Invasive Pneumococcal Infections Research Articles

Invasive Pneumococcal Disease in Infants Younger Than 60 Days

To review the epidemiology and clinical course of invasive pneumococcal diseases of infants younger than 60 days. All Streptococcus pneumoniae strains isolated from blood and cerebrospinal fluid cultures of infants below the age of 60 days during the years 1999-2009 were included in this study. Demographic, clinical, and laboratory data were collected from medical records. In all, 24 cases of pneumococcal invasive infections were identified. The primary diagnoses were bacteremia without a focus (n = 13), meningitis (n = 6), bacteremia with otitis media (n = 3), and joint infection with bacteremia (n = 2). Only one of the serotypes found is included in the heptavalent pneumococcal conjugated vaccine (PCV7). Streptococcus pneumoniae should be considered and treated empirically in infants with suspected invasive bacterial disease during the first 60 days of life. Routine vaccination with PCV7 in not expected to substantially reduce the incidence of invasive pneumococcal disease in Israeli infants of this age as a result of herd immunity.

Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study

Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus.

Air Pollution And Environmental Tobacco Smoking During Infancy May Increase The Risk Of Bronchiolitis

M O N D A Y 623 Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study J. Lee, H. Yang, W. Atrouni, L. Baddour, B. Yawn, Y. Juhn; Department of Pediatrics,Samsung Changwon Hospital, Changwon-si, REPUBLIC OF KOREA, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, Department of Pediatrics,Soonchunhyang University Hospital, Seoul, REPUBLIC OF KOREA, Division of Infectious Diseases, Department of Internal Medicine,University of Kansas Medical Center, Kansas, KS, Division of Infectious Diseases, Department of Medicine,Mayo Clinic, Rochester, MN, Department of Research, Olmsted Medical Center, Rochester, MN. RATIONALE: Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus. METHODS: Subjects were adult residents of Olmsted County, MN, who developed community-associated BSI caused by S. aureus between 1998 and 2005; three ageand sex-matched controls were also evaluated. The associations between asthma and community-associated BSI caused by S. aureus were assessed by Fischer exact test. RESULTS: Of the 43 BSI cases, 70% were male, 86% were Caucasians, and the median age was 59 years. Five (11.6%) of them were asthmatics as compared to 9 (7%) of 129 controls (p50.34). Compared to non-asthmatics, asthmatics had a lower ICU admission rate (34% vs 0%, p50.3) and lower Pitt-bacteremia scores (2.362.7 vs. 0.860.5, p50.13), a shorter hospital stay (13.6614.7 days vs. 11.462.1 days,p50.59), and lower mortality rates (13.0% vs. 0.0%, p51.0), but these differences were not statistically significant. CONCLUSIONS: Unlike IPD, asthma is not significantly associated with risk and severity of BSI caused by S. aureus. Designation of specific pathogenmay be one of several key factors in an association of asthmawith risk and severity of BSI. However, a small sample size significantly limited the current investigation.

Asthma and Severity of Blood Stream Infection Caused by Escherichia coli: A Population-Based Study

M O N D A Y 623 Asthma and Risk of Community-Associated Blood Stream Infection Due to Staphylococcus aureus: A Population-Based Case-Control Study J. Lee, H. Yang, W. Atrouni, L. Baddour, B. Yawn, Y. Juhn; Department of Pediatrics,Samsung Changwon Hospital, Changwon-si, REPUBLIC OF KOREA, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN, Department of Pediatrics,Soonchunhyang University Hospital, Seoul, REPUBLIC OF KOREA, Division of Infectious Diseases, Department of Internal Medicine,University of Kansas Medical Center, Kansas, KS, Division of Infectious Diseases, Department of Medicine,Mayo Clinic, Rochester, MN, Department of Research, Olmsted Medical Center, Rochester, MN. RATIONALE: Patients with asthma harbor an increased risk of invasive pneumococcal infection (IPD). It is unknown whether there is a similar association between asthma and community-associated blood stream infection (BSI) caused by Staphylococcus aureus. METHODS: Subjects were adult residents of Olmsted County, MN, who developed community-associated BSI caused by S. aureus between 1998 and 2005; three ageand sex-matched controls were also evaluated. The associations between asthma and community-associated BSI caused by S. aureus were assessed by Fischer exact test. RESULTS: Of the 43 BSI cases, 70% were male, 86% were Caucasians, and the median age was 59 years. Five (11.6%) of them were asthmatics as compared to 9 (7%) of 129 controls (p50.34). Compared to non-asthmatics, asthmatics had a lower ICU admission rate (34% vs 0%, p50.3) and lower Pitt-bacteremia scores (2.362.7 vs. 0.860.5, p50.13), a shorter hospital stay (13.6614.7 days vs. 11.462.1 days,p50.59), and lower mortality rates (13.0% vs. 0.0%, p51.0), but these differences were not statistically significant. CONCLUSIONS: Unlike IPD, asthma is not significantly associated with risk and severity of BSI caused by S. aureus. Designation of specific pathogenmay be one of several key factors in an association of asthmawith risk and severity of BSI. However, a small sample size significantly limited the current investigation.

Streptococcus pneumoniae – a review of carriage, infection, serotype replacement and vaccination

Invasive pneumococcal infection remains a leading global cause of morbidity and mortality in young children. In developed nations, a substantial decrease in the incidence of IPD has been achieved with inclusion of the 7 valent protein conjugated pneumococcal vaccines (7vPCV) into paediatric vaccine schedules. In contrast, the incidence of IPD has changed little in developing nations. This is likely due to poor access to medical care and pneumococcal vaccination, the accompanying HIV and malnutrition burden, and the fact that 7vPCV does not contain the most common serotypes (1,5, 6A) responsible for IPD in many developing nations. The battle against IPD in developed nations is not over, with the rise of non-7vPCV serotypes since routine 7vPCV vaccination. This has necessitated the development and distribution of pneumococcal vaccines containing 3 or 6 additional serotypes. This article provides an overview on pneumococcal carriage and risk factors for IPD, the rise of non-7vCPV serotypes in the era of 7vPCV vaccination, and the current and newly available broader valent pneumococcal vaccines.

Invasive pneumococcal pneumonia is the major cause of paediatric haemolytic‐uraemic syndrome in Taiwan

Streptococcus pneumoniae-associated haemolytic uraemic syndrome (SP-HUS) is a major concern of paediatric acute renal failure in Taiwan; it leads to significant morbidity and mortality during the acute phase and to long-term morbidity after an acute episode. Twenty children diagnosed with HUS between 1 May 1995, and 31 December 2008 was enrolled. Clinical variables related to laboratory data, organ involved, and outcomes were examined between patients with and without SP-HUS. Thirteen of the 20 (13/20, 65%) patients required dialysis, nine (9/20, 45.0%) developed hepatic dysfunction, disseminated intravascular coagulation (DIC), gastrointestinal bleeding, and hypertension, respectively. They were the second most common extrarenal complication except empyema (11/20, 55%). Two (10%) died and seven (35%) of the survivors developed long-term renal morbidity. Twelve of the 20 patients (60%) were diagnosed with SP-HUS. Younger age, female children, higher white blood cell count, higher alanine transaminase, higher lactate dehydrogenase and high incidence of DIC were significantly common in SP-HUS cases. All SP-HUS cases were complicated with pleural effusion, empyema, or both. Positive Thomsen-Freidenreich antigen (T-Ag) activation was 83% sensitive and 100% specific for SP-HUS, and a positive direct Coombs' test was 58% sensitive and 100% specific. Invasive pneumococcal infection is the most common cause of HUS in Taiwan. Positive T-Ag activation and a direct Coombs' test are rapid predictors of SP-HUS in children with invasive pneumonia.

Potential serotype coverage of three pneumococcal conjugate vaccines against invasive pneumococcal infection in Italian children

Since the introduction of the 7-valent vaccine, invasive pneumococcal disease have greatly decreased; however, changes in the distribution of pneumococcal serotypes have recently highlighted the need for vaccines with wider coverage. The aim of the work was to assess the potential serotype coverage of three pneumococcal conjugate vaccines (7-, 10- and 13-valent) against bacteremic pneumococcal pneumonia and meningitis/sepsis in Italian children. We determined pneumococcal serotypes in immunocompetent patients who had been admitted to hospital with suspicion of invasive bacterial disease and had confirmed bacteremic pneumococcal pneumonia or meningitis/sepsis determined by molecular detection of Streptococcus pneumoniae in a normally sterile site. Positive samples were serotyped using Realtime-PCR. Between April 2008 and March 2011, a total of 144 patients (age median 4.1 years; Interquartile range 1.8-5.6) with pneumococcal meningitis/sepsis (n=43) or pneumonia (n=101) from 83 participating centers located in 19 of 20 Italian regions were serotyped. The 10 most prevalent serotypes were 1 (29.9%), 3 (16.0%), 19A (13.2%), 7F (8.3%), 5 (4.2%), 14 (4.2%), 6A (3.5%), 6B (3.5%), 18C (3.5%), 19F (3.5%). Overall, serotype coverage for PCV-7, -10 and -13 were respectively 19.4%, 61.8% and 94.4% with no statistical difference between pneumonia and meningitis/sepsis. Potential coverage was similar for children 0-2 or 2-5 years of age. Cultures resulted positive in 35/99 (35.4%) samples simultaneously obtained for both culture and RT-PCR. These findings indicate that increasing the potential serotype coverage by introducing PCV13 in the vaccination schedule for infancy could provide substantial added benefit for protection from pneumococcal pneumonia or meningitis/sepsis in Italy in children below 2 years as well in older children. The importance of molecular methods for diagnosis and serotyping of invasive pneumococcal disease was confirmed.

Acquisition of Pneumococci Specific Effector and Regulatory Cd4+ T Cells Localising within Human Upper Respiratory-Tract Mucosal Lymphoid Tissue

The upper respiratory tract mucosa is the location for commensal Streptococcus (S.) pneumoniae colonization and therefore represents a major site of contact between host and bacteria. The CD4+ T cell response to pneumococcus is increasingly recognised as an important mediator of immunity that protects against invasive disease, with data suggesting a critical role for Th17 cells in mucosal clearance. By assessing CD4 T cell proliferative responses we demonstrate age-related sequestration of Th1 and Th17 CD4+ T cells reactive to pneumococcal protein antigens within mucosal lymphoid tissue. CD25hi T cell depletion and utilisation of pneumococcal specific MHCII tetramers revealed the presence of antigen specific Tregs that utilised CTLA-4 and PDL-1 surface molecules to suppress these responses. The balance between mucosal effector and regulatory CD4+ T cell immunity is likely to be critical to pneumococcal commensalism and the prevention of unwanted pathology associated with carriage. However, if dysregulated, such responses may render the host more susceptible to invasive pneumococcal infection and adversely affect the successful implementation of both polysaccharide-conjugate and novel protein-based pneumococcal vaccines.

Serotype changes in adult invasive pneumococcal infections in Portugal did not reduce the high fraction of potentially vaccine preventable infections

We determined the serotype and antimicrobial susceptibility of 1100 isolates responsible for adult invasive pneumococcal infections (IPD) in Portugal between 2006 and 2008. Serotypes 3 (13%), 1 (12%), 7F (11%), 19A (10%) and 14 (7%) were the most frequent causes of IPD and the two later serotypes accounted for the majority of erythromycin and penicillin nonsusceptible isolates. Serotype 1 was associated with younger adults whereas serotype 3 was associated with older adults. Despite the availability of the 23-valent polysaccharide vaccine (PPV23) in Portugal since 1996, the proportion of PPV23 preventable IPD remained stable and above 80%. Comparing with previous data from Portugal, we showed a continued decline of the serotypes included in the 7-valent conjugate vaccine (PCV7) in adult IPD and a rise of serotypes included in the 13-valent conjugate vaccine, increasing its potential coverage of adult IPD to 70% in 2008. Penicillin non-susceptibility remained stable (17%) whereas erythromycin resistance (18%) has continued to rise in the post-PCV7 years.

Streptococcus pneumoniae induces exocytosis of Weibel-Palade bodies in pulmonary endothelial cells

Invasive pneumococcal infections due to Streptococcus pneumoniae lead to inflammatory infiltration of leucocytes into lung alveolus, meninges and to septic dissemination within the vascular system. The lung microvasculature is covered by pulmonary endothelial cells containing Weibel-Palade bodies (WPB) releasing procoagulant von Willebrand factor (vWF) and other proteins in response to inflammatory stimuli. The influence of pathogenic pneumococci on secretion of WPB proteins is unknown. Here, we report that adherence of S. pneumoniae to primary human pulmonary microvascular endothelial cells (HPMEC) stimulates the WPB exocytosis and the secretion of vWF and interleukin 8 (IL-8). Moreover, infection analyses performed with pneumococcal mutants deficient in the expression of cytotoxic pneumolysin demonstrated that, in addition to direct bacterial adherence, sublytic concentrations of pneumolysin stimulated vWF secretion. The release of vWF was induced after infection with pneumococci from both the apical and the basal cell surfaces, which implies a stimulation of WPB exocytosis in both directions: from inside the vasculature and also following invasive pneumococcal transmigration from pulmonary tissue into the bloodstream. In conclusion, this study demonstrates that the most relevant pulmonary pathogen S. pneumoniae induces release of proinflammatory and procoagulative components directly contributing to pathophysiological processes leading to fatal tissue injury during course of infection.

Invasive Pneumococcal Infection in Children Aged Less than Five Years: A Report from Tertiary Care Hospital from Western India

Background<italic>Streptococcus pneumoniae</italic> is the leading cause of morbidity and mortality worldwide especially among children less than 5 years of age.To detect the prevalence of invasive <italic>Streptococcus pneumoniae</italic> in children aged less than 5 years and to determine the antimicrobial susceptibility profile with special reference to penicillin resistance in a tertiary care hospital.MethodsClinical specimens like pus, blood, cerebrospinal fluid and other sterile body fluids obtained from infected children were processed for isolation and identification of <italic>Streptococcus pneumoniae.</italic> Kirby Bauer disc diffusion test was performed to determine the antimicrobial susceptibility profile. Minimum inhibitory concentration was determined for penicillin in those isolates showing resistance to this antibiotic on disc diffusion test.ResultsPrevalence of invasive pneumococcal infection was found to be 33.4% in children aged less than 5 years. Penicillin resistance was encountered in 3.4% cases of invasive isolates. These isolates exhibited 25.4% &amp; 10.1% resistance to co-trimoxazole and chloramphenicol respectively.Invasive pneumococcal infections in children may have a poor prognosis and penicillin-resistant strains have become increasingly common. This study emphasises the importance of judicious use of antibiotics, especially to refrain their use in mild self-limiting upper respiratory infections.

Conjugate pneumococcal vaccines and influence on the ear, nose and throat area

The importance of anti-pneumococcal vaccines has increased due to the gradually increasing incidence rate of pneumococcal infections and their antibiotic resistance. Conjugate pneumococcal vaccine began to be used routinely in the USA in 2000. An important property of this conjugate vaccine is the ability to create immunity in infants after two months. Thus, conjugate vaccines allow us to protect children below the age of two years against to invasive and mortal pneumococcal infections. The first pneumococcal conjugate vaccine (PCV7) contains the seven most common pneumococcal serotypes in the USA. Pneumococci are also the most important bacterial agents in acute otitis media (AOM) and recurrent acute otitis media. Acute otitis media is the most common infectious disease in childhood and resistance to treatment has rapidly increased over the last decade. The incidence of AOM and applications of tympanostomy tubes saw statistically significant decreases in the USA after implementation of PCV7 in national immunization programs. PCV7 was implemented in the national immunization program in Turkey in 2008. For this reason, reductions in the incidence of upper respiratory tract infectious diseases and especially AOM should be expected in our country.

Actualités en matière de vaccination

The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009–2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve – but for how long ? – the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine calendars that cover a whole lifetime should be promoted, since the vaccination of adults and seniors is a determining factor of good health at all ages.

A novel mutation in the C3 gene and recurrent invasive pneumococcal infection: A clue for vaccine development

BackgroundWe identified a 4 year-old boy born to a consanguineous marriage with C3 deficiency after three episodes of invasive pneumococcal disease. The efficacy of anti-pneumococcal vaccination in C3 deficient patients is not clear. ObjectivesOur objective was to identify the genetic defect resulting in his C3 deficiency and measure his ability to mount an adaptive immune response. MethodsFibroblast cell lines were generated from the patient and parents. DNA was isolated and the C3 gene sequenced. Quantitation of C3 expression was performed by immunoprecipitation of 35S-methionine labeled protein. Isotype specific anti-pneumococcal antibodies present in the patients sera was quantitated after administration of Prevnar-7 and Pneumovax vaccines. ResultsPneumococcal types 14, 10B and 29 were identified from the blood on three separate occasions over a period of 20 months. C3 levels in the blood was <10, 71, and 66 for the patient, mother and father, respectively (90–180mg/dl, normal). Sequencing revealed a homozygous deletion of one nucleotide located in exon 31 (delA in position 3997 of cDNA) which resulted in a transcriptional stop signal thirteen codons later. The parents were heterozygous for the mutation. No detectable C3 was noted by immunoprecipitation. The patient mounted adequate antibody responses to the protein-conjugated Prevnar and tetanus vaccines but not to the polysaccharide antigen based Pneumovax vaccine. Major immunoglobulin class levels were normal. ConclusionC3 deficiency results in the selective impairment to mount a response against polysaccharide-based antigens. Protein-conjugated vaccines are likely to be efficacious in immunizing against encapsulated organisms in these patients.

Vaccination of Patients with Diabetes Mellitus - a Retrospective Study

402 subjects with diabetes mellitus have been vaccinated of the total of 34,000 vaccinees immunized during the study period of 9 and half months. Altogether 229 diabetic patients (56.97%) have been vaccinated'against tick-borne encephalitis (TBE) and 74 (18.4%) against viral hepatitis (41 types A+B, 30 type A, 3 type B). The average age in four most commonly administered vaccines (FSME IMMUN 0.5 ML, Twinrix Adult, Typhim Vi, and Havrix 1440) was 65, 52, 56, and 54 years, respectively. Live attenuated vaccines have been given to 6 patients with diabetes (1.49%)--- 5 travellers to endemic countries received the yellow fever vaccine Stamaril (1 female, 4 male) and one male patient varicella vaccine Varilrix. Among the least common vaccines in diabetic patients were those against invasive pneumococcal and meningococcal infections. Not a single unexpected side effect has been observed following the vaccination procedure in any diabetic patient. Based on the results of this retrospective study we can conclude that vaccination in diabetic patients is free of any ri-k- provided that there are no other contraindications, e.g. allergy to vaccine components or severe acute febrile illness. In the case of unstable glycaemia and significantly impaired immune system due to diabetes mellitus, vaccination with live attenuated vaccines should be carefully considered and measured against the risks of exposure to each and every specific infectious agent. There is no reason to be afraid of vaccination in diabetic patients provided that general contraindications are respected. On the contrary, this risk group can benefit from vaccination more remarkably since it may have some life-saving potential.

Ten Years of Surveillance for Invasive Streptococcus pneumoniae during the Era of Antiretroviral Scale-Up and Cotrimoxazole Prophylaxis in Malawi

ObjectiveTo document trends in invasive pneumococcal disease (IPD) in a central hospital in Malawi during the period of national scale-up of antiretroviral therapy (ART) and cotrimoxazole prophylaxis.MethodsBetween 1 January 2000 and 31 December 2009 almost 100,000 blood cultures and 40,000 cerebrospinal fluid (CSF) cultures were obtained from adults and children admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi with suspected severe bacterial infection.Results4,445 pneumococcal isolates were obtained over the 10 year period. 1,837 were from children: 885 (19.9%) from blood and 952 (21.4%) from CSF. 2,608 were from adults: 1,813 (40.8%) from blood and 795 (17.9%) from CSF. At the start of the surveillance period cotrimoxazole resistance was 73.8% and at the end was 92.6%. Multidrug resistance (MDR) was present in almost one third of isolates and was constant over time. Free ART was introduced in Malawi in 2004. From 2005 onwards there was a decline in invasive pneumococcal infections with a negative correlation between ART scale-up and the decline in IPD (Pearson's correlation r = −0.91; p<0.001).ConclusionDuring 2004–2009, national ART scale-up in Malawi was associated with a downward trend in IPD at QECH. The introduction of cotrimoxazole prophylaxis in HIV-infected groups has not coincided with a further increase in pneumococcal cotrimoxazole or multidrug resistance. These data highlight the importance of surveillance for high disease burden infections such as IPD in the region, which will be vital for monitoring pneumococcal conjugate vaccine introduction into national immunisation programmes.

Pneumococcal native aortic valve endocarditis with mycotic abdominal aortic aneurysm, paraspinal and iliopsoas abscesses and pneumonia revealing a multiple myeloma

We report a rare case of multiple myeloma presenting with native aortic valve endocarditis with secondary embolic mycotic abdominal aortic aneurysm, contiguous paraspinal and iliopsoas abscesses, and pneumonia due to Streptococcus pneumoniae in a Chinese man. He was treated with aortic valve replacement, endovascular stenting of aneurysm, image-guided drainage of abscesses, and a 6-week course of endocarditic antibiotic therapy followed by chronic suppressive antibiotic therapy. Cases of multiple myeloma presenting with invasive pneumococcal infection were reviewed.

Complement C2 deficiency disarranging innate and adaptive humoral immune responses in a pediatric patient: Treatment with rituximab

Introduction Complement deficiencies (CDs) are classified as primary immunodeficiency disorders (PIDs) because diminished opsonization or the inability to form the membrane attack complex increases the susceptibility to pyogenic bacterial infections (1). Moreover, diverse autoimmune manifestations occur that vary with the particular CD (1–3). Complement C2 deficiency (C2D; MIM217000) is classically associated with early-onset invasive pneumococcal infections and systemic lupus erythematosus (SLE) or SLE-like manifestations, which typically present in early or middle adulthood (3,4). Due to its low prevalence ( 1:20,000) (4) and variable clinical manifestations, publications on the treatment of C2D are scarce. In this case report, we describe a C2D patient with the earliest onset of SLE published, to our best knowledge, thus far. We report on rare complications such as immune complex–mediated leukocytoclastic vasculitis (LCV), destructive follicular bronchiolitis (DFB) with polyclonal B cell proliferation, and disturbed humoral immune responses, including dysgammaglobulinemia and specific antibody deficiency, therefore defining a novel phenotype. Providing a detailed histologic, immunologic, and genetic workup, we discuss the pathophysiology of C2D as a complex disorder at the interface between innate and adaptive humoral immunity. Finally, we describe, for the first time, the effective treatment with rituximab (RTX), implicating B cell depletion as a therapeutic strategy for the autoimmune manifestations of the PID.

Syndrome hémolytique et urémique au décours d’une infection materno-fœtale à Escherichia coli K1

Hemolytic uremic syndrome (HUS) is primarily a disease of infancy and early childhood. In its classic form, it is preceded by a prodrome of Escherichia coli-mediated bloody mucoid diarrhea. Typical HUS is commonly related to an infection by shiga-toxin producing E.coli. Stool cultures may detect this bacteria or its toxin, and PCRs can detect the shiga-toxin virulence genes. Atypical cases of HUS are mainly related to abnormalities of the alternative complement pathway and mutations of H, I, or B factors. Some atypical cases of HUS may also be related to von Willebrand factor or vitamin B12 metabolism abnormalities. A number of HUS cases related to invasive pneumococcal infections (pneumonia or meningitis) have been reported. We report a case of HUS associated with a bacterial E.coli K1 infection in a newborn baby, with a good clinical outcome: there was no need for dialysis and normal renal function was quickly regained. The workup did not favor a toxinic origin or an abnormality on the alternative complement pathway.

Immunization with DnaJ (hsp40) could elicit protection against nasopharyngeal colonization and invasive infection caused by different strains of Streptococcus pneumoniae

Increasing mortality, morbidity and economic costs have been paid to pneumococcal diseases every year. Currently, vaccination is the most promising strategy to reduce the occurrence of pneumococcal infection. In this study, we investigated the protective efficacy of immunization with recombinant DnaJ (hsp40) protein against infections of different serotypes of Streptococcus pneumoniae. We demonstrated that mucosal immunization with DnaJ antigen could induce both systemic and mucosal antibodies for DnaJ and stimulate the release of high levels of IL-10, IFN-γ and IL-17A. Moreover, this mucosal vaccination could reduce nasal or lung colonization of pneumococcus and elicit protection against different serotypes of invasive pneumococcal infections. As well, we found that intraperitoneal immunization with DnaJ could also protect against invasive infections caused by different serotypes of pneumococcus, and passive immunization with antibodies specific for DnaJ confirmed that this protection was antibody-mediated. Our results therefore support the potential of DnaJ as a conserved pneumococcal protein vaccine.