Severe parainfluenza pneumonia in a case of transient hypogammalobulinemia of infancy

Human parainfluenza viruses (HPIVs) infection, largely known to cause self-limiting bronchiolitis and pneumonia in immune competent patients, can lead to severe to fatal pulmonary disease in immune disorders, such as primary or acquired-immune deficiencies. We report the case of a 1-year-old child who developed an acute respiratory distress syndrome. Because of a progressive respiratory failure unresponsive to conventional treatment extracorporeal membrane oxygenation (ECMO) was rapidly started. HPIV-3 infection was diagnosed on the rhinopharyngeal fluid and immunological examinations revealed a hypogammaglobulinemia. A combination therapy with ribavirin, intravenous immunoglobulin (IVIG) and steroid under ECMO support was started with considerable improvement. Subsequent analysis and more specific immunological assessment resulted normal confirming the diagnosis of transient hypogammaglobulinemia of infancy (THI). This case highlights the importance of prompt therapy with early ECMO support in combination with ribavirin, IVIG and steroids in patients affected by severe HPIV-3 pneumonia and THI

Early antiretroviral treatment (eART) limits viral diversity over time in a long-term HIV viral suppressed perinatally infected child

HIV genetic diversity implicates major challenges for the control of viral infection by the immune system and for the identification of an effective immunotherapeutic strategy. With the present case report we underline as HIV evolution could be effectively halted by early antiretroviral treatment (eART). Few cases supported this evidence due to the difficulty of performing amplification and sequencing analysis in long-term viral suppressed patients. Here, we reported the case of limited HIV-1 viral evolution over time in a successful early treated child

Familial Hemophagocytic Lymphohistiocytosis Type 3 Diagnosed at School Age: A Case Report

Familial hemophagocytic lymphohistiocytosis (HLH) is a rare, life-threatening condition characterized by immune hyperactivation and clinical signs of extreme inflammation. We describe a 7-year-old male who presented with fever resistant to antibiotic therapy, pancytopenia, splenomegaly, hypertriglyceridemia, and hyperferritinemia. Bone marrow aspirate showed hemophagocytosis. Epstein-Barr virus genome was positive in blood. Functional screening showed reduced capacity of cytotoxic degranulation. Mutation analysis of the FHL-related genes revealed compound heterozygous for UNC13D mutations: c. 753+ 1G>T, and the novel c.544C>T (p.P182S). Patients with a clinical presentation of HLH, even if older than typically seen, should be screened for familial HLH by mutation analysis

Relapsing Campylobacter jejuni Systemic Infections in a Child with X-Linked Agammaglobulinemia

X-linked agammaglobulinemia (XLA) is a primary immunodeficiency of the humoral compartment, due to a mutation in the Bruton tyrosine kinase (BTK) gene, characterized by a severe defect of circulating B cells and serum immunoglobulins. Recurrent infections are the main clinical manifestations; although they are especially due to encapsulated bacteria, a specific association with Campylobacter species has been reported. Here, we report the case of a boy with XLA who presented with relapsing Campylobacter jejuni systemic infections. His clinical history supports the hypothesis of the persistence of C. jejuni in his intestinal tract. Indeed, as previously reported, XLA patients may become chronic intestinal carriers of Campylobacter, even in absence of symptoms, with an increased risk of relapsing bacteraemia. The humoral defect is considered to be crucial for this phenomenon, as well as the difficulties to eradicate the pathogen with an appropriate antibiotic therapy; drug resistance is raising in Campylobacter species, and the appropriate duration of treatment has not been established. C. jejuni should always be suspected in XLA patients with signs and symptoms of systemic infection, and treatment should be based on antibiogram to assure the eradication of the pathogen

Artificial Intelligence Applied to in vitro Gene Expression Testing (IVIGET) to Predict Trivalent Inactivated Influenza Vaccine Immunogenicity in HIV Infected Children

The number of patients affected by chronic diseases with special vaccination needs is burgeoning. In this scenario, predictive markers of immunogenicity, as well as signatures of immune responses are typically missing even though it would especially improve the identification of personalized immunization practices in these populations. We aimed to develop a predictive score of immunogenicity to Influenza Trivalent Inactivated Vaccination (TIV) by applying deep machine learning algorithms using transcriptional data from sort-purified lymphocyte subsets afterin vitrostimulation. Peripheral blood mononuclear cells (PBMCs) collected before TIV from 23 vertically HIV infected children under ART and virally controlled were stimulatedin vitrowith p09/H1N1 peptides (stim) or left unstimulated (med). A multiplexed-qPCR for 96 genes was made on fixed numbers of 3 B cell subsets, 3 T cell subsets and total PBMCs. The ability to respond to TIV was assessed through hemagglutination Inhibition Assay (HIV) and ELIspot and patients were classified as Responders (R) and Non Responders (NR). A predictive modeling framework was applied to the data set in order to define genes and conditions with the higher predicted probability able to inform the final score. Twelve NR and 11 R were analyzed for gene expression differences in all subsets and 3 conditions [med, stim or Delta (stim-med)]. Differentially expressed genes between R and NR were selected and tested with the Adaptive Boosting Model to build a prediction score. The score obtained from subsets revealed the best prediction score from 46 genes from 5 different subsets and conditions. Calculating a combined score based on these 5 categories, we achieved a model accuracy of 95.6% and only one misclassified patient. These data show how a predictive bioinformatic model applied to transcriptional analysis deriving fromin-vitrostimulated lymphocytes subsets may predict poor or protective vaccination immune response in vulnerable populations, such as HIV-infected individuals. Future studies on larger cohorts are needed to validate such strategy in the context of vaccination trials

Immunisation practices in centres caring for children with perinatally acquired HIV: A call for harmonisation

Background Current national immunisation schedules differ between countries in terms of vaccine formulation, timing of vaccinations and immunisation programme funding and co-ordination. As a result, some HIV infected paediatric population may be left susceptible to vaccine preventable infections. Vaccines used in healthy population should be subjected to high quality ethical research and be explicitly validated for use in children with special vaccination needs such as those infected with HIV. This survey was completed to assess current vaccination practices and attitudes toward vaccination among pediatricians who care for vertically HIV infected children. Methods An online questionnaire was completed by 46 experts in paediatric HIV-infection from the Paediatric European Network for Treatment of AIDS (PENTA). Data were collected between November 2013 and March 2014. Results 46 units looking after 2465 patients completed the questionnaire. The majority of units (67%) reported that common childhood immunisation were administered by the family doctor or local health services rather than in the HIV specialist centre. Vaccination histories were mostly incomplete and difficult to obtain for 40% of the studied population. Concerns were reported regarding the use of live attenuated vaccines, such as varicella and rotavirus, and these were less frequently recommended (61% and 28% of the units respectively). Monitoring of vaccine responses was employed in a minority of centres (41%). A range of different assays were used resulting in diverse units of measurement and proposed correlates of protection. Conclusion Vaccination practices for perinatally HIV-infected children vary a great deal between countries. Efforts should be made to improve communication and documentation of vaccinations in healthcare settings and to harmonise recommendations relating to additional vaccines for HIV infected children and the use of laboratory assays to guide immunisation. This will ultimately improve coverage and vaccine induced immunity in this vulnerable patient group