Systematic review of current and emerging strategies for reducing morbidity from malaria in sickle cell disease

Abstract

Sickle cell disease (SCD) is a chronic debilitating disorder affecting erythrocytes, which is especially prevalent throughout Sub-Saharan Africa and among individuals of African descent. Because malaria is thought to be a significant cause of morbidity and mortality in patients with SCD, malaria chemoprophylaxis is often recommended for these patients. In SCD, malaria chemoprophylaxis reduces malaria parasite count, anaemia and the need for blood transfusion, and improves clinical outcomes. However, the effectiveness of malaria chemoprophylaxis in the setting of SCD is based on a few studies conducted prior to the emergence of widespread antimalarial drug resistance. Consequently, it is uncertain what the optimal strategy for managing patients with SCD in malarious areas should be. Despite the widespread use of hydroxyurea in non-malarious regions, little is known about its effect in malaria-endemic areas or on malaria-related outcomes. On the one hand, hydroxyurea upregulates intercellular cell adhesion molecule 1 (ICAM-1), the cell surface receptor for adhesion of Plasmodium falciparum-infected erythrocytes, and theoretically, it could enhance parasite replication. On the other hand, hydroxyurea increases levels of foetal haemoglobin, which is protective against malaria. We explore what is currently known about the interactions between SCD and malaria and review the published literature on the efficacy of malaria chemoprophylaxis in SCD. We also consider alternative strategies, including hydroxyurea, in the reduction of malaria-associated morbidity and mortality in patients with SCD.

Novel use Of Hydroxyurea in an African Region with Malaria (NOHARM): a trial for children with sickle cell anemia

“…The incidence of malaria in our cohort was low, suggesting effective protection by insecticide-treated bed nets and monthly oral malaria prophylaxis with sulfadoxine-pyrimethamine provided to all study participants, or possibly a decreased risk of clinical malaria in children with SCA. Some form of malaria prophylaxis for children with SCA is a standard recommendation in most African countries, 27 and insecticide-treated bed net use for children ,5 years of age in malaria endemic areas of Africa has increased dramatically over the past decade, to an average of .60% coverage, 28 so the preventive measures used in this study are similar to those in many other malaria endemic areas where children with SCA live. However, adherence to these recommendations is highly variable, so our study findings may not apply to children with SCA not on malaria prophylaxis and/or not using insecticide-treated bed nets.…”

The spleen and sickle cell disease: the sick(led) spleen

“…Malaria chemoprophylaxis is thus recommended in SCA patients living in malaria endemic regions (World Health Organization (WHO), ) despite limited evidence of a beneficial effect on sickle cell‐related events. Reductions of blood transfusion requirements and, possibly, severe malarial anaemia have nevertheless been demonstrated (Aneni et al , ). Antimalarial chemoprophylaxis is also indicated for SCA patients from non‐endemic countries travelling to endemic countries.…”

Alteration of lymphocyte phenotype and function in sickle cell anemia: Implications for vaccine responses

“…In sub‐Saharan Africa, where the burden of SCA is highest, pneumococcal vaccines are currently being introduced. Besides bacterial infections, children with SCA in sub‐Saharan Africa are also at risk of mortality from malaria which is endemic in the region . Thus, besides vaccines against bacterial infections, introduction of a malaria vaccine could have enormous impact on mortality in children with SCA in sub‐Saharan Africa .…”