Infections in sickle cell disease

Abstract

Sickle cell disease (SCD) is one of the commonest severe inherited disorders in the world. Infection accounts for a significant amount of the morbidity and mortality, particularly in sub-Saharan Africa, but is relatively poorly studied and characterized. Patients with SCD have significant immunodeficiency and are more likely to suffer severe and life-threatening complications of infection, and additionally infections can trigger complications of SCD itself. Those with more severe forms of SCD have functional asplenia from a very early age, which accounts for much of the morbidity in young children, particularly invasive infections from encapsulated bacteria including Streptococcus pneumoniae, Haemophilus influenzae, Salmonella typhi and meningococcal disease. Additionally, there are other defects in immune function in SCD, associated with anemia, tissue infarction and impaired adaptive immunity. Complications of infections in SCD include acute chest syndrome, acute painful episodes, osteomyelitis, meningitis, urinary tract infections, overwhelming sepsis and death. Viral infections cause significant morbidity, particularly severe anemia associated with parvovirus, and to a lesser extent other infections such as influenza and coronavirus disease 2019. The relationship between malaria and SCD is complicated and discussed in this review. Unlike many of the genetic risk factors for poor outcomes in SCD, it is theoretically possible to modify the risks associated with infections with established public health measures. These include the provision of vaccination, prophylactic antibiotics and access to clean water and mosquito avoidance, although current financial restraints and political priorities have made this difficult.

Figure 1.

Diagrammatic overview of key infections in sickle cell disease by organ system. EBV: Epstein-Barr virus; CMV: cytomegalovirus; HIV: human immunodeficiency infarction and hemolysis, which leads to an overactive and dysregulated immune system, as shown by an increased incidence of autoimmune diseases, and evidence of uncontrolled macrophage activation causing various complications, such as severe hemolytic transfusion reactions. There is also evidence of immunodeficiency, with abnormalities of both the innate and adaptive immune systems. In addition to hyposplenism, innate immunity is impaired by tissue infarction allowing increased entry of bacteria through the skin, as occurs with leg ulcers, and the gastrointestinal tract; areas of infarcted tissue within the body, particularly in bones, further act as foci of infection.