Drop-out of medical follow-up among people living with HIV in Tel-Aviv area.

Access to HIV anti-retroviral treatment (ART) has significantly improved survival and the quality of life of people living with HIV (PLHIV). However, effective therapy necessitates high adherence to ART. The aim of this study was to identify the extent to which PLHIV in Israel were not retained in therapy and their obstacles to accessing care. The Department of Tuberculosis and AIDS (DTA) and the two existing HIV clinics in the Tel-Aviv metropolitan area performed a retrospective study for all PLHIV who were consulted at these clinics during 2008-2011, but were absent in 2012. From that population, 25% were randomly chosen for qualitative interviews. This study included 278 PLHIV not retained in care (13.4% of registered patients), of whom 194 (69.8%) were male, and 58.3% were Israeli citizens. Total number of clinic visits was 1959 (mean: 7.05 visits per patient; range: 1-39; SD: ±7.2) and the total person-years of follow-up for 267 PLHIV was 1,044 (mean: 3.9 py; 0-23; SD: ±4.4). Identified risk groups were: Originating from Generalized Epidemic countries (43.5%, 82.6% were non-Israelis); Men having Sex with Men (22.6%); Injecting Drug Users (12.9%) and Others (28.9%). Among Israelis, major reasons for clinic nonattendance included distance to the clinics and perceived lack of time. The major impediment to seeking care among undocumented migrants was lack of medical insurance. The DTA acted swiftly to make HIV-related services accessible to undocumented migrants. Barriers described by Israeli participants were generally more individual in nature, and should be addressed at the clinic level.

Causes of death and mortality trends of all individuals reported with HIV/AIDS in Israel, 1985-2010.

Background: Highly active antiretroviral therapy (HAART) has changed life-expectancy and mortality trends among people living with HIV/AIDS (PLWHA) since 1996. This retrospective cohort study aimed to assess the mortality epidemiology of PLWHA in Israel and analyze the causes of death. Methods: This cohort study included all adult Israeli-citizens PLWHA between 1985 and 2010 and crossed matched with the Civil Registry to identify those who died. Death certificates were classified into AIDS or non-AIDS deaths related-causes. Standardized mortality-ratio (SMR) represented mortality excess. Results: Of all 5140 PLWHA who were followed-up for 36 955 person-years, 1066 (20.7%) died. The ratio of AIDS-related deaths to non-AIDS related deaths reduced from 1.2:1 before 1996 to 0.6:1 after 1997, and case-fatality rates reduced from 12.0 to 0.9%, respectively (P < 0.001). SMR were 3.0 (95% CI: 2.3-3.5) for males and 3.9 (95% CI: 3.3-4.5) for females. Fatality cases were more likely older Israeli-born males, co-infected with tuberculosis, reported before 1996 and acquired HIV by drug-injection or infected-blood products. Deaths of AIDS-related causes were common among Israeli-born gay men, while non-AIDS deaths were common among those reported after 1997 and drug users. Conclusions: Death rates declined since HAART introduction. Yet, SMR remained high, and PLWHA infected by drug-use or blood-products have not enjoyed relative longevity.

Structure and variation of CRISPR and CRISPR-flanking regions in deleted-direct repeat region Mycobacterium tuberculosis complex strains.

BACKGROUND: CRISPR and CRISPR-flanking genomic regions are important for molecular epidemiology of Mycobacterium tuberculosis complex (MTBC) strains, and potentially for adaptive immunity to phage and plasmid DNA, and endogenous roles in the bacterium. Genotyping in the Israel National Mycobacterium Reference Center Tel-Aviv of over 1500 MTBC strains from 2008-2013 showed three strains with validated negative 43-spacer spoligotypes, that is, with putatively deleted direct repeat regions (deleted-DR/CRISPR regions). Two isolates of each of three negative spoligotype MTBC (a total of 6 isolates) were subjected to Next Generation Sequencing (NGS). As positive controls, NGS was performed for three intact-DR isolates belonging to T3_Eth, the largest multiple-drug-resistant (MDR)-containing African-origin cluster in Israel. Other controls consisted of NGS reads and complete whole genome sequences from GenBank for 20 intact-DR MTBC and for 1 deleted-DR MTBC strain recognized as CAS by its defining RD deletion. RESULTS: NGS reads from negative spoligotype MTBC mapped to reference H37Rv NC_000962.3 suggested that the DR/CRISPR regions were completely deleted except for retention of the middle IS6110 mobile element. Clonally specific deletion of CRISPR-flanking genes also was observed, including deletion of at least cas2 and cas1 genes. Genomic RD deletions defined lineages corresponding to the major spoligotype families Beijing, EAI, and Haarlem, consistent with 24 loci MIRU-VNTR profiles. Analysis of NGS reads, and analysis of contigs obtained by manual PCR confirmed that all 43 gold standard DR/CRISPR spacers were missing in the deleted-DR genomes. CONCLUSIONS: Although many negative spoligotype strains are recorded as spoligotype-international-type (SIT) 2669 in the SITVIT international database, this is the first time to our knowledge that it has been shown that negative spoligotype strains are found in at least 4 different 24 loci MIRU-VNTR and RD deletion families. We report for the first time negative spoligotype-associated total loss of CRISPR region spacers and repeats, with accompanying clonally specific loss of flanking genes, including at least CRISPR-associated genes cas2 and cas1. Since cas1 deleted E.coli shows increased sensitivity to DNA damage and impaired chromosomal segregation, we discussed the possibility of a similar phenotype in the deleted-DR strains and Beijing family strains as both lack the cas1 gene.

Towards tuberculosis elimination: an action framework for low-incidence countries.

This paper describes an action framework for countries with low tuberculosis (TB) incidence (<100 TB cases per million population) that are striving for TB elimination. The framework sets out priority interventions required for these countries to progress first towards "pre-elimination" (<10 cases per million) and eventually the elimination of TB as a public health problem (less than one case per million). TB epidemiology in most low-incidence countries is characterised by a low rate of transmission in the general population, occasional outbreaks, a majority of TB cases generated from progression of latent TB infection (LTBI) rather than local transmission, concentration to certain vulnerable and hard-to-reach risk groups, and challenges posed by cross-border migration. Common health system challenges are that political commitment, funding, clinical expertise and general awareness of TB diminishes as TB incidence falls. The framework presents a tailored response to these challenges, grouped into eight priority action areas: 1) ensure political commitment, funding and stewardship for planning and essential services; 2) address the most vulnerable and hard-to-reach groups; 3) address special needs of migrants and cross-border issues; 4) undertake screening for active TB and LTBI in TB contacts and selected high-risk groups, and provide appropriate treatment; 5) optimise the prevention and care of drug-resistant TB; 6) ensure continued surveillance, programme monitoring and evaluation and case-based data management; 7) invest in research and new tools; and 8) support global TB prevention, care and control. The overall approach needs to be multisectorial, focusing on equitable access to high-quality diagnosis and care, and on addressing the social determinants of TB. Because of increasing globalisation and population mobility, the response needs to have both national and global dimensions.

Antibody response in elderly vaccinated four times with an mRNA anti-COVID-19 vaccine.

The humoral response after the fourth dose of a mRNA vaccine against COVID-19 has not been adequately described in elderly recipients, particularly those not exposed previously to SARS-CoV-2. Serum anti-RBD IgG levels (Abbott SARS-CoV-2 IgG II Quant assay) and neutralizing capacities (spike SARS-CoV-2 pseudovirus Wuhan and Omicron BA.1 variant) were measured after the third and fourth doses of a COVID-19 mRNA vaccine among 46 elderly residents (median age 85 years [IQR 81; 89]) of an assisted living facility. Among participants never infected by SARS-CoV-2, the mean serum IgG levels against RBD (2025 BAU/ml), 99 days after the fourth vaccine, was as high as 76 days after the third vaccine (1987 BAU/ml), and significantly higher (p = 0.030) when the latter were corrected for elapsed time. Neutralizing antibody levels against the historical Wuhan strain were significantly higher (Mean 1046 vs 1573; p = 0.002) and broader (against Omicron) (Mean 170 vs 375; p = 0.018), following the fourth vaccine. The six individuals with an Omicron breakthrough infection mounted strong immune responses for anti-RBD and neutralizing antibodies against the Omicron variant indicating that the fourth vaccine dose did not prevent a specific adaptation of the immune response. These findings point out the value of continued vaccine boosting in the elderly population.

Genomic, phenotypic and demographic characterization of Mycobacterium tuberculosis in Israel in 2021.

According to World Health Organization WHO, Tuberculosis (TB) is the second cause of death from infectious disease worldwide. During 2021, 10.6 million people were infected with TB, and 1.6 million people died. TB is caused by pathogens belonging to the Mycobacterium tuberculosis complex (MTBC), mainly by Mycobacterium tuberculosis (M.tb). Members of this complex are acid-fast bacilli, which can cause intrapulmonary and extra pulmonary TB, and can be divided into various lineages, based on genomic markers. The main public health threat comes from drug resistant M.tb strains, which are responsible for about 25% of TB death and treatment failure worldwide. Treating drug resistant TB patients significantly raises the costs of TB treatment. This study provides an overview of the demographic and drug susceptibility characteristics of newly diagnosed TB patients in Israel in 2021. The State of Israel has a very low level of TB endemicity and is at a pre-elimination phase. Notably, only 11.7% of the newly diagnosed TB patients were born in Israel. In this report, of the 154 new laboratory-confirmed TB patients, 66.7% had pulmonary TB, while 16% had extrapulmonary TB. Males accounted for 52% of the patients, with the most prevalent age group being 21-40. Most patients were citizens of Israel (53.9%), while 37.7% had no Israeli citizenship. Among non-citizens, there was a predominance of males and patients aged 21-40. The susceptibility profile showed a high resistance rate to streptomycin (18.2%) and to a lower extent to isoniazid (13.6%), pyrazinamide (8.4%), rifampicin (7.8%), and ethambutol (3.2%). Only 2 cases of XDR-TB and 10 MDR-TB strains were detected in Israel in 2021, with both XDR strains and 5 out of 10 MDR strains belonging to the Beijing lineage. Most of Beijing isolates were resistant to at least one tested drug. Genomic sequencing of 134 out of 156 strains and bioinformatics analysis using the MTBseq program and WHO mutation catalogue shows a good match with only 9 discrepancies between phenotypic and genotypic susceptibility profiles in first line drugs. The most common lineage is Delhi-Cas (23%) followed by the Beijing lineage (17%). Most patients from the Delhi-Cas lineage were born in Africa, while patients with Beijing isolates were born in different countries. Minimum spanning tree analysis identified 15 clusters. The study highlights the need for ongoing surveillance of TB using molecular and phenotypic tools to further decreasing the spreading level of the disease and develop effective treatment strategies.

High-risk behaviour in steady and in casual relationships among men who have sex with men in Israel.

OBJECTIVE: To explore the differences in sexual risk behaviour between men who have sex with men (MSM) with steady partners versus casual partner(s) in the gay community. METHODS: This online cross-sectional convenience-sampling study assessed MSM practices, their knowledge and their motivation regarding safe sex. Participants not knowing their HIV status or who performed insertive or receptive unprotected anal intercourse (UAI) or with a sex partner whose HIV status was unknown or discordant were considered 'at-risk'. RESULTS: Of all 2569 participants who completed the questionnaire, 907/2569 (35.3%) had a steady partner, and 896/2569 (34.9%) had a casual partner(s) in the past 6 months. 262/907 (28.9%) with steady partners and 248/896 (27.7%) with casual partners demonstrated at-risk sexual behaviour. Of all participants with steady partners, 108/907 (11.9%) performed UAI with their partner without undergoing mutual HIV testing. Of all participants with steady partners, 476/907 (52.5%) had a concurrent casual partner, and 144/476 (30.3%) performed UAI with both the steady and the casual partner. Of all participants with steady partners, 775/907 (85.4%) negotiated the possibility of sex outside their relationship with their main partner. The length of the steady relationship correlated with the number of concurrent casual partners. CONCLUSIONS: At-risk sexual behaviour was associated with insufficient negotiation skills, difficulties in condom use and a general risk-taking profile. Health educators should encourage MSM with steady partners to perform HIV testing before practising UAI, to improve their negotiation skills during the contact and to support open discussions with regard to sexual contact besides the steady relationship, as it may not be monogamous.

A comparative examination of tuberculosis immigration medical screening programs from selected countries with high immigration and low tuberculosis incidence rates.

BACKGROUND: Tuberculosis (TB) in migrants is an ongoing challenge in several low TB incidence countries since a large proportion of TB in these countries occurs in migrants from high incidence countries. To meet these challenges, several countries utilize TB screening programs. The programs attempt to identify and treat those with active and/or infectious stages of the disease. In addition, screening is used to identify and manage those with latent or inactive disease after arrival. Between nations, considerable variation exists in the methods used in migration-associated TB screening. The present study aimed to compare the TB immigration medical examination requirements in selected countries of high immigration and low TB incidence rates. METHODS: Descriptive study of immigration TB screening programs. RESULTS: 16 out of 18 eligible countries responded to the written standardized survey and phone interview. Comparisons in specific areas of TB immigration screening programs included authorities responsible for TB screening, the primary objectives of the TB screening program, the yield of detection of active TB disease, screening details and aspects of follow up for inactive pulmonary TB. No two countries had the same approach to TB screening among migrants. Important differences, common practices, common problems, evidence or lack of evidence for program specifics were noted. CONCLUSIONS: In spite of common goals, there is great diversity in the processes and practices designed to mitigate the impact of migration-associated TB among nations that screen migrants for the disease. The long-term goal in decreasing migration-related introduction of TB from high to low incidence countries remains diminishing the prevalence of the disease in those high incidence locations. In the meantime, existing or planned migration screening programs for TB can be made more efficient and evidenced based. Cooperation among countries doing research in the areas outlined in this study should facilitate the development of improved screening programs.

HIV Pre-Exposure Prophylaxis (PrEP) purchase patterns and STI occurrence among Israeli men: A cohort analysis.

BACKGROUND: HIV Pre-exposure prophylaxis (PrEP) is the regular use of antiretroviral medication by people who are not infected with HIV to prevent seroconversion. Israel approved PrEP for continuous use in 2017, and Israeli Health Maintenance Organizations (HMO) offered PrEP with a copayment to eligible members. METHODOLOGY: This retrospective cohort study included all people who were dispensed PrEP between September 2017 to June 2019 in the second largest HMO in Israel. Statistical analysis, including Kaplan Meier, was conducted to evaluate user PrEP purchase, adherence to medical follow-up, and clinical outcomes. RESULTS: In total, a cohort of 757 PrEP users were followed for 657.8 person-years. All but one user were male; median age was 35 years. At baseline, 0.8% had gonorrhea and 1.5% had chlamydia infections and 4.4% had recent syphilis infection. Continuous use of PrEP (without interruption/discontinuation) was observed in 29.9%, while 39.9% interrupted and 30.3% discontinued use. Median time to first interruption/discontinuation was 4.0 months. At 6-12 months after initiation, 79.8% of users had a documented HIV test, 77.3% a Chlamydia-Gonorrhea panel, and 78.9% a creatinine test. There was one new case of HIV among the cohort, five months after PrEP discontinuation. Estimated first-year infection rates were 5.0%, 8.6% and 6.8% for gonorrhea, chlamydia and first-time syphilis, respectively. CONCLUSIONS: This study shows heterogeneous PrEP purchase patterns and required medical follow-up, and an increase in STIs among consistent PrEP users. Improving adherence to recommended medical follow-up during PrEP use is essential in PrEP's integration into Israel's national HIV prevention strategy.

Epidemiology and Transmitted HIV-1 Drug Resistance among Treatment-Naïve Individuals in Israel, 2010-2018.

Despite the low prevalence of HIV-1 in Israel, continuous waves of immigration may have impacted the local epidemic. We characterized all people diagnosed with HIV-1 in Israel in 2010-2018. The demographics and clinical data of all individuals (n = 3639) newly diagnosed with HIV-1 were retrieved. Subtypes, transmitted drug-resistance mutations (TDRM), and phylogenetic relations, were determined in >50% of them. In 39.1%, HIV-1 transmission was through heterosexual contact; 34.3% were men who have sex with men (MSM); and 10.4% were people who inject drugs. Many (>65%) were immigrants. Israeli-born individuals were mostly (78.3%) MSM, whereas only 9% of those born in Sub-Saharan Africa (SSA), Eastern Europe and Central Asia (EEU/CA), were MSM. The proportion of individuals from SSA decreased through the years 2010-2018 (21.1% in 2010-2012; 16.8% in 2016-2018) whereas those from EEU/CA increased significantly (21% in 2010-2012; 27.8% in 2016-2018, p < 0.001). TDRM were identified in 12.1%; 3.7, 3.3 and 6.6% had protease inhibitors (PI), nucleotide reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI) TDRM, respectively, with the overall proportion remaining stable in the studied years. None had integrase TDRM. Subtype B was present in 43.9%, subtype A in 25.2% (A6 in 22.8 and A1 in 2.4%) and subtype C in 17.1% of individuals. Most MSM had subtype B. Subtype C carriers formed small clusters (with one unexpected MSM cluster), A1 formed a cluster mainly of locally-born patients with NNRTI mutations, and A6 formed a looser cluster of individuals mainly from EEU. Israelis, <50 years old, carrying A1, had the highest risk for having TDRM. In conclusion, an increase in immigrants from EEU/CA and a decrease in those from SSA characterized the HIV-1 epidemic in 2010-2018. Baseline resistance testing should still be recommended to identify TDRM, and improve surveillance and care.

HIV outbreaks among people who inject drugs in Europe, North America, and Israel.

During 2011-16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks.

Rationale and staff evaluation of using a "therapeutic milieu" for substance users within a tuberculosis ward.

Approximately 30% of tuberculosis (TB) patients in Israel were treated, in part, in two dedicated hospital wards during the years 2003-2005. A portion of them manifested severe psychosocial conditions. An intervention based on the "Therapeutic Milieu" (TM) model was implemented in the larger ward and included a staff evaluation of this intervention. The concept of TM, based on psychosocial paradigms and behavioral medicine, is aimed at providing a supportive environment for patients. Weekly group patients' meetings and monthly group staff supervisions were performed during 15 months (2003-2005). Forty of the 196 (20%) TB patients, mainly "complex," and 13 of 20 staff members (65%) attended regularly and discussed how to deal with substance abuse, personality disorders, and immigration-related crises. Out of 40 TB cases, 30 (75%) were also substance users. Ten staff members self-analyzed the impact of this intervention in terms of (1) having given adequate tools for the staff, (2) reducing physical violence, (3) increasing adherence to TB treatment, and (4) more efficient treatment for their substance use. No direct evaluation was done among the TB patients. According to staff members, this intervention had a positive overall impact. However, using Therapeutic Milieu in TB ward hospitalization, as a "window of opportunity," remains the first step in a longer journey for rehabilitation. The study's limitations are noted.

The risk of tuberculosis in cancer patients is greatest in lymphoma and myelodysplastic syndrome/myeloproliferative neoplasm: a large population-based cohort study.

Patients with cancer are at high risk for tuberculosis (TB). This study combined the Israeli databases of cancer and TB and examined the development of TB among all newly diagnosed cancer cases from 1993 to 2013. Patients were classified into groups according to their different malignancies. Among 495,335 cancer patients, 335 developed TB following cancer diagnosis. The cumulative incidence of TB following cancer diagnosis was highest among MDS/MPN (148.8/100,000 patients) and lymphoma (154.1/100,000 patients) (p = .023). The HR of TB following cancer among hematologic patients was 2.51 (p < .001), relative to patients with in situ carcinomas/skin cancer and highest among MDS/MPN and lymphoma patients (2.74, p = .012 and 2.70, p < .001, respectively). Among lymphoma patients, a significant increased HR was found only among NHL patients (2.72, p < .001). The limitations include lack of information regarding risk factors for TB and of anti-cancer treatments. In conclusion, these data may encourage a heightened awareness for TB among patients with a background of lymphoma and MDS/MPN.

Ensuring HIV care to undocumented migrants in Israel: a public-private partnership case study.

BACKGROUND: Undocumented migrants in Israel, mostly originating from HIV endemic countries, are not covered by Israel's universal healthcare coverage. We initiated a Public-Private Partnership (PPP) to handle this public health and humanitarian challenge. The PPP venture included the Ministry of Health (MoH), pharmaceutical companies, pharmacies, and specialized HIV clinics, the Israeli HIV Medical Society (from the Israel Medical Association), and non-governmental organizations. This study describes the national policy process in conceptualizing and implementing access to HIV services for undocumented migrants through a PPP, and analyzes the preliminary results. METHODS: This case study describes the process of creating a temporary Public-Private Partnership to provide HIV care for undocumented migrants based on institutional records of the Department of Tuberculosis and AIDS (DTA) and memories and reflections from partners. This case was analyzed according to the OECD-DAC criteria for development assistance (relevance, effectiveness, efficiency, sustainability and impact). Demographic and serological data of patients referred between 2014 to 2018 were collected to monitor progress. and analyze preliminary medical and biological outcomes. Ethical approval was obtained from the Ministry of Health. RESULTS: Creating a policy to extend HIV care to undocumented migrants was a 15 year process that confronted several challenges within Israeli and international discourse, particularly concerning governmental response to the migration crisis. The use of a PPP model involving numerous stakeholders provided a solid, local feasibility demonstration that extending HIV care as a matter of policy would have positive implications for public health in Israel. During the first 2 years of the program (2014-2015), the MoH funded medical follow-up and the pharmaceutical companies provided antiretroviral treatment (ART) free of charge for only 100 patients at any given time, in addition to ART provided by the MoH for pregnant women. Since 2016, the MoH has fully covered this service and integrated it within the Israeli health system; this constitutes the major success of the PPP program. As of December 2018, the national program has monitored 350 patients and treated 316 (90.3%). The most prevalent disease present upon referral was Tuberculosis. CONCLUSIONS: To our knowledge, this study documents the first example of a successful PPP with government partnership in a high-income country to address undocumented migrants' lack of access to health services in general and HIV care in particular. In light of the intensification of North-South migration, this Israeli case study could be useful for other countries facing similar challenges. It also has lessons within Israel, as the country grapples with other health problems among uninsured communities.

Tuberculosis behind bars in Israel: policy making within a dynamic situation.

BACKGROUND: The crowded environment of correctional facilities may enhance infectious diseases transmission, such as tuberculosis. OBJECTIVES: To define the tuberculosis burden in prisons in Israel, a country of low TB incidence (7.9 cases:100,000 population in 2004), in which about 13,000 inmates are being incarcerated annually, and to recommend policy adaptations for TB control. METHODS: All prison clinic lung records from 1998 through 2004 in Israel were reviewed to identify pulmonary TB patients. Additionally, we reviewed TB epidemiological investigation files from one northern prison (years 2002 through 2005) to evaluate possible transmission of the disease. RESULTS: During the study period 23 Israeli inmates had pulmonary TB (25 cases/100,000 prisoners), which was 3.5 times higher than in the general population. Of those, 18 (78%) were born in the Former Soviet Union and immigrated to Israel after 1990. Four pulmonary TB cases in the evaluated prison were reported, and 22% (149/670) of all inmates and staff were referred for treatment of latent TB infection. CONCLUSIONS: To prevent future TB cases, we recommend new prevention measures, including a symptom questionnaire for all new inmates and selective tuberculin skin testing for inmates infected with human immunodeficiency virus/AIDS, those who inject drugs, and those who emigrated from the former Soviet Union after 1990. New staff should be screened by the two-step tuberculin skin test and annual symptoms questionnaire thereafter. Incarceration may be used as a point of detection for TB and a window of opportunity for treatment in this hard-to-reach population.

["Injecting clean or being clean?" The international and Israeli experiences of Syringe Exchange Programs among injecting drug users].

Injecting drug users (IDU) are a hard-to-reach population. The treatment objectives are to reduce their risk factors, to guide them to total abstinence or to antagonist treatment. When IDU are not ready for detoxification, they are referred to Syringe Exchange Programs (SEP). The objective of SEP is harm reduction of blood-borne viruses (of HIV, HBV, HCV). The authors aimed to define the issues related to harm reduction, to discuss the results of SEP in the world, and to describe our experience. We analyzed the world literature and our experience. In this article, we describe the rehabilitation school of thought (which supports complete drug abstinence), the harm reduction school of thought (which refers to drug addiction as a chronic disease), and the possible continuum between these two schools of thought. The AIDS pandemic and the epidemiology of world drug addiction by injection are described, together with the principles of SEP and their evaluation in the world. In addition, we describe drug use in Israel and HIV infection among IDU. Finally, we analyze our preliminary results of the SEP pilot in Israel, during the years 2004-2005, and included 462 IDUs. In conclusion, considering the difficulties that exist with IDUs, most articles emphasize the importance of SEP in this population while sometimes also expressing its effectiveness in preventing transmissions of blood-borne viruses. In Israel, a pilot project has existed since the end of 2003, and has expanded progressively to three cities. An overall evaluation of this program is under preparation.

Use of Geographically Weighted Poisson Regression to examine the effect of distance on Tuberculosis incidence: A case study in Nam Dinh, Vietnam.

OBJECTIVES: This study aimed to examine the potential of combining routine tuberculosis (TB) surveillance and demographic and socioeconomic variables into the Geographic Information System (GIS) to describe the geographical distribution of TB notified incidence in relation to distances to health services as well as local demographic and socioeconomic factors, including population density, urban/rural status, and household poverty rates in Nam Dinh, Vietnam. It also aimed to compare the conventional Generalized Linear Models (GLM) Poisson regression model and Geographically Weighted Poisson Regression (GWPR) models in order to determine the best fitting model that can be used to investigate the relationship between TB notified incidence and distances and the social risk factors. METHODS: The data of new and relapse patients with all forms of TB aged ≥15 years residing in Nam Dinh (Vietnam) from 2012 to 2015 were collected from the Administration of Medical Services' (Ministry of Health of Vietnam) TB surveillance database. Data on the population and household poverty rates from 2012 to 2015 were gathered from the Nam Dinh Statistical Office. Distances between communes and the nearest TB diagnostic facilities in districts were computed. The TB notified incidence per 100,000 population was denoted by indirect age and sex standardized incidence ratio. GLM Poisson regression and GWPR were performed to assess the relationship between distance and TB incidence. RESULTS: The average notified TB incidence level measured from 2012 to 2015 is 82 per 100,000 population (range: 79-84/100,000). The distance to the nearest TB diagnosis presents a negative effect on TB notified incidence. By capturing spatial heterogeneity, the GWPR may be better at fitting data (corrected Aikake information criterion [AICc] = 245.71, residual deviance = 221.12) than the traditional GLM (AICc = 251.53, residual deviance = 241.21). CONCLUSIONS: GIS technologies benefit TB surveillance system. Distances should be considered when planning methods of improving access for those who live far from TB diagnostic services, thereby improving TB detection. Additional studies must confirm the association between geographic distance and TB case detection and must explore other factors that may affect TB notified incidence.

Evaluation of the virtues and pitfalls in an HIV screening algorithm based on two fourth generation assays - A step towards an improved national algorithm.

BACKGROUND: Fourth-generation immunoassays used for HIV screening, simultaneously detect anti-HIV antibodies and HIV-1 P24 antigen, but are prone to false-positive results. Usually, they are followed by highly specific third-generation assay, able to differentiate between HIV-1/2 infections. In Israel, screening algorithm is based on consecutive testing by two fourth-generation assays and confirmation by a third-generation test. OBJECTIVES: To evaluate the performance of this algorithm. STUDY DESIGN: Architect HIV1/2 Combo (Combo) reactive results were tested by Vidas HIV Duo Ultra (VD). Confirmation was by INNO-LIA HIV 1/2 or Geenius assays. Five-year results were retrospectively analyzed. HIV true positives (TPs), acute infected (AI), false-positives (FPs) and HIV negatives, were as defined by the algorithm. RESULTS: 501,338 individuals were screened, of which 956 were TPs, 64 AI and 30 F Ps. Specificity was almost 100% and positive predictive value 97%. VD was negative in 94% of confirmed Combo false-reactive individuals. The Combo results in the first tested sample differed substantially between TPs, AI and FPs, enabling the determination of a cutoff value that distinguished 94% of TPs and AI from FPs. CONCLUSIONS: An algorithm is suggested that will use a single sample collection. HIV negative diagnosis will be based on Combo unreactive or Combo reactive/VD negative results. HIV positive diagnosis will be based on Combo reactive/ VD positive results, given a Combo value above a designated cutoff. Below this cutoff samples will be tested by a molecular assay. Since HIV-2 rarely occurs in Israel, the use of a third-generation confirmation assay should be discussed.

Diagnosis of HIV-1 infection: Performance of Xpert Qual and Geenius supplemental assays in fourth generation ELISA-reactive samples.

BACKGROUND: Architect (AR) and Vidas (VD) fourth generation HIV screening immunoassays, which identify early stages of HIV infections, could have false positive results especially at low signal/cutoff (S/C) AR values. Geenius HIV1/2 (GS) is a specific confirmation line immunoassay that is not highly sensitive to early HIV infections. An HIV-1 RNA assay may better detect such infections. OBJECTIVES: To evaluate all AR-VD reactive samples with GS results, and to assess Xpert Qual HIV-1 RNA assay (XQ) as an alternative to GS, in the first low S/C AR-VD-reactive samples from a tested individual. STUDY DESIGN: First AR-VD-reactive-GS-tested results from all individuals with resolved HIV status, collected between March 2015 and March 2017 (n = 749), were retrospectively assessed. Samples with AR-VD-reactive-GS-discordant results and those with low S/C AR-VD-reactive results, were tested by XQ. Receiver operating characteristic (ROC) analysis of GS and XQ sensitivity/specificity was performed. RESULTS: Overall, 94.1% (705/749) of AR-VD-reactive results were true HIV-1 positive. All samples with <3 S/C AR values were false positive. XQ resolved all first samples with AR-VD-reactive-GS-discordant results. The diagnostic accuracy of XQ in low (≤33 S/C) AR-VD-reactive samples was better than that of GS (97.6%, 81/83 versus 73.5%, 61/83, p < 0.01). ROC analysis for low S/C AR samples was optimal for pooled XQ and GS results. CONCLUSIONS: Incorporating XQ in the current screening algorithm for the first AR-VD-reactive-GS-discordant samples may significantly reduce overall turn-around time of HIV-1 diagnosis.