Vanda Friman

Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics.

Goals To examine if intake of Lactobacillus plantarum can prevent gastrointestinal side effects in antibiotic-treated patients. Background Diarrhea is a common side effect of treatment with antibiotics. Some studies indicate that the risk of antibiotic-associated diarrhea can be reduced by administration of certain probiotic microorganisms. Study Patients treated for infections at a university hospital infectious diseases clinic were randomized to daily intake of either a fruit drink with L. plantarum 299v (1010 colony forming units/d) or a placebo drink, until a week after termination of antibiotic treatment. Subjects recorded the number and consistency of stools as well as gastrointestinal symptoms until up to 3 weeks after last intake of test drink. Fecal samples were collected before the first intake of test drink and after termination of antibiotic therapy and analyzed for Clostridium difficile toxin. Results Clinical characteristics on admission were similar in the 2 groups. The overall risk of developing loose or watery stools was significantly lower among those receiving L. plantarum [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.52-0.92; P=0.012], as was development of nausea (OR, 0.51; 95% CI, 0.30-0.85; P=0.0097). Diarrhea defined as ≥3 loose stools/24 h for ≥2 consecutive days was unaffected by the treatment (OR, 1.4; 95% CI, 0.33-6.0; P=0.86). No significant differences regarding carriage of toxin producing C. difficile were observed between the groups. Conclusions Our results indicate that intake of L. plantarum could have a preventive effect on milder gastrointestinal symptoms during treatment with antibiotics.

Immunoglobulin prophylaxis in 350 adults with IgG subclass deficiency and recurrent respiratory tract infections: A long-term follow-up

350 adult patients in Sweden were included in a retrospective study covering more than 2000 patient-y, to evaluate the efficacy of immunoglobulin (Ig) prophylaxis. All patients had selective or combined IgG subclass deficiency, without IgA deficiency, and suffered from recurrent respiratory tract infections (RTIs). The patients had been given Ig prophylaxis for 0.5–21 y (mean 5.5 y). In total, 164/350 of the patients had a concomitant lung disease. Because of the heterogeneity of this retrospective material we evaluated only those patients with 4 or more antibiotic-demanding (i.e. presumably bacterial) episodes of RTI per y treated with an Ig dose of about 100 mg/kg/week (132/350). The frequency of antibiotic treated RTIs prior to and during latest y/s of Ig prophylaxis was compared. No difference in response could be found between patients with and without chronic lung diseases. In 92/132 a ≥50% reduction of the rate of episodes of antibiotic-demanding RTIs was recorded (p < 0.001). The overall reduction of the RTI frequency was for IgG1 57%, IgG2 59%, IgG3 63% and for the combinations 61% (all p<0.001).

Speech and hearing in adults with 22q11.2 deletion syndrome

The purpose of the study was to investigate the prevalence of velopharyngeal impairment, compensatory articulation, reduced intelligibility, and to rate the general impression of speech in adults with 22q11.2 deletion syndrome. The second purpose was to study the prevalence and type of hearing impairment in these adults. A referred, consecutive series of 24 adults with confirmed 22q11.2 deletion, 16 female and 8 males, with a mean age of 25 years (19–38 years) was included in the study. A blind assessment of speech by three experienced speech‐ language pathologists was performed. Sixteen (66%) patients had a mild to severe velopharyngeal impairment. The most prevalent symptoms of velopharygeal impairment were hypernasality and audible nasal airflow. The mean nasalance score was 33% (6–66%). Only two patients had disordered articulation; one of these had glottal articulation. A mean of 96% (88–100%) of single words were rated to be intelligible. To achieve these results half of the patients previously had velopharyngeal flap surgery. Forty‐one percent (9/22) had mild–moderate hearing impairment; three had sensorineural type, four conductive and two had a mixed type. In conclusion the majority of the patients had no articulation errors and good intelligibility; while one‐third still had moderate to severe problems with velopharyngeal impairment. Around 40% still had some hearing impairment, in most cases with a mild to moderate conductive component. Thus, a high prevalence of speech and hearing problems seems to be a part of the phenotype in adults with 22q11.2DS.

The antibody response to pandemic H1N1 2009 influenza vaccine in adult organ transplant patients

Limited data are available regarding antibody response and the safety of the monovalent influenza A H1N1/09 vaccine for immunocompromised patients. In this study, the humoral response to this vaccine in solid organ transplant (SOT) recipients and healthy individuals was evaluated. Eighty‐two SOT recipients and 28 healthy individuals received two doses of the influenza A H1N1/09 AS03 adjuvanted vaccine containing 3.75 mg of haemagglutinin at a 3‐ to 4‐week interval. Serum samples were drawn at baseline and 3–4 weeks after the first and second vaccine doses. Seroprotective titres were measured with a haemagglutination inhibition. After the first dose seroprotective titres were observed in 69% of the SOT patients and in 96% of the healthy controls (P = 0.006), and increased after the second dose to 80% and 100%, respectively (P = 0.003). All controls and 77% of the SOT recipients achieved a ≥4‐fold titre rise after the first immunisation (P = 0.005). The vaccine was well tolerated and no acute rejection was observed. Influenza A H1N1/09 vaccine elicited a protective antibody response in the majority of SOT recipients, but the response was lower when compared with controls. A second dose significantly improved vaccine immunogenicity in SOT recipients. (ClinicalTrials.gov number: NCT01254955)

Antibody deficiency in adults with 22q11.2 deletion syndrome

There are limited data on immunological disorders, infection profile, and autoimmunity among adults with the 22q11.2 deletion syndrome (22q11.2DS) in the literature. To expand this knowledge base, we evaluated immunoglobulin levels, lymphocyte subsets, and T‐cell function in 26 adults, consecutively referred to our 22q11.2DS multidisciplinary team. Their medical records were also reviewed with respect to frequency and severity of infections and autoimmune disorders. Six patients had low immunoglobulin levels; among these patients, one had a combined IgA and IgG1 deficiency, one had an isolated IgG3 deficiency, and four had a profound antibody deficiency comparable to common variable immunodeficiency (CVID). Three of the patients with profound antibody deficiency showed signs of reduced T‐cell function measured as a low response to mitogen and/or antigen stimulation. The four patients with profound antibody deficiency suffered from more severe infections than the rest of the patient group. Three of them also had a history of both immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AHA). Our results suggest that a subgroup of individuals with 22q11.2DS can develop a severe antibody deficiency associated with lower respiratory tract infections and autoimmune conditions. Early diagnosis of hypogammaglobulinemia among these individuals is important in order to provide optimal treatment. We therefore recommend an immunological evaluation and follow‐up among adults with 22q11.2DS who have a history of autoimmune conditions or recurrent infections.

Clinical features and incidence of Mycobacterium avium infections in children.

Mycobacterium avium is the most common pathogen in children presenting as non-tuberculous mycobacterial lymphadenitis. In Sweden non-tuberculous mycobacterial infection is a notifiable disease. The goal of our study was to determine the annual incidence of M. avium infection in Swedish children, 1998–2003, and describe clinical features related to age and treatment of children with M. avium lymphadenitis. To do this, we retrospectively analysed patient records of 162 children less than 7 y of age from the entire country with culture-verified M. avium disease. The incidence of M. avium infection in Sweden was lower in 2000–2003 than in 1998–1999. Young children (≤24 months old) had more constitutional symptoms at onset of disease than older children. One-third of the children had received 2 or more antibiotic courses before diagnosis. Disfiguring scars after healing were more common in children who were not treated with surgical extirpation of the affected lymph nodes. The decreasing incidence of M. avium infection among Swedish children in recent y is in contrast to reports of increasing non-tuberculous mycobacterial disease from other countries. Our results support the view that M. avium lymphadenitis should be treated by surgical removal of the affected tissue.

Common variants at PVT1 , ATG13 – AMBRA1 , AHI1 and CLEC16A are associated with selective IgA deficiency

Selective immunoglobulin A deficiency (IgAD) is the most common primary immunodeficiency in Europeans. Our genome-wide association study (GWAS) meta-analysis of 1,635 patients with IgAD and 4,852 controls identified four new significant (P < 5 × 10−8) loci and association with a rare IFIH1 variant (p.Ile923Val). Peak new variants (PVT1, P = 4.3 × 10−11; ATG13–AMBRA1, P = 6.7 × 10−10; AHI1, P = 8.4 × 10−10; CLEC16A, P = 1.4 × 10−9) overlapped with autoimmune markers (3/4) and correlated with 21 putative regulatory variants, including expression quantitative trait loci (eQTLs) for AHI1 and DEXI and DNase hypersensitivity sites in FOXP3+ regulatory T cells. Pathway analysis of the meta-analysis results showed striking association with the KEGG pathway for IgA production (pathway P < 0.0001), with 22 of the 30 annotated pathway genes containing at least one variant with P ≤ 0.05 in the IgAD meta-analysis. These data suggest that a complex network of genetic effects, including genes known to influence the biology of IgA production, contributes to IgAD.

Secondary immunodeficiency in lymphoproliferative malignancies.

Secondary immunodeficiencies occur as a consequence of various diseases, including hematological malignancies, and the use of pharmacological therapies, such as immunosuppressive, anti‐inflammatory, and biological drugs. Infections are the main cause of morbidity and mortality in multiple myeloma (MM) and chronic lymphocytic leukemia (CLL) patients. Recent advances in treatment have prolonged the duration of remission and the time between relapse phases in MM and CLL patients. However, managing multiple relapses and the use of salvage therapies can lead to cumulative immunosuppression and a higher risk of infections. The pathogenesis of immune deficiency secondary to lymphoproliferative malignancy is multifactorial including disease‐ and treatment‐related factors. Supportive treatment, including early vaccination, anti‐infective prophylaxis, and replacement immunoglobulin, plays a key role in preventing infections in MM and CLL. This article provides an overview of the basic immunology necessary to understand the pathogenesis of secondary immunodeficiency and the infectious complications in MM and CLL. We also discuss the evidence supporting the role of prophylactic replacement immunoglobulin treatment in patients with antibody failure secondary to MM and CLL and the indications for its use. Copyright

Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti-thymocyte globulin, and total body irradiation are additive risk factors

C. Kullberg‐Lindh, K. Mellgren, V. Friman, A. Fasth, H. Ascher, S. Nilsson, M. Lindh. Opportunistic virus DNA levels after pediatric stem cell transplantation: serostatus matching, anti‐thymocyte globulin, and total body irradiation are additive risk factors.
Transpl Infect Dis 2011: 13: 122–130. All rights reserved

Reduced Phase Switch Capacity and Functional Adhesin Expression of Type 1-Fimbriated Escherichia coli from Immunoglobulin A-Deficient Individuals

ABSTRACT The mannose-specific adhesin of type 1 fimbriae is the most common adhesin in Escherichia coli. One receptor for this adhesin is the carbohydrate chains of secretory immunoglobulin A (S-IgA), and intestinal E. coli from IgA-deficient individuals has a reduced capacity to adhere to mannose-containing receptors. Here, we investigated the expression of the mannose-specific adhesin and its capacity to switch to the fimbriated phenotype in colonic resident and transient E. coli strains isolated from control (n = 16) and IgA-deficient (n = 17) persons. Resident E. coli strains from IgA-deficient individuals displayed weaker mannose-specific adherence to colonic cells than resident strains from control individuals (21 versus 44 bacteria/cell, P = 0.0009) due to three mechanisms: a lower carriage rate of the fimH gene (90% versus 97%, not significant), more frequent failure to switch on the fim genes (30% versus 6%, P = 0.02), and the reduced adhesive potential of fimH+ isolates capable of phase switch (26 versus 46 bacteria/cell, P = 0.02). On the other hand, resident strains from IgA-deficient individuals displayed stronger mannose-resistant adherence than resident strains from control individuals (P = 0.04) and transient strains from IgA-deficient individuals (P = 0.01). The presence of S-IgA appears to favor the establishment of E. coli clones which readily express mannose-specific adhesins in the bowel microbiota.