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Invasive MDR NTS Hotspots in Kenya: opportunities for vaccine introduction
Sam Kariuki
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Background• In Kenya invasive NTS infections, are of great
public health importance, especially in poor-resource settings where clean water supply and sanitation conditions are inadequate.
• Invasive NTS, frequent in children, associated with anemia, malnutrition, malaria or HIV
• The epidemiology, transmission dynamics and spatial-geographic distribution of these infections, are critical info in instituting appropriate disease management and prevention strategies
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Aims
Hypothesis: That there are unique genotypes of NTS in hotspots that cause invasive illnesses in children, perpetuated by specific host and environmental factors
• A 5-year study of population-based surveillance for invasive NTS in <16 yr olds
• Describe the spatial and spatio-temporal
clustering in reference to household and
environmental risk factors.
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• Mukuru informal settlement 25 km from Nairobi city centre
• One of the largest slums in the city, approx. 250,000 people (KNBS, 2010).
• Densely populated, extreme poverty, overcrowding, substandard housing, insufficient water, and inadequate sanitation, contribute to a high incidence of infectious diseases and increased mortality
Study sites
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METHODS
Recruitment and evaluation of patients
• <16 years of age on the date of presentation
• History of at least 3 days of fever and have an axillary temperature of at least 37.5oC or they present with a history of fever
• Three or more loose or liquid stools in the 24 hours before presentation, or one or more loose or liquid stool with visible blood.
• Controls: Age matched children from same clinic coming for routine vaccination.
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Laboratory Procedures• Blood for culture
• 1-3 ml for children < 5 years of age and 5-10 ml for 5-16 year olds using Bactec Culture
• Blood for HIV-testing- On site after counselling
• Stool cultures• The rectal swab or loopful of the stool specimen cultured on
selenite F broth aerobically at 37oC overnight.
• subcultured on MacConkey agar and Salmonella-Shigella and incubated at 37o C overnight.
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Genotyping of NTS isolates and GIS mapping
• WGS of NTS from blood and stool for detection of phylogenetically informative recently acquired genetic variation.
• GIS mapping of serotypes onto DSS site and correlation with environmental and socidemographic factors.
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ResultsHH Census
• 35,000 households covered in Household Census
• Data from 2,553 households from Mukuru Reuben and 970 from Mukuru kwa Njenga was missing because the occupants were away during the scheduled visits
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Patient recruitment
330
1496 1550
735792
2107
2601
10261122
3603
4151
1761
0
500
1000
1500
2000
2500
3000
3500
4000
4500
2013 2014 2015 2016
No. of patients and controls recruited
Cases
Controls
Total
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Salmonella positive samples- all sites
12
18
83
34
12
22
58
38
30
58
67
31
0
10
20
30
40
50
60
70
80
90
2013 2014 2015 2016
Positives- All sites
CsBlood
CsStool
Controlsst
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25.9
39.6
22.8
11.7
0
5
10
15
20
25
30
35
40
45
SEROTYPE S.Tyhimurium S.Typhi S.Enteritidis Other sal spp
%
Salmonella serotypes (n=505)
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26.424.1 24.1
810.3
6.9
0 00
5
10
15
20
25
30
0 -2 2 - 4 4 - 6 6 - 8 8 - 10 10 - 12 12 - 14 14 - 16
S
A
L
M
O
N
E
L
L
A
+
V
E
%
AGE CLUSTER
Proportions of Salmonella positives by Age -%
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0
10
20
30
40
50
60
70
AMP AMC CHL CPD CRO NAL CIP
Resistance Patterns of S. Typhimurium Isolates from
2013-2016 (N=131)
ANTIBIOTICS
% R
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0
5
10
15
20
25
30
AMP CHL AMC CPD CRO NAL CIP
Resistance Patterns of S. Enteritidis Isolates from 2013-2016 (N=115)
% R
ANTIBIOTICS
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Conclusion
• This is a high density slum area with endemic enteric diseases including high incidence of iNTS
• We have mapped hotspots of disease close to key water vending points and close to healthcare centres
• Rates of MDR high for both Typhimurium and Enteritidis
• We recommend these hotspots to be considered for any planned vaccine intervention.
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Acknowledgement
KEMRI, Nairobi
Cecilia Mbae
Frida Njeru
Ronald Ngetich
Susan Kavai
Anthony
Field workers
Sanger Institute/University of
Cambridge
Gordon Dougan
Vanessa Wong
Kate Auger
Sally Kay
Aga Khan Hospital,
Nairobi
Gunturu Revathi
Funding
• Wellcome Trust
• NIH Grant 5R01AI099525
Study site clinicians Field workers