Association Between Malaria and Invasive Nontyphoidal Salmonella Infection in a Hospital Study: Accounting for Berkson's Bias

TY - JOUR

T1 - Association Between Malaria and Invasive Nontyphoidal Salmonella Infection in a Hospital Study: Accounting for Berkson's Bias

AU - Krumkamp, Ralf

AU - Kreuels, Benno

AU - Sarpong, Nimako

AU - Boahen, Kennedy Gyau

AU - Foli, Geoffrey

AU - Hogan, Benedikt

AU - Jaeger, Anna

AU - Reigl, Lisa

AU - Zeeb, Hajo

AU - Marks, Florian

AU - Adu-Sarkodie, Yaw

AU - May, Jürgen

N1 - © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

PY - 2016/3/15

Y1 - 2016/3/15

N2 - BACKGROUND: There is growing evidence for a positive association between malaria and invasive nontyphoidal Salmonella (iNTS) disease. However, case-control studies conducted within healthcare facilities also report inverse associations. This may be due to Berkson's bias, a selection bias that acts when both exposure and outcome are associated with hospital attendance and study participants are selected among attendees only. This study describes the effect of Berkson's bias on the malaria-iNTS association and provides a less biased effect estimate.METHODS: Data collected in 2 Ghanaian hospitals were analyzed using 2 case-control approaches. In both approaches, cases were defined as iNTS-positive children, and concomitant malaria infection was the exposure of interest. In the first conventional sampling approach, children without any febrile bloodstream infection served as controls. In the second control-disease approach, children with non-iNTS bacteremia were used as controls.RESULTS: Data from 6746 children were suitable for the analyses. One hundred sixty children with iNTS infection were study cases. In the conventional case-control approach 6301 children were controls, and in the control-disease approach 285 children were controls. In the conventional case-control study, malaria was estimated to protect against iNTS disease (odds ratio [OR], 0.4; 95% confidence interval [CI], .3-.7), whereas in the control-disease approach, malaria was identified to be a risk factor for iNTS disease (OR, 1.9; 95% CI, 1.1-3.3).CONCLUSIONS: The study highlights how a selection bias may reverse results if an unsuitable control group is used and adds further evidence on the malaria-iNTS disease association.

AB - BACKGROUND: There is growing evidence for a positive association between malaria and invasive nontyphoidal Salmonella (iNTS) disease. However, case-control studies conducted within healthcare facilities also report inverse associations. This may be due to Berkson's bias, a selection bias that acts when both exposure and outcome are associated with hospital attendance and study participants are selected among attendees only. This study describes the effect of Berkson's bias on the malaria-iNTS association and provides a less biased effect estimate.METHODS: Data collected in 2 Ghanaian hospitals were analyzed using 2 case-control approaches. In both approaches, cases were defined as iNTS-positive children, and concomitant malaria infection was the exposure of interest. In the first conventional sampling approach, children without any febrile bloodstream infection served as controls. In the second control-disease approach, children with non-iNTS bacteremia were used as controls.RESULTS: Data from 6746 children were suitable for the analyses. One hundred sixty children with iNTS infection were study cases. In the conventional case-control approach 6301 children were controls, and in the control-disease approach 285 children were controls. In the conventional case-control study, malaria was estimated to protect against iNTS disease (odds ratio [OR], 0.4; 95% confidence interval [CI], .3-.7), whereas in the control-disease approach, malaria was identified to be a risk factor for iNTS disease (OR, 1.9; 95% CI, 1.1-3.3).CONCLUSIONS: The study highlights how a selection bias may reverse results if an unsuitable control group is used and adds further evidence on the malaria-iNTS disease association.

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/cid/civ950

DO - 10.1093/cid/civ950

M3 - SCORING: Journal article

C2 - 26933027

VL - 62 Suppl 1

SP - S83-9

JO - CLIN INFECT DIS

JF - CLIN INFECT DIS

SN - 1058-4838

ER -