Anna Grzeszczuk

Feasibility and Effectiveness of Indicator Condition-Guided Testing for HIV: Results from HIDES I (HIV Indicator Diseases across Europe Study)

Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009– February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42–2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.

Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients

Background:Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined. Methods:Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft–Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m2 or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m2 or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m2 or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression. Results:Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8–113.0) ml/min per 1.73 m2. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5–14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype. Conclusion:Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.

Serological and Molecular Evidence of Human Granulocytic Ehrlichiosis Focus in the Białowieża Primeval Forest (Puszcza Białowieska), Northeastern Poland

Abstract.Human granulocytic ehrlichiosis (HGE) is an emerging tickborne zoonosis. First described in the USA, it is being increasingly reported from several European countries. This study was undertaken to provide serological and molecular evidence of the occurrence of the HGE focus in the Białowieża Primeval Forest, located in northeastern Poland. To this end, the seroprevalence of HGE in this area, where Lyme borreliosis and tickborne encephalitis are highly endemic, was determined by means of an indirect immunofluorescence antibody assay. In addition, the frequency of granulocytic Ehrlichia spp. infection in Ixodes ricinus ticks from the same area was estimated using a polymerase chain reaction method with EHR 521 and EHR 747 primers, which amplified a fragment of 16S rDNA. The rate of seropositivity for HGE was 6.2% (8/130 subjects). Individuals seropositive for Lyme borreliosis were more likely to have anti-HGE antibodies than seronegative ones (P<0.05; OR=6.34, 95%CI=1.12–36.98). There was no association between self-reported frequency of tick bites or forestry employment and HGE seropositivity. Sixty of 376 (16%) Ixodes ricinus ticks tested were positive for the Ehrlichia phagocytophila genogroup by polymerase chain reaction. Ehrlichial DNA was present in 59 of 302 (19.5%) adult ticks and in 1 of 74 nymphs (1.4%). There was a significantly higher infection rate among female ticks (32.9%; 49/149) than among male ticks (6.5%; 10/153) (P<0.05). Dual infection with Ehrlichia spp. and Borrelia burgdorferi sensu lato was detected in 10 samples that were positive for ehrlichiae. The results obtained confirm the perpetuation of the HGE agent in the primeval forest ecosystem of northeastern Poland.

The current perspective on tick-borne encephalitis awareness and prevention in six Central and Eastern European countries: Report from a meeting of experts convened to discuss TBE in their region

Tick-borne encephalitis (TBE) is a potentially life-threatening disease in humans and is caused by a flavivirus spread by infected ticks (Ixodes ricinus and Ixodes persulcatus). TBE is endemic across much of Central and Eastern Europe and the incidence is increasing, with numbers estimated to be as many as 8755 cases per year. The reasons for this increase are multi-faceted and may involve improvements in diagnosis and reporting of TBE cases, increases in recreational activities in areas inhabited by infected ticks and changes in climatic conditions affecting tick habitats. Vaccination is the most effective method of preventing TBE; following a successful nationwide vaccination campaign in Austria, the annual number of TBE cases fell to about 10% of those reported in the pre-vaccination era. This report describes the findings of a group of leading experts from six Central and Eastern European countries who convened to discuss TBE in their region during the 28th Annual Meeting of the European Society for Paediatric Infectious Diseases (ESPID) Nice, France, 4-8 May 2010.

Human Alveolar Echinococcosis in Poland: 1990–2011

Background Alveolar echinococcosis (AE) caused by Echinococcus multilocularis infections is a dangerous old disease in the Northern Hemisphere. The aim of the paper was to collect and analyze data on human AE in Poland in the last two decades. Methodology/Principal Findings The sources of data were both the cases officially registered and detected by an active field and laboratory surveillance. The cases were verified by clinical, epidemiological, and laboratory criteria. Altogether 121 human cases of AE were detected. Among these 83 (68,6%) cases were classified as confirmed, 16 as probable and 22 as possible. During the two decades a continuous increase in detection rate was noticed. The cases were 6–82 years old at the time of diagnosis (mean - 47.7 years). Sex ratio M/F was 0.86/1.0. The AE was fatal in 23 (19%) patients (mean age at death - 54.1 years). Family agglomeration of AE was found in 4 foci, involving 9 patients. Seventy six of the cases were diagnosed in an advanced stage of disease. In all cases the liver was the primary location of AE. In 30 (24.8%) patients a spread to other organs was observed. Ninety four of the patients were treated with albendazole. In 73 (60%) patients a surgical operation was performed, including 15 liver transplantations. Conclusions/Significance The studies confirmed that AE is an emerging disease in Poland, which is the fourth country in Europe with over 120 cases detected. The results also indicate the need of a wider national programme for implementation of screening in the highest AE risk areas (north-eastern Poland) with an effort to increase the public awareness of the possibility of contracting E. multilocularis, and above all, training of the primary care physicians in the recognition of the risk of AE to allow for an early detection of this dangerous disease.

Auditing HIV Testing Rates across Europe: Results from the HIDES 2 Study.

European guidelines recommend the routine offer of an HIV test in patients with a number of AIDS-defining and non-AIDS conditions believed to share an association with HIV; so called indicator conditions (IC). Adherence with this guidance across Europe is not known. We audited HIV testing behaviour in patients accessing care for a number of ICs. Participating centres reviewed the case notes of either 100 patients or of all consecutive patients in one year, presenting for each of the following ICs: tuberculosis, non-Hodgkins lymphoma, anal and cervical cancer, hepatitis B and C and oesophageal candidiasis. Observed HIV-positive rates were applied by region and IC to estimate the number of HIV diagnoses potentially missed. Outcomes examined were: HIV test rate (% of total patients with IC), HIV test accepted (% of tests performed/% of tests offered) and new HIV diagnosis rate (%). There were 49 audits from 23 centres, representing 7037 patients. The median test rate across audits was 72% (IQR 32–97), lowest in Northern Europe (median 44%, IQR 22–68%) and highest in Eastern Europe (median 99%, IQR 86–100). Uptake of testing was close to 100% in all regions. The median HIV+ rate was 0.9% (IQR 0.0–4.9), with 29 audits (60.4%) having an HIV+ rate >0.1%. After adjustment, there were no differences between regions of Europe in the proportion with >0.1% testing positive (global p = 0.14). A total of 113 patients tested HIV+. Applying the observed rates of testing HIV+ within individual ICs and regions to all persons presenting with an IC suggested that 105 diagnoses were potentially missed. Testing rates in well-established HIV ICs remained low across Europe, despite high prevalence rates, reflecting missed opportunities for earlier HIV diagnosis and care. Significant numbers may have had an opportunity for HIV diagnosis if all persons included in IC audits had been tested.

Prevalence of antibodies against tick-borne encephalitis among residents of north-eastern Poland.

In 37 out of 613 (6%) residents of north eastern Poland, IgG antibodies to tick-borne encephalitis virus (TBEV) were detected at levels exceeding the diagnostic value of 60 VIEU/ml. The prevalence of the antibodies was not related to sex or place or residence. However, significantly higher antibody levels were found in the group of forest workers than in individuals not professionally connected with forestry.

The impact of interleukin 28B rs12979860 single nucleotide polymorphism and liver fibrosis stage on response-guided therapy in HIV/HCV-coinfected patients.

Objective:According to the European AIDS Clinical Society (EACS) guidelines for response-guided therapy (RGT) of chronic hepatitis C virus (HCV) infection in HIV-positive patients, HCV-genotype (GT) and rapid virologic response (RVR) exclusively determine the duration of antiviral therapy with pegylated interferon and ribavirin (PEGIFN+RBV). The aim of this study was to investigate the impact of interleukin 28B rs12979860 single nucleotide polymorphism (IL28B) and liver fibrosis stage on RGT in HIV/HCV-coinfected patients. Design:Four hundred and thirty HIV/HCV-coinfected patients treated with PEGIFN+RBV were included in this multinational, retrospective analysis. Methods:Advanced liver fibrosis was defined as either METAVIR F3/F4 or liver stiffness more than 9.5 kPa. Results:In patients with GT1/4 without RVR (GT1/4-noRVR), higher sustained virologic response (SVR) rates were observed in patients with extended treatment duration (48 weeks: 35% vs. 72 weeks: 60%; P = 0.008). In GT1/4-noRVR patients without advanced liver fibrosis (48 weeks: 45% vs. 72 weeks: 61%; P = 0.176), or with IL28B C/C (48 weeks: 48% vs. 72 weeks: 69%; P = 0.207), SVR rates did not vary significantly throughout the treatment duration subgroups. In contrast, in patients with advanced liver fibrosis (48 weeks: 11% vs. 72 weeks: 45%; P = 0.031), or IL28B non-C/C (48 weeks: 28% vs. 72 weeks: 56%; P = 0.011), extended treatment duration was associated with substantially higher SVR rates. GT2/3 patients with RVR (GT2/3-RVR) with shortened treatment duration (24 weeks) displayed SVR rates ranging from 83 to 100%, regardless of IL28B and liver fibrosis stage. Conclusion:Our study confirms the concept of RGT in HIV/HCV coinfection and supports the extension of therapy duration to 72 weeks for patients with GT1/4-noRVR, especially in patients with IL28B non-C/C or advanced liver fibrosis. The results of our study strongly support the shortening of therapy duration to 24 weeks in GT2/3-RVR patients, regardless of IL28B and advanced liver fibrosis.

Highly Variable Year-to-Year Prevalence of Anaplasma phagocytophilum in Ixodes ricinus Ticks in Northeastern Poland: A 4-Year Follow-up

Abstract:  Anaplasma phagocytophilum is transmitted mainly by Ixodes ricinus ticks in Europe. We followed‐up A. phagocytophilum infection rate in I. ricinus in three selected collection sites in northeastern Poland during a four‐year period. Overall infection rate was 14.1% (208/1474) with highest infection rate among females (36.8% verses males 8.2% and nymphs 0.9%). We noted a very big year‐to‐year variation of infection prevalence in each collection cite every year reflecting changeable granulocytic anaplasmosis risk for humans and animals.

Hepatitis B virus vaccine for patients with hepatitis C virus infection.

SummaryHepatitis C is a disease with varying rates of progression. The role of hepatitis B virus (HBV) as a cofactor in the development of hepatitis C virus (HCV)-related cirrhosis and hepatocellular carcinoma (HCC) has been suggested and the use of HBV vaccine in all HCV-infected patients has been advocated. This review presents the implications of HBV and HCV coinfection and addresses the issues of HBV vaccine immunogenicity and safety in patients with chronic HCV infection.