Ralf Krumkamp1, Benno Kreuels2, Nimako Sarpong3, Kennedy Gyau Boahen3, Geoffrey Foli3, Benedikt Hogan4, Anna Jaeger4, Lisa Reigl1, Hajo Zeeb5, Florian Marks6, Yaw Adu-Sarkodie7, Jürgen May1. 1. Bernhard Nocht Institute for Tropical Medicine, Hamburg German Center for Infection Research, Hamburg-Borstel-Lübeck. 2. Bernhard Nocht Institute for Tropical Medicine, Hamburg German Center for Infection Research, Hamburg-Borstel-Lübeck Division of Tropical Medicine, Department of Internal Medicine I, University Medical Centre Hamburg Eppendorf, Germany. 3. Kumasi Centre for Collaborative Research in Tropical Medicine, Ghana. 4. Bernhard Nocht Institute for Tropical Medicine, Hamburg. 5. Leibniz Institute for Prevention Research and Epidemiology-BIPS GmbH, Bremen, Germany. 6. International Vaccine Institute, Seoul, South Korea. 7. Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.
Abstract
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.
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.
Authors: William L Still; Milagritos D Tapia; Sharon M Tennant; Mamadou Sylla; Aliou Touré; Henry Badji; Adama Mamby Keita; Samba O Sow; Myron M Levine; Karen L Kotloff Journal: Clin Infect Dis Date: 2020-07-29 Impact factor: 9.079