How we prevent and manage infection in sickle cell disease

Abstract

Summary Sickle cell disease (SCD) affects approximately 100 000 people in the US, 12 500 in the UK, and millions worldwide. SCD is typified by painful vaso‐occlusive episodes, haemolytic anaemia and organ damage. A secondary complication is infection, which can be bacterial, fungal or viral. Universal newborn screening, routine use of penicillin prophylaxis, availability of conjugated vaccines against S. pneumoniae and comprehensive care programmes instituted during the past few decades in industrialized countries have dramatically reduced childhood mortality and improved life expectancy. Yet patients with SCD remain at increased risk of infection. Unfortunately, the treatment of most bacterial infections that are common in SCD is not based on the results of randomized controlled clinical trials. In their absence, treatment decisions are based on consensus guidelines, clinical experience or adapting treatment applied in other diseases. This leads to wide variation in treatment among institutions and even between treating physicians in a single institution. Prevention of infection, when possible, is most important and we focus on prevention through targeted prophylaxis and vaccination. We will share our management strategies for managing the more common infections in SCD and provide the rationale for our recommendations.

Hypoxia‐enhanced adhesion of red blood cells in microscale flow

“…SCD is one of the most prominent genetic diseases in the world, mainly in Africa . About 100 000 people suffer from SCD in the United States alone, where its treatment and care are estimated to cost more than 8 million dollars in the life span of a patient . The origin of the name “sickle” comes from the unique crescent shape of RBCs first discovered in 1910 .…”

“…31 About 100 000 people suffer from SCD in the United States alone, where its treatment and care are estimated to cost more than 8 million dollars in the life span of a patient. [48][49][50] The origin of the name "sickle" comes from the unique crescent shape of RBCs first discovered in 1910. 7,51,52 In SCD, hemoglobin molecules polymerize when deoxygenated, due to a point mutation in the beta globin chain, which leads to an increase in stiffness and adherence of RBCs.…”

Randomized phase 2 trial of monthly vitamin D to prevent respiratory complications in children with sickle cell disease

“…10 Improved vaccination and penicillin prophylaxis have greatly reduced the risk of bacterial pathogens but are ineffective against viruses and atypical organisms that now predominate as risks for ACS. 11 Vitamin D, in addition to its role in calcium and bone homeostasis, is a multifunctional regulator of innate and adaptive immune responses and of inflammation. [12][13][14][15][16] Vitamin D acts, in part, through its metabolite 1,25-dihydroxyvitamin D [1,25(OH) 2 D], 17,18 which binds to the vitamin D receptor to function as a transcription factor, inducing vitamin D-responsive genes that are present in most, if not all, cells of the immune system.…”

A Toll‐like receptor 2 genetic variant modulates occurrence of bacterial infections in patients with sickle cell disease

“…However, hyposplenism does not completely explain the higher occurrence of infections in SCD. Patients with SCD are also at greater risk of bacterial infections caused by non‐encapsulated bacteria (Morrissey et al , ; Sobota et al , ). In addition, even among patients carrying the same SCD genotype and presenting hyposplenism, occurrence of bacterial infections is highly variable.…”