Lyme neuroborreliosis with encephalitis; a systematic literature review and a Scandinavian cohort study

Background Lyme neuroborreliosis (LNB) presenting with encephalitis is rare and scarcely described. Objectives To describe the available literature on LNB encephalitis and to characterize this patient group through a Scandinavian retrospective cohort study. Data sources Medline, Embase, Scopus, Cochrane library. Study eligibility criteria There was no discrimination on study type, time of publication or language. Participants Review: All articles with definite LNB and confirmed/possible encephalitis. Cohort: LNB cohorts from Denmark, Sweden and Norway 1990–2019 were screened for patients with encephalitis. Methods Review: Adhering to PRISMA guidelines; two authors extracted reviews and assessed quality of studies. Cohort: Data on demography, symptoms, cerebrospinal fluid findings, differential diagnostic examinations, treatment, residual symptoms, 1-year mortality were registered. Results Review: 2330 articles screened on title/abstract, 281 full texts, yielding 42 articles (case reports/series or cohort studies), including 45 patients from 18 countries spanning 35 years. Altered mental status ranged from personality changes and confusion to unconsciousness. Common focal symptoms were hemiparesis, ataxia and dysarthria; seven patients had seizures. Median time from symptom onset to hospital was 2 weeks (IQR 2–90 days). Of 38 patients with available follow-up after median 12 months (IQR 5–13), 32 had fully or partially recovered, two had died. Cohort: Thirty-five patients (median age 67 years, IQR 48–76) were included. The encephalitis prevalence was 3.3% (95% CI 2.2–4.4%) among 1019 screened LNB patients. Frequent encephalitis symptoms were confusion, personality changes, aphasia, ataxia. EEGs and neuroimaging showed encephalitis in 93.8% and 20.6%, respectively. Median delay from symptom onset to hospital was 14 days (IQR 7–34), with further 7 days (IQR 3–34) delay until targeted therapy. At follow-up (median 298 days post-treatment; IQR 113–389), 65.6% had residual symptoms. None had died. Conclusions This study shows that encephalitis is an uncommon, but likely overlooked clinical manifestation of LNB. As the high frequency of residual symptoms may be related to prolonged treatment delay, prompt LNB testing of patients with encephalitis in Borrelia burgdorferi-endemic areas should be considered.publishedVersio

Use of antiretroviral therapy in pregnancy and association with birth outcome among women living with HIV in Denmark:A nationwide, population-based cohort study

OBJECTIVE: To describe antiretroviral therapy (ART) regimens during pregnancy among women living with HIV (WLWH) in Denmark and to examine the association between ART use in pregnancy and adverse birth outcomes. METHODS: A population‐based cohort study including all pregnancies among WLWH in Denmark between 2000 and 2019. Data were collected through national registries. Temporal trends of ART use in pregnancy were evaluated. Logistic regression models were used to examine the association of ART use in pregnancy and other risk factors with adverse birth outcomes. RESULTS: In total, 589 pregnancies were included. Combination treatment with a nucleoside reverse transcriptase inhibitor (NRTI) and a protease inhibitor (PI) was the most common ART regimen (96%). ART regimen, PI use in pregnancy and timing of ART initiation were not significantly associated with increased odds of preterm birth, small for gestational age or low birth weight. First‐trimester initiation of ART was significantly associated with increased odds of intrauterine growth restriction in the multivariate analysis [adjusted odds ratio (aOR) = 3.78, 95% confidence interval (CI): 1.23–11.59], while first trimester PI use was associated with increased odds of IUGR in the univariate analysis only [OR = 3.24, 95% CI: 1.13–9.30]. Smoking, comorbidity, and maternal HIV RNA ≥ 50 copies/mL were independently associated with increased odds of adverse birth outcomes. CONCLUSIONS: Pregnant WLWH living in Denmark are generally well treated with HIV RNA < 50 copies/mL at delivery and NRTI + PI as the most common ART regimen used in pregnancy. Initiation of ART in the first trimester may be associated with poor fetal growth. The association between ART use in pregnancy and adverse birth outcomes may partly be explained by maternal risk factors

Tuberculosis screening in patients with HIV:use of audit and feedback to improve quality of care in Ghana

Background: Tuberculosis screening of people living with HIV (PLHIV) can contribute to early tuberculosis diagnosis and improved patient outcomes. Evidence-based guidelines for tuberculosis screening are available, but literature assessing their implementation and the quality of clinical practice is scarce. Objectives: To assess tuberculosis screening practices and the effectiveness of audit and performance feedback to improve quality of tuberculosis screening at HIV care clinics in Ghana. Design: Healthcare providers at 10 large HIV care clinics prospectively registered patient consultations during May and October 2014, before and after a performance feedback intervention in August 2014. The outcomes of interest were overall tuberculosis suspicion rate during consultations and provider adherence to the International Standards for Tuberculosis Care and the World Health Organizations’ guidelines for symptom-based tuberculosis screening among PLHIV. Results: Twenty-one healthcare providers registered a total of 2,666 consultations; 1,368 consultations before and 1,298 consultations after the feedback intervention. Tuberculosis suspicion rate during consultation increased from 12.6 to 20.9% after feedback (odds ratio, OR 1.83; 95% confidence interval, CI: 1.09–3.09). Before feedback, sputum smear microscopy was requested for 58.7% of patients with suspected tuberculosis, for 47.2% of patients with cough ≥2 weeks, and for 27.5% of patients with a positive World Health Organization (WHO) symptom screen (any of current cough, fever, weight loss or night sweats). After feedback, patients with a positive WHO symptom screen were more likely to be suspected of tuberculosis (OR 2.21; 95% CI: 1.19–4.09) and referred for microscopy (OR 2.71; 95% CI: 1.25–5.86). Conclusions: A simple prospective audit tool identified flaws in clinical practices for tuberculosis screening of PLHIV. There was no systematic identification of people with suspected active tuberculosis. We found low initial tuberculosis suspicion rate compounded by low referral rates of relevant patients for sputum smear microscopy. Adherence to recommended standards and guidelines for tuberculosis screening improved after performance feedback

Prevalence and distribution of cervical high-risk human papillomavirus and cytological abnormalities in women living with HIV in Denmark - the SHADE

BACKGROUND: Women living with HIV (WLWH) are at increased risk of persistent human papillomavirus (HPV) infection, cervical dysplasia and cervical cancer compared with women from the general population (WGP). We assessed the prevalence and distribution of cervical high-risk (hr) HPV infection and cytological abnormalities in WLWH compared with WGP in Denmark. Predictors of HPV and cytological abnormalities were estimated in WLWH. METHODS: WLWH consecutively enrolled in the Study on HIV, cervical Abnormalities and infections in women in Denmark (SHADE) in 2011 and were examined for cervical HPV and cytological abnormalities. WLWH were matched on age and prior cytological findings with WGP from an earlier study. HIV demographics were retrieved from the nationwide Danish HIV Cohort Study. Logistic regression was used to estimate predictors of hrHPV and cytological abnormalities. RESULTS: Of 334 included WLWH 26.4 % were positive for hrHPV as opposed to 16.6 % WGP (p < 0.0001). WLWH had a higher number of multiple infections (>1 h genotype present) (38.5 % versus 25.7 %, p = 0.030). Hr genotypes in descending order of frequency were HPV58 (7.1 %), 52 (5.4 %), and 16 (4.8 %) in WLWH versus HPV16 (4.1 %), 52 (2.8 %) and 58 (2.4 %) in WGP. Predictors of hrHPV in WLWH were short duration of HAART (adjusted OR per year 0.90 (95 % CI 0.84-0.96)), AIDS prior to inclusion (adjusted OR 3.61 (95 % CI 1.75-7.46)), ≥5 lifetime sexual partners (adjusted OR 2.20 (95 % CI 1.08-4.49)), sexual debut <16 years of age (adjusted OR 2.05 (95 % CI 1.03-4.10)) and CD4 < 350 cells/μL (adjusted OR 2.53 (95 % CI 1.20-5.40)). Cytological abnormalities were prevalent in 10.4 % vs. 5.2 % (p = 0.0003) of WLWH and WGP. In WLWH with hrHPV, short duration of HAART predicted cervical dysplasia (adjusted OR per year 0.83 (95 % CI 0.71-0.97)). CONCLUSIONS: WLWH presented with more cervical hrHPV infections and cytological abnormalities, and a different distribution of hrHPV genotypes compared with WGP. Cervical hrHPV and cytological abnormalities were predicted by short duration of HAART. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2881-1) contains supplementary material, which is available to authorized users

Antibody response following the third and fourth SARS-CoV-2 vaccine dose in individuals with common variable immunodeficiency

BackgroundThe antibody response after vaccination is impaired in common variable immunodeficiency (CVID).ObjectiveWe aimed to study the spike receptor-binding domain IgG antibody (anti-S-RBD) levels during a four-dose SARS-CoV-2 vaccination strategy and after monoclonal antibody (mAB) treatment in CVID. Moreover, we assessed the anti-S-RBD levels in immunoglobulin replacement therapy (IgRT) products.MethodsIn an observational study, we examined anti-S-RBD levels after the second, third, and fourth dose of mRNA SARS-CoV-2 vaccines. Moreover, we measured anti-S-RBD after treatment with mAB. Finally, anti-S-RBD was assessed in common IgRT products. Antibody non-responders (anti-S-RBD &lt; 7.1) were compared by McNemar’s test and anti-S-RBD levels were compared with paired and non-paired Wilcoxon signed rank tests as well as Kruskal–Wallis tests.ResultsAmong 33 individuals with CVID, anti-S-RBD levels increased after the third vaccine dose (165 BAU/ml [95% confidence interval: 85; 2280 BAU/ml], p = 0.006) and tended to increase after the fourth dose (193 BAU/ml, [−22; 569 BAU/ml], p = 0.080) compared to the previous dose. With increasing number of vaccinations, the proportion of patients who seroconverted (anti-S-RBD ≥ 7.1) increased non-significantly. mAB treatment resulted in a large increase in anti-S-RBD and a higher median level than gained after the fourth dose of vaccine (p = 0.009). IgRT products had varying concentrations of anti-S-RBD (p &lt; 0.001), but none of the products seemed to affect the overall antibody levels (p = 0.460).ConclusionMultiple SARS-CoV-2 vaccine doses in CVID seem to provide additional protection, as antibody levels increased after the third and fourth vaccine dose. However, anti-S-RBD levels from mAB outperform the levels mounted after vaccination.Clinical ImplicationsBoosting with SARS-CoV-2 vaccines seems to improve the antibody response in CVID patients.Capsule summaryThe third and possibly also the fourth dose of mRNA SARS-CoV-2 vaccine in CVID improve the antibody response as well as stimulate seroconversion in most non-responders

Determinants of long-term survival in late HIV presenters : The prospective PISCIS cohort study

Late HIV diagnosis (i.e CD4≤350 cells/µL) is associated with poorer outcomes. However, determinants of long-term mortality and factors influencing immune recovery within the first years after antiretroviral treatment (ART) initiation are poorly defined. From PISCIS cohort, we included all HIV-positive adults, two-year survivors after initiating ART between 2005-2019. The primary outcome was all-cause mortality according to the two-year CD4 count. We used Poisson regression. The secondary outcome was incomplete immune recovery (i.e., two-year CD4500 cells/µL, reference population). Overall, 113 patients (4·2%) died. Mortality was higher among LP with two-year CD4 count 200-500 cells/µL (aMRR 1·95[95%CI:1·06-3·61]) or 500 cells/µL, regardless of being initially LP or non-LP (aMRR 1·05[0·50-2·21]). Mortality rates within each two-year CD4 strata were not affected by the initial CD4 count at ART initiation (test-interaction, p = 0·48). The stronger factor influencing immune recovery was the CD4 count at ART initiation. First-line integrase-inhibitor-(INSTI)-based regimens were associated with reduced mortality compared to other regimens (aMRR 0·54[0·31-0·93]) and reduced risk of incomplete immune recovery in LP (aOR 0·70[0·52-0·95]). Two-year immune recovery is a good early predictor of long-term mortality in LP after surviving the first high-risk 2 years. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-LP. INSTI-based regimens were associated with higher rates of successful immune recovery and better survival compared to non-INSTI regimens. Southern-Denmark University, Danish AIDS-foundation, and Region of Southern Denmark