Improved plasmablast response after repeated pneumococcal revaccinations following primary immunization with 13-valent pneumococcal conjugate vaccine or 23-valent pneumococcal polysaccharide vaccine in patients with chronic lymphocytic leukemia.

BACKGROUND: Patients with chronic lymphocytic leukemia (CLL) show an immune dysfunction with increased risk of infections and poor response to vaccination. Streptococcus pneumoniae is a common cause of morbidity and mortality in CLL patients. In a previous randomized clinical trial, we found a superior immune response in CLL patients receiving conjugated pneumococcal vaccine compared to non-conjugated vaccine. The response to revaccination in CLL patients is scarcely studied. In this study, early humoral response to repeated revaccinations with pneumococcal vaccines was evaluated, by determination of B cell subsets and plasmablast dynamics in peripheral blood. METHOD: CLL patients (n = 14) and immunocompetent controls (n = 31) were revaccinated with a 13-valent pneumococcal conjugate vaccine (PCV13) after previous primary immunization (3-6 years ago) with PCV13 or a 23-valent pneumococcal polysaccharide vaccine (PPSV23). Eight weeks after the first revaccination, all CLL patients received a second revaccination with PCV13 or PPSV23. B cell subsets including plasmablasts were analyzed in peripheral blood by flow cytometry, before and after the first and the second revaccination. RESULTS: None of the CLL patients, but all controls, had detectable plasmablasts at baseline (p < 0.001). After the first revaccination with PCV13, the plasmablast proportions did not increase in CLL patients (p = 0.13), while increases were seen in controls (p < 0.001). However, after a second revaccination with PCV13 or PPSV23, plasmablasts increased compared to baseline also in CLL patients (p < 0.01). If no response was evident after first revaccination, only a second revaccination with PCV13 increased plasmablasts in contrast to PPSV23 revaccination. Patients with hypogammaglobulinemia and ongoing/previous CLL specific treatment responded poorly, also to a second revaccination. CONCLUSION: In CLL patients, pneumococcal revaccination induced minor early plasmablast response compared to controls, but the response improved using a strategy of repeated doses with of conjugated T cell dependent pneumococcal vaccine.

Impact of ribotype on Clostridioides difficile diagnostics.

This study investigates the performance of diagnostic methods for detection of Clostridioides difficile infection in Sweden, including impact of PCR ribotype on diagnostic performance. Between 2011 and 2016, a total of 17,878 stool samples from 26 laboratories were tested by either well-type enzyme immunoassays (EIAs), membrane bound EIAs, cell cytotoxicity neutralization assay (CTA), or nucleic acid amplification tests (NAATs) and subsequently cultured for C. difficile. Roughly half of the samples (9454/17878) were subjected to diagnostic testing both on the fecal sample and on the 1323 isolated C. difficile strains. All C. difficile isolates were typed by PCR ribotyping, and the isolates were classified as toxigenic or non-toxigenic based on the empirical knowledge of the association between toxin-positivity and ribotype. The overall sensitivity, specificity, and positive and negative predictive values were highest for NAATs and membrane EIAs. Ribotype-specific sensitivity varied greatly between methods and ribotypes. All methods had 100% sensitivity against ribotype 027 and 013. For other types, the sensitivity ranged from 33 to 85% in fecal samples and from 78 to 100% on isolates. For the most prevalent ribotypes (014, 020, and 001), the sensitivity varied between 38 and 100% in the fecal samples, with the lowest sensitivity observed for well-type EIAs and CTA. The large variation in diagnostic sensitivity implies that type distribution significantly affects the outcome when evaluating diagnostic performance. Furthermore, performing comparative studies of diagnostic tests in settings with high prevalence of ribotype 027 will overestimate the general performance of diagnostic tests.

Preoperative preparation of eye with chlorhexidine solution significantly reduces bacterial load prior to 23-gauge vitrectomy in Swedish health care.

BACKGROUND: Bacteria in the conjunctiva present a potential risk of vitreous cavity infection during 23-gauge pars plana vitrectomy (PPV). Current preoperative procedures used in Sweden include irrigation with chlorhexidine solution (CHX) 0.05% only and no iodine solutions. We evaluated the bacterial diversity and load before and after this single antibacterial measure. METHODS: In a prospective, consecutive cohort we investigated bacterial growth in samples from 40 eyes in 39 consecutive individuals subjected to vitrectomy. A conjunctival specimen was collected from each preoperative patient before and after irrigating of eye with CHX, 0.05% solution. Iodine was not used during any part of the surgery. One drop of chloramphenicol was administered prior to surgery. Samples from vitreous cavity were collected at the beginning and end of vitrectomy. All conjunctival specimens were cultured for different species and quantified using colony forming units (CFU). RESULTS: There was a significant 82% reduction in the total number of CFUs for all bacteria in all eyes (P < 0.0001), and 90% reduction for coagulase negative staphylococci (CoNS) alone (P = 0.0002). The number of eyes with positive bacterial growth in conjunctival samples decreased from 33 to 18 after irrigation with CHX (P = 0.0023). The most common bacteria prior to surgery were CoNS (70%), Propionibacterium acnes (55%) and Corynebacterium species (36%). No case of post-vitrectomy endophthalmitis was reported during mean follow-up time, which was 4.6 ± 2.3 (range; 1.5 to 9) months. CONCLUSIONS: Patients undergoing PPV harbored bacteria in conjunctiva capable of causing post-vitrectomy endophthalmitis. Preoperative preparation with CHX significantly reduced the bacterial load in the conjunctival samples subsequently leading to very low inoculation rates in recovered vitreous samples. Thus, CHX used as a single disinfectant agent might be an effective preoperative procedure for eye surgery in Sweden. This is a relatively small study but the results could be a reference for other intraocular surgeries.

An extra priming dose of hepatitis A vaccine to adult patients with rheumatoid arthritis and drug induced immunosuppression - A prospective, open-label, multi-center study.

BACKGROUND: Previous studies have indicated that a pre-travel single dose of hepatitis A vaccine is not sufficient as protection against hepatitis A in immunocompromised travelers. We evaluated if an extra dose of hepatitis A vaccine given shortly prior to traveling ensures seroconversion. METHOD: Patients with rheumatoid arthritis (n = 69, median age = 55 years) treated with Tumor Necrosis Factor inhibitor(TNFi) and/or Methotrexate (MTX) were immunized with two doses of hepatitis A vaccine, either as double dose or four weeks apart, followed by a booster dose at six months. Furthermore, 48 healthy individuals, median age = 60 years were immunized with two doses, six months apart. Anti-hepatitis A antibodies were measured at 0, 1, 2, 6, 7 and 12 months. RESULTS: Two months after the initial vaccination, 88% of the RA patients had protective antibodies, compared to 85% of the healthy individuals. There was no significant difference between the two vaccine schedules. At twelve months, 99% of RA patients and 100% of healthy individuals had seroprotective antibodies. CONCLUSION: An extra priming dos of hepatitis A vaccine prior to traveling offered an acceptable protection in individuals treated with TNFi and/or MTX. This constitutes an attractive pre-travel solution to this vulnerable group of patients.

Clostridium difficile infection diagnostics - evaluation of the C. DIFF Quik Chek Complete assay, a rapid enzyme immunoassay for detection of toxigenic C. difficile in clinical stool samples.

Diagnostic testing for Clostridium difficile infection (CDI) has, in recent years, seen the introduction of rapid dual-EIA (enzyme immunoassay) tests combining species-specific glutamate dehydrogenase (GDH) with toxin A/B. In a prospective study, we compared the C. DIFF Quik Chek Complete test to a combination of selective culture (SC) and loop-mediated isothermal amplification (LAMP) of the toxin A gene. Of 419 specimens, 68 were positive in SC including 62 positive in LAMP (14.7%). The combined EIA yielded 82 GDH positives of which 47 were confirmed toxin A/B positive (11%) corresponding to a sensitivity and specificity of 94% for GDH EIA compared to SC and for toxin A/B EIA a sensitivity of 71% and a specificity of 99% compared to LAMP. Twenty different PCR ribotypes were evenly distributed except for UK 081 where only 25% were toxin A/B positive compared to LAMP. We propose a primary use of a combined GDH toxin A/B EIA permitting a sensitive 1-h result of 379 of 419 (90%, all negatives plus GDH and toxin EIA positives) referred specimens. The remaining 10% being GDH positive should be tested for toxin A/B gene on the same day and positive results left to a final decision by the physician.

Clindamycin resistant strains of Clostridium difficile isolated from cases of C. difficile associated diarrhea (CDAD) in a hospital in Sweden.

Fifty three strains of C. difficile recovered from the stools of 13 patients with clinical C. difficile associated diarrhea (CDAD) were analyzed for the presence of the ermB gene, for toxigenicity and fingerprinting profile by PCR based assays. Forty five percent of the isolates were resistant to clindamycin and positive for the ermB gene. All clindamycin resistant isolates were ermB positive and belonged to the same fingerprinting group, suggesting clonal spread. These preliminary results suggest that clindamycin resistant isolates may be common etiologic agents of CDAD in Sweden.