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.

Immunogenicity, safety and reactogenicity of the pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in 2-17-year-old children with asplenia or splenic dysfunction: A phase 3 study.

BACKGROUND: Immunization with pneumococcal vaccines is an important prophylactic strategy for children with asplenia or splenic dysfunction, who are at high risk of bacterial infections (including S. pneumoniae). This study aimed to assess immunogenicity and safety of pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, GSK) in this at-risk population. METHODS: This phase III, multi-centre, open-label, controlled study, in which at-risk children with asplenia or splenic dysfunction were enrolled (age strata: 2-4, 5-10 and 11-17years), was conducted in Poland and the Russian Federation. For the 2-4years at-risk group, healthy age-matched children were enrolled as control. Unprimed children (not previously vaccinated with any pneumococcal vaccine) received 2 PHiD-CV doses (≥2months apart) and pneumococcal vaccine-primed children received 1 dose. Immune responses were assessed pre-vaccination and one month post-each dose. Solicited and unsolicited adverse events (AEs) were recorded for 4 and 31days post-vaccination, respectively, and serious AEs (SAEs) throughout the study. RESULTS: Of 52 vaccinated children (18 at-risk primed, 28 at-risk unprimed and 6 control unprimed), 45 (18, 23 and 4, respectively) were included in the according-to-protocol cohort for immunogenicity. Post-vaccination (post-dose 1 in primed and post-dose 2 in unprimed children), for each vaccine pneumococcal serotype and vaccine-related serotype 6A all at-risk children had antibody concentrations ≥0.2µg/mL, and for vaccine-related serotype 19A at least 94.4%. Increases in antibody geometric mean concentrations were observed. For most serotypes, all at-risk children had post-vaccination opsonophagocytic activity (OPA) titers ≥8 and increases in OPA geometric mean titers were observed. No safety concerns were raised. One non-fatal SAE (respiratory tract infection, considered not vaccine-related) was reported by one at-risk unprimed child. CONCLUSION: PHiD-CV was immunogenic and well tolerated in 2-17-year-old children with asplenia or splenic dysfunction. Clinical Trial Registry: www.clinicaltrials.gov, NCT01746108.

Nano-sized titanium dioxide-induced splenic toxicity: a biological pathway explored using microarray technology.

Titanium dioxide nanoparticles (TiO2 NPs) have been widely used in various areas, and its potential toxicity has gained wide attention. However, the molecular mechanisms of multiple genes working together in the TiO2 NP-induced splenic injury are not well understood. In the present study, 2.5, 5, or 10mg/kg body weight TiO2 NPs were administered to the mice by intragastric administration for 90 consecutive days, their immune capacity in the spleen as well as the gene-expressed characteristics in the mouse damaged spleen were investigated using microarray assay. The findings showed that with increased dose, TiO2 NP exposure resulted in the increases of spleen indices, immune dysfunction, and severe macrophage infiltration as well as apoptosis in the spleen. Importantly, microarray data showed significant alterations in the expressions of 1041 genes involved in immune/inflammatory responses, apoptosis, oxidative stress, stress responses, metabolic processes, ion transport, signal transduction, cell proliferation/division, cytoskeleton and translation in the 10 mg/kg TiO2 NP-exposed spleen. Specifically, Cyp2e1, Sod3, Mt1, Mt2, Atf4, Chac1, H2-k1, Cxcl13, Ccl24, Cd14, Lbp, Cd80, Cd86, Cd28, Il7r, Il12a, Cfd, and Fcnb may be potential biomarkers of spleen toxicity following exposure to TiO2 NPs.

Síndrome de sepsis grave postesplenectomía secundario a meningococcemia / Overwhelming postsplenectomy infection (OPSI) syndrome secondary to meningococcemia

Resumen Los pacientes esplenectomizados o con hipoesplenia son susceptibles a desarrollar infecciones y sepsis grave. A esta entidad se le denomina sídrome de sepsis postesplenectomía (SSPE). Reportamos el caso de una paciente que presentó SSPE secundario a Neisseria meningitidis serogrupo CR7, 10 años después de practicársele esplenectomía por púrpura trombocitopénica idiopática. El SSPE tiene una elevada mortalidad, su evolución es fulminante, las manifestaciones son graves y el pronóstico es malo. Es fundamental que los pacientes esplenectomizados sean vacunados, reciban antibióticos profilácticos y atención médica ante cualquier manifestación de un proceso infeccioso. Es prioritario implementar una política de salud pública para el desarrollo de guías relacionadas al seguimiento de los pacientes esplenectomizados y sobre la profilaxis, diagnóstico y manejo del SSPE, y difundir entre los pacientes esplenectomizados y con disfunción esplénica así como al grupo médico tratante programas educacionales relacionados con esta enfermedad.

Abstract Patients with splenectomy or splenic dysfunction are likely to suffer from severe infections and sepsis. This syndrome is called overwhelming postsplenectomy infection (OPSI). We present the case of an adult who developed OPSI syndrome secondary to Neisseria meningitidis serogroup CR 7, ten years after being splenectomized due to idiopathic thrombocytopenic purpura. OPSI syndrome has a high mortality. Its course is fulminating, the clinical symptoms are serious and the prognosis is poor. It is important for splenectomized patients to receive immunizations, antibiotic prophylaxis and seek medical attention at the earliest sign of minor infection. Public health politics should be implemented for the development of guidelines related to the monitoring of splenecto-mized patients and prophylaxis, diagnosis and treatment of OPSI syndrome and make reliable information on this disease available to patients and physicians.