Impact of COVID-19 & Response Measures on HIV-HCV Prevention Services and Social Determinants in People Who Inject Drugs in 13 Sites with Recent HIV Outbreaks in Europe, North America and Israel.

HIV/HCV prevention among people who inject drugs (PWID) is of key public health importance. We aimed to assess the impact of COVID-19 and associated response measures on HIV/HCV prevention services and socio-economic status of PWID in high-HIV-risk sites. Sites with recent (2011-2019) HIV outbreaks among PWID in Europe North America and Israel, that had been previously identified, were contacted early May 2020. Out of 17 sites invited to participate, 13 accepted. Semi-structured qualitative site reports were prepared covering data from March to May 2020, analyzed/coded and confirmed with a structured questionnaire, in which all sites explicitly responded to all 103 issues reported in the qualitative reports. Opioid maintenance treatment, needle/syringe programs and antiretroviral treatment /hepatitis C treatment continued, but with important reductions and operational changes. Increases in overdoses, widespread difficulties with food and hygiene needs, disruptions in drug supply, and increased homelessness were reported. Service programs rapidly reformed long established, and politically entrenched, restrictive service delivery policies. Future epidemic control measures should include mitigation of negative side-effects on service provision and socio-economic determinants in PWID.

RESUMEN: La prevención del VIH/VHC entre las personas que se inyectan drogas (PWID) es de vital importancia para la salud pública. Nuestro objetivo fue evaluar el impacto de COVID-19 y las medidas de respuesta asociadas en los servicios de prevención del VIH/VHC y el estado socioeconómico de las PWID en sitios de alto riesgo de VIH. Se contactó con sitios con brotes recientes (2011­2019) de VIH entre PWID en Europa, América del Norte e Israel, que habían sido previamente identificados, a principios de mayo de 2020. De los 17 sitios invitados a participar, 13 aceptaron. Se prepararon informes cualitativos semiestructurados del sitio que cubrían los datos de marzo a mayo de 2020, analizados/codificados y confirmados con un cuestionario estructurado, en el que todos los sitios respondieron explícitamente a los 103 asuntos reportados en los informes cualitativos. El tratamiento de mantenimiento con opiáceos, los programas de agujas/jeringas y el tratamiento antirretroviral/tratamiento de la hepatitis C continuaron, pero con importantes reducciones y cambios operativos. Se reportaron aumentos en las sobredosis, dificultades generalizadas con las necesidades alimentarias y de higiene, interrupciones en el suministro de medicamentos y aumento de personas sin hogar. Los programas de servicios reformaron rápidamente las políticas restrictivas de prestación de servicios, establecidas desde hace mucho tiempo y políticamente arraigadas. Las futuras medidas de control de epidemias deben incluir la mitigación de los efectos secundarios negativos en la prestación de servicios y los determinantes socioeconómicos en las PWID.

Tuberculosis treatment outcomes of non-citizen migrants: Israel compared to other high-income countries.

BACKGROUND: In TB low incidence countries, the outcome of TB treatment among non-citizen migrants from endemic countries affects ability to eliminate TB. This study compares TB treatment outcomes among non-citizen migrants in select pre-elimination country based on their policies for non-citizen migrant TB patients in order to determine how policy affects TB outcomes. METHODS: A literature review was conducted via PUBMED, MEDLINE (2000-2017) on TB policy among non-citizen migrants and treatment outcome. Treatment outcome among migrants diagnosed in Israel during 2000-2014 was analysed. RESULTS: In total, 18 publications met the inclusion criteria. All the countries reviewed except the United States offered free TB treatment to undocumented migrants. Successful TB treatment outcome for non-citizen migrants in Israel was 87%, the Netherlands was 90.7%, the UK was 82.1%, and outcomes in the US and Australia were not published. CONCLUSIONS: There is a need to standardize results based on international definitions of migrants, asylum seekers, and refugees in order to determine status-specific barriers and to facilitate international comparisons. Policies insuring free access to TB care for non-citizen migrants are an important element for TB elimination in low incidence countries.

Ongoing tuberculosis transmission among second-generation Ethiopian immigrants.

Despite considerable efforts to control tuberculosis (TB) among Ethiopian immigrants in Israel, an outbreak of TB among second-generation Ethiopian immigrants that involved native Israelis occurred between January 2011 and December 2019. The aim of this article is to report on this outbreak and discuss the patient and health system barriers that led to its propagation. Overall, 13 culture-positive TB patients were diagnosed in this outbreak. An additional 36 cases with identical mycobacterium tuberculosis genotypes were identified through cross-checking with the National TB Laboratory Registry. Among the 32 close contacts of the index case, 18 (56.3%) reported for screening and treatment of latent TB infection (LTBI) was recommended for 11 (61.1%) of them. However, none completed treatment and eight eventually developed TB. Of the 385 close contacts identified in this outbreak, 286 (74.3%) underwent contact investigation, 154 (53.8%) were recommended LTBI treatment, but only 26 (16.9%) completed the treatment. Routine contact investigation and treatment practice measures failed to contain the cascade of infection and disease, leading to the spread of the infecting strain of TB. This report highlights the challenges to identify the high-risk group and address barriers to care among such a vulnerable population.

Cost utility analysis of HIV pre exposure prophylaxis among men who have sex with men in Israel.

BACKGROUND: Between 2011 and 2015, Men who have sex with men (MSM) accounted for nearly half of new HIV cases among men in Israel. This study carries out a cost-utility analysis of PrEP (HIV Pre Exposure Prophylaxis), an antiretroviral medication that can protect against the acquisition of HIV infection, whose incidence rate in Israel is around 1.74 per 1000 MSM. METHOD: Epidemiological, demographic, health service utilisation and economic data were integrated into a spread-sheet model in order to calculate the cost per averted disability-adjusted life year (DALY) of the intervention from a societal perspective, in mid-2018 US$ using a 3% discount rate. Cost utility analyses were performed for both types of PrEP delivery (continuous regimen and on-demand), together with sensitivity analyses on numbers of condom users who take up PrEP (baseline 25%) and subsequently abandon condom use (baseline 75%), PrEP efficacy (baseline 86%), PrEP prices and monitoring costs. RESULTS: Around 21.3% of MSM are high risk (as defined by having unprotected anal intercourse). Offering PrEP to this group would have a ten year net cost of around 1563 million USD, preventing 493 persons from becoming HIV-positive, averting around 1616 DALYs at a cost per averted DALY of around 967,744 USD. This will render the intervention to be not cost-effective. PrEP drug prices would have to fall dramatically (by 90.7%) for the intervention to become cost-effective (i.e. having a cost per averted DALY less than thrice GNP per capita) in Israel. PrEP remains not cost-effective (at 475,673 USD per averted DALY) even if intervention costs were reduced by using an "on demand" instead of a daily schedule. Even if there were no changes in condom use, the resultant 411,694 USD cost-utility ratio is still not cost-effective. CONCLUSIONS: Despite PrEPs high effectiveness against HIV, PrEP was found not to be cost-effective in the Israeli context because of a combination of relatively low HIV incidence, high PrEP costs, with a likelyhood that some low-risk MSM (ie: who use condoms) may well begin taking PrEP and as a consequence many of these will abandon condom use. Therefore, ways of minimizing these last two phenomena need to be found.

HIV infection among men who have sex with men in Israel: a 35-year epidemiological and clinical overview, 1981-2015.

BACKGROUND: This study is the first to describe major epidemiological trends and clinical characteristics among Israeli men who have sex with men (MSM), who are at a higher risk for HIV infection. METHODS: This retrospective study includes all individuals reported to the Israeli Ministry of Health with HIV and self-identified as MSM between 1981 and 2015. The incidence rates of HIV infection and AIDS-defining diseases were analyzed and Kaplan-Meier survival estimates were calculated from time of HIV infection notification to AIDS diagnosis and death across three consecutive periods representing antiretroviral treatment availability. RESULTS: The trend of increase in HIV incidence is similar to Western Europe, although Israeli rates are lower. Of 2052 HIV/AIDS Israeli MSM diagnosed during the follow-up, 296 (14.6%) developed AIDS. MSM constitute 28.4% of all HIV/AIDS cases and 41.5% of cases among men. Average times from HIV-notification until AIDS diagnosis were 15.5 [14.0-16.9], 16.0 [15.5-16.4], and 6.7 [6.7-6.8] years, within 1981-1996, 1997-2007, and 2008-2015, respectively. The HIV-incidence rate among Israeli MSM slightly declined from 2012, after peaking in 2011 at 6.2 per 100,000. CONCLUSIONS: The recent reduction in HIV-incidence and in AIDS diagnoses among Israeli MSM is encouraging. Nevertheless, the disproportionate incidence of HIV among MSM requires sustained efforts to abate further infections.

Identification and characterization of HIV positive Ethiopian elite controllers in both Africa and Israel.

OBJECTIVES: HIV elite controllers (ECs) are a unique subgroup of HIV-positive patients who are long-term virologically suppressed in the absence of antiretroviral treatment (ART). The prevalence of this subgroup is estimated to be < 1%. Various cohorts of ECs have been described in developed countries, most of which have been demographically heterogeneous. The aim of this study was to identify ECs in two large African cohorts and to estimate their prevalence in a relatively genetically homogenous population. METHODS: We screened two cohorts of HIV-positive Ethiopian patients. The first cohort resided in Mekelle, Ethiopia. The second was comprised of HIV-positive Ethiopian immigrants in Israel. In the Mekelle cohort, ART-naïve subjects with stable CD4 counts were prospectively screened using two measurements of viral load 6 months apart. Subjects were defined as ECs when both measurements were undetectable. In the Israeli cohort, subjects with consistently undetectable viral loads (mean of 17 viral load measurements/patient) and stable CD4 count > 500 cells/µL were defined as ECs. RESULTS: In the Mekelle cohort, 16 of 9515 patients (0.16%) fitted the definition of EC, whereas seven of 1160 (0.6%) in the Israeli cohort were identified as ECs (P = 0.011). CONCLUSIONS: This is the first large-scale screening for HIV-positive ECs to be performed in entirely African cohorts. The overall prevalence of ECs is within the range of that previously described in developing countries. The significant difference in prevalence between the two cohorts of similar genetic background is probably a consequence of selection bias but warrants further investigation into possible environmental factors which may underlie the EC state.

Cross-border outbreak of extensively drug-resistant tuberculosis linked to a university in Romania.

Extensively drug-resistant (XDR) tuberculosis (TB) poses a threat to public health due to its complicated, expensive and often unsuccessful treatment. A cluster of three XDR TB cases was detected among foreign medical students of a Romanian university. The contact investigations included tuberculin skin testing or interferon gamma release assay, chest X-ray, sputum smear microscopy, culture, drug susceptibility testing, genotyping and whole-genome sequencing (WGS), and were addressed to students, personnel of the university, family members or other close contacts of the cases. These investigations increased the total number of cases to seven. All confirmed cases shared a very similar WGS profile. Two more cases were epidemiologically linked, but no laboratory confirmation exists. Despite all the efforts done, the source of the outbreak was not identified, but the transmission was controlled. The investigation was conducted by a team including epidemiologists and microbiologists from five countries (Finland, Israel, Romania, Sweden and the UK) and from the European Centre for Disease Prevention and Control. Our report shows how countries can collaborate to control the spread of XDR TB by exchanging information about cases and their contacts to enable identification of additional cases and transmission and to perform the source investigation.

Mother-to-child HIV transmissions in Israel, 1985-2011.

Mother-to-child transmission (MTCT) is the leading cause of paediatric HIV-infection in Israel. This study aimed to assess MTCT rates and analyse temporal changes in relation to highly active antiretroviral therapy (HAART) introduction in 1996. This historical prospective study included all HIV-infected women who delivered in Israel between 1988 and 2011. Demographic, clinical, laboratory and therapy characteristics were compared between HIV-infected newborns with all others, and between infants born before and after 1996. Of all 796 infants born in Israel to HIV-infected women, 25 (3·1%) were infected. MTCT rates decreased significantly after HAART introduction compared with infants who were born before 1996 (16·3% vs. 1·7%). Mothers who infected vertically were more likely to be younger, Ethiopian-born, delivered trans-vaginally, not treated with HAART during pregnancy/labour and delivered before 1996 compared with mothers who did not transmit the HIV to their neonates. Newborns who did not receive antiretroviral therapy postpartum were more commonly HIV-infected and their mortality rate was higher. In conclusion, HAART during pregnancy/labour decreased MTCT significantly. Most MTCT in Israel was recorded among Ethiopian migrants, yet, in decreasing rates. Continuous efforts should be employed to encourage early HIV testing and allow effective HAART to pregnant women who belong to a key risk-group.

Successful control of a large outbreak of HIV infection associated with injection of cathinone derivatives in Tel Aviv, Israel.

OBJECTIVES: Outbreaks of HIV infection have been linked to injectable drug abuse, but specific triggers often remain obscure. We report on an outbreak of primary HIV infection among people who inject drugs (PWID) in Tel Aviv, associated with a local shift in drug-use practices. METHODS: A cluster of primary HIV infection cases in PWID was detected in May 2012. Retrospective and prospective multi-hospital case finding was initiated. PWID were interviewed and risk factors for primary HIV infection were identified. Starting in December 2012, a multifaceted intervention was implemented, including educational activities, increasing syringe exchange supplies, active screening, early initiation of antiretroviral therapy, and referral to drug withdrawal programmes. RESULTS: Forty-two PWID with primary HIV infection were detected between May 2012 and April 2013. Compared with the corresponding pre-outbreak period, the annual incidence of primary HIV infection in PWID increased from 0 to 20 cases/1000 population (p <0.0001). Sixty-nine per cent were hospitalized because of concomitant bacterial infections and sepsis. Phylogenetic analysis of HIV isolates from case patients showed tight clustering suggesting a single common source of infection. The outbreak was temporally related to a widespread shift from heroin to injectable cathinone-derivatives and buprenorphine, which entailed high-risk injection practices. Targeted intervention resulted in a dramatic and sustained reduction in HIV infection in the PWID population. CONCLUSIONS: Injectable amphetamines are gaining momentum among PWID worldwide. Tracing of this outbreak to cathinone use and implementing a targeted intervention programme effectively terminated the outbreak.

Mortality after anti-tuberculosis treatment completion: results of long-term follow-up.

BACKGROUND: Mycobacterium tuberculosis affects the lung parenchyma even after successful treatment. OBJECTIVE: To assess long-term mortality in a cohort of individuals who had recovered from tuberculosis (TB), and to compare their mortality rate and causes of death with those of the general population. METHODS: This retrospective cohort study of all Israeli citizens who recovered from tuberculosis between 2000 and 2010 included all patient files and death certificates and/or hospitalisation records of deceased individuals. Death rates were computed using standard mortality rates (SMR). Cox proportional hazard regression was conducted to identify risk factors for death, and causes of death were compared with those in the general Israeli population. RESULTS: Over 11 years of follow-up, comprising 18,246 person-years, 389 (12.0%) Israeli citizens died after completion of anti-tuberculosis treatment, giving an SMR of 3.7. The SMR was strongly correlated with age, and was highest in males and individuals aged 25-44 years. Compared to the general population, among individuals who recovered from TB there were more deaths due to septicaemia and pneumonia, and fewer deaths due to cerebrovascular diseases, stroke and diabetes (P < 0.05). CONCLUSIONS: Individuals who recover from TB are at higher risk of long-term mortality than the general population, and their causes of death are different. Periodical follow-up might be beneficial for individuals to facilitate early diagnosis.

Molecular epidemiology and mapping of tuberculosis in Israel: do migrants transmit the disease to locals?

SETTING: Israel receives migrants from various countries, some of which have high tuberculosis (TB) prevalence. OBJECTIVE: To assess the predominant Mycobacterium tuberculosis strains in Israel isolated during 2008-2010 among Israeli-born and migrant patients, and to investigate possible transmission of TB from migrants to the local population. METHODS: Molecular characterisation employed 43-spacer spoligotyping and 16-loci mycobacterial interspersed repetitive units-variable number of tandem repeats typing. All patients were classified according to those who were members of a cluster and those who were not. RESULTS: Among 684 M. tuberculosis strains isolated from new patients genotyped and assigned to their specific cohort populations during the study period, major spoligotype families were Central Asian (CAS) (n = 140, 20%), Beijing (n = 101, 15%) and T (n = 160, 23%). Most Beijing strains (66%) were isolated from patients from the former Soviet Union (FSU), while CAS strains were mainly (74%) from Ethiopia, Eritrea and Sudan (EES). For the heterogeneous T-clade, patient countries of origin were 38% EES and 33% FSU. CONCLUSIONS: Predominant M. tuberculosis genotypes in Israel in 2008-2010 were similar to genotypes endemic to the migrants' countries of origin. Epidemiological investigations did not demonstrate transmission between migrants and Israeli-born patients sharing the same cluster.

Drug-resistant tuberculosis in Israel: risk factors and treatment outcomes.

SETTING: All culture-positive tuberculosis (TB) isolates in Israel. OBJECTIVES: To outline the magnitude of drug-resistant TB in Israel, describe treatment outcomes and identify risk factors. DESIGN: Retrospective study of laboratory data of all strains of adult TB patients tested for resistance to first- and second-line anti-tuberculosis drugs between 1999 and 2010. RESULTS: Of 4652 reported TB cases, 3552 (76.3%) underwent culture (annual range 73-81%); 445 (12.5%) were resistant to one or more first-line drugs, while 207 (5.8%) had multidrug-resistant TB (MDR-TB). Risk factors for MDR-TB included being male, age 30-59 years, migrants (mainly from the former Soviet Union [FSU]) who had stayed in Israel >2 years, and having pulmonary TB, human immunodeficiency virus (HIV) infection and sputum smear positivity. Of all MDR-TB patients, 71.0% achieved treatment success, while 19.8% died. Twelve Israeli citizens had extensively drug-resistant TB (5.8% of MDR-TB cases). All had emigrated from the FSU and had pulmonary TB; 1 was HIV-infected. Seven (58.4%) achieved treatment success and 5 (41.6%) died. CONCLUSIONS: Drug-resistant TB in Israel is influenced by migration, especially from the FSU, where the patients were probably infected. Rapid sputum sampling performed in the early stages of the disease, patient isolation and drug susceptibility testing should be the standard of care to avoid further transmission and improve TB control.

Mortality of tuberculosis patients during treatment in Israel, 2000-2010.

SETTING: Tuberculosis (TB) epidemiology in Israel is similar to that reported from other industrialised countries where most patients are foreign-born. OBJECTIVES: To assess TB case fatality rate (CFR) and mortality trends during treatment and to identify risk factors associated with mortality. DESIGN: Retrospective cohort study of all TB patients in Israel diagnosed between 2000 and 2010. Cause of death was classified by TB-specific and non-TB-specific causes. RESULTS: During the study period, 451 TB patients died during treatment, representing a CFR of 9.9%. Of these, 72.5% died due to TB-related causes, giving a TB-related CFR of 7.2%. Both the overall and TB-related CFR decreased over the study period. Risk factors for death included male sex, older age, human immunodeficiency virus coinfection, culture positivity and multidrug-resistant TB (MDR-TB). Patients aged ≥65 years comprised 70% of the TB-related deaths, and more than half of these (54.9%) were born in the former Soviet Union, Europe (excluding the former Soviet Union) or the USA. CONCLUSION: Both the overall and TB-related CFR decreased over the study period. Physicians who treat older male TB patients with MDR-TB or HIV should increase the index of suspicion to include the possibility of a higher risk of mortality.

What do we need to learn for policy decision-making on sexually transmitted infections prevention and treatment in Israel?

The rising trend of sexually transmitted infections (STIs) reported in several western countries has also affected Israel. To review epidemiological trends and to address additional issues needed for a wider overview on STIs in Israel, we analysed notified data on infectious syphilis, gonorrhoea, Chlamydia trachomatis and HIV/AIDS during 1998-2007, by age groups, and each available publication on STIs in Israel. The trend of each disease had a unique pattern, probably influenced by different screening procedures, case definition, mix of populations and better access to care for high-risk populations. Higher rates were found among patients aged 25-34 years. Rates found in different peak years for gonorrhoea, HIV, chlamydia and infectious syphilis reached 43.6, 18.9, 10.8 and 8.1 cases per 100,000 population, respectively. We compare trends to those of countries from World Health Organization (WHO) European Region and discuss interventions for subpopulations on which additional data are needed for evidence-based policy-making. Incidence rates of syphilis, gonorrhoea, chlamydia and HIV/AIDS are still low in Israel. We propose additional components needed for a more comprehensive evidence-based policy on STIs.

Pediatric tuberculosis immigration screening in high-immigration, low-incidence countries.

BACKGROUND: Tuberculosis (TB) screening in migrant children, including immigrants, refugees and asylum seekers, is an ongoing challenge in low TB incidence countries. Many children from high TB incidence countries harbor latent TB infection (LTBI), and some have active TB disease at the point of immigration into host nations. Young children who harbor LTBI have a high risk of progression to TB disease and are at a higher risk than adults of developing disseminated severe forms of TB with significant morbidity and mortality. Many countries have developed immigration TB screening programs to suit the needs of adults, but have not focused much attention on migrant children. OBJECTIVE: To compare the TB immigration medical examination requirements in children in selected countries with high immigration and low TB incidence rates. DESIGN: Descriptive study of TB immigration screening programs for systematically selected countries. RESULTS: Of 18 eligible countries, 16 responded to the written survey and telephone interview. CONCLUSION: No two countries had the same approach to TB screening among migrant children. The optimal evidenced-based manner in which to screen migrant children requires further research.

Tuberculosis contact investigation in low prevalence countries: a European consensus.

Contact investigation to identify individuals with tuberculosis and latent infection with Mycobacterium tuberculosis is an important component of tuberculosis control in low tuberculosis incidence countries. This document provides evidence-based and best-practice policy recommendations for contact tracing among high- and medium-priority contacts in a variety of settings. It provides a basis for national guidelines on contact investigation and tuberculosis outbreak management, and should support countries and tuberculosis control managers in evaluating and revising national policies. A review of existing guidelines, a literature search, several meetings and consultation with experts were used to formulate and grade recommendations for action during contact investigation. Available tests to identify individuals with latent infection with M. tuberculosis are designed to identify immune response against mycobacterial antigens and have variable predictive value for the likelihood to develop active tuberculosis in different populations. Contact investigation should therefore be limited to situations with a clear likelihood of transmission or to those with a higher probability of developing active tuberculosis, for instance, young children and immunocompromised persons. A risk assessment-based approach is recommended, where the need to screen contacts is prioritised on the basis of the infectiousness of the index case, intensity of exposure and susceptibility of contacts.

Gay men who engage in substance use and sexual risk behaviour: a dual-risk group with unique characteristics.

'Recreational' substances used among men having sex with men, and their association with risky unprotected anal intercourse (RUAI) were examined--for the first time in Israel--in an internet-based questionnaire assessing knowledge, practices and motivation. Between March and May 2005, 2873 participants completed the entire questionnaire. Of the total, 669 (23%) reported RUAI during the last six months, and 1319 (46%) used substances during sex. Use of substance was significantly higher among those performing RUAI than those who did not (31.5% versus 26.4%, P=0.03). Involvement in both substance use and RUAI was reported by 366 participants (13%). HIV rates were higher in this dual-risk group (P<0.01), and individuals reported more partners in the last six months than those not part of this dual risk (11.6 versus 8.2, P=0.02). In multivariate analyses, Tel-Aviv residency, lower education, performing receptive RUAI, misperception of HIV transmission and limited negotiation skills were positively associated with this dual-risk behaviour.