Sophie Blumental

Invasive mold infections in chronic granulomatous disease: a 25-year retrospective survey.

BACKGROUND Invasive fungal infection (IFI) represents a life-threatening condition for patients with chronic granulomatous disease (CGD) and causes one-third of deaths in this population. This study offers a descriptive review of invasive mold infection (mIFI) in children with CGD over an extended period of time. METHODS In a cohort of patients with CGD registered in the French National database for Primary Immunodeficiency, we performed a retrospective review of proven mIFI episodes (European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group 2008 criteria) occurring from 1984 through 2009. RESULTS Twenty-nine proven mIFIs were identified in 24 patients. Thirteen (54%) of 24 children were receiving itraconazole prophylaxis. Seven episodes were caused by Aspergillus fumigatus, 10 by Aspergillus nidulans, 2 by Aspergillus species, and 6 by other opportunistic molds (4 patients only had positive pathological examination findings). First proven mIFI occurred later in the group that received itraconazole than in the group without (median time to mIFI, 10 vs 4 years; P < .01), with a higher proportion of infections due to A. nidulans and other opportunistic molds (P < .05). Course of IFI was complex, with the median duration of therapy and hospitalization reaching 446 and 153 days, respectively. Combined antifungal therapy was commonly used. Four patients received geno-identical hematopoietic stem cell transplantation as salvage therapy. Global cure rate among the cohort reached 75%, but sequelae were frequent. Prognosis has improved over time (43% mortality during 1985-1990 vs 6% thereafter; P = .06). Mortality tended to be lower in the group that recieved itraconazole prophylaxis but at the cost of a longer duration of therapy among cured patients. CONCLUSIONS Management of mIFI remains challenging in patients with CGD, but significant improvements have been made over the past decade.

Dynamic pattern and genotypic diversity of Staphylococcus aureus nasopharyngeal carriage in healthy pre-school children

OBJECTIVES It is common wisdom that persistent carriage of Staphylococcus aureus is more frequent in young children than in adults. The objectives of this study were to assess the S. aureus temporal carriage pattern among a healthy community of pre-school children, with concomitant description of genotype diversity, toxin-encoding genes and antibiotic resistance. METHODS Among 333 children 3-6 years of age, S. aureus nasopharyngeal carriage was assessed over one school year by culture of three sequential nasopharyngeal aspirates. Identification, methicillin resistance and toxin production profile were determined by PCR. Genotyping was performed by spa sequencing and multilocus sequence typing (MLST). RESULTS Out of 830 samples collected, 286 (34%) yielded S. aureus from 185 carriers (55%). Based on consecutive genotype analysis, only 40/268 (15%) children could be classified as persistent carriers, and the remaining 118 (44%) showed intermittent carriage. spa typing revealed 82 types clustered into 13 spa clonal complexes (CCs). Fourteen strains isolated from 11 (3%) children were methicillin-resistant S. aureus (MRSA), half of these strains belonged to the commonly hospital-associated spa t008-ST8-SCCmec IV. Methicillin-susceptible S. aureus (MSSA) were genotypically more diverse. Toxic shock syndrome toxin and egc1/2 complexes were highly prevalent (24%). Contrastingly, Panton-Valentine leucocidin (PVL) was carried only by three MSSA strains (0.6% of children). Exfoliative toxins were detected in 10 (3.5%) MSSA strains, of which 5 were related to the impetigo clone CC121. CONCLUSIONS Although S. aureus nasopharyngeal carriage was high among healthy pre-school children, persistent carriage seems to be less frequent than previously reported. The prevalence of MRSA carriage was 3%, but was not associated with PVL.

Varicella paediatric hospitalisations in Belgium: a 1-year national survey

Background Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. Methods Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. Results Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105 person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105 person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105 person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106 and fatality ratio 0.2% among our cohort. Conclusions Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium.

Virulence Factors of Streptococcus pneumoniae. Comparison between African and French Invasive Isolates and Implication for Future Vaccines.

Background Many surface proteins thought to promote Streptocococcus pneumoniae virulence have recently been discovered and are currently being considered as future vaccine targets. We assessed the prevalence of 16 virulence genes among 435 S. pneumoniae invasive isolates from France and the “African meningitis belt” region, with particular focus on serotype 1 (Sp1), to compare their geographical distribution, assess their association with site of infection and evaluate their potential interest as new vaccine candidates. Methods Detection by PCR of pspA (+families), pspC (+pspC.4), pavA, lytA, phtA,B,D,E, nanA,B,C, rrgA (Pilus-1), sipA (Pilus-2), pcpA and psrp was performed on all isolates, as well as antibiotic resistance testing and MLVA typing (+MLST on 54 representative strains). Determination of ply alleles was performed by sequencing (Sp1 isolates). Results MLVA and virulence genes profiles segregated Sp1 isolates into 2 groups that followed continent distribution. The ply allele 5 and most of the genes that were variable (nanC, Pilus-2, psrp, pcpA, phtD) were present in the French Sp1 isolates (PMEN clone Sweden1-28, ST306) but absent from the African ones. Whereas all African Sp1 isolates clustered into a single MLST CC (CC217), MLVA distinguished two CCs that followed temporal evolution. Pilus-2 and psrp were more prevalent in bacteraemic pneumonia yielded isolates and phtB in meningitis-related isolates. Considering vaccine candidates, phtD was less prevalent than anticipated (50%) and pcpA varied importantly between France and Africa (98% versus 34%). Pilus-1 was carried by 7-11% of isolates and associated with β-lactams resistance. Conclusions Most virulence genes were carried by the European ST306 clone but were lacking on Sp1 isolates circulating in the African meningitis belt, where a more serious pattern of infection is observed. While virulence proteins are now considered as vaccine targets, the geographical differences in their prevalence could affect the efficacy expected from future vaccines.

First Documented Transmission of Trypanosoma cruzi Infection through Blood Transfusion in a Child with Sickle-Cell Disease in Belgium.

The affiliation for the fifth author is incorrect. Hanane El Kenz is affiliated with Brugmann University Hospital Center and Queen Fabiola University Children Hospital Blood Bank Department, Brussels, Belgium.

The ABC of pneumococcal infections and vaccination in patients with chronic kidney disease

Background In the general population, pneumococcal polysaccharide vaccines (PPV) decrease the incidence of invasive pneumococcal disease (IPD) whereas the impact on the prevention of noninvasive pneumococcal disease is less clear. As compared with PPV, pneumococcal conjugate vaccines (PCV) provoke a higher, longer-lasting immune response resulting in a 45% decreased incidence in vaccine-type pneumonia, and a 75% decrease in vaccine-type IPD. Methods Literature review on pneumococcal vaccination in end-stage renal disease. Results As compared with the general population, patients with chronic kidney disease (CKD) suffer increased mortality and morbidity from pneumococcal disease (PD), being up to 10-fold for those treated with dialysis. Numerous, usually small and methodological heterogeneous studies demonstrate that PPV provokes a serological response in dialysis patients, kidney transplant recipients, children with nephrotic syndrome and CKD patients receiving immunosuppressive medication. This response is of less intensity and duration than in healthy controls. Similar observations were made for the PCV. The protective value of these vaccine-elicited anti-pneumococcal antibodies in the CKD population remains to be substantiated. For patients treated with dialysis, epidemiological data demonstrate a correlation—which does not equal causality—between pneumococcal vaccination status and a slightly decreased total mortality. Clinical outcome data on the effectiveness of pneumococcal vaccination in the prevention of morbidity and mortality in the CKD population are lacking. Conclusions Awaiting better evidence, pneumococcal vaccination should be advocated in all patients with CKD, as early in their disease course as possible. The ACIP schedule recommends a PCV-13 prime vaccination followed by a PPV-23 repeated vaccine at least 8 weeks later in pneumococcal non-vaccinated patients, and a PCV-13 vaccine at least 1 year after the latest PPV vaccine in previously vaccinated patients. In the UK, vaccination with PPV-23 only is recommended. There exist no good data supporting re-vaccination after 5 years in the dialysis population.

Streptococcus pneumoniae Serotype 1 Burden in the African Meningitis Belt: Exploration of Functionality in Specific Antibodies

ABSTRACT Streptococcus pneumoniae serotype 1 (Sp1) constitutes an important cause of seasonal endemic meningitis in all age groups in the African meningitis belt. Despite a higher meningitis incidence, the Burkinabé population has an Sp1-specific antibody seroprevalence similar to that reported in the United Kingdom (UK). We aimed to establish whether the opsonophagocytic activity (OPA) of pneumococcal IgG naturally present in Burkina Faso differs from that seen in individuals in the UK and to compare the OPAs generated by natural and vaccine-induced immunity. Samples collected from pneumococcal vaccine-naive Burkinabé and UK subjects were matched for age (1 to 39 years) and anti-Sp1 IgG level, analyzed for OPA to 3 S. pneumoniae serotypes (1, 5, and 19A), and compared to postvaccine samples. Furthermore, the Burkinabé samples were assessed for IgG avidity and serotype-specific IgM concentrations. One hundred sixty-nine matched serum samples from both populations were selected. A greater proportion of Burkinabé subjects aged 1 to 19 years had functional Sp1 activity (OPA ≥ 8) compared to UK subjects (12% versus 2%, P < 0.001); however, the proportions were similar among adults (9%). The correlation between Sp1 IgG concentration and OPA was good (P < 0.001), but many individuals had nonfunctional IgG, which was not related to avidity. While the Sp1 IgM concentrations correlated with OPA, not all of the function in serum samples with low IgG could be attributed to IgM. Finally, vaccine-induced Sp1-specific IgG was more functional than equivalent amounts of naturally occurring IgG. In conclusion, despite a substantially higher pneumococcal meningitis incidence, no decreased functional immunity to Sp1 could be evidenced in the Burkinabé population compared to that in the population from the UK. Furthermore, the naturally induced antibodies were less functional than vaccine-induced antibodies.

HIV Transmission Through Breastfeeding: Still Possible in Developed Countries

We describe here the case of a 13-month-old boy who acquired HIV infection postnatally through breastfeeding in a developed country in 2012. His mother had regular pregnancy follow-up and was found to be seronegative for HIV on 2 consecutive screening tests (during pregnancy and just after delivery). However, 1 year later, diagnosis of HIV infection arose in both of them after a pediatric emergency department visit for bronchitis when unexplained hepatosplenomegaly and inflammatory syndrome were noted. The negative maternal viral load found just after delivery confirmed that the mother’s seroconversion occurred postnatally, which allowed for active HIV transmission during lactation and lack of the efficient preventive measures that have implemented in Belgium for years. We discuss this uncommon but still existing mode of HIV transmission in industrialized countries and highlight the importance of implementing new targeted health education interventions in addition to constant clinicians’ awareness.

Enteroviral Infection of a Cardiac Prosthetic Device

BACKGROUND Identification of the causative pathogen may be challenging in culture negative infective endocarditis (IE). METHODS A 4 month-old 21-trisomic boy with congenital atrioventricular septal defect presented 3 episodes of dehiscence of his prosthetic patch, attributed to IE. He presented heart failure, but neither fever, nor inflammatory syndrome. RESULTS Surgical and histopathological findings confirmed the diagnosis of IE, but blood cultures remained sterile. Extensive work up failed to demonstrate bacterial or fungal etiology. Coxsackie B2 virus was cultured from the excised patch, nasopharyngeal secretions and stools. CONCLUSIONS Viral IE has only been described in animal models. This case is the first reported probable human viral IE. We suggest that a viral etiology should be considered in case of culture negative IE.

Pyogenic streptococcal omphalitis and foot’s cellulitis in an 11 day old infant

Omphalitis is a rare infection in our countries. Streptoccus pyogenes is one of the most frequently encountered germs. Complications are rare but include septicemia and necrotizing fasciitis with a high mortality rate. The case reported in this article is that of an 11 days old infant with pyogenic streptococcal omphalitis who developed cellulitis of left food. An intravenous antibiotic treatment allowed complete resolution of the symptoms. The article is the opportunity to review of the risk factors of this affection, its complications and treatments.