Increasing hepatitis B vaccination coverage and decreasing hepatitis B co-infection prevalence among people with HIV-1 in Germany, 1996-2019. Results from a cohort study primarily in men who have sex with men.

OBJECTIVES: Viral hepatitis co-infection among people living with HIV is known to accelerate the progression of liver disease and AIDS. An increased prevalence and incidence of hepatitis B virus (HBV) infection among people living with HIV demands continuous monitoring to adapt targeted prevention strategies to reach the global goals of eliminating viral hepatitis as a public health threat. METHODS: We determined the prevalence and incidence of HBV for the years 1996-2019 from yearly blood sample testing and questionnaire reports among people living with HIV belonging to a nationwide, multicentre observational, prospective cohort study. RESULTS: Among this study population of 3479 participants, the majority (87%) indicated that being men who have sex with men (MSM) was their likely HIV transmission route; 51% were recruited from Berlin. HBV prevalence for acute/chronic and resolved infections decreased from 4.1% and 45% in 1996-1999 to 1.3% and 16% in 2019, respectively. Simultaneously, participants with a serological status indicating HBV vaccination increased from 25% in 1996-1999 to 69% in 2019. Among vaccinated participants with relevant information (n = 1135), 38% received their first HBV vaccination after HIV infection. The HBV incidence rate in 565 eligible participants decreased from 6.9/100 person-years in 2004-2007 to 0.45/100 person-years in 2015. CONCLUSION: Increasing vaccination coverage because of a general HBV vaccination recommendation and catch-up vaccination efforts among risk groups decreased HBV infection prevalence over time among this study population of people living with HIV, primarily MSM and from Berlin. Despite this success, the prevalence and incidence of HBV remains higher than in the general population in Germany. This emphasizes the need for continued HBV prevention by promoting HBV vaccination and HBV screening at regular intervals based on the individual risk behaviour.

HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: Results from a prospective observational study in Germany.

Aims: Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. Methods: The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). Results: During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the 2nd quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in 1st quarter of 2020, to 7 partners in 4th quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. Conclusion: The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis.

Occurrence of enzymes of free radical metabolism suggests the possible cytotoxic capacity of the transitional epithelium of the human ureter.

Three enzymes, viz., tartrate-resistant acid phosphatase (TRAP), nitric oxide synthase I (NOS-I), and superoxide dismutase (SOD), involved in the production and metabolism of free radicals or radical equivalents, were demonstrated by immunocytochemistry in the urothelium of the ureters of six patients of various ages. Two of these enzymes (TRAP and NOS-I) were colocalized in the most apical and lateral border of the superficial cells of the urothelium. In contrast, SOD showed a patchy or granular distribution within the supranuclear region of these cells. Intra- and subepithelial macrophages exhibited a weak TRAP, but no NOS-I or SOD, immune reaction. On the basis of the immunocytochemical findings, arguments in favor of a cytotoxic function of the superficial cells of the human urothelium are presented.

Purple acid phosphatase from bovine spleen. Interactions at the active site in relation to the reaction mechanism.

Oxidation of the reduced (pink) phosphate-free bovine spleen acid phosphatase with 1.5 mol H2O2 or sodium peroxodisulfate/mol, in the presence of Mes or Bistris pH 5, leads to a species with an absorption maximum at 558 nm. Addition of acetate or oxidation in the presence of acetate buffer engenders a species with a maximum at 550 nm. Addition of phosphate to both species shifts the maximum immediately to 540 nm; this is the species also found after preparation from the spleen. The assumption that these species represent strongly bidentate-binding hydroxo, acetato and phosphato complexes of the Fe(III)-Fe(III) system is supported by replacement reactions with other ligating oxoanions followed by their typical spectral shifts. These oxoanion complexes cannot be dissociated by gel filtration; this is possible only after reduction to the Fe(II)-Fe(III) system. The oxidized species without EPR signals below g values of 2 still reveals 5% activity which cannot be reduced to zero even in the presence of higher concentrations of peroxodisulfate. The pH optimum of the reaction with alpha-naphthyl phosphate shifts from 5.9 to 5.3 in the oxidized species. The apparent pK values around 4.5 as derived from the pH dependence of activity, of the EPR spectra, and the spectral shifts of the phosphate-saturated reduced and oxidized species are assigned to an aquo/hydroxo equilibrium at the Fe(III) or an equilibrium, where the phosphato ligand is replaced by a hydroxo ligand. A reaction mechanism is proposed in which a hydroxo ligand at the chromophoric Fe(III) attacks the phosphoric acid ester group only when that is monoprotonated and pre-oriented by electrostatic interaction with the nonchromophoric metal ion. Binding and inhibition studies with the oxoanions indicate that they compete with the catalytically active hydroxo group of the reduced and oxidized enzyme with nearly the same inhibition constants. Catalysis is not affected by the oxoanions which replace the additional mu-hydroxo ligand in the 558-nm-absorbing Fe(III)-Fe(III) species. In contrast to hemerythrin and ribonucleotide reductase, a binuclear iron center is proposed for the purple acid phosphatase, which is bridged by a carboxylato and two aquo/hydroxo groups, but without a mu-oxo bridge.

Tartrate-resistant, purple acid phosphatase in Gaucher cells of the spleen. Immuno- and cytochemical analysis.

Bioptic material from the spleen of a three-year-old boy with a type 1 Gaucher disease was studied by immuno- and cytochemical methods with special regard to the macrophage-derived Gaucher cells. These cells were positive with PAS and Prussian blue staining, and were immuno-positive with the monoclonal 25 F9 antibody, specific to mature, non-inflammatory macrophages. Large Gaucher cells and their postulated small precursor cells revealed strong tartrate-resistant acid phosphatase (TRAP) and unspecific carboxylate esterase activities. Using a polyclonal antibody to bovine spleen purple phosphatase, a lysosomal TRAP from splenic macrophages, the TRAP of the Gaucher cells could be identified to belong to this group of iron-containing, purple acid phosphatases immunocytochemically. The origin of splenic Gaucher cells from blood monocytes and their further development are discussed.

Immunohistochemical characterization of purple acid phosphatase-containing leucocytes in the human placenta.

A tartrate-resistant acid phosphatase activity was detected in the human placenta. This enzyme displayed immunological properties similar to those of the group of purple acid phosphatases that can be demonstrated with a rabbit polyclonal antibody against bovine spleen purple acid phosphatase. The placental enzyme was mainly localized immunohistochemically to neutrophil granulocytes of the maternal blood between the placental villi and within foetal capillaries using the bovine spleen antibody and the commercial monoclonal antibody M1 directed against an antigen found on mature granulocytes. A minor activity was detected in decidual cells and the syncytiotrophoblast. The presence of purple acid phosphatase in placental granulocytes may be related to special immunological conditions of pregnancy.

Purple acid phosphatase of human brain macrophages in AIDS encephalopathy.

Brains from AIDS patients with an HIV-induced encephalopathy but without opportunistic infections or indications for an inflammation were studied by immuno- and enzyme-histochemical methods. It was found that the macrophages of these brains expressed a lysosomal tartrate-resistant acid phosphatase which gave a good immunological cross-reaction with an antibody to the well-characterized iron-containing bovine spleen purple acid phosphatase, belonging to the group of purple phosphatases, which are regarded as a marker for a special phenotype of activated macrophages. It was discussed that the numerous brain macrophages found in AIDS encephalopathy derive from latently infected monocytes which are believed to be drawn to the brain from the bloodstream.

Histochemical and immunological demonstration of purple acid phosphatase in human and bovine alveolar macrophages.

A tartrate-resistant purple acid phosphatase was localized in human and bovine alveolar macrophages by enzyme- and immuno-histochemistry using an antibody to bovine spleen purple phosphatase. The enzyme could be detected in human and bovine lung tissues as well as on cytospin preparations of alveolar macrophage suspensions from bronchoalveolar lavages. The immunological identity of human and bovine purple phosphatases from alveolar macrophages was demonstrated by Western blot analysis of material separated by polyacrylamide gel electrophoresis. A possible significance of the purple phosphatase as a marker enzyme of activated cells of the mononuclear phagocyte system is discussed.

Histochemical investigations on the localization of the purple acid phosphatase in the bovine spleen.

The localization of the purple tartrate-resistant, iron-containing acid phosphatase in the bovine spleen was studied by enzyme histochemistry at the light and electron microscopic levels as well as by immunohistochemistry. The purple phosphatase was localized only in lysosome-like-organelles of cells belonging to the reticulo-phagocytic system. The same cells were identified as containing large iron(III)-deposits as ferritin in homogeneously granular accumulations and freely in the cytoplasm, or as hemosiderin in siderosomes. The phagocytosing cells containing purple phosphatase and ferritin often had close contact with clusters of aged and deformed erythrocytes. A possible catabolic role of the purple enzyme as a phosphatase degrading phosphoproteins of the erythrocyte membrane and the cytoskeleton was assumed.