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Tomialoic R.,Centers for Disease Control and Prevention | Tomialoic R.,National Institute of Public HealthNational Institute of Hygiene | Stefanoff P.,National Institute of Public HealthNational Institute of Hygiene | Paradowska-Stankiewicz I.,National Institute of Public HealthNational Institute of Hygiene | And 2 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

Parapertussis leads to similar symptoms as pertussis, both being caused by bacteria from the genus Bordetella. Poland does not routinely diagnose nor conduct surveillance for parapertussis. We estimated parapertussis incidence and determined predictors of parapertussis diagnosis in the Polish population. Between July 2009 and April 2011, we conducted a prospective cohort study among patients attending 78 general practices. We included patients aged ≥3 years, with cough lasting >2 weeks, interviewed patients and collected a nasopharyngeal swab. We confirmed cases by real-time PCR. We estimated parapertussis incidence rates by dividing the number of cases by the summed person-time of observation in respective practices. We assessed predictors of PCR-confirmed parapertussis by comparing cases with patients testing negative. Using logistic regression, we calculated odds ratios (ORs) and 95 % confidence intervals (95%CI). We identified 78 cases among 1,231 patients meeting inclusion criteria. The incidence rate was 39/100,000 person-years (95%CI 31–49). The highest rates (140/100,000; 95%CI 74–239), were among children 3–5 years of age and the lowest (24/100,000; 95%CI 13–40) among persons aged 20–39 years of age. Boys aged 3–5 years (7.1; 2.1–25.3) and women aged >40 years (4.1; 1.4–11.7) or living in crowded households (4.3; 1.4–12.9) or contacting persons with prolonged cough (2.3; 1.1–4.5) were more likely to be diagnosed. Our results suggest that laboratory diagnosis could be prioritized for children in the preschool age and women aged over 40 who were referred to their GP with prolonged cough. In the absence of vaccine, post-exposure prophylaxis for close contacts of parapertussis cases could an adequate preventative measure. © 2014, Springer-Verlag Berlin Heidelberg.

Hernik A.,National Institute of Public HealthNational Institute of Hygiene | Strucinski P.,National Institute of Public HealthNational Institute of Hygiene | Buckley B.T.,Rutgers University | Goralczyk K.,National Institute of Public HealthNational Institute of Hygiene | And 7 more authors.
Human and Ecological Risk Assessment | Year: 2016

The long-term health threats posed to humans exposed to pollutants acting as endocrine disruptors (EDs) is yet to be quantified. There is insufficient knowledge about the sources and magnitude of exposure to selected polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) during the most sensitive period of fetal development, suggesting the need for a study. Organochlorine pesticides, classified as being persistent organic pollutants (POPs) and potential EDs, were also included in this analysis. Xenobiotics were measured in paired fetal cord blood and maternal breast milk samples. There were no significant differences in the concentrations of PCB-101, PBDE-47, and PBDE-99 between maternal milk and cord blood according to the Wilcoxon test, and the Spearman tests demonstrated significant correlations in β-HCH, γ-HCH, p,p'-DDE, and PCB-118 between maternal milk and cord blood from the same subjects. All others tested (HCB, β-HCH, γ-HCH, p,p'-DDE, p,p'-DDD, p,p'-DDT, PCB-101, PCB-138, PCB-153, PCB-170, PCB-180, PBDE-153) demonstrated significant differences in the same subject women with concentrations significantly higher in maternal milk than in cord blood. The presence of these compounds found in cord blood and maternal milk indicates that both are a source of perinatal exposure to these pollutants. This study opens up the opportunity for new research in estimating a prenatal exposure based on breast milk concentrations of organohalogen compounds. © 2016 Taylor & Francis Group, LLC

Borkowski P.K.,Medical University of Warsaw | Brydak-Godowska J.,Medical University of Warsaw | Basiak W.,Medical University of Warsaw | Switaj K.,Medical University of Warsaw | And 4 more authors.
PLoS Neglected Tropical Diseases | Year: 2016

Purpose: To assess the impact of intensive antifolate treatment, followed by secondary antifolate prophylaxis (A-SP) on the recurrence rate of toxoplasmic retinochoroiditis (TRC). To investigate whether there are any other factors potentially predisposing for recurrence. Material and Methods: A total of 637 medical records of TRC patients, who had been treated in the years 1994–2013 were reviewed. All patients were treated with pyrimethamine /sulfadoxine one 25mg/500mg tablet daily (P/S 25/500mg) for 21 days with a double loading dose for the first two days. From Day 2 the patients also received prednisone at a starting dose of 40mg and spiramycine 3 million IU three times daily, given for 10 days followed by azithromycin 500mg once daily for another 6 days. The analysis of the recurrence rate involved 352 patients who had completed 6-month secondary prophylaxis (P/S one 25 mg/500mg tablet twice a week). Results: When secondary antifolate prophylaxis (A-SP) was instituted immediately after the treatment for TRC, the probability of 3-year recurrence–free survival after the first course of A-SP was 90.9%. A recurrence was most likely approximately 3.5 years after the first treatment. A univariate Cox regression model demonstrated that a risk for recurrence was 2.82 times higher (p = 0.02) in patients with retinal scars. In the multivariate analysis, the risk for recurrence was 2.41 higher (p = 0.06). In patients with haemorrhagic lesions the risk for recurrence was lower, aRR = 0.17 (approaching borderline statistical significance p = 0.08). Conclusions: With the institution of A-SP of immediately after the intensive treatment for TRC, i.e. when a reactivation was most likely, there was no recurrence during A-SP. Following A-SP the recurrence rates were low and recurrence-free periods tended to be longer. The treatment regimen employed had a beneficial effect on the recurrence interval as it reduced and delayed the highest probability of recurrence. © 2016 Borkowski et al.

Kuryk L.,Targovax | Kuryk L.,University of Helsinki | Kuryk L.,National Institute of Public HealthNational Institute of Hygiene | Haavisto E.,Targovax | And 7 more authors.
International Journal of Cancer | Year: 2016

Malignant mesothelioma (MM) is a rare cancer type caused mainly by asbestos exposure. The median overall survival time of a mesothelioma cancer patient is less than 1-year from diagnosis. Currently there are no curative treatment modalities for malignant mesothelioma, however treatments such as surgery, chemotherapy and radiotherapy can help to improve patient prognosis and increase life expectancy. Pemetrexed-Cisplatin is the only standard of care (SoC) chemotherapy for malignant mesothelioma, but the median PFS/OS (progression-free survival/overall survival) from the initiation of treatment is only up to 12 months. Therefore, new treatment strategies against malignant mesothelioma are in high demand. ONCOS-102 is a dual targeting, chimeric oncolytic adenovirus, coding for human GM-CSF. The safety and immune activating properties of ONCOS-102 have already been assessed in phase 1 study (NCT01598129). In this preclinical study, we evaluated the antineoplastic activity of combination treatment with SoC chemotherapy (Pemetrexed, Cisplatin, Carboplatin) and ONCOS-102 in xenograft BALB/c model of human malignant mesothelioma. We demonstrated that ONCOS-102 is able to induce immunogenic cell death of human mesothelioma cell lines in vitro and showed anti-tumor activity in the treatment of refractory H226 malignant pleural mesothelioma (MPM) xenograft model. While chemotherapy alone showed no anti-tumor activity in the mesothelioma mouse model, ONCOS-102 was able to slow down tumor growth. Interestingly, a synergistic anti-tumor effect was seen when ONCOS-102 was combined with chemotherapy regimens. These findings give a rationale for the clinical testing of ONCOS-102 in combination with first-line chemotherapy in patients suffering from malignant mesothelioma. © 2016 UICC

Ziemska J.,National Institute of Public HealthNational Institute of Hygiene | Guspiel A.,National Institute of Public HealthNational Institute of Hygiene | Jarosz J.,Polish Academy of Sciences | Nasulewicz-Goldeman A.,Polish Academy of Sciences | And 5 more authors.
Bioorganic and Medicinal Chemistry | Year: 2016

We report a study of a series of isoquinoline derivatives, including their synthesis, in vitro microsomal leucine aminopeptidase (LAP) inhibition and antiproliferative activity on cancer cell lines. Among fourteen tested compounds, one (compound 3b) was determined to have good activity against LAP and significant antiproliferative activity against HL-60 human promyelocytic leukemia, Burkitt's lymphoma Raji, camptothecin resistant CEM/C2 leukemia cells with mutated catalytic site of topoisomerase I, its parental cell line CCRF/CEM and LoVo colon cancer. Its influence on the cell cycle was also observed. Moreover, we have confirmed that antiproliferative activity towards cancer cells is due to LAP inhibition. Docking simulation based on positioning compound 3b into the LAP active site was performed to explore the possible binding mode. The compound was able to form hydrogen bonds with Gly362 and coordinate zinc ions, which was previously suggested to be essential for inhibitory activity. Compound 3b was also characterized with a good selectivity index for cancer versus normal mammalian cells. Toxicological studies involving examination of skin sensitization, acute skin irritation/corrosion, acute dermal toxicity, acute oral toxicity and acute eye irritation/corrosion established that compound 3b is safe for use. © 2016

Strucinski P.,National Institute of Public HealthNational Institute of Hygiene | Morzycka B.,Voivodship SanitaryEpidemiological Station | Goralczyk K.,National Institute of Public HealthNational Institute of Hygiene | Hernik A.,National Institute of Public HealthNational Institute of Hygiene | And 7 more authors.
Human and Ecological Risk Assessment | Year: 2015

ABSTRACT: The aim of this study was to characterize short- and long-term risk for consumers associated with dietary intake of pesticide residues in fruits, vegetables, and other foodstuffs available on the Polish market based on 2010–2013 official surveillance results. Among 779 samples collected from 2010 to 2013 no pesticide residue was found in 39.7% samples while 58.5% contained residues at or below the EU Maximum Residue Levels (MRLs). Non-compliances (residues above the respective MRLs) were found in 14 samples (1.8%). Most of the estimated daily intakes were well below 1% of respective acceptable daily intake (ADI) values. The highest intake for children and adults was about 7% and 1.5% of ADI, respectively. For non-compliant results acute risk was characterized. Predicted short-term intakes for children and adults ranged from 0.7% to 425%, and from 0.2% to 100% of respective acute reference dose, respectively. Results of chronic risk characterization show that consumers in Poland are adequately protected; however, incidental cases where residue levels may potentially pose a threat to consumers’ health due to acute exposure cannot be excluded. © 2015, Copyright © Taylor & Francis Group, LLC.

Staniszewska M.,National Institute of Public HealthNational Institute of Hygiene | Bondaryk M.,National Institute of Public HealthNational Institute of Hygiene | Zukowski K.,Warsaw University of Technology | Chudy M.,Warsaw University of Technology
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2015

The production of hydrolytic enzymes is considered a key virulence determinant of Candida albicans. Aminopeptidase 2 (Ape2) facilitates the penetration of C. albicans into the host tissue, by providing free amino acids to support fungal growth and proliferation. The objective of this study was to estimate the APE2 expression profile in C. albicans cells during invasion of the human epithelium. Sixty-one clinical fungal isolates and five reference strains were included in this study. The wild-type APE2 sequence was analyzed by polymerase chain reaction (PCR) amplification using genomic DNA from pathogenic isolates. Amplicons were verified in 1 % agarose gel and visualized by illumination with ultraviolet (UV) light. The APE2 expression levels were analyzed with reverse transcription quantitative real-time PCR (RT-qPCR) and APE2 quantification was normalized against the reference gene in C. albicans cells grown in YEPD and during Caco-2 invasion. The APE2-specific PCR product band was found in all C. albicans and C. dubliniensis strains, but not in other common pathogenic fungi. APE2 transcript abundance was elevated in the clinical isolates growing on the Caco-2 cell line in comparison to their counterparts grown in YEPD. Our data indicate a potential role for Ape2 in the invasion of epithelial cells. APE2 expression is also strain-specific, and it is not related to isolation site or disease entity. © 2015, Springer-Verlag Berlin Heidelberg.

Mosiej E.,National Institute of Public HealthNational Institute of Hygiene | Zawadka M.,National Institute of Public HealthNational Institute of Hygiene | Krysztopa-Grzybowska K.,National Institute of Public HealthNational Institute of Hygiene | Polak M.,National Institute of Public HealthNational Institute of Hygiene | And 3 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014

This study aimed to characterise Bordetella pertussis isolates circulating in Poland since 1959. Sequence analysis of ptxA, ptxC, prn, tcfA, fim2, fim3 and ptxP for 175 clinical isolates and currently and previously used vaccine strains was performed. Clinical isolates from the period 1995–2013 were found to be different to three currently used vaccine strains harbouring the allelic combination ptxA2–ptxC1–ptxP1–prn1–tcfA2–fim2-1–fim3-1, seen frequently in Poland in the early pertussis vaccination period but not found after 1995. Generally, among B. pertussis isolates from the period 2000–2013, two genotypes predominated, ptxA1–ptxC1–ptxP1–prn1–tcfA2–fim2-2–fim3-1 and ptxA1–ptxC1–ptxP1–prn2–tcfA2–fim2-1–fim3-1, with frequencies of 45 % and 32.5 %, respectively. The isolates harbouring ptxA1–ptxC2–ptxP3–prn2–tcfA2–fim2-1–fim3-2 and ptxA1–ptxC2–ptxP3–prn2–tcfA2–fim2-1–fim3-1 profiles, currently highly prevalent within other European Union (EU) countries, were rarely found in Poland, as they circulated in the period 2000–2013 with frequencies of 10 % and 5 %, respectively. We hypothesise that several previous changes of strain composition in whole-cell pertussis vaccine produced locally and used since 1960 in Poland resulted in a more diverse immune pressure in the population, resulting in different prevalence of alleles compared to elsewhere. © 2014, Springer-Verlag Berlin Heidelberg.

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