Prevalence and persistence of Neisseria meningitidis carriage in Swedish university students.

The bacterium Neisseria meningitidis causes life-threatening disease worldwide, typically with a clinical presentation of sepsis or meningitis, but can be carried asymptomatically as part of the normal human oropharyngeal microbiota. The aim of this study was to examine N. meningitidis carriage with regard to prevalence, risk factors for carriage, distribution of meningococcal lineages and persistence of meningococcal carriage. Throat samples and data from a self-reported questionnaire were obtained from 2744 university students (median age: 23 years) at a university in Sweden on four occasions during a 12-month period. Meningococcal isolates were characterised using whole-genome sequencing. The carriage rate among the students was 9.1% (319/3488; 95% CI 8.2-10.1). Factors associated with higher carriage rate were age ≤22 years, previous tonsillectomy, cigarette smoking, drinking alcohol and attending parties, pubs and clubs. Female gender and sharing a household with children aged 0-9 years were associated with lower carriage. The most frequent genogroups were capsule null locus (cnl), group B and group Y and the most commonly identified clonal complexes (cc) were cc198 and cc23. Persistent carriage with the same meningococcal strain for 12 months was observed in two students. Follow-up times exceeding 12 months are recommended for future studies investigating long-term carriage of N. meningitidis.

Novel purine analogues regulate IL-1ß release via inhibition of JAK activity in human aortic smooth muscle cells.

Purine analogues bearing a nitrate ester motif were previously discovered as cardioprotective and anti-inflammatory agents, but the anti-inflammatory mechanism remains to be established. We therefore investigated the anti-inflammatory effect of two purine analogues, MK118 bearing a nitrate ester moiety and the methyl-substituted analogue MK196 in Aortic Smooth Muscle Cells (AoSMCs), with emphasis on IL-1ß release. The AoSMCs were stimulated with LPS with or without purine analogue, followed by ELISA, Olink proteomics, Western blot and real time PCR of NLRP3 inflammasome components. Both purine analogues inhibited the release of proteins involved in inflammation, such as TRAIL, CCL4, CSF1 and IL-1ß in AoSMCs, as well as intracellular gene and protein expression of IL-1ß and NLRP3 inflammasome components. MK196, but not MK118, also inhibited the LPS-induced release of IL-7, CXCL10, PD-L1, FLT3L and CCL20. We also showed that MK118 and possibly MK196 act via inhibition of JAKs. In silico studies showed that the purine moiety is a competent hinge binding motif and that the purine-piperazine scaffold is well accommodated in the lipophilic groove of JAK1-3. Both compounds establish interactions with catalytic amino acids in the active site of JAK1-3 and the terminal nitrate ester of MK118 was revealed as a promising pharmacophore. Our data suggest that MK118 and MK196 inhibit the release of proinflammatory proteins in AoSMCs, and targets JAK1-3 activation. Purine analogues also inhibit the expression of NLRP3 inflammasome genes and proteins and may in the future be evaluated for anti-inflammatory aspects on inflammatory diseases.

Discordance between Providers Estimated and Caregivers Self Reported Adherence to HAART and Immunological Response among HIV Infected Children in Ethiopia

Purpose: Poor concordance between patient and physician reports of adherence might lead to inappropriate decisions regarding therapy. This study was undertaken to determine the rate of discordance between caregivers of children and physicians on adherence to Highly Active Antiretroviral Therapy (HAART). Methods: In a cross sectional study involving 390 respondents that was conducted in five hospitals in Addis Ababa; agreement between caregiver-reported adherence and providers' estimate of adherence was compared using Kappa (k) statistic. The association between the CD4 counts and measure of adherence was evaluated using a receiver operating characteristic (ROC) curve. Results: Caregivers reported dose adherence was 87in the last 7 days and physician estimated 84of the children as adherent based on their judgment. Fair agreement was observed between caregivers-reported dose adherence and providers' estimate adherence (Kappa = 0.27; p=0.0001). In a ROC curve; the association between a current CD4 count slope and physician estimated was poor. Conclusions: There is fair agreement and high rate of discordance (18) between physicians estimated and caregivers reported adherence. These recall for an intervention to augment better mutual understanding between physicians and caregivers on the issue of adherence to HAART under clinical care programme