TABLE 4.
Approaches to adjust iron and vitamin A biomarkers for inflammation and malaria infection: the BRINDA project1
| Approach | Method | |
| Unadjusted | • No adjustments for AGP, CRP, or malaria infection. | |
| Exclusion | • Exclude from the data set individuals with a CRP concentration >5 mg/L or AGP concentration >1 g/L or malaria-infection positive. | |
| • Calculate the estimated prevalence of micronutrient deficiency with the use of the remaining subsample. | ||
| CF | • Stratify the data set into groups by inflammation or malaria-infection status depending on the data availability and MB (types of categorizations listed below). | |
| • Calculate the CF (ratio of the MB value’s GM in the reference group to that of the respective inflammation or malaria-infection group) for each categorization with the use of the equation shown below. | ||
| • Multiply the raw MB values by the appropriate group CF. | ||
Equation 
| ||
| where i denotes the data set, ref denotes the reference group, and j denotes the group. | ||
| Category group: | ||
| CRP: 1) no inflammation (CRP concentration ≤5 mg/L) (reference); 2) inflammation (CRP concentration >5 mg/L) | ||
| AGP: 1) no inflammation (AGP concentration ≤1 g/L) (reference); 2) inflammation (AGP concentration >1 g/L) | ||
| Malaria: 1) malaria-infection negative (reference); 2) malaria-infection positive. | ||
| CRP and AGP: 1) no inflammation (CRP concentration ≤5 mg/L and AGP concentration ≤1 g/L) (reference); 2) incubation (CRP concentration >5 mg/L and AGP concentration ≤1 g/L); 3) early convalescence (CRP concentration >5 mg/L and AGP concentration >1 g/L); 4) late convalescence (CRP concentration ≤5 mg/L and AGP concentration >1 g/L). | ||
| AGP and malaria (sTfR only) (9): 1) no inflammation and no malaria infection (AGP concentration ≤1 g/L and negative malaria infection); 2) inflammation and no malaria infection (AGP concentration >1 g/L and malaria-infection negative); 3) no inflammation and malaria infection (AGP concentration ≤1 g/L and positive malaria infection); and 4) inflammation and malaria infection (AGP concentration >1 g/L and positive malaria infection). | ||
| RC | • Run linear regression models; outcome variable is ln MB; depending on available data, ln CRP and ln AGP (continuous) and malaria infection (dichotomous) can be included in the model as explanatory variables. | |
| • Extract slopes from explanatory variables and input into RC equation shown below (slope values multiplied by the CRP, AGP, and malaria infection observations and subtracted from the MB observations). | ||
| • Back-transform adjusted MB values before applying MB cutoffs. | ||
Equation: 
| ||
| where β1 is the CRP regression coefficient, β2 is the AGP regression coefficient, β3 is the malaria regression coefficient, obs denotes the observed value, and ref denotes the reference value. MBs CRP, AGP, CRPref, and AGPref are on the ln scale; refs are the maximum values of the lowest CRP and AGP deciles obtained from the combined BRINDA database. The unlogged reference concentrations are as follows—CRP in PSC: 0.10 mg/L; CRP in WRA: 0.16 mg/L; AGP in PSC = 0.59 g/L; and AGP in WRA = 0.53 g/L; only apply adjustments to individuals with either CRP concentrations > CRPref, AGP concentrations > AGPref, or both. | ||
1
sTfR was adjusted for AGP and malaria infection but not for CRP per a biological rationale as described elsewhere (9). AGP, α-1-acid-glycoprotein; BRINDA, Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia; CF, correction factor; CRP, C-reactive protein; GM, geometric mean; MB, micronutrient biomarker; PSC, preschool children; RC, regression correction; sTfR, soluble transferrin receptor; WRA, women of reproductive age.