Conjugate Haemophilus influenzae type b vaccines for sickle cell disease.

BACKGROUND: People affected with sickle cell disease are at high risk of infection from Haemophilus influenzae type b. Before the implementation of Haemophilus influenzae type b conjugate vaccination in high-income countries, this was responsible for a high mortality rate in children under five years of age. In African countries, where coverage of this vaccination is still extremely low, Haemophilus influenzae type b remains one of the most common cause of bacteraemias in children with sickle cell disease. The increased uptake of this conjugate vaccination may substantially improve the survival of children with sickle cell disease. OBJECTIVES: The primary objective was to determine whether Haemophilus influenzae type b conjugate vaccines reduce mortality and morbidity in children and adults with sickle cell disease.The secondary objectives were to assess the following in children and adults with sickle cell disease: the immunogenicity of Haemophilus influenzae type b conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. SEARCH METHODS: We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group\u27s Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search: 23 November 2015. SELECTION CRITERIA: All randomised and quasi-randomised controlled trials comparing Haemophilus influenzae type b conjugate vaccines with placebo or no treatment, or comparing different types of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease. DATA COLLECTION AND ANALYSIS: No trials of Haemophilus influenzae type b conjugate vaccines in people with sickle cell disease were found. MAIN RESULTS: There is an absence of evidence from randomised controlled trials relating to the subject of this review. AUTHORS\u27 CONCLUSIONS: There has been a dramatic decrease in the incidence of invasive Haemophilus influenzae type b infections observed in the post-vaccination era in people with sickle cell disease living in high-income countries. Therefore, despite the absence of evidence from randomised controlled trials, it is expected that Haemophilus influenzae type b conjugate vaccines may be useful in children affected with sickle cell disease, especially in African countries where there is a high prevalence of the disease. The implementation of childhood immunisation schedules, including universal Haemophilus influenzae type b conjugate vaccination, may substantially improve the survival of children with sickle cell disease living in low-income countries. We currently lack data to evaluate the potential effect of Haemophilus influenzae type b vaccination among unvaccinated adults with sickle cell disease. Further research should assess the optimal Hib immunisation schedule in children and adults with sickle cell disease

Chronic organ injuries in children with sickle cell disease

Median life expectancy of patients with sickle cell disease has increased to up to 55 years but there are still frequent cases of premature death, mostly in patients with pre-existing organ failure such as pulmonary hypertension, kidney injury, and cerebral vasculopathy. Most organ injuries remain asymptomatic for a long time and can only be detected through early systematic screening. Protocols combining assessment of velocities on transcranial Doppler and regular transfusions in patients with abnormal velocities have been demonstrated to dramatically reduce the risk of stroke. In contrast, no consensus has been reached on systematic screening or therapy for silent cerebral infarcts. The prognostic significance of increased tricuspid regurgitant jet velocity on echocardiography has not yet been identified in children, whereas increased albuminuria is a good predictor of kidney injury. Finally, screening for hip and eye disorder is recommended; however, different countries adopt different screening strategies. Hydroxyurea is probably of potential benefit in preventing chronic organ damage but this requires further study in order to be fully demonstrated. Efficacy and safety of the other new drugs available are also under investigation

Innate immune cells, major protagonists of sickle cell disease pathophysiology

Sickle cell disease (SCD), considered the most common monogenic disease worldwide, is a severe hemoglobin disorder. Although the genetic and molecular bases have long been characterized, the pathophysiology remains incompletely elucidated and therapeutic options are limited. It has been increasingly suggested that innate immune cells, including monocytes, neutrophils, invariant natural killer T cells, platelets and mast cells, have a role in promoting inflammation, adhesion and pain in SCD. Here we provide a thorough review of the involvement of these novel, major protagonists in SCD pathophysiology, highlighting recent evidence for innovative therapeutic perspectives

EHA Research Roadmap on Hemoglobinopathies and Thalassemia: An Update

The inherited disorders of hemoglobin, which include sickle cell disease and thalassemias, are the most common and widespread distributed monogenic disorders. Due to a selective advantage in malaria regions, these hemoglobin defects are particularly frequent in Africa, Asia, or in the Mediterranean areas, where malaria was endemic until the last century. In recent decades, the globalization of migration has contributed to generate multiethnic European societies. Due to migration from countries or regions with high hemoglobinopathy frequencies such as Africa, Middle East, or Asia, large numbers of patients with these disorders are living in almost every European country today. Furthermore, the numbers are increasing because of increasing refugee flows toward Europe. Additional requirements are the development of European recommendations and guidelines for diagnosis and effective therapeutic approaches. These, together with the advancement of clinical trials using new drugs and therapeutic procedures could ameliorate the quality of life of patients affectedwith these diseases and increase their life expectancy. Lastly, coordinated efforts should bemade todevelop diagnostic pathways for thalassemias and hemoglobinopathies, in order to plan interventions, including prenatal diagnosis and cure. For these reasons, the development of new tools to reliably diagnose anemias is urgently needed and fits well with the needs of personalized medicine. In the last 15 years, hematology research has made many big leaps forward. Our general aim will be to solve several hematologic problems using these new approaches. We expect that the development of such a diagnostic tool will improve timely diagnosis throughout Europe, especially in those countries where it is difficult to gain access to \u201cclassical\u201d diagnostic tests