Abstract
Severe anaemia and invasive bacterial infections are common causes of childhood sickness and death in sub-Saharan Africa. Accumulating evidence suggests that severely anaemic African children may have a higher risk of invasive bacterial infections. However, the mechanisms underlying this association remain poorly described. Severe anaemia is characterized by increased haemolysis, erythropoietic drive, gut permeability, and disruption of immune regulatory systems. These pathways are associated with dysregulation of iron homeostasis, including the downregulation of the hepatic hormone hepcidin. Increased haemolysis and low hepcidin levels potentially increase plasma, tissue and intracellular iron levels. Pathogenic bacteria require iron and/or haem to proliferate and have evolved numerous strategies to acquire labile and protein-bound iron/haem. In this review, we discuss how severe anaemia may mediate the risk of invasive bacterial infections through dysregulation of hepcidin and/or iron homeostasis, and potential studies that could be conducted to test this hypothesis.
Highlights
Child mortality due to preventable causes remains disproportionately high in sub-Saharan Africa [1]
The commonest bacterial isolates observed in African children are Streptococcus pneumoniae, Staphylococcus aureus, non-typhoidal Salmonellae (NTS), Haemophilus influenzae, and Escherichia coli [10,11,12]
Iron deficiency is a common cause of anaemia in sub-Saharan Africa [4], but is less frequently raised hepcidin leovbseelrsvemd ian ychpildrroentewcitthasgevaeirne santaienmviaa[d8,9i,n15g]. pDeaftichieoncgieesnosf v[i1ta9m,i2n0A], aennd hviatanmcinedB12iron sequestration may increase susc(ceopbatliabmiinli)tayre taolsoicnotmrmaocneilnluAflraicraninchfieldcretnio[9n],san[d2a1re].asRsoecigateednweirthasteivveere aannaeameima [9i,a15s]. are characterized In sickle cell disease, anaemia is secondary to haemoglobin polymerization leading to red blood cell by high reticulocydteeforcmoautionntasnddluyseis.tSoickilne ccerlledaisseeasde mhaayealmsooinldyusceisiroonrdehfiacieenmcyoanrarehmaiagtehro[u1g4h]i.ncIrneasseud b-Saharan Africa, little is known abiroonuuttitlihzaetiopn tuo treaptliavceedaameatgieodlroedgbiloeosd coefllssoer uvreinraery aironnaloesms [1i6a]
Summary
Child mortality due to preventable causes remains disproportionately high in sub-Saharan Africa [1]. Iron deficiency is a common cause of anaemia in sub-Saharan Africa [4], but is less frequently observed in children with severe anaemia [8,9,15]. Are characterized In sickle cell disease, anaemia is secondary to haemoglobin polymerization leading to red blood cell by high reticulocydteeforcmoautionntasnddluyseis.tSoickilne ccerlledaisseeasde mhaayealmsooinldyusceisiroonrdehfiacieenmcyoanrarehmaiagtehro[u1g4h]i.ncIrneasseud b-Saharan Africa, little is known abiroonuuttitlihzaetiopn tuo treaptliavceedaameatgieodlroedgbiloeosd coefllssoer uvreinraery aironnaloesms [1i6a]. Severe anaemia caused by haemolytic mechanisms (chemical, parasitic or parasitic or antiboadntyib-omdy-emdediaiatteedd),)b,ubt nuott bnyopthlbebyotopmhyl,einbcroeatsoems suys,ceipnticbrileityastoeisnvsausivsecbeapctteriibalilinifteyctitoonsinvasive bacterial infections [33,34,35,36].[3T3–h36e].pTahethpaothpohphyyssiioololgoygoyf hoafemhoalyetmic aonlayemtiiac ias ncoamepmlexi.aOinse ccroitmicapl fleeatxu.reOisntisesuceriirtoincal feature is tissue overload and increased serum iron that exceeds the transferrin binding capacity. We outline the hypothesis that severe anaemia contributes to the burden of invasive bacterial infections in African children through the disruption of iron homeostasis and/or iron-regulatory proteins
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