The German National Registry of Primary Immunodeficiencies (2012-2017)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment

Bacteremia Caused by a Novel Helicobacter Species in a 28-Year-Old Man with X-Linked Agammaglobulinemia ▿

We report on a case of bacteremia caused by a previously unknown urease-negative Helicobacter strain, IMMIB HP-28/08, isolated from blood cultures of a 28-year-old man with X-linked agammaglobulinemia. The identification of the isolate was based on 16S rRNA gene sequencing. In the phylogenetic tree, the isolate fell into a cluster which included Helicobacter canadensis, Helicobacter equorum, and Helicobacter pullorum. This is the first report of bacteremia caused by this fastidious organism. Further investigations are necessary to determine the potential role of this species as a pathogen of bloodstream infections

In vitro activity of mecillinam and nitroxoline against Neisseria gonorrhoeae - re-purposing old antibiotics in the multi-drug resistance era

In 2018, the European Centre for Disease Prevention and Control reported the first cases of extensively drug-resistant Neisseria gonorrhoeae infections in Europe. Seeking new options for antimicrobial therapy we investigated the susceptibility of N. gonorrhoeae to nitroxoline (NIT) and mecillinam (MCM), both of which are currently only indicated to treat uncomplicated urinary tract infections. Clinical N. gonorrhoeae isolates with non-susceptibility to penicillin from two German medical centres were included (n = 27). Most isolates were also non-susceptible to a range of other anti-gonococcal antimicrobials (cefotaxime, ciprofloxacin, azithromycin, tetracycline). All isolates were further characterized by multi-locus sequence typing. MICs of penicillin and cefotaxime were determined by agar gradient diffusion. Production of penicillinase was tested by cefinase disk test. Susceptibility of MCM was investigated by agar dilution, NIT by agar dilution and disk diffusion. Penicillin MICs ranged from 0.125 to 64 mg l(-1) and MICs of cefotaxime ranged from 128 mg l(-1) whereas MICs of NIT ranged from 0.125 to 2 mg l(-1). NIT disk diffusion (median zone diameter 32 mm) correlated well with results from agar dilution. We demonstrated excellent in vitro activity of NIT against clinical N. gonorrhoeae isolates with non-susceptibility to standard anti-gonococcal antibiotics. MCM activity was unsatisfactory. Correlation of agar dilution and disk diffusion in NIT susceptibility testing is an important aspect with potential clinical implications

Implementation of EACS vaccination recommendations among people living with HIV

Objectives With modern combination antiretroviral Treatment (cART) a normal life expectancy among people living with HIV (PLWH) has become reality if started early enough prior to the onset of more pronounced immunodeficiency. Therefore, prevention measures against other infectious diseases among this vulnerable group have gained increased attention. Indeed, the EACS guidelines recommend vaccinations against HAV, HBV, HPV, Influenza, Neisseria meningitidis, Streptococcus pneumoniae and VZV in HIV-infected adults. Methods All PLWH under cART attending our ID outpatient clinic between April to June 2018, were assessed during consultation for vaccination status regarding pneumococcus, Hepatitis A and B, influenza, varicella, meningococcus and HPV using a pre-defined questionnaire, vaccination certificates and medical records. In addition, the cohort database was screened for Hepatitis A and B serology and HIV surrogate markers. Results A total of 305 PLWH (82.3% male, 17.7% female) was included, median age was 48 years (IQR 47-51). Median CD4 + T cell count was 543 (IQR 304-770), and for 297 (97.4%) PLWH CD4 + T cell count was >= 200/ul. The viral load was undetectable (< 40 copies/ml) in 289 (94.8%) cases. Highest vaccination rates were observed for HAV (87.4%), Streptococcus pneumoniae (77.4%) and Influenza (76.5%). 64.3% PLWH got vaccinated against HBV, whereas VZV vaccination only played a minor role, in the context of the high rate of cleared infections (99.0%). Lowest vaccination rates were detected for HPV (0%) and Neisseria meningitidis (3.0%). Conclusions Our data suggest that vaccination rates among PLWH are higher compared to the general German population. Implementation of EACS guidelines into daily routine though is not fully executed and the need for improving vaccination rates has to be emphasized. Centrally organized vaccination registers as well as electronic medical records could be helpful tools to detect a lack of vaccination coverage and send digital vaccination reminders particularly among risk groups

Moderate endurance training (marathon-training) – effects on immunologic and metabolic parameters in HIV-infected patients: the 42 KM cologne project

Abstract Background Improved treatment options of HIV have resulted in regular physical activities of many HIV-infected patients. However, data on effects of sports in HIV-patients are scarce. Methods 21 HIV-infected persons were monitored prospectively while preparing for a marathon run. Multiple parameters with regard to immunology, quality of life and metabolism were measured at 4 time points (at baseline 1 year before the marathon run, 3 and 6 months after beginning of training, and immediately before marathon). Results 13 out of 21 participants completed the marathon (12 male, 1 female; median age 42 years [27–50]; CD4 = 620/μl [146–1268]; 11 were on ART since 3.5 years [1–7]). 8 participants ceased training early. All reasons for stopping (besides one pre-existing metatarsal fracture) were not regarded as training-related (e.g. time limitation n = 3; newly diagnosed anal cancer n = 1; personal reasons/unknown n = 3). We observed a significant increase in absolute CD4-T-cells (620/μl [146–1268] vs. 745 [207–1647]; p = 0.001) with simultaneous decrease of CD4-T-cell apoptosis (53% [47–64] vs. 32% [14–42]); p < 0.01). No effects on viral load independent of ART occurred. Systolic blood pressure and cholesterol improved significantly, although moderate and normal at baseline (cholesterol 185 mg/dl [98–250] vs. 167 [106–222], p = 0.02; RRsys 125 mmHg [100–145] vs. 120 [100–140], p = 0.01). Blood count, liver enzymes, creatinine and CK remained unchanged. Conclusions The results of this pilot study indicated improved metabolic and immunologic parameters in HIV-infected patients undergoing moderate endurance training. Although training effects or ART cannot be ultimately separated as underlying mechanisms, we conclude that marathon training is safe for HIV-infected patients and potentially improves general health. Trial registration DRKS00011592 (retrospectively registered on February 9th 2017)

Survival and HLA-B*57 in HIV/HCV Co-Infected Patients on Highly Active Antiretroviral Therapy (HAART).

HLA class I alleles, in particular HLA-B*57, constitute the most consistent host factor determining outcomes in untreated HCV- and HIV-infection. In this prospective cohort study, we analysed the impact of HLA class I alleles on all-cause mortality in patients with HIV-, HCV- and HIV/HCV- co-infection receiving HAART.In 2003 HLA-A and B alleles were determined and patients were prospectively followed in 3-month intervals until 2013 or death. HLA-A and B alleles were determined by strand-specific oligonucleotide hybridisation and PCR in 468 Caucasian patients with HCV- (n=120), HIV- (n=186) and HIV/HCV-infection (n=162). All patients with HIV-infection were on HAART. In each patient group, HLA class I-associated survival was analysed by Kaplan-Meier method and Cox regression analysis.At recruitment the proportion of patients carrying a HLA-B*57 allele differed between HIV- (12.9%) and HCV-infection (4.2%). Kaplan Meier analysis revealed significantly increased mortality in HLA-B*57-positive patients with HIV-infection (p=0.032) and HIV/HCV-co-infection (p=0.004), which was apparently linked to non-viral infections. Cox logistic regression analysis confirmed HLA-B*57 (p=0.001), serum gamma-glutamyltranspeptidase (p=0.003), serum bilirubin (p=0.022) and CD4 counts (p=0.041) as independent predictors of death in HIV-infected patients.Differences in the prevalence of HLA-B*57 at study entry between HIV- and HCV- infected patients may reflect immune selection in the absence of antiviral therapy. When patients were treated with HAART, however, HLA-B*57 was associated with increased mortality and risk to die from bacterial infections and sepsis, suggesting an ambiguous role of HLA-B*57 for survival in HIV/HCV infection depending on the circumstances

HPV-associated anal lesions in HIV+ patients: long-term results regarding quality of life

Purpose!#!HIV infection and concomitant HPV-associated anal lesions may significantly impact on patients' quality of life (QoL), as they are predicted to have negative effects on health, psyche, and sexuality.!##!Material and methods!#!Fifty-two HIV+ patients with HPV-associated anal lesions were enrolled in a survey approach after undergoing routine proctologic assessment and therapy for HPV-associated anal lesions if indicated over a time span of 11 years (11/2004-11/2015). Therapy consisted of surgical ablation and topic treatment. QoL was analyzed using the SF-36 and the CECA questionnaires.!##!Results!#!Fifty-two of 67 patients (77.6%) were successfully contacted and 29/52 provided full information. The mean age was 43.8 ± 12.8 years. The median follow-up from treatment to answering of the questionnaire was 34 months. Twenty-one percent (6/29) of the patients reported suffering from recurrence of condyloma acuminata, three patients from anal dysplasia (10.3%). In the SF-36, HIV+ patients did not rate their QoL as significantly different over all items after successful treatment of HPV-associated anal lesions. In the CECA questionnaire, patients with persisting HPV-associated anal lesions reported significantly higher emotional stress levels and disturbance of everyday life compared to patients who had successful treatment (71.9/100 ± 18.7 vs. 40.00/100 ± 27.4, p = 0.004). Importantly, the sexuality of patients with anal lesions was significantly impaired (59.8/100 ± 30.8 vs. 27.5/100 ± 12.2, p = 0.032).!##!Conclusion!#!HPV-associated anal lesions impact significantly negative on QoL in HIV+ patients. Successful treatment of HPV-associated anal lesions in HIV+ patients improved QoL. Specific questionnaires, such as CECA, seem to be more adequate than the SF-36 in this setting

Exposure to previous cART is associated with significant liver fibrosis and cirrhosis in human immunodeficiency virus-infected patients - Fig 1

<p>Correlation between TE and APRI score (A) and FIB4 score (B). Panel C depicts the prevalence of fibrosis and cirrhosis stratified by the different cART regimes. The TE levels in patients with and without history of ddI (D) and AZT (E).</p