Tolerance and humoral immune response to the yellow fever vaccine in sickle cell disease children treated with hydroxyurea: a multicentre prospective study.

BACKGROUND: Sickle cell disease (SCD) children are frequent travellers to countries where yellow fever (YF) is endemic, but there are no data regarding the safety and immunogenicity of the vaccine in such children treated with hydroxyurea (HU). The main objective of this study was to compare the tolerance and immune response to YF vaccination in SCD children treated or not with HU. METHOD: SCD children < 18 years attending the international travel clinics of three large paediatric centres and requiring a first YF vaccination were included in a prospective study. Adverse events were collected 2 weeks after vaccination. YF vaccine antibody titres were measured ~6 months after vaccination. RESULTS: Among the 52 SCD children vaccinated against YF, 17 (33%) were treated with HU. Only mild adverse events, mainly fever and local reaction, were observed in the HU group with a similar frequency in the non-HU group (57 and 35%, respectively, P = 0.30). YF antibody titres were measured in 15/17 patients in the HU group and 23/35 patients in the non-HU group after a median of 6.0 months (3.5-8.5) following vaccination. The geometric mean of YF antibody titre was similar in both groups. A protective antibody level was observed in 85% of the children in the HU group vs 100% in the non-HU group (P = 0.14), suggesting a lower effectiveness of the vaccine in patients on HU similarly to what has been described in patients on immune suppressive therapy for other vaccines. CONCLUSION: YF vaccination seems to be safe and efficient in SCD children treated with HU. Considering the potential risk of severe complications in cases of YF while travelling in Africa for those patients, the benefit-to-risk ratio argues for YF vaccination in all SCD children. Control of a protective antibody titre may also be useful to ascertain an adequate response in those treated with HU.

An Evaluation of Three Ways of Communicating Carrier Status Results to the Parents of Children in a Neonatal Sickle Cell Screening Programme.

Aim: Sickle cell disease (SCD) is the most frequent monogenic disease worldwide; ~5-7% of the world population carry a hemoglobin disorder trait. In the US, one in every 1,941 newborns has SCD, whereas one in every 3,000 newborns in France is affected - resulting in 385 new cases and 5,883 newly identified carriers per year. The objective of the present study was to evaluate three different ways of providing information to parents at risk of having a child with SCD, with a view to increasing the parental screening rate and decreasing the number of new cases per year in France. Method: In a randomized study, we contacted 300 couples of parents after their child had been identified as a SCD carrier in the French national newborn screening programme: 100 couples received an information letter (the standard procedure in France: arm A), 100 couples received a letter and then a follow-up phone call (arm B), and 100 received a letter and then three follow-up text messages at 5-day intervals (arm C). The primary endpoint was the number of parents in each arm screened in the 120 days after the letter had been sent. In a modified intention-to-treat analysis, the screening rate was 17% in arm A, 35% in arm B, and 30% in arm C. Results: Telephone and text message follow-ups were associated with higher screening rates, compared with no follow-up. After being informed of their child's carrier status, some parents had consulted a healthcare professional but had not been referred for screening (16% in arm A, 19% in arm B, and 13% in arm C). Conclusion: A letter followed by a phone call or three text messages is more effective than a letter alone for informing parents at risk of having a child with SCD. The effective implementation of this follow-up programme probably requires better training of all the healthcare professionals involved.

Endothelial-dependent vasodilation is impaired in children with sickle cell disease.

Impairment of endothelial-dependent vasodilation has been demonstrated in adults with sickle cell anemia (SCA). We enrolled 21 SCA children, mean age 10.4+/-3.3 yrs, and 23 Afro-Caribbean controls. We examined flow-mediated (FMD) and nitroglycerine-mediated (GTNMD) dilation of the brachial artery, using echotracking techniques, and measured intima-media thickness (IMT) and mechanical properties of the common carotid artery. FMD was significantly decreased in SCA children vs controls (5.6+/-0.2 vs 8.0+/-0.2%, p=0.008), while IMT, stiffness of the common carotid artery, and GTNMD were comparable. In conclusion, endothelial dysfunction is present as early as childhood in SCA patients.