dr michelle groome michelle...dr michelle groome department of science and technology/national...
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![Page 1: Dr Michelle Groome Michelle...Dr Michelle Groome Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases; Medical Research Council: Respiratory](https://reader034.vdocument.in/reader034/viewer/2022052518/5f08e7d67e708231d4244b15/html5/thumbnails/1.jpg)
Dr Michelle GroomeDepartment of Science and Technology/National Research Foundation:
Vaccine Preventable Diseases; Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand,
Johannesburg, South Africa
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• Population ~53 million; 1 084 397 births in 2013.
• Diarrhoea was a leading cause of death (18%) in South African
children < 5years of age in 2009.1
• ~25% rotavirus detection among children hospitalised for diarrhoea
in South Africa.
• Estimated to cause 17 644 to 25 630 hospitalisations.2
• Vaccine efficacy against severe rotavirus-diarrhoea:
• 77% (95% CI: 56%–88%) during the first year of life. 3
• 59% (95% CI: 1%–83%) over two consecutive rotavirus seasons. 4
1. Statistics South Africa ; 2. Seheri J Infect Dis. 2010; 3. Madhi e NEJM 2010 ; 4. Madhi Vaccine 2012
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• First African country to introduce rotavirus vaccine into national
immunisation programme, beginning August 2009.
• Rotarix recommended at 6 and 14 weeks of age.
• Children receive OPV concurrent with HRV at the 6-week
immunisation visit.
• The estimated national HIV prevalence in 2011 was 30% among
pregnant women aged 15–49 years.
• The national HIV prevalence estimate among children < 5 years was
4.1% in 2009, decreasing to 3.5% by 2013.
• The rollout of ART in the public sector started in 2004.
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• We conducted a case-control study to estimate the effectiveness of
the monovalent oral live-attenuated human rotavirus vaccine
against hospitalisation for rotavirus gastroenteritis in children under
two years of age in South Africa.
• April 2010 to October 2012 (for this analysis).
• Existing rotavirus surveillance programme, with addition of two
sites.
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Red Cross War Memorial Children’s Hospital Cape Town (urban)
Chris Hani BaragwanathAcademic Hospital Johannesburg (urban)
NgwelezaneHospital Empangeni (rural)
Edendale Hospital Pietermaritzburg (peri-urban)
Dr. George Mukhari Hospital Ga-Rankuwa (peri-urban)
Matikwana and MapulanengHospitals Bushbuckridge (rural)
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• Children hospitalised overnight with physician-diagnosed acute diarrhoea.
• Age-eligible to have received at least one dose of HRV (i.e. born after 14 June 2009).
• Assessed for eligibility, invited to participate and consent obtained.
• Stool specimen collected within 48 hours of admission.
• Testing was done using enzyme immunoassay (ProSpecTELISA, Oxoid, UK).
• Rotavirus-positive samples genotyped using standardized methods.
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• Cases: hospitalised for acute diarrhoea (≤7days duration at admission, ≥3 loose stools in a 24-hour period) with stool sample positive for rotavirus (EIA).
• Controls:
• Hospitalised for acute diarrhoea with stool sample negative for rotavirus (EIA).
• Respiratory controls (selected sites).
• Demographic indicators, clinical history: parent interview.
• Vaccination status (exposure): Road-to-Health card.
• Medical record review.
• HIV infection status.
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• Primary analysis: adjusted VE (aVE) of two HRV doses compared to no vaccination against hospitalisation for acute rotavirus-diarrhoea in children 18 weeks–23 months of age using rotavirus-negative controls.
• Secondary analyses: limited to children from three hospitals where respiratory controls were enrolled.
• Stratified analyses: age (18 weeks–11 months and 12–23 months), HIV-exposure status in HIV-uninfected children.
• Exclusions: no stool sample, no vaccination history available.
• A dose was counted if administered ≥14 days before hospitalisation.
• Unconditional logistic regression models: estimate adjusted odds ratio (aOR) with associated 95% confidence intervals .
• aVE: (1- aOR) × 100%.
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Fulfilling case definitiona
n=2295
Rotavirus-positive cases
n=577
Rotavirus-negative controls
n=1522
Rotavirus positive cases
n=540
Rotavirus negative controls n=1434
Diarrhoea >7 days duration at
admission or <3 stools in a 24-hour period n=86
No stool available/
insufficient sample
n=196
No vaccination
history available
n=37
Previously a
case/controlb n=3
No vaccination
history available n=85
Enrolled n= 2381
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0
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0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36 38 40 42 44 46 48 50 52
Nu
mb
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vacc
inat
ed
Age in weeks
First HRV dose
Second HRV dose
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• Compared with rotavirus negative controls, cases were:
• Younger
• Socioeconomic factors such as type of housing, access to electricity, toilet type and water source, as well as maternal education were similar
• Compared with respiratory controls, cases were:
• Similar in age
• Less access to electricity, a flush toilet and brick housing
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• Hospital, birth month, birth year, month by year of birth
(interaction term), hospitalisation quarter, hospitalisation
year, quarter by year of hospitalisation (interaction term)
were included in the models a priori.
• Inclusion of gender, race, history of breastfeeding, maternal
education, daycare attendance, birth weight, and variables of
household characteristics did not alter the adjusted odds ratio
by >5% and were, therefore, not included in the final models.
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All hospitals
No (%) of
rotavirus-positive
cases
(n=540)
Rotavirus-negative controls (n=1434)
Number of HRV
dosesbNo (%)
aVE
% (95% CI)
0 (Reference) 136 (25) 244 (17) -
1 126 (23) 334 (23) 40 (16–57)
2 278 (52) 856 (60) 57 (40–68)
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All hospitals
No (%) of
rotavirus-positive
cases
Rotavirus-negative controls
Number of HRV
dosesNo (%)
a VE
% (95% CI)
18 weeks to 11 months
n=389 n=947
0 (Reference) 90 (23) 149 (16) -
1 92 (24) 231 (24) 39 (9–59)
2 207 (53) 567 (60) 54 (32–68)
12 to 23 months
n=151 n=487
0 (Reference) 46 (30) 95 (20) -
1 34 (23) 103 (21) 40 (-7–66)
2 71 (47) 289 (59) 61 (35–77)
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• HIV-infected cases; n=45.
• Not powered to assess effectiveness in HIV-infected children.
• HIV-exposure status was available for 98% of HIV-uninfected children.
• 31% were HEU and 69% were HUU.
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All hospitals
No (%) of rotavirus-
positive cases
Rotavirus-negative controls
Number of HRV doses No (%)aVE
% (95% CI)
Total HIV- uninfected
n=454 n=1174
0 (Reference) 110 (24) 191 (16) -
1 106 (23) 265 (23) 37 (10–56)
2 238 (52) 718 (61) 57 (39–70)
HIV-exposed-uninfected (HEU)
n=131 n=396
0 (Reference) 30 (23) 50 (13) -
1 26 (20) 90 (23) 61 (22–81)
2 75 (57) 256 (65) 64 (34–80)
HIV-unexposed-uninfected (HUU)
n=320 n=741
0 (Reference) 79 (25) 132 (18) -
1 79 (25) 166 (22) 24 (-17–51)
2 162 (51) 443 (60) 54 (31–69)
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Subset of hospitalsa
No (%) of
rotavirus
positive
cases
(n=370)
Rotavirus-negative
controls (n=1024)
Respiratory controls
(n=1069)
Number of
HRV dosesbNo (%)
aVEc
% (95% CI)No (%)
aVEc
% (95% CI)
0
(Reference)94 (25) 181 (18) - 140 (13) -
1 87 (24) 238 (23) 35 (4–56) 232 (22) 54 (31–69)
2 189 (51) 605 (59) 52 (29–67) 697 (65) 63 (45–75)
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• The predominant rotavirus strains (n=538) over the
study period:
43%
14%
12%
8%
7%
5%
11%G12P[8]
G2P[4]
G1P[8]
G9P[8]
G8P[4]
G2P[6]
Other
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• aVE for two doses of HRV against G12P[8] was 71%
(95% CI: 55%–82%).
• Against any homotypic/partially heterotypic strains (G
protein and/or P protein were of the same type as the
vaccine strain): 62% (95% CI: 45%–74%, cases: n=369).
• Against any fully heterotypic strains (both G and P
proteins were different from those of the vaccine
strain): 52% (95% CI: 20%–72%, cases: n=155)
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• All-cause diarrhoeal hospitalisations 2006−2013.
• Chris Hani Baragwanath Academic Hospital.
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Rotavirus vaccine introduction Aug 2009
0
50
100
150
200
250
300
Num
ber
of ho
spitalis
ations
Jan 2
006
Jul 2
006
Jan 2
007
Jul 2
007
Jan 2
008
Jul 2
008
Jan 2
009
Jul 2
009
Jan 2
010
Jul 2
010
Jan 2
011
Jul 2
011
Jan 2
012
Jul 2
012
Jan 2
013
Jul 2
013
Jan 2
014
Admission month and year
Under 1 year
1 Year
2-4 Years
Age group
Monthly count of diarrhoeal hospitalisations among children under 5 years, Soweto, South Africa, 2006-2013
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Rotavirus vaccine introduction Aug 2009
0
25
50
75
Num
ber
of ho
spitalis
ations
Jan 2
006
Jul 2
006
Jan 2
007
Jul 2
007
Jan 2
008
Jul 2
008
Jan 2
009
Jul 2
009
Jan 2
010
Jul 2
010
Jan 2
011
Jul 2
011
Jan 2
012
Jul 2
012
Jan 2
013
Jul 2
013
Jan 2
014
Admission month and year
Under 1 year
1 Year
2-4 Years
Age group
HIV-infected (assuming same prevalence in untested)
Monthly count of diarrhoeal hospitalisations among children under 5 years, Soweto, South Africa, 2006-2013
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Rotavirus vaccine introduction Aug 2009
0
50
100
150
200
250
300
Num
ber
of ho
spitalis
ations
Jan 2
006
Jul 2
006
Jan 2
007
Jul 2
007
Jan 2
008
Jul 2
008
Jan 2
009
Jul 2
009
Jan 2
010
Jul 2
010
Jan 2
011
Jul 2
011
Jan 2
012
Jul 2
012
Jan 2
013
Jul 2
013
Jan 2
014
Admission month and year
Under 1 year
1 Year
2-4 Years
Age group
HIV-uninfected (assuming unknown are HIV-uninfected)
Monthly count of diarrhoeal hospitalisations among children under 5 years, Soweto, South Africa, 2006-2013
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• Two doses of HRV provided protection against hospitalisation for acute
rotavirus-diarrhoea of ~60% among children < 2 years using rotavirus
negative controls, with similar effectiveness observed using respiratory
controls in a subset of hospitals.
• Vaccine effectiveness appeared to be sustained through the second
year of life.
• Similar protection among HIV-exposed and HIV-unexposed HIV-
uninfected children.
• Protection against homotypic/partially heterotypic strains as well as
fully heterotypic strains, but were not powered to assess strain-
specific protection, except for G12P[8], or the durability of this
protection into the second year of life.
• Time series analysis – deceased hospitalisations especially in < 1 year.
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• Chris Hani Baragwanath Academic Hospital• Dept of Paediatrics• Shabir Madhi• Susan Nzenze, Tselane Makgobo, study
nurses• Red Cross Children’s Hospital
• Heather Zar, Ralph Diedericks, Christine Mulligan
Earl Dietrich• Ngwelezane Hospital
• Constant Kapongo, Dianette Conradie• Rotavirus surveillance group• Centre for Enteric Diseases, NICD
• Nicola Page, Jocelyn Moyes, Cheryl Cohen
• Division of Viral Diseases, CDC• Umesh Parashar, Margaret Cortese
• PATH• Jessica Fleming
• Bill and Melinda Gates Foundation• Duncan Steele
• Support for this project was provided by PATH through funding from the GAVI Alliance.
• The views expressed by the authors do not necessarily reflect the views of GAVI, PATH, or the Centers for Disease Control and Prevention.