Acquired immune deficiency syndrome (AIDS) and late presentation in Poland - data from Test and Keep in Care (TAK) Polska project.

OBJECTIVES: Late presentation (LP) at HIV diagnosis is associated with worse prognosis and an increase in the number of new infections. We analyse the proportion of patients diagnosed late and factors related to LP in Poland in 2016-2017. METHODS: Data were obtained from 13 out of 17 HIV centres in Poland from 2016 and 2017, including date of diagnosis, age, sex, transmission route, anti-hepatitis C virus (anti-HCV), Venereal Diseases Research Laboratory (VDRL) antibodies, AIDS diagnosis, baseline HIV viral load and CD4 count. RESULTS: Out of 1522 patients, 88.9% were male with median age of 33.6 years. Men who have sex with men (MSM) comprised 69.4% of all new infections, heterosexual route of transmission (HTX) 18.2% and injecting drug use (IDU) 4.7%. Late presenters comprised 44.8% of the study group. Factors associated with LP were female sex [odds ratio (OR) = 1.5, 95% confidence interval (95% CI): 1.09-2.08], older age (OR = 1.59, 95% CI: 1.42-1.79 per decade), route of transmission (HTX: OR = 1.96, 95% CI: 1.50-2.56; IDU: OR = 3.17, 95% CI: 1.92-5.37), positive HCV results (OR = 1.90, 95% CI: 1.23-2.95) and syphilis diagnosis (OR = 2.06, 95% CI: 2.29-3.31). Adjusting for these factors, the only independent factors associated with LP were age (OR = 1.52, 95% CI: 1.35-1.71) and route of transmission (HTX: OR = 1.73, 95% CI: 1.23-2.44; IDU: OR = 2.24, 95% CI: 1.25-4.10). CONCLUSIONS: Late presentation in Poland follows European trends. A total of 44.8% of all newly diagnosed patients in Poland continue to present late or at the AIDS stage. Independent factors associated with LP/AIDS were older age, IDU and HTX. Patients from these groups should be targeted to improve early diagnosis and medical care.

Long-term trends in HIV care entry: over 15 years of clinical experience from Poland.

INTRODUCTION: Delay in HIV diagnosis and consequently late care entry with low CD4 counts remain a major challenge for the control of the HIV/AIDS epidemic. The aim of this study was to analyse the evolution of characteristics of the HIV epidemic in Poland. METHODS: Cross-sectional data were collected for 3972 HIV-infected patients followed up in 14 of 17 Polish HIV treatment centres in the years 2000-2015. Clinical data were analysed and factors associated with late presentation (baseline CD4 count < 350 cells/µL or history of AIDS-defining illness) and advanced HIV disease (baseline CD4 count < 200 cells/µL or history of AIDS) were identified. RESULTS: The majority (57.6%) of patients entered care late, while 35.6% presented with advanced HIV disease. The odds of being linked to care late or with advanced HIV disease increased consistently across age categories, increasing from 2.55 [95% confidence interval (CI) 1.46-4.47] for late presentation and 3.13 (95% CI 1.49-6.58) for advanced disease for the 21-30-year-old category to 5.2 (95% CI 1.94-14.04) and 8.15 (95% CI 2.88-23.01), respectively, for individuals > 60 years of age. Increased risks of late entry and advanced HIV disease were also observed for injecting drug users [adjusted odds ratio (aOR) 1.74 (95% CI 1.16-2.60) and 1.55 (95% CI 1.05-2.30), respectively], with lower aOR associated with the men who have sex with men transmission route [aOR 0.3 (95% CI 0.31-0.59) and 0.39 (95% CI 0.29-0.53), respectively]. The frequencies of cases in which patients were linked to care late and with advanced HIV disease decreased over time from 67.6% (2000) to 53.5% (2015) (P < 0.0001) and from 43.5% (2000) to 28.4% (2015) (P = 0.001), respectively. CONCLUSIONS: Despite improvements over time, most patients diagnosed with HIV infection entered care late, with a third presenting with advanced HIV disease. Late care entry remains common among people who inject drugs and heterosexual groups.

Hepatitis C virus (HCV) genotype 1 NS5A resistance-associated variants are associated with advanced liver fibrosis independently of HCV-transmission clusters.

OBJECTIVES: The aim of the study was to characterize the differences in the frequencies of NS3 and NS5A resistance-associated variants (RAVs) among Polish therapy-naive genotype 1 (G1) hepatitis C virus (HCV)-monoinfected and human immunodeficiency virus (HIV)/HCV-coinfected patients including clustering patterns and association of RAV frequency with liver fibrosis. METHODS: NS3/NS5A RAVs were identified by population sequencing in 387 directly acting antiviral treatment-naive G1-infected individuals (54 with genotype 1a (G1a) and 333 with genotype 1b (G1b)). Liver fibrosis was assessed based on histopathology or ultrasound elastography. Phylogenetic clusters were identified using maximum likelihood models. For statistics, chi-squared or two-sided Fisher's exact tests and multivariate logistic regression models were used, as appropriate. RESULTS: NS3 RAVs were found in 33.33% (18/54) for G1a and 2.62% (8/297) for G1b whereas NS5A variants were present in 5.55% (3/54) G1a and 9.31% (31/333) G1b sequences. Variations in NS5A 31 and 93 codon positions were found only in G1b (4.2% (14/333) for L31I/F/M and 5.39% (17/333) for Y93H). NS5A RAVs were more frequent among patients with advanced liver fibrosis (17.17% (17/99) for F3-F4 versus 6.94% (17/245) for F0-F2; p 0.004) or liver cirrhosis (20.34% (12/59) for F4 versus 7.72% (22/285) for F0-F3; p 0.003). Liver cirrhosis (F4) was associated with higher odds ratio of the NS5A RAVs among HCV-infected patients (odds ratio 2.34, 95% CI 1.004-5.291; p 0.049). NS5A RAVs were less frequent among sequences forming clusters and pairs (5.16% (8/155) versus 11.21% (26/232); p 0.039). CONCLUSIONS: Presence of NS5A RAVs correlated with progression of liver fibrosis and represents de novo selection of variants rather than transmission of drug resistance. Hence, the presence of NS5A RAVs may be a predictor for a long-lasting HCV infection.

The human immunodeficiency virus (HIV1) protease inhibitor sanquinavir activates autophagy and removes lipids deposited in lipid droplets.

Reduction in mortality and increased average life span of the human immunodeficiency virus (HIV)-infected patients treated with antiretroviral therapy (ART) are associated with the risk of unwanted effects, such as insulin resistance and dyslipidemia with cardiovascular complications. Antiretroviral therapy may also be associated with lipodystrophy characterized as peripheral lipoatrophy with central fat accumulation. Understanding the molecular mechanisms of lipodystrophy caused by ART is important for therapeutic strategy and the prediction of side-effects. Influence of protease inhibitor saquinavir (SQV) on preadipocyte differentiation was analyzed in in vitro human Chub-S7 cell line model. For measurement of the effects of SQV the drug was added to differentiated or non-differentiated cells. The influence of SQV on changes in the profile of gene expression was verified by microarray and changes in lipid species content were analyzed using GC-MS/MS. Results were confirmed by real-time PCR and analysis of autophagy. Addition of SQV to differentiated Chub-S7 cells lead to removal of lipids deposited in lipid droplets, down-regulation of expression of transcription factors and markers of adipocyte differentiation. Antiviral activity of SQV based on its non-selective inhibition of proteases resulted in proteasome inhibition, induction of endoplasmic reticulum stress and induction of macroautophagy. This activity was accompanied by an increase in PI, PEPL, PC lipid species especially with MUFA and PUFA. Additionally up-regulation of miR-100-3p, miR-222-5p, miR-483-5p were found, which correlated with obesity, insulin resistance, increasing insulin secretion and activation of lipolysis. Our results indicated that SQV, by inhibition of proteasome protein degradation, activated the unfolded protein response resulting in autophagic breakdown of lipids deposited in adipose tissue causing lipodystrophy.

The diagnostic value of cytokine and nitric oxide concentrations in cerebrospinal fluid for the differential diagnosis of meningitis.

PURPOSE: In several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF-α), interleukin-1ß (IL-1ß), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis. MATERIAL AND METHODS: Sixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1ß and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients. RESULTS: The results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis. CONCLUSIONS: The assessment of TNF-α, IL-1ß and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required.

[The role of cytokines in bacterial meningitis]. / Rola cytokin w bakteryjnym zapaleniu opon mózgowo-rdzeniowych.

Bacterial meningitis is the serious infection of the central nervous system (CNS), and stimulated by bacteria inflammatory host response has crucial role in its pathogenesis. The most important elements of this response are cytokines, especially tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10), which have antiinflammatory activity. Production of cytokines in the CNS triggers a cascade of inflammatory mediators. Better understanding of mechanisms which take place during the course of the bacterial meningitis can be useful in differential diagnosis, prognosis and treatment of this disease. Investigations on the role of cytokines in the bacterial meningitis, have great therapeutic implications, and can result in introduction to the treatment antiinflammatory drugs, which can help to reduce mortality rate and number of complications.

[Meningitis with acute respiratory distress syndrome in adults and jaundice--case report]. / Zapalenie opon mózgowo-rdzeniowych przebiegajace z zespolem ostrej niewydolnosci oddechowej u doroslych i zóltaczka--opis przypadku.

The case of leptospirosis with adult respiratory distress syndrome (ARDS) and severe jaundice in young abattoir worker has been presented. Institution of invasive therapeutic methods: continuous mandatory ventilation (CMV) with positive end-expiratory pressure (PEEP) and plasmapheresis, together with antibioticotherapy resulted in complete recovery. We discuss some characteristic features of the leptospirosis, which with the data from epidemiological history can lead to early diagnosis of this forgotten disease.

[Post-traumatic bacterial meningitis]. / Pourazowe ropne zapalenia opon mózgowordzeniowych.

10 patients with posttraumatic bacterial meningitis were treated in the Department of Infectious Diseases of the Jagielloniam University--Collegium Medicum during the period of 63 months. Traffic accidents were responsible for 80% of all cases of trauma. The most common place of injury was the base of anterior cranial fossa. Infecting agent was established in 8 cases. Gram-positive aerobic cocci (Streptococcus pneumoniae, Enterococcus faecalis, and Enterococcus spp.) were found in 4 patients, Gram-negative aerobic cocci (Neisseria meningitidis) in 2 patients, and Gram-negative aerobic rods (Acinetobacter baumanii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli) in 3 patients. Streptococcus pneumoniae was still highly sensitive to penicillin, ampicillin and cefotaxime. Enterococcus faecalis and Enterococcus spp. were sensitive to vancomycin and teicoplanin. Neisseria meningitidis was sensitive to penicillin, cefotaxime, amoxicillin/clavulonate. Gram negative aerobic rods were sensitive to third-generation cephalosporins, carbapenems and aminoglycosides. Among 10 patients treated for posttraumatic bacterial meningitis 1 patient died and in 1 preserved vegetative state was diagnosed. In 4 patients severe or moderate disabilities developed, however 4 recovered completely. 6 patients after regression of the CNS infection were qualified to neurosurgical intervention. In 3 patients reconstructive operation of the basis of anterior cranial fossa with tissue glue Beriplast P. was done, the recovery was complete. 3 patients didn't agree to surgical operation, and we don't know what has happened with them. They have not come to the control visit.

[Modifications in treatment of tetanus and prognosis--observations from the Cracow Department of Infectious Diseases]. / Zmiany w leczeniu tezca, a rokowanie--obserwacje krakowskiej Kliniki chorób Zakaznych.

The assessment of modifications in the tetanus treatment, which included using metronidazol and midazolam instead penicillin and diazepam, was presented. According to our own observations and previous investigations, mentioned above changes in the tetanus therapy improve survival rate, reduce psychiatric disturbances and shorten hospitalisation time.

[Remarks on injuries which were the source of tetanus and were based on observations from the Clinic of Infectious Diseases in Cracow]. / Uwagi o urazach bedacych przyczyna tezca na podstawie obserwacji Kliniki Chorób Zakaznych w Krakowie.

From 1992 to 1996, 95 patients with tetanus were treated in the Chair and Department of Infectious Diseases in Cracow. Most of them came from rural area, and at old age (median 68 years). Small, trivial skin injuries were the most often identified portal of entry. Only few patients applied to doctor after injury for prophylaxis against tetanus. The authors emphasise that small skin injuries, which may be portal of entry for tetanus, should not be left abandoned.

[Encephalitis as a severe complication of rubella--case report]. / Zapalenie mózgu ciezkim powiklaniem rózyczki--opis przypadku.

The case of severe encephalitis in the course of rubeola in young woman was presented. The self-limited increased level of aminotransferases and hyperglycaemia were reported during the course of disease. Any late complications of the encephalitis were observed and the patient was discharge from the hospital in good condition.