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.

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.

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.

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.

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.

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.

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.

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.

A national strategic plan for reducing the burden of sexually transmitted infections in Israel by the year 2025.

BACKGROUND: There is on ongoing debate in the literature regarding the real burden of STIs (sexually transmitted infections) in Western countries and the proper strategies needed to estimate and to prevent them. Our purpose is to present an evidence-based national strategic plan for STI prevention in Israel through assessing the current burden of illness, leading international preventive strategies, and practical policymaking experience. METHODS: Epidemiologic and health policy data on STIs were analyzed from various sources: a) systematic national surveillance data for the years 2002-2014; b) the international scientific literature (published between 2002-16; keywords: Sexually Transmitted Diseases (STD) (or STI) AND prevention AND intervention AND gonorrhea OR chlamydia OR syphilis; c) internal Ministry of Health (MOH) analyses and reports, and d) expert opinion. RESULTS: Incidence rates in Israel of Chlamydia trachomatis (chlamydia), Neisseria gonorrhea (gonorrhea) and Treponema pallidum (syphilis) are lower than in most Western countries. However, rates vary among population subgroups: chlamydia, gonorrhea and syphilis are higher in Jews than in non-Jews, and this gap has increased for chlamydia over the past decade. Primary and secondary syphilis rates have increased among men having sex with men (MSM). It is likely that STIs are under-reported and that incidence is even rising due to migration. A key recommendation is the establishment of an active surveillance system of STIs, utilizing active case finding in high risk populations, along with regular contact with STI clinics run by the four national health management organizations and by the MoH. As with most European countries, the low prevalence of chlamydia and gonorrhea does not justify population-wide screening. Conversely, the increasing incidence of syphilis among MSM should lead to regular screening among this group. CONCLUSIONS: A national STIs prevention strategy for the year 2025 was presented. Although the current burden of illness is low relatively to other Western countries, this is thought to reflect a certain degree of underreporting. These and other gaps suggest a need for focused epidemiologic and health services research to better characterize health risk behaviors as well as provider practice patterns. Innovative implementation strategies have been described, together with the capacity building components needed for developing specific and implementable policy recommendations for the year 2025.

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.

Invasive pneumococcal disease (IPD) in HIV infected patients in Israel since the introduction of pneumococcal conjugated vaccines (PCV): Analysis of a nationwide surveillance study, 2009-2014.

STUDY AIM: to assess the incidence, risk factors and outcome of invasive pneumococcal disease (IPD) among the Israeli HIV population. A matched case-control study nested in a nationwide, prospective, population-based, cohort of adult IPD was performed. In addition, the HIV-IPD patients were compared to the general adult HIV population in Israel. STUDY PERIOD: from the introduction of PCV into the national immunization program (NIP) in July 2009 to June 2014. Each HIV patient within the IPD cohort was matched to 4 non-HIV controls. Serotyping was performed by a central laboratory using the Quellung reaction. Thirty-five IPD episodes in 33 HIV patients were identified, with a median annual incidence of 128/100,000 HIV+ persons compared to 5.1/100,000 in the age-matched, non-HIV population. Compared to the general HIV population, HIV-IPD patients practiced intravenous drug use more frequently and originated from a country with generalized epidemic (OGE), mainly non-citizens lacking medical insurance. The proportion of men who have sex with men (MSM) was lower than in the general HIV population. Pneumonia was the most common clinical presentation (81%), while meningitis occurred in only one patient. Outcomes were similar to those of the IPD non-HIV population. Nineteen serotypes were identified, of which only 42% were covered by PCV13 vaccine. By 2014, none of the HIV-IPD cases belonged to serotypes covered by PCV13. In conclusion, most HIV IPD cases were from marginalized populations with poor access to health services. A decrease in IPD cases covered by PCV 13 was observed.

Should Men who have sex with Men be allowed to donate blood in Israel?

BACKGROUND: The present permanent deferral policy in Israel for MSM was established in 1977 and was based on the previous (now outdated) USA Food and Drug Administration standards. This study analyses epidemiological data regarding blood donations among MSM, in order to estimate the risk for HIV transfusion transmitted infection (TTI) if the policy is changed to allow at-risk MSM to donate blood. METHODS: An Excel based spreadsheet model integrated demographic, epidemiological data from the HIV National Register, laboratory, blood donation and testing data in order to calculate TTI due to false-negatives in known HIV+ donors, windows period donations, asymptomatic carriers and laboratory misclassification errors. A sensitivity analysis of our estimated TTIs for deferral periods for MSM was performed based on a literature review regarding this overall policy issue worldwide. RESULTS: MSM in Israel have a considerably higher relative risk (RR) of both prevalence (115) and incidence (143) of being HIV+ than persons without a risk factor. Allowing MSM to donate blood, without any deferral period, will add an additional five HIV TTI cases over the next decade. Imposition of a 1 or 5 years deferral of abstinence will increase the number of HIV TTI cases only by 0.10 and 0.05 cases, respectively. CONCLUSION: A 1 year deferral period for blood donations from MSM in Israel is recommended.

Impact of Male Circumcision among heterosexual HIV cases: comparisons between three low HIV prevalence countries.

BACKGROUND: Studies performed in high-HIV prevalence countries showed a strong epidemiological association between male circumcision (MC) and the prevention of HIV transmission. We estimated the potential impact of MC on the general heterosexual population in low-HIV prevalence countries. METHODS: Cross-national comparisons, including data on newly diagnosed HIV cases among heterosexuals living in Israel (where almost all males undergo MC), to similar data from the Netherlands and France (where <10 % of males are circumcised) were performed. National data from HIV registers and Bureaus of Statistics for the period of 2004-2010, global rates, rates by sex, age, and year of HIV-diagnosis were compared. MC and potential biases were examined. RESULTS: Annual rates of new HIV diagnoses per 100,000 were significantly lower in Israel compared to the Netherlands and France (for men: 0.26-0.70, 1.91-2.28, and 2.69-3.47, respectively; for women: 0.10-0.34, 1.10-2.10 and 2.41-3.08, respectively). Similarly, HIV-rates were much lower in Israel when comparing by age groups. Although Gross National Income per capita in 2010 was lower in Israel compared to the Netherlands and France, access to HIV testing and treatment were not different between countries. Also, the number of sexual-partners and condom-use in the general population showed a high similarity between the countries. CONCLUSIONS: The lower rate of HIV among heterosexuals in Israel compared to the Netherlands and France might be explained by MC routinely practiced in Israel, since other parameters of influence on HIV transmission were rather similar between the countries. However, recommendation for systematic MC in low HIV prevalence countries requires further investigations.

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.