Underreporting of meningococcal disease incidence in the Netherlands: results from a capture-recapture analysis based on three registration sources with correction for false positive diagnoses.

In order to come to a reliable evaluation of the effectiveness of the chosen vaccination policy regarding meningococcal disease, the completeness of registrations on meningococcal disease in the Netherlands was estimated with the capture-recapture method. Data over 1993-1998 were collected from (A) mandatory notifications (n = 2926); (B) hospital registration (n = 3968); (C) laboratory surveillance (n = 3484). As the standard capture-recapture method does not take into account false positive diagnoses, we developed a model to adjust for the lack of specificity of our sources. We estimated that 1363 cases were not registered in any of the three sources in the period of study. The completeness of the three sources was therefore estimated at 49% for source A, 67% for source B and 58% for source C. After adjustment for false positive diagnoses, the completeness of source A, B, and C was estimated as 52%, 70% and 62%, respectively. The capture-recapture methods offer an attractive approach to estimate the completeness of surveillance sources and hence contribute to a more accurate estimate of the disease burden under study. However, the method does not account for higher-order interactions or presence of false positive diagnoses. Being aware of these limitations, the capture-recapture method still elucidates the (in)completeness of sources and gives a rough estimate of this (in)completeness. This makes a more accurate monitoring of disease incidence possible and hence attributes to a more reliable foundation for the design and evaluation of health interventions such as vaccination programs

Newly diagnosed HIV and use of HIV-PrEP among non-western born MSM attending STI clinics in the Netherlands: a large retrospective cohort study

IntroductionThe World Health Organization recommends HIV-PrEP for all people at risk for HIV infection, which includes men who have sex with men (MSM). Substantial part of new HIV diagnoses in the Netherlands are in non-western born MSM. This study evaluated new HIV diagnoses and reported PrEP use among non-western born MSM and compared it to western-born MSM. To inform public health efforts in the context of equitable PrEP access, we further assessed sociodemographic factors related to higher HIV risk and lower PrEP use among non-western born MSM.MethodsSurveillance data of consultations among MSM in all Dutch STI-clinics (2016–2021) were analyzed. STI-clinics provide PrEP via the national pilot-program since August 2019. In non-western born MSM (born in Eastern-Europe/Latin-America/Asia/Africa/Dutch-Antilles/Suriname), sociodemographic factors were evaluated for association with HIV (by multivariable generalized estimating equations) and reported PrEP use in the past 3 months (by multivariable logistic regression; restricted to an at-risk for HIV person-level data-subset from August 2019).ResultsNew HIV infections were diagnosed among 1.1% (493/44,394) of non-western born MSM-consultations (vs. 0.4% among western-born MSM, 742/210,450). Low education (aOR: 2.2, 95%CI: 1.7–2.7, vs. high education) and age under 25 years (aOR: 1.4, 95%CI: 1.1–1.8, vs. age above 35 years) were associated with new HIV diagnoses. PrEP use in the past 3 months was 40.7% in non-western born MSM (1,711/4,207; 34.9% among western-born MSM, 6,089/17,458). PrEP use was lower among non-western born MSM aged under 25 years (aOR: 0.3, 95%CI: 0.2–0.4), living in less urban areas (aOR: 0.7, 95%CI: 0.6–0.8), and having low education level (aOR: 0.6, 95%CI: 0.5–0.7).ConclusionOur study confirmed that non-western born MSM are an important key population in HIV prevention. Access to HIV prevention, including HIV-PrEP, should be further optimized to all non-western born MSM at risk for HIV, and specifically to those who are younger, live in less urban areas, and have a low education level

Gr1+IL-4-producing innate cells are induced in response to Th2 stimuli and suppress Th1-dependent antibody responses

Alum is used as a vaccine adjuvant and induces T<sub>h</sub>2 responses and T<sub>h</sub>2-driven antibody isotype production against co-injected antigens. Alum also promotes the appearance in the spleen of Gr1+IL-4+ innate cells that, via IL-4 production, induce MHC II-mediated signaling in B cells. To investigate whether these Gr1+ cells accumulate in the spleen in response to other T<sub>h</sub>2-inducing stimuli and to understand some of their functions, the effects of injection of alum and eggs from the helminth, Schistosoma mansoni, were compared. Like alum, schistosome eggs induced the appearance of Gr1+IL-4+ cells in spleen and promoted MHC II-mediated signaling in B cells. Unlike alum, however, schistosome eggs did not promote CD4 T cell responses against co-injected antigens, suggesting that the effects of alum or schistosome eggs on splenic B cells cannot by themselves explain the T cell adjuvant properties of alum. Accordingly, depletion of IL-4 or Gr1+ cells in alum-injected mice had no effect on the ability of alum to improve expansion of primary CD4 T cells. However, Gr1+ cells and IL-4 played some role in the effects of alum, since depletion of either resulted in antibody responses to antigen that included not only the normal T<sub>h</sub>2-driven isotypes, like IgG1, but also a T<sub>h</sub>1-driven isotype, IgG2c. These data suggest that alum affects the immune response in at least two ways: one, independent of Gr1+ cells and IL-4, that promotes CD4 T cell proliferation and another, via Gr1+IL-4+ cells, that participates in the polarization of the response

Reduction in PA28αβ activation in HD mouse brain correlates to increased mHTT aggregation in cell models

Huntington’s disease is an autosomal dominant heritable disorder caused by an expanded CAG trinucleotide repeat at the N-terminus of the Huntingtin (HTT) gene. Lowering the levels of soluble mutant HTT protein prior to aggregation through increased degradation by the proteasome would be a therapeutic strategy to prevent or delay the onset of disease. Native PAGE experiments in HdhQ150 mice and R6/2 mice showed that PA28αβ disassembles from the 20S proteasome during disease progression in the affected cortex, striatum and hippocampus but not in cerebellum and brainstem. Modulating PA28αβ activated proteasomes in various in vitro models showed that PA28αβ improved polyQ degradation, but decreased the turnover of mutant HTT. Silencing of PA28αβ in cells lead to an increase in mutant HTT aggregates, suggesting that PA28αβ is critical for overall proteostasis, but only indirectly affects mutant HTT aggregation

Oropharyngeal Chlamydia trachomatis in women; Spontaneous clearance and cure after treatment (FemCure)

Objectives: Women attending STI clinics are not routinely tested for oropharyngeal Chlamydia trachomatis (CT) infections. We aimed to assess spontaneous clearance of oropharyngeal CT and cure after antibiotic treatment in women. Methods: Women with vaginal or rectal CT (n=560) were recruited at STI clinics in 2016-2017, as part of the FemCure study (prospective cohort study). We included participants' data from week -1, that is, the diagnosis at initial visit, when clinics applied selective oropharyngeal testing. At week -1, a total of 241 women were oropharyngeally tested (30 positive) and 319 were untested. All FemCure participants provided nurse-collected oropharyngeal samples at study enrolment, that is, week 0, just prior to treatment (n=560), and after treatment at weeks 4 (n=449), 8 (n=433) and 12 (n=427). Samples were tested by nucleic acid amplification test, and at week 0 also by viability testing by viability PCR. Proportions of oropharyngeal CT test results were presented to represent spontaneous clearance and cure. Results: Of 30 women diagnosed with oropharyngeal CT at week -1, fifteen (50%) were negative at week 0 after a median of 9 days, that is, € spontaneous clearance'. At week 0, a total of 560 participants were tested, and 46 (8.8%) were oropharyngeal CT positive; 12 of them (26.1%) had viable CT. Of the 46 positive, 36 women had an oropharyngeal test after treatment; 97.2% (35/36) were negative at week 4, that is, € cure'. Of all women with follow-up visits, the proportion of oropharyngeal CT positive was between 0.5% and 1.6% between weeks 4 and 12. Of those not tested at week -1 (n=319), 8.5% (n=27) were oropharyngeal positive at week 0. Conclusions: The clinical importance of oropharyngeal CT in women is debated. We demonstrated that spontaneous clearance of oropharyngeal CT among women is common; of those who did not clear for CT, three-quarters had non-viable CT. After regular treatment with azithromycin or doxycycline, cure rate (97%) of oropharyngeal CT is excellent. Trial registration number: NCT02694497