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 We also contacted relevant pharmaceutical companies to identify unpublished trials.Date of last search: 23 November 2015.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

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

Adults with sickle cell anaemia: specific patient competencies required for day-to-day management of hydroxyurea treatment

Introduction: Sickle cell disease (SCD) is a genetic haemoglobin abnormality responsible for various complications including chronic haemolytic anaemia and vaso-occlusive crises. Hydroxyurea (HU) therapy is used in patients with severe symptoms to improve the clinical course. To be effective and safe, hydroxyurea therapy must be monitored and patients must acquire specific competencies. Objectives: To establish competency standards relative to HU treatment for adults with SCD. Methods: A group of professionals experienced with SCD and trained in therapeutic patient education (TPE) held three day-long meetings to discuss HU-related competencies. Results: The competencies were listed in a single document. An assessment grid and a knowledge questionnaire for individual patient education sessions were also created. Discussion: HU is a chemotherapy agent whose use requires careful monitoring and specific patient competencies, which can be acquired via TPE. Furthermore, TPE can address the concerns and misconceptions associated with HU. Competency standards have proved helpful for designing TPE programmes. The competency standards reported here are unique, as they focus on a specific treatment used in a specific disease, instead of on the full range of issues related to a disease. Conclusion: This work is a first step towards harmonising TPE programmes for adults taking HU for SCD

Sickle cell disease and malaria: decreased exposure and asplenia can modulate the risk from Plasmodium falciparum

Background Patients with sickle cell disease (SCD), an inherited haemoglobinopathy, have increased risk of malaria, at least in part due to impaired splenic function. Infection with Plasmodium falciparum in SCD patients can trigger painful vaso-occlusive crisis, increase the severity of anaemia, and contribute to early childhood mortality. Case presentation A 17 year-old Tanzanian male with known SCD was admitted to Muhimbili National Hospital, a tertiary referral centre in Dar-es-Salaam, following an attack of malaria. From 2004 to 2007 the patient had lived in USA, and from 2010 to 2016 in France where, on account of hypersplenism and episodes of splenic sequestrations, in 2014 the spleen was removed. After appropriate clinical and laboratory assessment the patient was re-started on hydroxyurea; and anti-malarial-prophylaxis with proguanil was instituted. The patient has remained well and malaria-free for the following 15 months. Conclusion SCD patients are highly vulnerable to malaria infection, and impaired splenic function is a feature of SCD patients, even in those who still anatomically have a spleen. This patient had a surgical splenectomy and, in addition, had probably lost some of the acquired malaria-immunity by having lived for several years in malaria-free areas. This patient is a compelling reminder that long-term anti-malarial prophylaxis should be offered to all patients with SCD who live in malaria-endemic areas

Severe nocturnal and postexercise hypoxia in children and adolescents with sickle cell disease.

Hypoxia is a common feature in children with sickle cell disease (SCD) that is inconsistently associated with painful crises and acute chest syndrome. To assess the prevalence and risk factors of hypoxia, we recorded daytime, nocturnal, and postexercise pulse oximetry (SpO2) values in 39 SCD patients with a median age of 10.8 years. Median daytime SpO2 was 97% (range, 89%-100%), and 36% of patients had daytime hypoxia defined as SpO2<96%. Median nocturnal SpO2 was 94.7% (range, 87.7%-99.5%), 50% of patients had nocturnal hypoxia defined as SpO2≤93%, and 11(37%) patients spent more than 10% of their total sleep time with SpO2<90%. Median postexercise SpO2 was 94% (range, 72%-100%) and 44.7% of patients had postexercise hypoxia defined as an SpO2 decrease ≥3% after a 6-minute walk test. Among patients with normal daytime SpO2, 35% had nocturnal and 42% postexercise hypoxia. Compared to 9 patients without daytime, nocturnal, or postexercise hypoxia, 25 patients with hypoxia under at least one of these three conditions had greater anemia severity (P = 0.01), lower HbF levels (P = 0.04), and higher aspartate aminotransferase levels (P = 0.03). Males predominated among patients with postexercise hypoxia (P = 0.004). Hypoxia correlated neither with painful crises nor with acute chest syndrome. Of 32 evaluable patients, 6 (18.8%) had a tricuspid regurgitation velocity ≥2.6 m/s, and this feature was associated with anemia (P = 0.044). Median percentage of the predicted distance covered during a 6-minute walk test was 86% [46-120]; the distance was negatively associated with LDH (P = 0.044) and with a past history of acute chest syndrome (P = 0.009). In conclusion, severe episodes of nocturnal and postexercise hypoxia are common in children with SCD, even those with normal daytime SpO2

Coexistent sickle-cell anemia and autoimmune disease in eight children: pitfalls and challenges

Abstract Background Patients with sickle cell disease (SCD) present a defective activation of the alternate complement pathway that increases the risk of infection and is thought to predispose to autoimmune disease (AID). However, coexisting AID and SCD is rarely reported, suggesting possible underdiagnosis due to an overlapping of the symptoms. Study design Among 603 patients with SCD followed between 1999 and June 2016, we retrospectively searched for patients with coexisting SCD and AID. Results We identified 8 patients aged from 7 to 17 years diagnosed with AID; juvenile idiopathic arthritis (n = 3), systemic lupus erythematosus (n = 2), Sjögren’s syndrome (n = 1) and autoimmune hepatitis (n = 2). The diagnosis of AID was often delayed due to similarities of the symptoms with those of SCD. Patients treated with steroids experienced multiple vaso-occlusive crises and received prophylactic chronic blood transfusions when it was possible. Tolerance to other immunosuppressive and biological treatments, such as anti-TNF agents, was good. A remission of AID was achieved in 4 patients, without worsening the course of the SCD. One patient underwent a geno-identical hematopoietic stem cell transplantation that cured both diseases. Another one underwent a successful liver transplantation. Conclusion Coexistence of AID and SCD generates diagnostic and therapeutic challenges. Early diagnosis of AID is important to define the best treatment, which may include targeted biological therapy