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Background: Within the ECDC-VEBIS project, we prospectively monitored vaccine effectiveness (VE) against COVID-19 hospitalisation and COVID-19-related death, using electronic health registries (EHR), between October 2021 and November 2022, in community-dwelling residents aged 65–79 and ≥80-years in six European countries. Methods: EHR linkage was used to construct population cohorts in Belgium, Denmark, Luxembourg, Navarre (Spain), Norway and Portugal. Using a common protocol, for each outcome (hospitalisation and death), VE was estimated monthly over eight-week follow-up periods, allowing one month-lag for data consolidation. Cox proportional-hazards regression models were used to estimate adjusted hazard ratios (aHR) and VE=(1 – aHR) x100. Site-specific estimates were pooled using random-effects meta-analysis. Results: For ≥80-years, VE against COVID-19 hospitalisation decreased from 66.9% (95%CI: 60.1; 72.6) to 36.1% (95%CI: -27.3; 67.9) for the primary vaccination and from 95.6% (95%CI: 88.0; 98.4) to 67.7% (95%CI: 45.9; 80.8) for the first booster. Similar trends were observed for 65-79-years. The second booster VE against hospitalisation ranged between 82.0% (95%CI: 75.9; 87.0) and 83.9% (95%CI: 77.7; 88.4) for the ≥80-years and between 39.3% (95%CI: -3.9; 64.5) and 80.6% (95%CI: 67.2; 88.5) for 65-79-years. The first booster VE against COVID-19-related death declined over time for both age groups, while the second booster VE against death remained above 80% for the ≥80-years. Conclusions: Successive vaccine boosters played a relevant role in maintaining protection against COVID-19 hospitalisation and death, in the context of decreasing VE over time. Multi-country data from EHR facilitate robust near-real-time monitoring of VE in the EU/EEA and supports public health decision-making.

BackgroundData on the comparative vaccine effectiveness (CVE) of the bivalent mRNA-booster vaccines containing the original SARS-CoV-2 and omicron BA.4-5 and BA.1 subvariants are limited.MethodsIn a period of BA.4-5 subvariants predominance, we estimated the CVE of the bivalent Comirnaty (Pfizer-BioNTech) and Spikevax (Moderna) BA.4-5 and BA.1 mRNA-booster vaccines given as a fourth dose in Denmark, Finland, Norway, and Sweden. From 1 July 2022 to 12 December 2022, we conducted nationwide cohort analyses using target trial emulation to compare risks of Covid-19 hospitalization and death in four-dose (second booster) with three-dose (first booster) vaccinated and between four-dose vaccinated individuals.ResultsCompared with having received three vaccine doses, receipt of a bivalent BA.4-5 booster as a fourth dose was associated with a country-combined CVE against Covid-19 hospitalization of 80.5% (95% confidence interval, 69.5% to 91.5%). The corresponding CVE for bivalent BA.1 boosters was 74.0% (68.6% to 79.4%). CVE against Covid-19 death was 77.8% (48.3% to 100%) and 80.1% (72.0% to 88.2%) for bivalent BA.4-5 and BA.1 boosters as a fourth dose, respectively. The CVE of bivalent BA.4-5 vs. BA.1 boosters were 32.3% (10.6% to 53.9%) for Covid-19 hospitalization and 12.3% (−36.1% to 60.7%) for death (the latter estimable in Denmark only).ConclusionsVaccination with bivalent BA.4-5 or BA.1 mRNA-booster vaccines as a fourth dose was associated with increased protection against Covid-19 hospitalization and death during a period of BA.4-5 predominance. Bivalent BA.4-5 boosters conferred moderately greater vaccine effectiveness against Covid-19 hospitalization compared with bivalent BA.1 boosters.

ObjectiveTo investigate the effectiveness of heterologous booster schedules with AZD1222 (Oxford-AstraZeneca, referred to as AZD), BNT162b2 (Pfizer-BioNTech, BNT), and mRNA-1273 (Moderna, MOD) vaccines compared with primary schedules and with homologous mRNA-vaccine booster schedules during a period of omicron predominance.DesignPopulation-based cohort analyses.SettingDenmark, Finland, Norway, and Sweden, 27 December 2020 to 28 February 2022.ParticipantsAdults that had received at least a primary vaccination schedule (ie, two doses) of the AZD, BNT, and/or MOD vaccines during the study period.Main outcome measuresUsing the Kaplan-Meier estimator, we compared country-specific risks of SARS-CoV-2 infection and severe COVID-19 outcomes in heterologous booster vaccinated with primary schedule vaccinated (matched analyses) and homologous booster vaccinated (weighted analyses) since emergence of omicron.ResultsHeterologous booster schedules improved protection against all outcomes compared with primary schedules, with the largest and most robust effects observed for severe COVID-19. Risk differences for documented infection ranged from -22.4% to -3.1% (comparative vaccine effectiveness [CVE] 9.7% to 60.9%; >63.2% for COVID-19 hospitalisation) across countries for AZD1BNT2BNT3 (AZD as primary dose followed by two doses of BNT) vs AZD1BNT2 and -22.2% to -3.2% (CVE 37.4% to 67.8%; >34.6% for hospitalisation) for BNT1BNT2MOD3 vs BNT1BNT2, the two most common heterologous booster schedules. Heterologous- and homologous booster schedules had comparable effectiveness. Risk differences of documented infection ranged from -0.4% to 4.4% (CVE -20.0% to 2.4%) for AZD1BNT2BNT3 vs BNT1BNT2BNT3 and -19.8% to 1.7% (CVE -14.6% to 53.8%) for BNT1BNT2MOD3 vs BNT1BNT2BNT3; for most comparisons, risk differences for severe COVID-19 outcomes were smaller than 1 per 1000 vaccinated. Previous infection followed by a booster dose conferred the greatest protection.ConclusionHeterologous booster vaccine schedules are associated with an increased protection against omicron-related COVID-19 outcomes that is comparable to that afforded by homologous booster schedules.

Understanding the epidemic growth of the novel SARS-CoV-2 Omicron variant is critical for public health. We compared the ten-day secondary attack rate (SAR) of the Omicron and Delta variants in households using Norwegian contact tracing data, December 2021 - January 2022. Omicron SAR was higher than Delta, with a relative risk (RR) of 1.41 (95% CI 1.27-1.56). We observed increased susceptibility to Omicron infection in household contacts compared to Delta, independent of contacts’ vaccination status. Among three-dose vaccinated contacts, the mean SAR was lower for both variants. We found increased Omicron transmissibility from primary cases to contacts in all vaccination groups, except 1-dose vaccinated, compared to Delta. Omicron SAR of three-dose vaccinated primary cases was high, 46% vs 11 % for Delta. In conclusion, three-dose vaccinated primary cases with Omicron infection can efficiently spread in households, while three-dose vaccinated contacts have a lower risk of being infected by Delta and Omicron.

BackgroundCOVID-19 vaccines have been crucial in the pandemic response and understanding changes in vaccines effectiveness is essential to guide vaccine policies. Though the Delta variant is no longer dominant, understanding vaccines effectiveness properties will provide essential knowledge to comprehend the development of the pandemic and estimate potential changes over time.MethodsIn this population-based cohort study, we estimated vaccine effectiveness against SARS-CoV-2 infections, hospitalisations, intensive care admissions, and death using Cox proportional hazard models, across different vaccine product regimens and age groups, between 15 July and 31 November 2021 (Delta variant period). Vaccine status is included as a time-varying covariate and all models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data from the entire adult Norwegian population were collated from the National Preparedness Register for COVID-19 (Beredt C19).ResultsThe overall adjusted vaccine effectiveness against infection decreased from 81.3% (confidence interval (CI): 80.7 to 81.9) in the first two to nine weeks after receiving a second dose to 8.6% (CI:4.0 to 13.1) after more than 33 weeks, compared to 98.6% (CI: 97.5 to 99.2) and 66.6% (CI: 57.9 to 73.6) against hospitalisation respectively. After the third dose (booster), the effectiveness was 75.9% (CI: 73.4 to 78.1) against infection and 95.0% (CI: 92.6 to 96.6) against hospitalisation. Spikevax or a combination of mRNA products provided the highest protection, but the vaccine effectiveness decreased with time since vaccination for all vaccine regimens.ConclusionsEven though the vaccine effectiveness against infection wanes over time, all vaccine regimens remained effective against hospitalisation after the second vaccine dose. For all vaccine regimens, a booster facilitated recovery of effectiveness. The results from this support the use of heterologous schedules, increasing flexibility in vaccination policy.Fundingno external funding

BackgroundCOVID-19 vaccination was recommended for adolescents in Norway since August 2021. In this population-based cohort study, we estimated the BNT162b2 vaccine effectiveness against any PCR-confirmed (symptomatic or not) SARS-CoV-2 infections caused by the Delta and Omicron variant among adolescents (12-17-years-old) in Norway from August 2021 to January 2022.MethodsUsing Cox proportional hazard models, we estimated the BNT162b2 vaccine effectiveness against any Delta and Omicron infections. Vaccine status was included as a time-varying covariate and models were adjusted for age, sex, comorbidities, county of residence, country of birth, and living conditions. Data were obtained from the National Preparedness registry for COVID-19, which contains individual-level data from national health and administrative registries.FindingsVaccine effectiveness against Delta infection peaked at 68% (95%CI: 64–71%) and 62% (95%CI: 57– 66%) in days 21-48 after the first dose among 12–15-year-olds and 16–17-year-olds respectively. Among 16–17-year-olds that received two doses, vaccine effectiveness peaked at 93% (95%CI: 90–95%) in days 35-62 and declined to 84% (95%CI: 76–89%) in 63 days or more after the second dose. For both age-groups, we found no protection against Omicron infection after receiving one dose. Among 16–17-year-olds, vaccine effectiveness against Omicron infection peaked at 53% (95%CI: 43–62%) in 7-34 days after the second dose and decreased to 23% (95%CI: 3–40%) in 63 days or more after vaccination. Vaccine effectiveness decreased with time since vaccination for both variants, but waning was observed to occur faster for Omicron.InterpretationOur results suggest reduced protection from BNT162b2 vaccination against any SARS-CoV-2 infection caused by the Omicron variant compared to the Delta. In addition, waning immunity was observed to occur faster for Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance.FundingNo funding was received.Research in contextEvidence before this studyBNT162b2 (Comirnaty, Pfizer-BioNTech) and mRNA-1273 (Spikevax, Moderna) vaccines have been approved for use in adolescents, based on results from randomized placebo-controlled trials demonstrating comparable immunogenicity and safety profile as in young adults. In addition, observational studies from Israel, the USA and England have reported high protection of BNT162b2 vaccines against SARS-CoV-2 Delta infection among adolescents. These studies also reported decrease in effectiveness with time since last vaccine dose. Evidence on the effect of an extended interval between doses, longer time since vaccination and the effect against different variants is limited. When we first planned this study in early February 2022, no data were available regarding vaccine effectiveness against SARS-CoV-2 Omicron infection among adolescents. To our knowledge when we completed this study and before submitting this article, only one study from England reported results in a preprint on vaccine effectiveness against symptomatic SARS-CoV-2 Omicron infection among adolescents. We searched for studies that evaluated vaccine efficacy or effectiveness after vaccination of adolescents during 2021-2022 in PubMed, medRxiv, bioRxiv, SSRN. We searched for studies with several variations of the primary key search terms “COVID-19”, “SARS-CoV-2”, and “vaccine” (including names of specific vaccines, as BNT162b2), “vaccine effectiveness”, “adolescents”, “children”.Added value of this studyThe rapid increase in the incidence of SARS-CoV-2 infection caused by the Omicron variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines in adults but also adolescents. In this population-based cohort study, we showed that the vaccine effectiveness against Omicron is lower than against Delta infections among adolescents, including symptomatic and asymptomatic infections. We should note that evidence suggests higher rates of asymptomatic carriage for Omicron than other variants of concern. Vaccine effectiveness that includes asymptomatic cases, as in the study from England, is expected to be lower than when including symptomatic cases only. We found that one and two doses of BNT162b2 among adolescents protected well against Delta. Vaccination provided high protection against Delta infections (>91%) among Norwegian 16-17-year-olds 7-62 days after the second dose. We found no protection against Omicron SARS-CoV-2 infection after one vaccine dose, and moderate effectiveness after two doses (peaked at 53%) among the 16-17-year-olds. Moreover, waning immunity was observed to occur faster for Omicron.Implications of all the available evidenceBased on the available evidence, the vaccine effectiveness among adolescents is similar to that reported among adults, also with an extended period of 8-12 weeks between doses which was used in Norway. Protection is significantly lower against Omicron than Delta infections and immunity wanes faster against Omicron. The impact of vaccination among adolescents on reducing infection and thus transmission is limited during omicron dominance. Policies should take into account the impact of vaccination campaigns among adolescents and their primary objective. Vaccine effectiveness should be re-evaluated when other variants appear as they might have different outcomes as shown between Delta and Omicron infections.

Understanding the rapid epidemic growth of the novel SARS-CoV-2 Omicron variant is critical for public health management. We compared the secondary attack rate (SAR) of the Omicron and Delta variants in households using Norwegian contact tracing data from December 2021 to January 2022. Omicron SAR was higher (51%) than Delta (36%), with a relative risk (RR) of 1.41 (95% CI 1.27–1.56). We observed increased susceptibility to Omicron infection in household contacts compared to Delta independent of vaccination status; however, considering booster vaccinated contacts, the mean SAR was lower for both variants. We found increased Omicron transmissibility in all vaccination groups of primary cases, except partially vaccinated, compared to Delta. In particular, Omicron SAR for boosted primary cases was high, 46% vs 11% for Delta (RR 4.34; 95% CI 1.52–25.16). In conclusion, booster doses decrease the infection risk of Delta and Omicron but have limited effect in preventing Omicron transmission.

Coronavirus disease 2019 (COVID-19) causes high morbidity and mortality in long-term care facilities (LTCFs). COVID-19 vaccine effectiveness against infection was 81.5% and 81.4% among fully vaccinated residents and staff in LTCFs. The vaccine effectiveness against COVID-19-associated death was 93.1% among residents, and no hospitalizations occurred among fully vaccinated staff.

BackgroundSARS-CoV-2 vaccines show high effectiveness against infection and (severe) disease. However, few studies estimate population level vaccine effectiveness against multiple COVID-19 outcomes, by age and including homologous and heterologous vaccine regimens.MethodsUsing Cox proportional hazard models on data from 4 293 544 individuals (99% of Norwegian adults), we estimated overall, age-, and product-specific vaccine effectiveness against SARS-CoV-2 infection, hospitalisation, ICU admission and death in Norway, using data from national registries. Vaccine status was included as time-dependent variable and we adjusted for sex, pre-existing medical conditions, country of birth, county of residence, and crowded living conditions.FindingsAdjusted vaccine effectiveness among fully vaccinated is 72·1% (71·2–73·0) against SARS-CoV-2 infection, 92·9% (91·2–94·2) against hospitalisation, 95·5% (92·6–97·2) against ICU admission, and 88·0% (82·5–91·8) against death. Among partially vaccinated, the effectiveness is 24·3% (22·3–26·2) against infection and 82·7% (77·7–86·6) against hospitalisation. Vaccine effectiveness against infection is 84·7% (83·1-86·1) for heterologous mRNA vaccine regimens, 78·3% (76·8-79·7) for Spikevax (Moderna; mRNA-1273), 69·7% (68·6-70·8) for Comirnaty (Pfizer/BioNTech; BNT162b2), and 60·7% (57·5-63·6) for Vaxzevria (AstraZeneca; ChAdOx nCoV-19; AZD1222) with a mRNA dose among fully vaccinated.InterpretationWe demonstrate good protection against SARS-CoV-2 infection and severe disease in fully vaccinated, including heterologous vaccine regimens, which could facilitate rapid immunization. Partially vaccinated were less likely to get severe disease than unvaccinated, though protection against infection was not as high, which could be essential in making vaccine prioritisation policies especially when availability is limited.FundingNorwegian Institute of Public Health, Helse Bergen Health Trust

Some variants of SARS-CoV-2 are associated with increased transmissibility, increased disease severity or decreased vaccine effectiveness (VE). In this population-based cohort study (n = 4,204,859), the Delta variant was identified in 5,430 (0.13%) individuals, of whom 84 were admitted to hospital. VE against laboratory confirmed infection with the Delta variant was 22.4% among partly vaccinated (95% confidence interval (CI): 17.0−27.4) and 64.6% (95% CI: 60.6−68.2) among fully vaccinated individuals, compared with 54.5% (95% CI: 50.4−58.3) and 84.4% (95%CI: 81.8−86.5) against the Alpha variant.

COVID-19 has caused high morbidity and mortality in long-term care facilities (LTCFs) worldwide. We estimated vaccine effectiveness (VE) among residents and health care workers (HCWs) in LTCFs using Cox regressions. The VE against SARS-CoV-2 infection was 81.5 (95%CI: 75.3 – 86.1 82.7%) and 81.4% (95%CI: 74.5-86.4%) ≥ 7 days after 2ndvaccine dose among residents and staff respectively. The VE against COVID-19 associated death was 93.1% among residents, no hospitalisations occurred among HCW ≥7 days after 2nddose.

The coronavirus disease 2019 (COVID-19) response in most countries has relied on testing, isolation, contact tracing, and quarantine (TITQ), which is labor- and time-consuming. Therefore, several countries worldwide launched Bluetooth-based apps as supplementary tools. The aim of using contact tracing apps is to rapidly notify people about their possible exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and thus make the process of TITQ more efficient, especially upon exposure in public places. We evaluated the Norwegian Google Apple exposure notification (GAEN)-based contact tracing app Smittestopp v2 under relevant “real-life” test scenarios. We used a total of 40 devices, representing six different brands, and compared two different exposure configurations, experimented with different time thresholds and weights of the Bluetooth attenuation levels (buckets), and calculated the true notification rates among close contacts (≤2 m and ≥15 min) and false notification of sporadic contacts. In addition, we assessed the impact of using different operating systems and locations of the phone (hand/pocket). The best configuration tested to trigger exposure notification resulted in the correct notification of 80% of the true close contacts and incorrect notification of 34% of the sporadic contacts. Among those who incorrectly received notifications, most (67%) were within 2 m but the duration of contact was per se, considered as “close contacts.” Lower sensitivity was observed when using the iOS operating systems or carrying the phone in the pocket instead of in the hand. The results of this study were used to improve and evaluate the performance of the Norwegian contact-tracing app Smittestopp.

Boil-water advisories (BWAs) are one of the several methods to prevent the spread of infectious diseases through contaminated water. However, for BWAs to be effective, consumers need to be aware of, understand and comply with the advisories. Although BWAs are a widely used preventive public health measure, compliance with BWAs is rarely examined. In Norway, only one previous study on compliance with BWAs has been conducted. Therefore, we conducted a cross-sectional study to estimate consumers’ perception of and compliance with a BWA following a contamination incident at an elevated reservoir in Konnerud (population 10,314), Norway. In total, 2,451 of the 9,312 (26.3%) invited residents responded to the questionnaire. Among the respondents, 97.6% remembered receiving the BWA, of whom 94.6% complied with the advice. Effective compliance with the BWA was thus 92.3%. Only 130 (5.4%) respondents did not comply with the BWA. The main reason for non-compliance was perceived low or no risk of getting sick from the water (34.2%). Our study revealed high awareness of and compliance with the BWA, but the people who did not comply maintained several misconceptions about waterborne infections and transmission. The findings can be used by local health authorities to improve future BWAs.

Chemokine receptors CCR5 and CXCR4 which lied on lymphocyte cell surface play important role in HIV infection and pathogenesis.The expression of these chemokine receptors will affect progressively the disease. The objectives of the study are to find the distributionof lymphocyte T cell subset and monocyte among the peripheral blood mononuclear cells and to know the determination of CCR5 andCXCR4 co receptors expression on T lymphocyte cells subset and monocyte. This study is a preliminary study to explore the distributionof co receptors CCR5 and CXCR4 expression in healthy people. The sample taken is peripheral blood mononuclear cells (PBMC) fromhealthy subjects. The identification of T lymphocyte cells subsets and monocyte, and the expression of CCR5 and CXCR4 co receptorswere determined using flowcytometry. The memory T cell (CD4+CD45RO) is found to be the largest proportion among T lymphocyte cell(66.2%), whereas the other T lymphocyte cell subset, regulatory T cell, which identified by CD25+ high expression was found between2.0-5.3% from the whole T lymphocyte cell. The proportion of CXCR4 co receptors was found higher compare to CCR5 co receptorson all T lymphocyte subsets and monocyte. Only small proportion of monocyte expresses both co receptors (2.85%), but most of the Tlymphocyte cell expressed both CCR5 and CXCR4. The expression of the CXCR4 on regulatory T cell (18.18%) is the lowest compared toother cells, but the fluorescence intensity of both co receptors was very high (CCR5 53.53 and CXCR4 49.33). The different distributionof CCR5 and CXCR4 co receptors among T lymphocyte cell subsets and monocyte will influence the vulnerability and the pathogenicityof HIV infection.

Contains fulltext : 121860.pdf (Publisher’s version ) (Closed access) BACKGROUND : The prevalence of anaemia in Africa is the highest in the world. Especially women are at risk because of blood loss during menstruation and increased iron requirements during pregnancy. This study examined determinants of the haemoglobin (Hb) level of African women at individual/household, cluster, district, and national level. Special attention was paid to socioeconomic factors and the presence of health facilities. METHODS : Data were derived from Demographic and Health Surveys conducted between 2003 and 2010 in 21 African countries. We included all women aged 15–49 who participated in a women's survey and had a Hb measurement. Multilevel models were used to examine the influence of various factors at different hierarchical levels simultaneously. RESULTS : 104 899 women were included in the study, of which 23.1% were anaemic (Hb

Method S1. Detailed description of the methods used in this manuscript. (DOCX 25 kb)

Table S1. Summary of model estimates from the compartmental model to estimate the burden of hepatitis C associated with people who inject drugs in Norway. (DOCX 21 kb)

OBJECTIVETo assess whether differences in surveillance methods or underlying populations significantly influence internationally reported national SSI rates by comparing surveillance data from 2 countries.DESIGNRetrospective cohort.SETTINGEngland and Norway.METHODSWe assessed the population under surveillance and surveillance methodology to compare SSI rates in 2 countries (September 2012–January 2015) for 4 surgical categories: coronary artery bypass graft (CABG), colon surgery, cholecystectomy, and hip prosthesis (HPRO). We compared the inpatient SSI incidence using logistic regression, adjusting for the following known risk factors: sex, age, ASA score, wound class, postoperative hospital days, and operation duration. Subsequently, we restricted further analyses to the procedures reported by both countries.RESULTSThere were important differences in case definitions for superficial infection, so we restricted our analyses to deep incisional and organ-space SSIs. For CABG, the crude odds ratio (OR) for England compared to Norway was 2.4 (95% CI, 1.4–4.4), whereas adjusted OR (aOR) lost significance (aOR, 1.1; 95% CI, 0.57–2.0). For colon surgery the decreased odds (OR, 0.68; 95% CI, 0.56–0.81) remained significant after adjustment (aOR, 0.42; 95% CI, 0.34–0.51). We found no associations for cholecystectomy. For HPRO, the crude OR suggested no significant difference (OR, 1.2; 95% CI, 0.72–2.1), whereas the aOR was significantly lower in England (aOR, 0.45; 95% CI, 0.25–0.81). Including only the subset of procedures reported by both countries yielded comparable results.CONCLUSIONDifferences in case definitions and population under surveillance in the English and Norwegian SSI surveillance systems affected SSI estimates, making the comparison of crude rates unreliable. Standardized definitions and adjustment for established risk factors are essential for European comparisons to guide related public health actions.Infect Control Hosp Epidemiol 2017;38:162–171

Summary objectives Total lymphocyte counts (TLC) may be used as an alternative for CD4 cell counts to monitor HIV infection in resource-limited settings, where CD4 cell counts are too expensive or not available. methods We used prospectively collected patient data from an urban HIV clinic in Indonesia. Predictors of mortality were identified via Cox regression, and the relation between TLC and CD4 cell counts was calculated by linear regression. Receiver operating characteristics (ROC) curves were used to choose the cut-off values of TLC corresponding with CD4 cell counts

Opioid use may affect HIV infection through altered expression of HIV co-receptors. This was examined in Indonesia among antiretroviral therapy-naive HIV patients, many of whom use drugs. C-C chemokine receptor type 5 (CCR5) expression on CD4+ cells was higher in heroin (P = 0.007), methadone (P = 0.024) and former opioid users (P = 0.003) compared to nonusers, whereas production of RANTES and other CCR5 ligands was similar or lower. This suggests that opioids can affect HIV susceptibility through up-regulation of CCR5 or down-regulation of its ligands.

Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate marker for CD4 cells in HIV-infected patients not receiving antiretroviral therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating the immunological response to ART. In a cohort of patients in Indonesia TLC, if measured after at least 1-year ART, correctly identified patients with

Introduction : Injecting drug use (IDU) is associated with tuberculosis but few data are available from low-income settings. We examined IDU in relation to active and latent tuberculosis (LTBI) among HIV-positive individuals in Indonesia, which has a high burden of tuberculosis and a rapidly growing HIV epidemic strongly driven by IDU. Methods : Active tuberculosis was measured prospectively among 1900 consecutive antiretroviral treatment (ART)-naive adult patients entering care in a clinic in West Java. Prevalence of LTBI was determined cross-sectionally in a subset of 518 ART-experienced patients using an interferon-gamma release assay. Results : Patients with a history of IDU (53.1%) more often reported a history of tuberculosis treatment (34.8% vs. 21.9%, p

Many studies have evaluated the total lymphocyte count (TLC) as a cheap surrogate marker for CD4 cells in HIV-infected patients not receiving antiretroviral therapy (ART). We assessed whether TLC can replace CD4 cell counts in evaluating the immunological response to ART. In a cohort of patients in Indonesia TLC, if measured after at least 1-year ART, correctly identified patients with200 CD4 cells, and reliably excluded immunological failure, obviating the need for CD4 cell measurement in 43% of patients.

Total lymphocyte counts (TLC) may be used as an alternative for CD4 cell counts to monitor HIV infection in resource-limited settings, where CD4 cell counts are too expensive or not available.We used prospectively collected patient data from an urban HIV clinic in Indonesia. Predictors of mortality were identified via Cox regression, and the relation between TLC and CD4 cell counts was calculated by linear regression. Receiver operating characteristics (ROC) curves were used to choose the cut-off values of TLC corresponding with CD4 cell counts200 and ≤350 cells/μl. Based on these analyses, we designed TLC-based treatment algorithms.Of 889 antiretroviral treatment (ART)-naïve subjects included, 66% had CD4 cell counts200 and 81% had 350 ≤ cells/μl at baseline. TLC and CD4 cell count were equally strong predictors of mortality in our population, where ART was started based on CD4 cell count criteria. The correlation coefficient (R) between TLC and √CD4 was 0.70. Optimal cut-off values for TLC to identify patients with CD4 cell counts200 and ≤350 cells/μl were 1500 and 1700 cells/μl, respectively. Treatment algorithms based on a combination of TLC, gender, oral thrush, anaemia and body mass index performed better in terms of predictive value than WHO staging or TLC alone. In our cohort, such an algorithm would on average have saved $14.05 per patient.Total lymphocyte counts is a good marker for HIV-associated mortality. Simple algorithms including TLC can prioritize patients for HIV treatment in a resource-limited setting, until affordable CD4 cell counts will be universally available.

Contains fulltext : 152970.pdf (Publisher’s version ) (Open Access) BACKGROUND: Opioid use is associated with increased incidence of infectious diseases. Although experimental studies have shown that opioids affect various functions of immune cells, only limited data are available from human studies. Drug use is an important risk factor for HIV transmission; however no data are available whether heroin and/or methadone modulate immune response. Therefore, we examined the effect of heroin and methadone use among HIV-infected individuals on the production of cytokines after ex vivo stimulation with various pathogens. METHODS: Treatment naive HIV-infected individuals from Indonesia were recruited. Several cohorts of individuals were recruited: 1) using heroin 2) receiving methadone opioid substitution 3) using heroin over 1 year ago and 4) controls (never used opioids). Whole blood was stimulated with Mycobacterium tuberculosis, Candida albicans and LPS for 24 to 48 hours. Cytokine production (IL-1 beta, IL-6, IL-10, IFN-alpha, IFN-gamma and TNF-alpha) was determined using multiplex beads assay. RESULTS: Among 82 individuals, the cytokine levels in unstimulated samples did not differ between groups. Overall, heroin users had significantly lower cytokine response after exposure to LPS (p

Contains fulltext : 152946.pdf (Publisher’s version ) (Open Access) BACKGROUND: Male injecting drug users drove the onset of the HIV epidemic in Indonesia but over time more women have been diagnosed. We examined the relative proportion of female patients in an HIV cohort and characterized their probable transmission route and reproductive profile. DESIGNS: Prospective cohort study in a referral hospital in West Java. METHODS: Interviews with standardized questionnaires, physical and laboratory examinations were done for 2622 individuals enrolled in HIV care between 2007 and 2012. The proportion of women in this cohort was compared with national estimates. The general characteristics of HIV-infected women and men as well as the sexual and reproductive health of HIV-infected women were described. RESULTS: The proportion of female patients enrolled in HIV care increased from 22.2 % in 2007 to 38.3 % in 2012, in line with national estimates. Women were younger than men, fewer reported a history of IDU (16.1 vs. 73.8 %, p < 0.001) and more were tested for HIV because of a positive partner (25.5 vs. 4.0 %, p < 0.001). The majority of women were in their reproductive age, had children, and were not using contraceptives at the time of enrolment. CONCLUSION: HIV-infected women in Indonesia have specific characteristics that differ them from women in the general population. Further research to elucidate the characteristics of women exposed to HIV, their access to testing and care and sexual and reproductive needs can help reduce transmission to women and children in the context of concentrated HIV epidemic in Indonesia.

Contains fulltext : 138731.pdf (Publisher’s version ) (Open Access) BackgroundThe HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4+ cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV.MethodsIn this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 inverted question mark> inverted question mark750cell/ inverted question markl & HIV inverted question mark< inverted question mark50 copies for inverted question mark2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands. We determined the CCR5 and CXCR4 expression among CD4+ and CD8+ lymphocyte subsets; memory (CD45RO+), naive (CD45RA+) cells and regulatory T-cells (CD4+CD25highFoxP3+). In addition, CCR5 inverted question mark32 polymorphism is related with disease progression and was therefore determined using polymerase chain reaction.ResultsThe percentage of CCR5-expressing CD4+ cells of LTNP was comparable with healthy controls; whereas HIV-infected individuals showed more CCR5-expressing cells. This was observed in memory and naive CD4+ cells, but not in regulatory T-cells. The mean fluorescence intensity of CCR5-expressing CD4+ cells was similar in all groups. All groups had comparable percentages of CXCR4-expressing cells. The mean fluorescence intensity of CXCR4-expressing cells was significantly higher in HIV-infected normally progressors in both memory and naive CD4+ cells, but not in CD8+ cells. The CCR5 inverted question mark32 polymorphism was not related to group.ConclusionsWe show that HIV affects -directly or indirectly- the expression of CCR5 in CD4+ T-lymphocytes; yet this effect is not seen in LTNP with viral control. Avoiding upregulation of CCR5 could be an important method via which LTNP counteracts the effects of HIV and suppresses viral replication. Exploring how LTNP suppress the upregulation of CCR5 could be an important step for discovering new therapeutics.

Contains fulltext : 138315.pdf (Publisher’s version ) (Open Access) Background: It remains unclear whether the natural course of human immunodeficiency virus (HIV) differs in subjects infected through injecting drug use (IDU) and no data have been published from low- or middle-income countries. We addressed this question in an urban cohort in Indonesia, which is experiencing a rapidly growing HIV epidemic strongly driven by IDU. Methods: All antiretroviral treatment (ART) naive HIV-positive patients who had at least two subsequent CD4 cell counts available before starting ART were included in this study. We examined the association between IDU and CD4 cell decline using a linear mixed model, with adjustment for possible confounders such as HIV viral load and hepatitis C antibodies. Results: Among 284 HIV-positive ART naive patients, the majority were male (56%) with a history of IDU (79% among men). People with a history of IDU had a statistically significant faster decline in CD4 cells (p

Contains fulltext : 127674.pdf (Publisher’s version ) (Open Access) Introduction: Previous studies, mostly from Africa, have shown that serum cryptococcal antigenemia may precede the development of cryptococcal meningitis and early death among patients with advanced HIV infection. We examined cryptococcal antigenemia as a risk factor for HIV-associated mortality in Indonesia, which is experiencing a rapidly growing HIV epidemic. Methods: We included ART-naive HIV patients with a CD4 cell count below 100 cells/muL and no signs of meningitis in an outpatient HIV clinic in Bandung, West Java, Indonesia. Baseline clinical data and follow-up were retrieved from a prospective database, and cryptococcal antigen was measured in stored serum samples using a semiquantitative lateral flow assay. Cox regression analysis was used to identify factors related to mortality. Results: Among 810 patients (median CD4 cell count 22), 58 (7.1%) had a positive cryptococcal antigen test with a median titre of 1:80 (range: 1:1 to 1:2560). Cryptococcal antigenemia at baseline was strongly associated with the development of cryptococcal meningitis and early death and loss to follow-up. After one year, both death (22.4% vs. 11.6%; p=0.016; adjusted HR 2.19; 95% CI 1.78-4.06) and the combined endpoint of death or loss to follow-up (67.2% vs. 40.4%; p