Refugees from Ukraine receiving antiretroviral therapy in destination countries and territories of the World Health Organization European Region, including EU/EEA countries, February 2022 to March 2023.

Between the start of the Russian Federation's invasion of Ukraine on 24 February 2022 and May 2023, more than 8 million individuals have been displaced from Ukraine. Ukraine has the second-largest HIV epidemic in the World Health Organization (WHO) European Region. From a humanitarian and public health perspective it is critical that Ukrainian refugees living with or at risk of HIV have access to testing, treatment and healthcare in their destination country. To gain better insight on the number of refugees from Ukraine receiving antiretroviral therapy (ART) in destination countries, the WHO Regional Office for Europe and the European Centre for Disease Prevention and Control conducted three surveys in July 2022, November 2022 and March 2023. Among 39 countries that responded to at least one survey, 31 had information on the number of refugees from Ukraine receiving ART in their country. A total of 6,519 refugees (1.5 per 1,000 refugees) received ART, lower than previous estimates by WHO, ECDC and partners of between 0.16% and 1.0%. This discrepancy may suggest a substantial number of undiagnosed and/or diagnosed but untreated HIV infections. Improving access to healthcare for people living with HIV among refugees from Ukraine is vital to ensure quality care.

Developing evidence-informed indicators to monitor HIV pre-exposure prophylaxis programmes across EU/EEA countries: a multi-stakeholder consensus.

Several countries in the European Union (EU) and European Economic Area (EEA) established and/or scaled up HIV pre-exposure prophylaxis (PrEP) programmes between 2016 and 2023. Data on PrEP programmes' performance and effectiveness in reaching those most in need will be needed to assess regional progress in the roll-out of PrEP. However, there is a lack of commonly defined indicators for routine monitoring to allow for minimum comparability. We propose a harmonised PrEP monitoring approach for the EU/EEA, based on a systematic and evidence-informed consensus-building process involving a broad and multidisciplinary expert panel. We present a set of indicators, structured along relevant steps of an adapted PrEP care continuum, and offer a prioritisation based on the degree of consensus among the expert panel. We distinguish between 'core' indicators deemed essential for any PrEP programme in the EU/EEA, vs 'supplementary' and 'optional' indicators that provide meaningful data, yet where experts evaluated their feasibility for data collection and reporting as very context-dependent. By combining a standardised approach with strategic opportunities for adaptation and complementary research, this monitoring framework will contribute to assess the impact of PrEP on the HIV epidemic in Europe.

HIV diagnoses among people born in Ukraine reported by EU/EEA countries in 2022: impact on regional HIV trends and implications for healthcare planning.

Following Russia's invasion in 2022, over 4.1 million Ukrainians sought refuge in the EU/EEA. We assessed how this impacted HIV case reporting by EU/EEA countries. Ukrainian refugees constituted 10.2% (n = 2,338) of all 2022 HIV diagnoses, a 10-fold increase from 2021. Of these, 9.3% (n = 217) were new diagnoses, 58.5% (n = 1,368) were previously identified; 32.2% had unknown status. Displacement of Ukrainians has partly contributed to increasing HIV diagnoses in EU/EEA countries in 2022, highlighting the importance of prevention, testing and care.

Late diagnosis of HIV: An updated consensus definition.

INTRODUCTION: In recent years, HIV testing frequency has increased, resulting in more people being diagnosed during seroconversion with a temporarily low CD4 count. Using the current consensus definition of late HIV presentation ('presenting for care with a CD4 count < 350 cells/µL or an AIDS-defining event, regardless of CD4 count') these individuals would be incorrectly assigned as being diagnosed late. METHODS: In spring 2022, a European expert group convened to revise the current late HIV presentation consensus definition. A survey on data availability to apply this revised definition was sent to nominated European focal points responsible for HIV surveillance (n = 53). RESULTS: Experts agreed that the updated definition should refer to late HIV diagnosis rather than presentation and include the following addition: People with evidence of recent infection should be reclassified as 'not late', with evidence of recent infection considered hierarchically. The individual must have: (i) laboratory evidence of recent infection; (ii) a last negative HIV test within 12 months of diagnosis; or (iii) clinical evidence of acute infection. People with evidence of being previously diagnosed abroad should be excluded. A total of 18 countries responded to the survey; 83% reported capturing CD4 count and/or AIDS at diagnosis through national surveillance, 67% captured last negative test and/or previous HIV diagnosis, 61% captured seroconversion illness at diagnosis and 28% captured incident antibody results. CONCLUSIONS: Accurate data on late diagnosis are important to describe the effects of testing programmes. Reclassification of individuals with recent infection will help to better identify populations most at risk of poor HIV outcomes and areas for intervention.

Country-specific approaches to latent tuberculosis screening targeting migrants in EU/EEA* countries: A survey of national experts, September 2019 to February 2020.

BackgroundMigrants in low tuberculosis (TB) incidence countries in the European Union (EU)/European Economic Area (EEA) are an at-risk group for latent tuberculosis infection (LTBI) and are increasingly included in LTBI screening programmes.AimTo investigate current approaches and implement LTBI screening in recently arrived migrants in the EU/EEA and Switzerland.MethodsAt least one TB expert working at a national level from the EU/EEA and one TB expert from Switzerland completed an electronic questionnaire. We used descriptive analyses to calculate percentages, and framework analysis to synthesise free-text responses.ResultsExperts from 32 countries were invited to participate (30 countries responded): 15 experts reported an LTBI screening programme targeting migrants in their country; five reported plans to implement one in the near future; and 10 reported having no programme. LTBI screening was predominantly for asylum seekers (n = 12) and refugees (n = 11). Twelve countries use 'country of origin' as the main eligibility criteria. The countries took similar approaches to diagnosis and treatment but different approaches to follow-up. Six experts reported that drop-out rates in migrants were higher compared with non-migrant groups. Most of the experts (n = 22) called for a renewed focus on expanding efforts to screen for LTBI in migrants arriving in low-incidence countries.ConclusionWe found a range of approaches to LTBI screening of migrants in the EU/EEA and Switzerland. Findings suggest a renewed focus is needed to expand and strengthen efforts to meaningfully include migrants in these programmes, in order to meet regional and global elimination targets for TB.

High monkeypox vaccine acceptance among male users of smartphone-based online gay-dating apps in Europe, 30 July to 12 August 2022.

We assess monkeypox vaccination acceptance among male adults in the European Region. We conducted an online survey through two dating apps targeting men who have sex with men, from 30 July to 12 August 2022. We developed Bayesian hierarchical logistic regression models to investigate monkeypox vaccination acceptance. Overall crude vaccination acceptance was 82% and higher in north-western compared to south-eastern European regions. Acceptance strongly rose with perception of increased disease severity and transmission risk, and in individuals linked to healthcare.

Economic, Mental Health, HIV Prevention and HIV Treatment Impacts of COVID-19 and the COVID-19 Response on a Global Sample of Cisgender Gay Men and Other Men Who Have Sex with Men.

There is an urgent need to measure the impacts of COVID-19 among gay men and other men who have sex with men (MSM). We conducted a cross-sectional survey with a global sample of gay men and other MSM (n = 2732) from April 16, 2020 to May 4, 2020, through a social networking app. We characterized the economic, mental health, HIV prevention and HIV treatment impacts of COVID-19 and the COVID-19 response, and examined whether sub-groups of our study population are disproportionately impacted by COVID-19. Many gay men and other MSM not only reported economic and mental health consequences, but also interruptions to HIV prevention and testing, and HIV care and treatment services. These consequences were significantly greater among people living with HIV, racial/ethnic minorities, immigrants, sex workers, and socio-economically disadvantaged groups. These findings highlight the urgent need to mitigate the negative impacts of COVID-19 among gay men and other MSM.

RESUMEN: Existe una necesidad urgente para medir los impactos de COVID-19 entre hombres gay y otros hombres que tienen sexo con hombres (HSH). Hemos conducido una encuesta multifuncional con una prueba mundial de hombres gay y otros HSH (n = 2732) desde el 16 de Abril hasta el 4 de Mayo del 2020, a través de una aplicación de red social. Nosotros caracterizamos los impactos económicos, de salud mental, prevención del VIH y tratamiento del VIH e impactos a COVID-19 y la respuesta de COVID-19, y examinamos si subgrupos de nuestra población de estudio fueron impactados desproporcionadamente por COVID-19. Muchos hombres no tan solo reportaron consecuencias económicas y de salud mental, sino también interrupciones de prevención y de pruebas de VIH, y cuidado del VIH y servicios de tratamiento. Encontramos consecuencias más significantes entre personas viviendo con VIH, grupos raciales/etnicos, migrantes, sexo servidores, y groupos socioeconomicamente disfavorecidos. Los resultados subrayan la necesidad crucial de mitigar los impactos multifacéticos de COVID-19 entre los hombres homosexuales y otros HSH, especialmente para aquellos con vulnerabilidades entrelazadas.

Post-migration acquisition of HIV: Estimates from four European countries, 2007 to 2016.

BackgroundThe assumption that migrants acquire human immunodeficiency virus (HIV) before migration, particularly those from high prevalence areas, is common.AimWe assessed the place of HIV acquisition of migrants diagnosed in four European countries using surveillance data.MethodsUsing CD4+ T-cell count trajectories modelled to account for seroconversion bias, we estimated infection year of newly HIV-diagnosed migrants residing in the United Kingdom (UK), Belgium, Sweden and Italy with a known arrival year and CD4+ T-cell count at diagnosis. Multivariate analyses identified predictors for post-migration acquisition.ResultsBetween 2007 and 2016, migrants constituted 56% of people newly diagnosed with HIV in the UK, 62% in Belgium, 72% in Sweden and 29% in Italy. Of 23,595 migrants included, 60% were born in Africa and 70% acquired HIV heterosexually. An estimated 9,400 migrants (40%; interquartile range (IQR): 34-59) probably acquired HIV post-migration. This proportion was similar by risk group, sex and region of birth. Time since migration was a strong predictor of post-migration HIV acquisition: 91% (IQR: 87-95) among those arriving 10 or more years prior to diagnosis; 30% (IQR: 21-37) among those 1-5 years prior. Younger age at arrival was a predictor: 15-18 years (81%; IQR: 74-86), 19-25 years (53%; IQR: 45-63), 26-35 years (37%; IQR: 30-46) and 36 years and older (25%; IQR: 21-33).ConclusionsMigrants, regardless of origin, sex and exposure to HIV are at risk of acquiring HIV post-migration to Europe. Alongside accessible HIV testing, prevention activities must target migrant communities.

Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

BACKGROUND: High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region. METHODS: A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit. RESULTS: We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries. CONCLUSIONS: The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.

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

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

Country level homophobia and protective sexual health behaviours among HIV negative or untested men who have sex with men in 45 countries.

Despite new, effective biomedical technologies to prevent the transmission of HIV, social and structural factors still impact the opportunity for gay, bisexual and other men who have sex with men (GBMSM) to access safe sexual health services. Within this paper we describe findings of a pilot analysis that seeks to identify relationships between country level homophobia, individual-level sexualised drug use and key sexual health protective behaviours in a sample of HIV negative men from 45 countries recruited via a large online survey. Responses to questions relating to HIV and STI testing history, use of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP) and engagement in sexualised drug use were treated as dependent variables within generalised linear mixed-effects model with logit link analysis, with country level homophobia (drawn from a recently published international index) operating as the dependent variable. In total, data from 9,356 respondents were included for analysis. Overall, uptake of behaviours known to be protective of sexual health overall was significantly lower in countries with high levels of homophobia. This paper is unique in linking a robust measure of country-level homophobia to engagement in health protective behaviours on a large-scale, multi-country level basis.

Use of, and likelihood of using, HIV pre-exposure prophylaxis among men who have sex with men in Europe and Central Asia: findings from a 2017 large geosocial networking application survey.

OBJECTIVE: Currently, seven European countries provide HIV pre-exposure prophylaxis (PrEP) through public health services, although there are numerous reports of off-licence use. The objective of this study was to examine current use of PrEP, likelihood of future use and indicators of potential PrEP candidacy among an opportunistic sample of men who have sex with men in Europe and Central Asia. METHODS: A survey was sent out in eight languages to users of the Hornet gay networking application in July and August 2017. Descriptive statistics present proportions of PrEP use, while factors associated with PrEP use are examined using logistic and linear regressions. RESULTS: Of 12 053 participants whose responses came from 55 European and Central Asian countries, 10 764 (89%) were not living with diagnosed HIV. Among these HIV-negative/untested men, 10.1% (n=1071) were currently taking PrEP or had done so within the previous 3 months. Current or recent PrEP users were significantly more likely to have taken postexposure prophylaxis (adjusted OR (AOR)=16.22 (95% CI 13.53 to 19.45)) or received an STI diagnosis (AOR=4.53 (95% CI 3.77 to 5.44)) in the previous 12 months than those who had not. Most commonly, these men obtained PrEP from a physician (28.1%) or the internet (24.8%), while 33.6% had not disclosed PrEP use to their doctor. Men reporting happiness with their sex life were more likely to have taken PrEP (AOR=1.73 (95% CI 1.59 to 1.89)). Nearly a quarter (21.5%) of those not on PrEP said they were likely to use it in the next 6 months. CONCLUSIONS: The majority of men using, or intending to use, PrEP appear to have a risk profile consistent with emerging guidance. A large proportion of these men are accessing PrEP outside of traditional healthcare settings, posing a challenge for routine monitoring.

Estimating the 'PrEP Gap': how implementation and access to PrEP differ between countries in Europe and Central Asia in 2019.

In 2019, only 14 European and Central Asian countries provided reimbursed HIV pre-exposure prophylaxis (PrEP). Using EMIS-2017 data, we present the difference between self-reported use and expressed need for PrEP in individual countries and the European Union (EU). We estimate that 500,000 men who have sex with men in the EU cannot access PrEP, although they would be very likely to use it. PrEP's potential to eliminate HIV is currently unrealised by national healthcare systems.

HIV in Europe and Central Asia: progress in 2018 towards meeting the UNAIDS 90-90-90 targets.

In 2018, 52 of 55 European and Central Asian countries reported data against the UNAIDS 90-90-90 targets. Overall, 80% of people living with HIV (PLHIV) were diagnosed, of whom 64% received treatment and 86% treated were virally suppressed. Subregional outcomes varied: West (87%-91%-93%), Centre (83%-73%-75%) and East (76%-46%-78%). Overall, 43% of all PLHIV were virally suppressed; intensive efforts are needed to meet the 2020 target of 73%.

Quantifying unmet prevention needs among MSM in Europe through a multi-site bio-behavioural survey.

IntroductionThe HIV epidemic represents an important public health issue in Europe particularly among men who have sex with men (MSM). Global AIDS Monitoring indicators (GAM) have been widely and jointly promoted as a set of crucial standardised items to be adopted for monitoring and responding to the epidemic.MethodsThe Sialon II study, implemented in 13 European cities (2013-14), was a complex multi-centre integrated bio-behavioural cross-sectional survey targeted at MSM, with a concomitant collection of behavioural and biological (oral fluid or blood specimens) data. Rigorous sampling approaches for hard-to-reach populations were used (time-location sampling and respondent-driven sampling) and GAM indicators were calculated; sampling frames were adapted to allow weighted estimates of GAM indicators.Results4,901 MSM were enrolled. HIV prevalence estimates ranged from 2.4% in Stockholm to 18.0% in Bucharest. When exploring city-level correlations between GAM indicators, prevention campaigns significantly correlated with levels of condom use and level of HIV testing among MSM.ConclusionThe Sialon II project has made an important contribution to the monitoring and evaluation of the HIV epidemic across Europe, integrating the use of GAM indicators within a second generation HIV surveillance systems approach and in participatory collaboration with MSM communities. It influenced the harmonisation of European data collection procedures and indicators via GAM country reporting and contributed essential knowledge informing the development and implementation of strategic, evidence-based HIV prevention campaigns for MSM.

The effectiveness and cost-effectiveness of screening for latent tuberculosis among migrants in the EU/EEA: a systematic review.

BackgroundMigrants account for a large and growing proportion of tuberculosis (TB) cases in low-incidence countries in the European Union/European Economic Area (EU/EEA) which are primarily due to reactivation of latent TB infection (LTBI). Addressing LTBI among migrants will be critical to achieve TB elimination. Methods: We conducted a systematic review to determine effectiveness (performance of diagnostic tests, efficacy of treatment, uptake and completion of screening and treatment) and a second systematic review on cost-effectiveness of LTBI screening programmes for migrants living in the EU/EEA. Results: We identified seven systematic reviews and 16 individual studies that addressed our aims. Tuberculin skin tests and interferon gamma release assays had high sensitivity (79%) but when positive, both tests poorly predicted the development of active TB (incidence rate ratio: 2.07 and 2.40, respectively). Different LTBI treatment regimens had low to moderate efficacy but were equivalent in preventing active TB. Rifampicin-based regimens may be preferred because of lower hepatotoxicity (risk ratio = 0.15) and higher completion rates (82% vs 69%) compared with isoniazid. Only 14.3% of migrants eligible for screening completed treatment because of losses along all steps of the LTBI care cascade. Limited economic analyses suggest that the most cost-effective approach may be targeting young migrants from high TB incidence countries. Discussion: The effectiveness of LTBI programmes is limited by the large pool of migrants with LTBI, poorly predictive tests, long treatments and a weak care cascade. Targeted LTBI programmes that ensure high screening uptake and treatment completion will have greatest individual and public health benefit.

The effectiveness and cost-effectiveness of screening for active tuberculosis among migrants in the EU/EEA: a systematic review.

BACKGROUND: The foreign-born population make up an increasing and large proportion of tuberculosis (TB) cases in European Union/European Economic Area (EU/EEA) low-incidence countries and challenge TB elimination efforts. Methods: We conducted a systematic review to determine effectiveness (yield and performance of chest radiography (CXR) to detect active TB, treatment outcomes and acceptance of screening) and a second systematic review on cost-effectiveness of screening for active TB among migrants living in the EU/EEA. Results: We identified six systematic reviews, one report and three individual studies that addressed our aims. CXR was highly sensitive (98%) but only moderately specific (75%). The yield of detecting active TB with CXR screening among migrants was 350 per 100,000 population overall but ranged widely by host country (110-2,340), migrant type (170-1,192), TB incidence in source country (19-336) and screening setting (220-1,720). The CXR yield was lower (19.6 vs 336/100,000) and the numbers needed to screen were higher (5,076 vs 298) among migrants from source countries with lower TB incidence (≤ 50 compared with ≥ 350/100,000). Cost-effectiveness was highest among migrants originating from high (> 120/100,000) TB incidence countries. The foreign-born had similar or better TB treatment outcomes than those born in the EU/EEA. Acceptance of CXR screening was high (85%) among migrants. Discussion: Screening programmes for active TB are most efficient when targeting migrants from higher TB incidence countries. The limited number of studies identified and the heterogeneous evidence highlight the need for further data to inform screening programmes for migrants in the EU/EEA.

The Human Immunodeficiency Virus Continuum of Care in European Union Countries in 2013: Data and Challenges.

BACKGROUND.: The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set a "90-90-90" target to curb the human immunodeficiency virus (HIV) epidemic by 2020, but methods used to assess whether countries have reached this target are not standardized, hindering comparisons. METHODS.: Through a collaboration formed by the European Centre for Disease Prevention and Control (ECDC) with European HIV cohorts and surveillance agencies, we constructed a standardized, 4-stage continuum of HIV care for 11 European Union countries for 2013. Stages were defined as (1) number of people living with HIV in the country by end of 2013; (2) proportion of stage 1 ever diagnosed; (3) proportion of stage 2 that ever initiated ART; and (4) proportion of stage 3 who became virally suppressed (≤200 copies/mL). Case surveillance data were used primarily to derive stages 1 (using back-calculation models) and 2, and cohort data for stages 3 and 4. RESULTS.: In 2013, 674500 people in the 11 countries were estimated to be living with HIV, ranging from 5500 to 153400 in each country. Overall HIV prevalence was 0.22% (range, 0.09%-0.36%). Overall proportions of each previous stage were 84% diagnosed, 84% on ART, and 85% virally suppressed (60% of people living with HIV). Two countries achieved ≥90% for all stages, and more than half had reached ≥90% for at least 1 stage. CONCLUSIONS.: European Union countries are nearing the 90-90-90 target. Reducing the proportion undiagnosed remains the greatest barrier to achieving this target, suggesting that further efforts are needed to improve HIV testing rates. Standardizing methods to derive comparable continuums of care remains a challenge.

Reduction in undiagnosed HIV infection in the European Union/European Economic Area, 2012 to 2016.

It is well-documented that early HIV diagnosis and linkage to care reduces morbidity and mortality as well as HIV transmission. We estimated the median time from HIV infection to diagnosis in the European Union/European Economic Area (EU/EEA) at 2.9 years in 2016, with regional variation. Despite evidence of a decline in the number of people living with undiagnosed HIV in the EU/EEA, many remain undiagnosed, including 33% with more advanced HIV infection (CD4 < 350 cells/mm3).