Associations of bacterial enteropathogens with systemic inflammation, iron deficiency, and anemia in preschool-age children in southern Ghana

Abstract

Anemia remains a pervasive public health problem among preschool-age children in Ghana. Recent analyses have found that anemia in Ghanaian children, particularly in Southern regions, is largely attributable to infectious causes, rather than nutritional factors. Infections with enteropathogens can reduce iron absorption and increase systemic inflammation, but few studies have examined direct links between enteropathogens and anemia. This study investigated associations between detection of individual bacterial enteropathogens and systemic inflammation, iron deficiency, and anemia among 6- to 59-month-old children in Greater Accra, Ghana. Serum samples were analyzed from a cross-sectional sample of 262 children for concentrations of hemoglobin (Hb), biomarkers of systemic inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)], and biomarkers of iron status [serum ferritin (SF) and serum transferrin receptor (sTfR)]. Stool samples were analyzed for ten bacterial enteropathogens using qPCR. We estimated associations between presence of each enteropathogen and elevated systemic inflammation (CRP > 5 mg/L and AGP > 1 g/L), iron deficiency (SF < 12 μg/L and sTfR > 8.3 mg/L) and anemia (Hb < 110 g/L). Enteropathogens were detected in 87% of children's stool despite a low prevalence of diarrhea (6.5%). Almost half (46%) of children had anemia while one-quarter (24%) had iron deficiency (low SF). Despite finding no associations with illness symptoms, Campylobacter jejuni/coli detection was strongly associated with elevated CRP [Odds Ratio (95% CI): 3.49 (1.45, 8.41)] and elevated AGP [4.27 (1.85, 9.84)]. Of the pathogens examined, only enteroinvasive Escherichia coli/Shigella spp. (EIEC/Shigella) was associated with iron deficiency, and enteroaggregative Escherichia coli (EAEC) [1.69 (1.01, 2.84)] and EIEC/Shigella [2.34 (1.15, 4.76)] were associated with anemia. These results suggest that certain enteroinvasive pathogenic bacteria may contribute to child anemia. Reducing exposure to enteropathogens through improved water, sanitation, and hygiene practices may help reduce the burden of anemia in young Ghanaian children.

Fig 1. Flow chart describing sample selection.

Fig 2. Prevalence of enteropathogens detected in children’s stool by age (months) in the Greater Accra Region, Ghana, October-November 2018 (n = 262).

Age categories: 6–11 months (n = 30), 12–23 months (n = 94), 24–35 months (n = 64), 36–47 months (n = 46), 48–59 months (n = 28). Abbreviations: aEPEC, atypical enteropathogenic Escherichia coli (E. coli); C. jejuni/coli, Campylobacter jejuni or Campylobacter coli; EAEC, enteroaggregative E. coli; EIEC, enteroinvasive E. coli; LT-ETEC, heat-labile enterotoxin-producing E. coli; STEC, Shiga toxin-producing E. coli; ST-ETEC, heat-stable enterotoxin-producing E. coli; tEPEC, typical enteropathogenic E. coli.

Fig 3. Associations between enteropathogen detection in children’s stool and systemic inflammation, iron deficiency, and anemia among children aged 6–59 months old in Greater Accra, Ghana (n = 262).

Higher odds of the outcome are represented in red and lower odds of the outcome are represented in blue, with darker shades of the colors representing stronger associations. Odds ratios and significance values are derived from adjusted logistic regression models controlling for child age and sex (S4 Table). Abbreviations: aEPEC, atypical enteropathogenic Escherichia coli (E. coli); AGP, α-1-acid glycoprotein; C. jejuni/coli, Campylobacter jejuni or Campylobacter coli; CRP, C-reactive protein; EAEC, enteroaggregative E. coli; EIEC, enteroinvasive E. coli; Hb, hemoglobin; LT-ETEC, heat-labile enterotoxin-producing E. coli; SF, serum ferritin; STEC, Shiga toxin-producing E. coli; ST-ETEC, heat-stable enterotoxin-producing E. coli; sTfR, serum transferrin receptor; tEPEC, typical enteropathogenic E. coli.