Point-of-care screening for syphilis and HIV in the borderlands: challenges in implementation in the Brazilian Amazon.

BACKGROUND: Point-of-care (POC) screening for HIV and syphilis using rapid testing was implemented in indigenous communities in the triple-border area of the Brazilian Amazon. We describe the context of the early introduction of POC screening, explore hindering and enabling factors for POC implementation, and recommend strategies for feasible, viable, and sustainable syphilis and HIV screening interventions. METHODS: This was a qualitative study based on grounded theory methodology. Data were collected using in-depth interviews, semi-structured questionnaires, and field observations and were analysed using the framework approach. Qualitative information was complemented by quantitative data for descriptive purposes. RESULTS: An overall high score for vulnerability to acquiring HIV and syphilis was observed among the indigenous communities. Health professionals reported satisfactory rapid testing acceptance, although concerns were raised about the pain of the fingerprick. Counselling-related challenges included ensuring the accuracy of translations, collaborating with translators and communicating positive test results. Over 3 months, 86.7% of the syphilis-positive individuals began treatment, and all of them notified their partners. Accessibility, measured as travel time via the local transportation network, was a barrier to health care access. A lack of gasoline for boats and other transportation was also a hindering factor at all levels of implementation. CONCLUSIONS: The recommendations address the preparation phase at the coordination level as well as at the training level. Tools such as strengths, weaknesses, opportunities, and threats (SWOT) analyses; checklists; context-adapted protocols; and fact sheets are very simple methods to facilitate implementation. The findings of this study are important because they may inform the implementation of new health technologies in low-resource national disease control programmes in remote communities

Rapid Point-of-Care Diagnostic Test for Syphilis in High-Risk Populations, Manaus, Brazil

We assessed the acceptability and operational suitability of a rapid point-of-care syphilis test and identified barriers to testing among high-risk groups and healthcare professionals in a sexually transmitted infections clinic in Manaus, Brazil. Use of this test could considerably alleviate the impact of syphilis in hard-to-reach populations in the Amazon region of Brazil

HIV and syphilis in the context of community vulnerability among indigenous people in the Brazilian Amazon.

BACKGROUND: Contextual factors shape the risk of acquiring human immunodeficiency virus (HIV) and syphilis. We estimated the prevalence of both infections among indigenous people in nine indigenous health districts of the Brazilian Amazon and examined the context of community vulnerability to acquiring these infections. METHODS: We trained 509 health care workers to screen sexually active populations in the community for syphilis and HIV using rapid testing (RT). We then assessed the prevalence of HIV and syphilis using RT. A multivariable analysis was used to identify factors associated with syphilis infection (sociodemographic, condom use, intrusion, population mobility, and violence). RESULTS: Of the 45,967 indigenous people tested, the mean age was 22.5 years (standard deviation: 9.2), and 56.5% were female. Overall, for HIV, the prevalence was 0.13% (57/43,221), and for syphilis, the prevalence was 1.82% (745/40,934). The prevalence in men, women, and pregnant women for HIV was 0.16%, 0.11%, and 0.07%, respectively, and for syphilis, it was 2.23%, 1.51%, and 1.52%, respectively. The district Vale do Javari had the highest prevalence of both infections (HIV: 3.38%, syphilis: 1.39%). This district also had the highest population mobility and intrusion and the lowest availability of prenatal services. Syphilis infection was independently associated with age (odds ratio [OR] 1.04, 95% confidence interval [CI]: 1.03-1.05), male sex (OR 1.32, 95% CI: 1.14-1.52), and mobility (moderate: OR: 7.46, 95% CI: 2.69-20.67; high: OR 7.09, 95% CI: 3.79-13.26). CONCLUSIONS: The large-scale integration of RT in remote areas increased case detection among pregnant women, especially for syphilis, in districts with higher vulnerability. Mobility is an important risk factor, especially in districts with higher vulnerability. Contextually appropriate approaches that address this factor could contribute to the long-term success of HIV and syphilis control programs

Antimicrobial resistance in Neisseria gonorrhoeae isolates from foreign-born population in the European Gonococcal Antimicrobial Surveillance Programme

International spread has contributed substantially to the high prevalence of antimicrobial resistant (AMR) Neisseria gonorrhoeae infections worldwide. We compared the prevalence of AMR gonococcal isolates among native persons to foreign-born (reporting country different from country of birth) persons, and describe the epidemiological and clinical characteristics of foreign-born patients and their associations to AMR. We analysed isolates and patient data reported to the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) 2010-2014 (n=9529). Forty-three per cent of isolates had known country of birth and 17.2% of these were from persons born abroad. Almost 50% of foreign-born were from the WHO European Region (13.1% from non-European Union [EU] and the European Economic Area [EEA] countries). Compared with isolates from natives, isolates from foreign-born had a similar level (p>0.05) of azithromycin resistance (7.5% vs 7.2%), ciprofloxacin resistance (50.0% vs 46.3%) and of decreased susceptibility to ceftriaxone (1.9% vs 2.8%); a lower rate of cefixime resistance (5.7% vs 3.6%, p=0.02), and a higher proportion of isolates producing penicillinase (8.4% vs 11.7%, p=0.02). Among isolates from persons born outside EU/EEA, the level of decreased susceptibility to ceftriaxone was higher (1.8% vs 3.5%, p=0.02), particularly in those from the WHO Eastern Mediterranean Region and non-EU/EEA WHO European countries (1.9% vs 9.6% and 8.7%, respectively, p<0.01). In multivariable analysis, foreign-born patients with AMR isolates were more likely to be from non-EU/EEA WHO European countries (adjusted OR [aOR]: 3.2, 95% CI 1.8 to 5.8), WHO Eastern Mediterranean countries (aOR: 1.8, 95% CI 1.1 to 3.3) and heterosexual males (aOR: 1.8, 95% CI 1.2 to 2.7). Importation of AMR strains remains an important threat in the EU/EEA. Research to improve understanding of sexual networks within foreign born and sexual tourism populations could help to inform effective tailor-made interventions. The Euro-GASP demonstrates the public health value of quality-assured surveillance of gonococcal AMR and the need for strengthened AMR surveillance, particularly in the non-EU/EEA WHO European Region

identifying patients with relapsing remitting multiple sclerosis using algorithms applied to us integrated delivery network healthcare data

Abstract Background Relapsing-remitting multiple sclerosis (RRMS) has a major impact on affected patients; therefore, improved understanding of RRMS is important, particularly in the context of real-world evidence. Objectives To develop and validate algorithms for identifying patients with RRMS in both unstructured clinical notes found in electronic health records (EHRs) and structured/coded health care claims data. Methods US Integrated Delivery Network data (2010–2014) were queried for study inclusion criteria (possible multiple sclerosis [MS] base cohort): one or more MS diagnosis code, patients aged 18 years or older, 1 year or more baseline history, and no other demyelinating diseases. Sets of algorithms were developed to search narrative text of unstructured clinical notes (EHR clinical notes–based algorithms) and structured/coded data (claims-based algorithms) to identify adult patients with RRMS, excluding patients with evidence of progressive MS. Medical records were reviewed manually for algorithm validation. Positive predictive value was calculated for both EHR clinical notes–based and claims-based algorithms. Results From a sample of 5308 patients with possible MS, 837 patients with RRMS were identified using only the EHR clinical notes–based algorithms and 2271 patients were identified using only the claims-based algorithms; 779 patients were identified using both algorithms. The positive predictive value was 99.1% (95% confidence interval [CI], 94.2%–100%) for the EHR clinical notes–based algorithms and 94.6% (95% CI, 89.1%–97.8%) to 94.9% (95% CI, 89.8%–97.9%) for the claims-based algorithms. Conclusions The algorithms evaluated in this study identified a real-world cohort of patients with RRMS without evidence of progressive MS that can be studied in clinical research with confidence

A phylogenetic and proteomic reconstruction of eukaryotic chromatin evolution

Histones and associated chromatin proteins have essential functions in eukaryotic genome organization and regulation. Despite this fundamental role in eukaryotic cell biology, we lack a phylogenetically comprehensive understanding of chromatin evolution. Here, we combine comparative proteomics and genomics analysis of chromatin in eukaryotes and archaea. Proteomics uncovers the existence of histone post-translational modifications in archaea. However, archaeal histone modifications are scarce, in contrast with the highly conserved and abundant marks we identify across eukaryotes. Phylogenetic analysis reveals that chromatin-associated catalytic functions (for example, methyltransferases) have pre-eukaryotic origins, whereas histone mark readers and chaperones are eukaryotic innovations. We show that further chromatin evolution is characterized by expansion of readers, including capture by transposable elements and viruses. Overall, our study infers detailed evolutionary history of eukaryotic chromatin: from its archaeal roots, through the emergence of nucleosome-based regulation in the eukaryotic ancestor, to the diversification of chromatin regulators and their hijacking by genomic parasites.Research in the A.S.-P. group was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research and Innovation Programme (grant agreement no. 851647) and the Spanish Ministry of Science and Innovation (PGC2018-098210-A-I00). We also acknowledge support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa and the CERCA Programme (Generalitat de Catalunya). C.N. is supported by an FPI PhD fellowship from the Spanish Ministry of Economy, Industry and Competitiveness (MEIC). X.G.-B. is supported by a Juan de la Cierva fellowship (FJC2018-036282-I) from MEIC. I.R.-T. was supported by a European Research Council (grant no. 616960). B.F.L. was supported by the Natural Sciences and Engineering Research Council of Canada (NSERC; RGPIN-2017-05411) and by the ‘Fonds de Recherche Nature et Technologie’, Quebec. P.L.-G. and D.M. were supported by a Moore and Simons foundations grant (GBMF9739) and by European Research Council advanced grants (322669, 787904). Research in the C.S. group was supported by the ERC through project TACKLE (advanced grant no. 695192)

The UALE project : a cross-sectional approach for trends in HIV/STI prevalence among key populations attending STI clinics in Guatemala

To describe and compare trends in prevalence, sexual behaviour and HIV transmission knowledge data related to sexually transmitted infections (STI) and HIV in patients attending three STI clinics over an 8-year period in Escuintla Department, Guatemala. STI clinic attendees were classified into transmission groups as follows: female sex workers (FSW), men who have sex with men (MSM) and 'high-risk heterosexuals' (HRH). Annual cross-sectional analysis and multivariable Poisson regression adjusted for sociodemographic variables were used for prevalence comparisons and adjusted prevalence trends for HIV/STI outcomes and used for adjusted trends in proportions in sexual behaviour and HIV transmission knowledge outcomes. Endocervical swabs were obtained to detect trichomonas, chlamydia and neisseria infections. Serologies for syphilis and HIV were performed using rapid tests. For reactive HIV samples, positivity was confirmed by an ELISA. All reactive syphilis samples were further confirmed for diagnosis of active syphilis disease. From a total of 4027 clinic attendees, 3213 (79.78%) were FSW, 229 (5.69%) were MSM and 585 (14.53%) were HRH. The proportion of FSW, MSM and HRH who had a single visit was 56.42%, 57.23% and 91.10%, respectively. Overall, HIV prevalence was 2.10% in FSW, 8.17% in MSM and 4.12% in HRH. Prevalence trends in HIV and syphilis decreased in FSW. Prevalence trends in gonorrhoea did not decrease over time neither in FSW nor in HRH. Chlamydia and trichomonas infections in HRH showed an increase prevalence trend. In FSW, trends in condom use in last sexual intercourse with regular and occasional clients were above 93%. FSW show a decreasing trend in HIV, syphilis and chlamydia prevalence. Gonorrhoea prevalence in FSW and HRH did not decrease over time. HRH is a hard to engage population with low follow-up rates and high potential to act as a bridge population

The MANGUA Project: A Population-Based HIV Cohort in Guatemala

Introduction. The MANGUA cohort is an ongoing multicenter, observational study of people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA application which is an electronic database to capture essential data from the medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive adults ≥16 years of age. A predefined set of sociodemographic, behavioral, clinical, and laboratory data are registered at entry to the cohort study. Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first 12 months after starting antiretroviral treatment 26.9% (n=3938) of the patients were lost to the program. Conclusions. The implementation of a cohort of HIV-positive patients in care in Guatemala is feasible and has provided national HIV indicators to monitor and evaluate the HIV epidemic. The identified percentages of late presenters and high rates of LTFU will help the Ministry to target their current efforts in improving access to diagnosis and care

The MANGUA Project : A Population-Based HIV Cohort in Guatemala

Introduction. The MANGUA cohort is an ongoing multicenter, observational study of people living with HIV/AIDS in Guatemala. The cohort is based on the MANGUA application which is an electronic database to capture essential data from the medical records of HIV patients in care. Methods. The cohort enrolls HIV-positive adults ≥16 years of age. A predefined set of sociodemographic, behavioral, clinical, and laboratory data are registered at entry to the cohort study. Results. As of October 1st, 2012, 21 697 patients had been included in the MANGUA cohort (median age: 33 years, 40.3% female). At enrollment 74.1% had signs of advanced HIV infection and only 56.3% had baseline CD4 cell counts. In the first 12 months after starting antiretroviral treatment 26.9% (n = 3938) of the patients were lost to the program. Conclusions. The implementation of a cohort of HIV-positive patients in care in Guatemala is feasible and has provided national HIV indicators to monitor and evaluate the HIV epidemic. The identified percentages of late presenters and high rates of LTFU will help the Ministry to target their current efforts in improving access to diagnosis and care

Aging-related tau astrogliopathy (ARTAG): not only tau phosphorylation in astrocytes

Aging-related tau astrogliopathy (ARTAG) is defined by the presence of two types of tau-bearing astrocytes: thorn-shaped astrocytes (TSAs) and granular/fuzzy astrocytes in the brain of old-aged individuals. The present study is focused on TSAs in rare forms of ARTAG with no neuronal tau pathology or restricted to entorhinal and transentorhinal cortices, to avoid bias from associated tauopathies. TSAs show 4Rtau phosphorylation at several specific sites and abnormal tau conformation, but they lack ubiquitin and they are not immunostained with tau-C3 antibodies which recognize truncated tau at Asp421. Astrocytes in ARTAG have atrophic processes, reduced glial fibrillary acidic protein (GFAP) and increased superoxide dismutase 2 (SOD2) immunoreactivity. Gel electrophoresis and western blotting of sarkosyl-insoluble fractions reveal a pattern of phospho-tau in ARTAG characterized by two bands of 68 and 64 kDa, and several middle bands between 35 and 50 kDa which differ from what is seen in AD. Phosphoproteomics of dissected vulnerable regions identifies an increase of phosphorylation marks in a large number of proteins in ARTAG compared with controls. GFAP, aquaporin 4, several serine-threonine kinases, microtubule associated proteins and other neuronal proteins are among the differentially phosphorylated proteins in ARTAG thus suggesting a hyper-phosphorylation background that affects several molecules, including many kinases and proteins from several cell compartments and various cell types. Finally, present results show for the first time that tau seeding is produced in neurons of the hippocampal complex, astrocytes, oligodendroglia and along fibers of the corpus callosum, fimbria and fornix following inoculation into the hippocampus of wild type mice of sarkosyl-insoluble fractions enriched in hyper-phosphorylated tau from selected ARTAG cases. These findings show astrocytes as crucial players of tau seeding in tauopathies