La Carga Global del Rotavirus - SabinLinhares AC, Bresee JS. Rotavirus vaccines and vaccination in...
Transcript of La Carga Global del Rotavirus - SabinLinhares AC, Bresee JS. Rotavirus vaccines and vaccination in...
Simposio Subregional de Nuevas Vacunas:
Neumococo, Rotavirus y HPV
Caracas, Venezuela
29-30 Enero 2008
La Carga Global del Rotavirus
Daniel C. Payne, PhD, MSPHUS Centers for Disease Control and Prevention
Epidemiology of rotavirus
• Diarrheal disease in young childrenVirtually all children infected by age 5 years‘Democratic’ virusHighest rates of disease between 6-24 monthsLess common before 3 months
• Natural infection confers protection against subsequent infection
Higher protection against severe disease
• Worldwide distribution
All children will get at least one rotavirus infection early in life
Reproduced with permission from Velázquez et al. N Engl J Med. 1996;335:1022-1028.
1.00.90.80.70.60.50.40.30.20.1
3 6 9 12 15 18 21 24
Prob
abili
ty o
f rot
aviru
s in
fect
ion
Age (months)
1st infection
2nd infection
3rd infection
4th infection
5th infection
Annual disease burden of rotavirus in the United States (US)
3.5 - 4.0 millones1:1
500,0001:7
55-70,0001:72
20-40<1:100,000
Riesgo a 5 anos Eventos
Muertes
Hospitalizaciones
Casos de diarrea
Consultas
La carga global del RotavirusLa carga global del Rotavirus
527,000 (475,000 – 580,000)
2.3 millones
24 millones
114 millones
1 : 285
1 : 58
1 : 5
1 : 1
Riesgo a 5 anos Eventos
WHO estimates, 2004
Muertes
Hospitalizaciones
Casos de diarrea
Consultas
5% of all deaths in children < 5are due to rotavirus
1 dot = 1000 deaths
Estimated global distribution of the 527,000 annual deaths caused by rotavirus
Estimated global distribution of the 527,000 annual deaths caused by rotavirus
14,751(11-17,000)
Why is rotavirus mortality not dropping as fast as with other diseases?
• Sanitation, safe water and hygiene improvements will prevent bacterial & parasitic infections but less true for rotavirus
• Antibiotics ineffective against rotavirus
• ORS may be less effective for rotavirus because of frequent vomiting lasting many days
2007 research - rotavirus often spreads beyond the intestines into the blood
stream
Rotavirus causes systemic viremia in 90% of infected children
(Blutt et al.)
And, rotavirus is more than a diarrheal disease
Differences in rotavirus epidemiology between developed and developing countries
DevelopedCountries9-15 mo.
65%Winter
4-5 commonUncommonUncommon
DevelopingCountries
6-9 mo.80%
Year-roundDiverse
CommonHIV, Malnutrition
Age - median% <1year
SeasonalityRv StrainsCo-infectionsCo-morbidity
US rotavirus hospital rates are highest for children 12-<24 months (NVSN, 2006)
0
10
20
30
40
50
60
70
< 6 6 - < 12 12 - < 18 18 - < 24 24 - < 30 30 - < 36
Age (Months)
Hos
pita
lizat
ion
rate
per
10,
000
child
ren
< 3
yrs
Rotavirus Non-Rotavirus
Payne, et al. Pediatrics, 2008
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
0 12 24 36 48
Age (months)
Cum
ulat
ive
% R
V po
sitiv
e
60
India
Myanmar
China
Vietnam
Thailand
Indonesia
Japan
TaiwanHong Kong
Malaysia
Korea
Age distribution of rotavirus hospitalizations in Asian countries and United States
J Bresee EIDJ 2005
United States
Causes of severe acute gastroenteritis among children <5 years
OtherOther
Bacterial Bacterial
Rotavirus
Developed Countries Developing Countries
Unknown Unknown Rotavirus
A. Kapikian Fields Virology 2003
Population-based rotavirus strains(NVSN sites in USA, 2006)
P[6], G9 -- 0.4%
P[6], G1 --1.8%
P[8], G12 -- 0.4%
P[8], G2 -- 0.4%
P[6], G12 -- 3.6%
P[4], G1 -- 0.4%
P[4], G2 -- 4.9%
Mixed -- 4.0%P[8], G184.0%
M ixed infections include:P[8], G1, G2 (0.4%)P[4], P[6], G2 (0.4%)P[4], P[8], G1 (2.7%)P[4], P[6], P[8], G1 (0.4%)
Circulating rotavirus s trains , 2006New Vaccine Surveillance Network
Note: RotaTeq® (M erck and Co., West Point, PA) includes G1, G2, G3, G4, and P[8] strains
Payne, et al. Pediatrics, 2008
G1, P8: 84%
Strain monitoring
Diversity of strains by regionDiversity of strains by region
Gentsch et al, JID, 2005
RotaTeq (Merck): G1, G2, G3, G4, P[8]
Rotarix (GSK): G1, P[8]+ Cross-protection?
Safety of RotaTeq in US
• Observed intussusception rates following vaccination are not greater than expected
• CDC continues to monitor rotavirus vaccine for safety
• CDC continues to support the ACIP recommendation for routine immunization of all U.S. infants with three doses of RotaTeq
Volume 354 January 5, 2006 Number 1
Safety and Efficacy of an Attenuated Vaccine against Severe Rotavirus Gastroenteritis
Guillermo M. Ruiz-Palacios, M.D., Irene Pérez-Schael, M.Sc., F. Raúl Velázquez, M.D., Hector Abate, M.D., Thomas Breuer, M.D., SueAnn Costa Clemens, M.D., Brigitte Cheuvart, Ph.D., Felix Espinoza, M.D., Paul Gillard, M.D., Bruce L. Innis, M.D., Yolanda Cervantes, M.D., Alexandre C. Linhares, M.D., Pío López, M.D., Mercedes Macías-Parra, M.D., Eduardo Ortega-Barría, M.D.,
Vesta Richardson, M.D., Doris Maribel Rivera-Medina, M.D., Luis Rivera, M.D., Belén Salinas, M.D., Noris Pavía-Ruz, M.D., Jorge Salmerón, M.D., Ricardo Rüttimann, M.D., Juan Carlos Tinoco, M.D.,
Pilar Rubio, M.D., Ernesto Nuñez, M.D., M. Lourdes Guerrero, M.D., Juan Pablo Yarzábal, M.D., Silvia Damaso, M.Sc., Nadia Tornieporth, M.D., Xavier Sáez-Llorens, M.D., Rodrigo F. Vergara,
M.D., Timo Vesikari, M.D., Alain Bouckenooghe, M.D., Ralf Clemens, M.D., Ph.D., Béatrice De Vos, M.D., Miguel O'Ryan, M.D., for the Human Rotavirus Vaccine Study Group
Volume 354 January 5, 2006 Number 1
Safety and Efficacy of a Pentavalent Human–Bovine (WC3) Reassortant Rotavirus Vaccine
Timo Vesikari, M.D., David O. Matson, M.D., Ph.D., Penelope Dennehy, M.D., Pierre Van Damme, M.D., Ph.D., Mathuram Santosham, M.D., M.P.H., Zoe
Rodriguez, M.D., Michael J. Dallas, Ph.D., Joseph F. Heyse, Ph.D., Michelle G. Goveia, M.D., M.P.H., Steven B. Black, M.D., Henry R. Shinefield, M.D., Celia D.C.
Christie, M.D., M.P.H., Samuli Ylitalo, M.D., Robbin F. Itzler, Ph.D., Michele L. Coia, B.A., Matthew T. Onorato, B.S., Ben A. Adeyi, M.P.H., Gary S. Marshall,
M.D., Leif Gothefors, M.D., Dirk Campens, M.D., Aino Karvonen, M.D., James P. Watt, M.D., M.P.H., Katherine L. O'Brien, M.D., M.P.H., Mark J. DiNubile, M.D., H Fred Clark, D.V.M., Ph.D., John W. Boslego, M.D., Paul A. Offit, M.D., Penny M.
Heaton, M.D., for the Rotavirus Efficacy and Safety Trial (REST) Study Team
WHO Generic Protocol
• Hospital-based surveillance• Simple data collection• Outcomes:
» Rates of rotavirus hospitalizations
» % Rv positive• Guidelines for strain typing• Platform for measuring
other outcomes» Outpatient visits» Costs» intussusception
Detection rate of rotavirus in hospitalized diarrhea cases, 1986-1999 vs. 2000-2004
0
10
20
30
40
50
60
70
80
100 1000 10000 100000
GNP Per Capita
% R
V Po
sitiv
e
2000-2004 1986-1999
Low incomeLow-middle
incomeHigh-middle
income High income
Parashar EIDJ, 2006
Global Rotavirus Surveillance
CDC, Atlanta
Murdoch Childrens Research InstituteMelbourne, Australia
MEDUNSAPretoria, S Africa
NMIMR, Univ. of GhanaLegon, Ghana
Health Protection AgencyLondon, UK
Reference Laboratory
PAHO (10)
SEARO/WPRO/EURO (14)
EMRO (10)
EURO (4)
AFRO (6)
Surveillance activities are scheduled to begin in 2006-2007
LEGEND
>40 countries
Introduction of subsidized vaccine to GAVI-eligible countries
PATH: RVP
Europe, Latin America
Africa, Asia
First rotavirus immunizations in Panama by President Martin Torrijos and his wife, Vivien de Torrijos
March 14, 2006
GRACIAS!
http://www.who.int/immunization_monitoring/burden/rotavirus_estimates/en/index.html
Linhares AC, Bresee JS. Rotavirus vaccines and vaccination in Latin America. Rev Panam Salud Publica 2000; 8:305-331.
“Data from a large catchment trial in Venezuela with a higher RRV-TV dose, of 4 x 10(5) PFU/dose, indicated an efficacy rate of 48% against all rotavirus diarrhea and 88% against severe rotavirus diarrhea. It appears that breast-feeding does not compromise the efficacy of RRV-TV if three doses of the vaccine are administered. Similarly, possible interference of oral poliovirus vaccine with the "take" of the rotavirus vaccine can be overcome by giving three doses of the rotavirus vaccine or by using a higher-titer formulation of it. Wild enteroviruses, however, may cause primary rotavirus vaccine failure in developing countries. Studies in Peru with RRV-TV have shown a trend towards higher vaccine efficacy rates against "pure" (rotavirus-only) diarrheal episodes.”
Strain diversity and trends
Kang et al JID, 2005
Rotavirus hospitalizations in the Asian Rotavirus Surveillance Network, 2001-3
Median = 45%
Vietnam: 54%
Bresee, Nelson, Hummelman, Glass, JID, 2005
China: 46%
Korea: 73%
Malaysia: 49%Indonesia: 54%
Myanmar: 56%
Hong Kong: 30%
Taiwan: 44%
Thailand: 43%
Proportion of hospitalizations attributable to rotavirus, Aug 2001 – July 2002, Asia
Site % RV+Past studies, range % RV+ Difference
China 46 26, 13, 41 +5 to +33Taiwan 44 15, 27, 41, 43 +1 to +29Hong Kong 30 26, 29, 34, 35 -5 to +4
Vietnam 54 22 +32Myanmar 56 22 +34Thailand 43 17, 17, 20, 25, 30,
33, 38, 55-12 to +26
Malaysia 49 28 +21Indonesia
MEDIAN
54
45
38
29
+16
+16
Updated rotavirus mortality estimate
Study Year DD Deaths (millions)
Study Year RV deaths
Snyder 1982 4.6
IOM 1986 3.5 870,000
Martines 1990 3.2
Bern 1992 3.3
WDR 1993 2.5
Murray 1998 2.4 – 2.9
CHERG 2003 1.56 39%608,000
25%
P[4]G2
P[8]G3
P[8]G4
otherP[6]G1
P[8]G1
P[8]G3
other
P[8]G4
P[6]G9P[6]G3
P[8]G1
P[4]G2P[8]G3
P[8]G4
mixed
P[9]G3
P[6]G2
P[8]G1
P[4]G2
P[8]G3P[8]G4
other
U.S., N=348 India, N=133
Examples of Unusual Strain Prevalence
Brazil, N=130 Malawi, N=100
P[6]G842%
P[4]G8 9%
P[8]G510%
P[8]G9P[6]G9
7.2% P[6]G917%
} P[6]G1, P[6]G2,P[6]G3, P[6]G4
J. Gentsch
P[8]G47.5%
P[8]G152.2%
P[6] or P[8], G9
2%
other18.2%
P[8]G32.8%
P[4]G211.5%
Limited Number of Globally Common Strains
N=21,256 (1993-2003)Gentsch et al, JID, 2005
Rare or regionally common strains (25 strainstotal): P[4]G1 (1.3%), P[6]G2 (0.8%), P[6]G1 (0.6%), P[6]G8 (0.6%), P[4], G3 (0.5%)
5.5%
GSK Rotarix® licensure (92 countries –2007):
WHO Region Countries that have licensed Rotarix®
Americas 22 Argentina, Aruba, Bolivia, Brazil, Chile, Colombia, Costa Rica, Curaçao, Dominican Republic, Ecuador, El Salvador, Guatemala, Honduras, Jamaica, Mexico, Nicaragua, Panama, Paraguay, Peru, Suriname, Trinidad/Tobago, Venezuela
Africa 19 Benin, Burkina Faso, Cameroun, Central African Republic, Congo, DRCongo, Gabon, Guinea, Ivory Coast, Kenya, Madagascar, Malawi, Mali, Mauritania, Mauritius, Nigeria, Senegal, South Africa, Togo
Europe 31 Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, Switzerland, Turkey, UK
Middle East 10 Bahrain, Egypt, Jordan, Morocco, Oman, Pakistan, Qatar, Saudi Arabia, UAE, Yemen
Southeast Asia 3 Bangladesh, Sri Lanka, Thailand
Western Pacific 7 Australia, Hong Kong, Malaysia, New Zealand, Philippines, Singapore, Taiwan
Courtesy Dr Robin Biellik
Merck RotaTeq™ licensure(47 countries –2007):
WHO Region Countries that have licensed RotaTeq®Americas 12 Argentina, Canada, Curação, Ecuador, El Salvador,
Guatemala, Honduras, Mexico, Nicaragua, Perú, Puerto Rico, USA
Africa 6 DRCongo, Guinea, Kenya, Niger, Rwanda, Togo
Europe 26 Austria, Belgium, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Ireland, Italy, Latvia, Lithuania, Luxembourg, Malta, Netherlands, Poland, Portugal, Slovakia, Slovenia, Spain, Sweden, Turkey, UK
Middle East 0Southeast Asia
0
Western Pacific
3 Australia, Hong Kong, Taiwan
Courtesy Dr Robin Biellik
1. US FDA licenses RotaTeq2. ACIP recommends RotaTeq for routine
immunization of all US children3. EMEA licenses Rotarix4. Brazil, Panama, Venezuela, Mexico, Nicaragua,
El Salvador begin programs of routine childhood immunization
5. GAVI approved investment case for Phase 1
2006 – momentum builds