Seattle San Francisco Omaha Kansas City Chicago Boston Hackensack Indianapolis Long Beach Fort Worth Atlanta Orlando

11 Number of Positive and Total Rotavirus Tests, United States, , 2008, 33 Continuously Reporting Labs 900 Total N Tests Total N Positive RotaTeq introduced

12 Longitudinal Variation of Rotavirus G Types in the United States ( ) RotaTeq introduced Number of Specimens NT G9 G4 G3 G G Hull, Teel et al, in prep Surveillance Year

13 Geographical Serotype Variation USA ( ) 2008) G9 39% other 3% 31% 6% G2 3% 4% G3 12% G2 15% G3 91% G3 96% Seattle WA, N=61 Omaha NE, N=40 Fort Worth TX, N=23 Hull, Teel et al, in prep

14 P and G Genotypes of Rotavirus Strains in United States (NRSSS) Other 7% P[4]G2 11% P[6]G9 1% Other 7% P[4]G2 13% P[8] 30% P[8]G9 3% P[8]G4 1% P[8]G3 2% P[8]G9 15% Hull, Teel et al, in prep TO P[8] 75% P[8]G3 35%

15 Genotyping by sequencing identified a major outbreak of genotype 2 in the United States (primers for 2 are not routinely present in multiplex RT-PCR) From Payne et al, PIDJ, 2009

16 Surveillance in Latin America and the Caribbean Set up starting 2004 to assess disease burden and strains Strains received from rotavirus sentinel hospital surveillance network analyzed at CDC Genotyping results from seven sites

17 Map of Countries Participating in the Rotavirus Surveillance Network in Latin America and the Caribbean St. Vincent & the Grenadines Venezuela Guyana Suriname Guatemala Honduras El Salvador Nicaragua Bolivia Chile Paraguay L Oliveira et al, JID 2009

18 Strains Circulating in Seven Latin American Countries ( ) other 7% untypeable 6% P[8] 32% P[8]G9 21% P[8]G8 10% P[8]G4 5% P[8]G3 1% P[4]G2 18% N=388 Adapted from L Oliveira et al, JID 2009

19 Regional Variation of Strains Circulating in the Latin American ( ) El Salvador Guatemala Guyana Honduras P[8]G9 20% P[8]G4 1% P[4]G2 11% untypeable other 5% 2% P[8] 61% P[8]G9 46% other 10% untypeable 4% P[8] 2% P[4]G2 38% P[8] 100% other 15% P[8]G9 9% untypeable 17% P[8]G4 2% P[8]G3 5% P[4]G2 52% Nicaragua St Vincent Suriname untypeable other 11% 4% P[8]G3 4% P[8] 6% P[6]2 7% other 5% untypeable 2% P[8] 2% P[8]G9 11% P[8]G4 70% P[8]G9 94% P[8]G8 84% Adapted from L Oliveira et al, JID 2009

20 Are Vaccination Programs Impacting Prevalence of Common Strains? Vaccination of populations with Rotarix Increased prevalence of P[4]G2 (Brazil, Australia) Vaccination with RotaTeq Increased prevalence of P[8]G3 (Australia, United States)

21 Temporal Variation in Predominant Strain,Central America P[8]G9 94% P[4]G2 81% P[8] 91% Vaccine El Salvador (Rotarix) Guatemala (none) P[8]G9 96% P[4]G2 72% P[8] 90% P[8]G9 40% P[4]G2 68% P[8 68% Honduras (none) Adapted from Patel et al., EID 2008; L Oliveira et al JID 2009

22 RotaTeq Vaccinated Population and increased P[8]G3 Rotavirus Genotypes in Nicaragua, P[4]G2 85% N=262, Patel et al, JAMA 2009

23 Conclusions and Future Directions No convincing evidence for immune selection, more likely natural variation Increasing prevalence P[4]G2, P[8]G3 in countries that have not adopted vaccines Supported by continued moderately high field efficacy of Rotarix vs P[4]G2 (e.g., Brazil, Australia [Snelling 2009, Nakagomi 2009], RotaTeq vs P[8]G3 [e.g., Boom et al 2008]) Long term effectiveness studies where serotype specific VE and overall disease trends can be assessed Needed to discriminate observed trends from natural strain fluctuations, emergence of new strains etc

24 CDC Umesh Parashar Margaret Cortese Manish Patel Dan Payne Jackie Tate Jazmin Vojdani Tara Kerin Mathew Esona Mike Bowen PAHO Lucia Helena de Oliveira M. Carolina Danovaro-Holliday Jon Kim Andrus Ana Maria Bispo de Fillipis Cuauhtemoc Ruiz Matus Epidemiological Surveillance of Ministries of Health from countries Members of the NVSN and NRSSS networks in the United States