An evaluation of assumptions underlying respondent-driven sampling and the social contexts of sexual and gender minority youth participating in HIV clinical trials in the United States.

INTRODUCTION: Respondent-driven sampling has been an effective sampling strategy for HIV research in many settings, but has had limited success among some youth in the United States. We evaluated a modified RDS approach for sampling Black and Latinx sexual and gender minority youth (BLSGMY) and evaluates how lived experiences and social contexts of BLSGMY youth may impact traditional RDS assumptions. METHODS: RDS was implemented in three cities to engage BLSGMY in HIV prevention or care intervention trials. RDS was modified to include targeted seed recruitment from venues, internet, and health clinics, and provided options for electronic or paper coupons. Qualitative interviews were conducted among a sub-sample of RDS participants to explore their experiences with RDS. Interviews were coded using RDS assumptions as an analytic framework. RESULTS: Between August 2017 and October 2019, 405 participants were enrolled, 1,670 coupons were distributed, with 133 returned, yielding a 0.079 return rate. The maximum recruitment depth was 4 waves among seeds that propagated. Self-reported median network size was 5 (IQR 2-10) and reduced to 3 (IQR 1-5) when asked how many peers were seen in the past 30 days. Qualitative interviews (n=27) revealed that small social networks, peer trust, and targeted referral of peers with certain characteristics challenged network, random recruitment, and reciprocity assumptions of RDS. HIV stigma and research hesitancy were barriers to participation and peer referral. CONCLUSIONS: Small social networks and varying relationships with peers among BLSGMY challenge assumptions that underlie traditional RDS. Modified RDS approaches, including those that incorporate social media, may support recruitment for community-based research but may challenge assumptions of reciprocal relationships. Research hesitancy and situational barriers must be addressed in recruitment and study designs.

The HIV care continuum among men who have sex with men in Moscow, Russia: a cross-sectional study of infection awareness and engagement in care.

OBJECTIVES: Early diagnosis and treatment of HIV infection is critical to improving clinical outcomes for HIV-infected individuals. We sought to characterise the HIV care continuum and identify correlates of being unaware of one's HIV infection among men who have sex with men (MSM) in Moscow, Russia. METHODS: Participants (N=1376) were recruited via respondent-driven sampling and completed a sociobehavioural survey and HIV testing from 2010 to 2013. Sample and population estimates were calculated for key steps along the HIV care continuum for HIV-infected MSM and logistic regression methods were used to examine correlates of being unaware of one's HIV infection. RESULTS: 15.6% (184/1177; population estimate: 11.6%; 95% CI 8.5% to 14.7%) of participants were HIV infected. Of these, only 23.4% (43/184; population estimate: 13.2; 95% CI 11.0 to 15.4) were previously aware of their infection, 8.7% (16/184 population estimate: 4.7; 95% CI 1.0 to 8.5) were on antiretroviral therapy (ART), and 4.4% (8/164; population estimate: 3.0; 95% CI 0.3 to 5.6) reported an undetectable viral load. Bisexual identity (reference: homosexual; adjusted odds ratio (AOR): 3.69; 95% CI 1.19 to 11.43), having ≥5 sexual partners in the last 6 months (reference: ≤1; AOR: 4.23; 95% CI 1.17 to 15.28), and employer HIV testing requirements (reference: no; AOR: 15.43; 95% CI 1.62 to 147.01) were associated with being unaware of one's HIV infection. HIV testing in a specialised facility (reference: private; AOR: 0.06; 95% CI 0.01 to 0.53) and testing ≥2 times in the last 12 months (reference: none; AOR: 0.17; 95% CI 0.04 to 0.73) were inversely associated with being unaware of HIV infection. CONCLUSIONS: There is a steep gradient along the HIV care continuum for Moscow-based MSM beginning with low awareness of HIV infection. Efforts that improve access to acceptable HIV testing strategies, such as alternative testing facilities, and linkage to care are needed for key populations.

Alcohol Use and Associated Sexual and Substance Use Behaviors Among Men Who Have Sex with Men in Moscow, Russia.

Alcohol use is a public health problem in the Russian Federation. This study explored relationships between alcohol use and behavioral risks for HIV transmission among men who have sex with men (MSM) in Moscow, Russia. Alcohol use disorder identification test (AUDIT) scores for 1367 MSM participating in a cross-sectional survey and HIV testing were categorized to: "abstinence/low use", "hazardous use", "harmful use/dependency". Multiple logistic regression models compared dependent variables for sexual and drug use behaviors across alcohol use strata. Hazardous and harmful/dependent alcohol use were significantly associated with high-risk sexual behaviors and drug use. Harmful use/dependency was associated with an increased odds of having more than five male sex partners (last 12 months; adjusted odds ratios-AOR 1.69; 95 % CI 1.25-2.27), inconsistent condom use during anal intercourse (AOR 2.19; 95 % CI 1.61-2.96) and, among those using recreational drugs, injection drug use (last month; AOR 4.38: 95 % CI 1.13-17.07) compared to abstinent/low-level users. Harmful/dependent use was marginally associated with HIV infection (AOR 1.48; 95 % CI 0.97-2.25). HIV prevention efforts for MSM in Moscow may benefit from addressing problem alcohol use to mitigate high-risk behaviors.

Anal human papillomavirus and HIV: A cross-sectional study among men who have sex with men in Moscow, Russia, 2012-2013.

Anal human papillomavirus (HPV) is prevalent among men who have sex with men (MSM), but has not been studied in the Russian Federation. A cross-sectional survey and HPV genotyping were conducted among HIV seropositive (n=58) and seronegative MSM (n=65)in Moscow. Multivariable logistic regression was performed to identify correlates of infection with oncogenic HPV genotypes 16 and/or 18 (HPV 16/18). Forty per cent (49/124) of all MSM were infected with at least one anal HPV genotype, 31.5% (39/124) had HPV16/18,and 11.5% (14/121) had high-grade squamous intraepithelial lesions (HSIL). HPV 16/18 was more prevalent in HIV seropositive than seronegative men (24/58,41.4% vs 15/65, 23.1%; p=0.03). HIV infection was independently associated with HPV 16/18 (adjusted odds ratio (AOR): 5.08; 95% confidence intervals (CI):1.49-17.34, p=0.01), as was having 2-4 steady male sex partners in the last year (vs ≤ 1 partner; AOR: 6.99;95%CI: 1.94­25.24, p<0.01). History of prison/detention,migration to/within Russia and use of incompatible lubricants were marginally associated with HPV16/18 (p<0.10). Comprehensive prevention options are needed to address HIV and HPV infection among MSM in Russia and may benefit from inclusion of young men in piloted HPV vaccination programmes.

Social and structural risks for HIV among migrant and immigrant men who have sex with men in Moscow, Russia: implications for prevention.

Moscow has a large population of immigrants and migrants from across the Former Soviet Union. Little is studied about men who have sex with men (MSM) within these groups. Qualitative research methods were used to explore identities, practices, and factors affecting HIV prevention and risks among immigrant/migrant MSM in Moscow. Nine interviews and three focus group discussions were conducted between April-June 2010 with immigrant/migrant MSM, analyzed as a subset of a larger population of MSM who participated in qualitative research (n=121). Participants were purposively selected men who reported same sex practices (last 12 months). Migrants were men residing in Moscow but from other Russian regions and immigrants from countries outside of Russia. A socioecological framework was used to describe distal to proximal factors that influenced risks for HIV acquisition. MSM ranged from heterosexual to gay-identified. Stigma and violence related to homophobia in homelands and concerns about xenophobia and distrust of migrants in Moscow were emerged as key themes. Participants reported greater sexual freedom in Moscow but feared relatives in homelands would learn of behaviors in Moscow, often avoiding members of their own ethnicity in Moscow. Internalized homophobia was prevalent and linked to traditional sexual views. Sexual risks included sex work, high numbers of partners, and inconsistent condom use. Avoidance of HIV testing or purchasing false results was related to reporting requirements in Russia, which may bar entry or expel those testing positive. HIV prevention for MSM should consider immigrant/migrant populations, the range of sexual identities, and risk factors among these men. The willingness of some men to socialize with immigrants/migrants of other countries may provide opportunities for peer-based prevention approaches. Immigrants/migrants comprised important proportions of the MSM population, yet are rarely acknowledged in research. Understanding their risks and how to reach them may improve the overall impact of prevention for MSM and adults in Russia.

Impact of pooling on accuracy of hepatitis B virus surface antigen screening of blood donations.

Expenditure on screening blood donations in developing countries can be reduced by testing donations in pools. This study evaluated serological screening in pools for hepatitis B virus (HBV) at the Israeli national blood bank and a hospital blood bank in Gaza, the Palestinian Authority. The accuracy of HBV surface antigen (HBsAg) enzyme immunoassay performed on pools of 3-24 samples was compared with individual tests. Delay in detecting positive samples due to dilution in pools and the possibility of antibody-antigen neutralization were analyzed. The sensitivity of pooled testing for HBsAg was 93-99%, prolonging the window period by 5 days (8.3%). Neutralization of HBsAg by hepatitis B surface antibodies (anti-HBs) could be minimized by testing immediately after pooling. Serological testing for HBsAg in pools may be performed using manually created pools of up to six samples, with 5% loss in sensitivity and a risk of neutralization by anti-HBs present in the donor population. Pooling can therefore be considered as an option only in countries with a low prevalence of HBV.

Risk factors for methadone outside treatment programs: implications for HIV treatment among injection drug users.

BACKGROUND: Diversion of methadone outside treatment programs occurs, yet reasons for use of 'street methadone' are characterized poorly. Self-medication for withdrawal symptoms is one plausible hypothesis. Among HIV-infected drug users, some antiretroviral medications can reduce potency of methadone, yet any association between such effects and the use of supplemental methadone sources remains undetermined. OBJECTIVE: To estimate the frequency and risk factors for use of street methadone. METHODS: Injection drug users (IDUs) recruited through extensive community outreach in 1988-89 and 1994 were followed semi-annually with questionnaires about health history, use of licit and illicit drugs including methadone and HIV-related assays. Analyses were performed using generalized estimating equation logistic regression. RESULTS: Of 2811 IDUs enrolled and eligible for analysis, 493 people reported use of street methadone over 12 316 person-years of follow-up (4.0/100 person-years). In multivariate analyses, street methadone use was more common among women, whites, those 40-59 years old, those who reported withdrawal symptoms, past methadone program attendance (6-12 months before visit), recent heroin injection with or without cocaine (but not cocaine alone), smoking or sniffing heroin and reported trading sex. Street methadone was not associated with HIV infection or treatment. CONCLUSION: The results suggest that older IDUs still using heroin may be using street methadone to treat signs of withdrawal. The absence of a higher rate of street methadone use in HIV seropositive IDUs reveals that antiretroviral/methadone interactions are not a primary determinant of use outside of treatment settings.

Early immunologic and virologic responses to highly active antiretroviral therapy and subsequent disease progression among HIV-infected injection drug users.

We examined the prevalence and prognostic value of early responses to highly active antiretroviral therapy (HAART) among community-based injection drug users (IDUs) in Baltimore. Virologic (HIV RNA <1000 copies/ml) and immunologic (CD4 >500 cells/ul or increase of 50 cells/ul from the pre-HAART level) responses were examined in the 1st year of HAART initiation. Cox regression was used to examine the effect of early response on progression to new AIDS diagnosis or AIDS-related death. Among 258 HAART initiators, 75(29%) had no response, 53(21%) had a virologic response only, 38(15%) had an immunologic response only and 92(36%) had a combined immunologic and virologic response in the first year of therapy. Poorer responses were observed in those who were older, had been recently incarcerated, reported injecting drugs, had not had a recent outpatient visit and had some treatment interruption within the 1st year of HAART. In multiple Cox regression analysis, the risk of progression was lower in those with combined virologic and immunologic response than in non-responders, (relative hazard [RH], 0.32; 95% confidence interval [CI], 0.17-0.60). Those with discordant responses had reduced risk of progression compared to non-responders but experienced faster progression than those with a combined response, although none of these differences was statistically significant. Early discordant and non response to HAART was common, often occurred in the setting of injection drug use and treatment interruption and was associated with poorer survival. Interventions to reduce treatment interruptions and to provide continuity of HIV care during incarceration among IDUs are needed to improve responses and subsequent survival.

Estimation of delay in detecting hepatitis C virus antibodies in pools compared to individual testing on seroconversion panels.

Testing for anti-hepatitis C virus (HCV) antibodies in pools may reduce blood screening costs, making this approach affordable for developing countries, provided that the dilution of infected blood does not significantly increase the number of undetectable viral particles, especially in seroconverters. This study assessed the delay in detection of HCV antibodies in five HCV seroconversion panels, tested in pools of 6-48 samples, and estimated the risk of transfusion-transmitted HCV caused by pooling. The delay in detection of positive samples was 5-12 days for pools of all sizes, adding 7% to the risk of HCV transmission that occurs when blood donors' samples are tested individually.

Evaluating survival model performance: a graphical approach.

In the last decade, many statistics have been suggested to evaluate the performance of survival models. These statistics evaluate the overall performance of a model ignoring possible variability in performance over time. Using an extension of measures used in binary regression, we propose a graphical method to depict the performance of a survival model over time. The method provides estimates of performance at specific time points and can be used as an informal test for detecting time varying effects of covariates in the Cox model framework. The method is illustrated on real and simulated data using Cox proportional hazard model and rank statistics.

Increased risk of bloodstream and urinary infections in intensive care unit (ICU) patients compared with patients fitting ICU admission criteria treated in regular wards.

Critically ill patients, eligible for admission into intensive care units (ICUs), are often hospitalized in other wards due to a lack of ICU beds. Differences in morbidity between patients managed in ICUs and elsewhere are unknown, specifically the morbidity related to hospital-acquired infection. Patients fitting ICU admission criteria were identified by screening five entire hospitals on four separate days. Hospital infections within a 30-day follow-up period were compared in ICU patients and in patients on other wards using Kaplan-Meier curves. Residual differences in the patients' case mix between ICUs and other wards were adjusted for utilizing multivariate Cox models. Of 13415 patients screened, 668 were critically ill. The overall infection rates (per 100 patient-days) were 1.2 for bloodstream infection (BSI) and 1.9 for urinary tract infection (UTI). The adjusted hazard ratios in ICU patients compared with patients on regular wards were 3.1 (P<0.001) for BSI and 2.5 (P<0.001) for UTI. This increased risk persisted even after adjusting for the disparity in the number of cultures sent from ICUs compared with ordinary wards. No interdepartmental differences were found in the rates of pneumonia, surgical wound infections and other infections. Minimizing the differences between characteristics of patients hospitalized in ICUs and in other wards, and controlling for the higher frequency of cultures sent from ICUs did not eliminate the increased risk of BSI and UTI associated with admission into ICUs.

Longitudinal patterns of drug injection behavior in the ALIVE Study cohort,1988-2000: description and determinants.

The objective of this study was to characterize longitudinal patterns of drug injection behavior for individuals and to identify their early determinants. Participants were 1,339 injection drug users recruited into the AIDS Link to Intravenous Experience (ALIVE) Study in Baltimore, Maryland, through community outreach efforts. The study was initiated in 1988, and follow-up continued through 2000, with semiannual visits. Patterns of self-reported drug injection (yes/no) were defined for each participant, based on the number of drug-use transitions. The effect of baseline factors was assessed using multinomial logistic regression models. Over the 12-year study period, four patterns were noted: 29% of participants remained persistent drug injectors, 20% ceased injection, 14% relapsed once, and 37% had multiple transitions. Persistent injectors had the shortest follow-up and the highest mortality. For persons who changed their behavior, 3.4 years elapsed before their first cessation attempt, on average. Factors differentiating the groups included history of incarceration, young age, participation in drug treatment programs, recent overdose, and commercial sex. The observed long-term injection patterns are consistent with the view of drug addiction as a chronic disease. This view emphasizes the need for prolonged efforts to sustain cessation and to prevent adverse health and social outcomes among injection drug users.

Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users.

OBJECTIVE: Studies have shown that HIV-infected injection drug users (IDUs) are less likely to receive antiretroviral therapy than non-drug users. We assess factors associated with initiating highly active antiretroviral therapy (HAART) in HIV-infected IDUs. METHODS: A cohort study of IDUs carried out between 1 January 1996 and 30 June 1999 at a community-based study clinic affiliated to the Johns Hopkins University, Baltimore, Maryland. The participants were a total of 528 HIV-infected IDUs eligible for HAART based on CD4+ cell count. The main outcome measure was the time from treatment eligibility to first self-reported HAART use, as defined by the International AIDS Society-USA panel (IAS-USA) guidelines. RESULTS: By 30 June 1999, 58.5% of participants had initiated HAART, most of whom switched from mono- or dual-combination therapy to a HAART regimen. Nearly one-third of treatment-eligible IDUs never received antiretroviral therapy. Cox proportional hazards regression showed that initiating HAART was independently associated with not injecting drugs, methadone treatment among men, having health insurance and a regular source of care, lower CD4+ cell count and a history of antiretroviral therapy. CONCLUSIONS: Self-reported initiation of HAART is steadily increasing among IDUs who are eligible for treatment; however, a large proportion continues to use non-HAART regimens and many remain treatment-naive. Although both groups appear to have lower health care access and utilization, IDUs without a history of antiretroviral therapy use would have more treatment options available to them once they become engaged in HIV care.

Is participation in cardiac rehabilitation programs associated with better quality of life and return to work after coronary artery bypass operations? The Israeli CABG Study.

OBJECTIVE: To explore the putative effect of cardiac rehabilitation programs on the 'health-related quality of life' and 'return to work' in pre-retirement patients one year after coronary artery bypass grafting. METHODS: Of the 2,085 patients aged 45-64 who survived one year after CABG and were Israeli residents, 145 (6.9%) had participated in rehabilitation programs. Of these, 124 (83%) who answered QOL questionnaires were individually matched with 248 controls by gender, age within 5 years, and the time the questionnaire was answered. All patients had full clinical follow-up including a pre-operative interview. The Short Form-36 QOL questionnaire as well as a specific questionnaire were mailed to surviving patients one year after surgery. Study outcomes included the scores on eight scales and two summary components of the SF-36, as well as 'return to work' and 'satisfaction with medical services' from the specific questionnaire. Analysis was done for matched samples. RESULTS: Cardiac rehabilitation participants had significantly higher SF-36 scores in general health, physical functioning, and social functioning. They had borderline significant higher scores in the physical summary component of the SF-36. The specific questionnaire revealed significantly better overall functioning, higher satisfaction with medical care, and higher rate of return to work. While participants in cardiac rehabilitation and their controls were similar in their socio-demographic and clinical profiles, participating patients tended to be more physically active and more fully employed than their controls. CONCLUSIONS: Rehabilitation participants had a self-perception of better HRQOL, most significantly in social functioning. Our findings of more frequent return to work and higher satisfaction with medical care should induce a policy to encourage participation in cardiac rehabilitation programs after CABG.

Sex differences in risk factors for hiv seroconversion among injection drug users: a 10-year perspective.

BACKGROUND: Injection drug use directly or indirectly accounts for nearly half the annual human immunodeficiency virus (HIV) infections in the United States. Prospective studies that investigate both sexual and parenteral HIV risks among injection drug users (IDUs) are needed. We studied factors for HIV seroconversion among male and female IDUs in Baltimore, Md. METHODS: The HIV-negative IDUs (1447 male and 427 female) were recruited into a prospective study from 1988 to 1989 or in 1994. Participants underwent semiannual HIV tests and surveys through December 1998. Poisson regression was used to identify risk factors for HIV seroconversion, stratified by sex. Behaviors were treated as time-dependent covariates that varied at each semiannual period. RESULTS: Subjects were primarily African American (91%), and median age at enrollment was 35 years. Incidence of HIV was 3.14 per 100 person years (95% confidence interval, 2.78-3.53) and did not significantly differ by sex. Younger age independently predicted HIV seroconversion for both men and women. Among men, factors that independently predicted HIV seroconversion were the following: less than a high school education, recent needle sharing with multiple partners, daily injection, and shooting-gallery attendance. The incidence of HIV was double for men recently engaging in homosexual activity and cocaine injection. Among women, the incidence of HIV was more than double for those recently reporting sexually transmitted diseases. CONCLUSIONS: The incidence of HIV remained high among IDUs in Baltimore over the past decade. Risk factors for HIV seroconversion differed markedly by sex. Predominant risks among men included needle sharing and homosexual activity; among women, factors consistent with high-risk heterosexual activity were more significant than drug-related risks. Human immunodeficiency virus interventions aimed at IDUs should be sex-specific and incorporate sexual risks.

Sociodemographic and clinical factors associated with low quality of life one year after coronary bypass operations: the Israeli coronary artery bypass study (ISCAB).

OBJECTIVES: We sought to examine the effect of sociodemographic characteristics and perioperative clinical factors 1 year after coronary bypass operations on low health-related quality of life. We also sought to assess the usefulness of an additional single question on overall health for identifying patients with low health-related quality of life. METHODS: This report is part of the Israeli coronary artery bypass study of 1994, in which every patient undergoing isolated coronary bypass grafting in Israel was included. The target population for this report comprised all survivors beyond 1 year who were 45 to 65 years of age. Patients were interviewed before the operations. Self-administered questionnaires regarding health-related quality of life (SF-36) were sent to 1724 patients who were successfully located 1 year postoperatively, and 1270 questionnaires were completed. Low health-related quality of life was defined as the lowest tertile of the distribution of scores for the 2 summary components of the SF-36 and the single question on overall health. Logistic models were constructed for each of the 3 outcomes. RESULTS: Female sex and low socioeconomic background were associated with low health-related quality of life in the logistic models. Other significant factors were symptoms of angina, sleep disturbances, hypertension, high severity of illness scores, hospital readmission, no rehabilitation, and hospitals with high perioperative mortality. Of the 3 study outcomes, the model for the single question on overall health was the most discriminating (C statistic = 0.76 vs 0.70 and 0.70, respectively). CONCLUSIONS: The study identifies patients who would most benefit from posthospitalization community support after bypass operations. Under circumstances of limited resources, these disadvantaged groups should be targeted as a priority. Encouraging participation in existing rehabilitation programs or introducing telephone hotlines could improve health-related quality of life after coronary bypass grafting without large investments.

The prescription pattern of oral nitrates in coronary artery disease. Appropriateness and cost considerations.

OBJECTIVES: To evaluate the prescription patterns of oral nitrates in terms of appropriateness and cost in a community setting. METHODS: A period prevalence, descriptive, applied study. Data including age, gender, type of medication, dosage and cost were extracted from the database of the largest health maintenance organisation (HMO) in Israel. The study population included enrollees over 35 years of age who received oral nitrates at least once during the 12-month study period. RESULTS: Oral nitrates were prescribed for 8007 patients (mean age 72.85+/-9.59 years, male:female ratio 1:1). A total of 52,694 prescriptions were issued for 56,553 medications, of these 88.1% for mononitrates, which constituted 95% of the annual cost for patients and the HMO. The mean prescribed daily dose for the various drugs ranged from 30% less than to 50% more than the recommended dose. Combination therapy with at least two nitrates, which is not the recommended treatment, was given to 5% of the patients. The recommended alternative treatment will alleviate the financial burden for providers and patients. CONCLUSIONS: Improved prescription habits can provide enhanced quality as well as cost savings for patients and providers.

Sequential logistic models for 30 days mortality after CABG: pre-operative, intra-operative and post-operative experience--The Israeli CABG study (ISCAB). Three models for early mortality after CABG.

OBJECTIVES: The goal of this paper was to examine the added effect of operative and post-operative variables on 30 days mortality, in addition to patients' case-mix factors. SETTING AND DESIGN: A prospective study of 4835 patients, 95% of all Israeli patients who underwent coronary artery bypass grafting (CABG) in 1994. Information related to risk of death was collected at admission to hospital (preceding the operation), at time of the operation and in the immediate post-operative period. Deaths were independently ascertained. METHOD: Data collectors followed every patient from admission to discharge. Sequential logistic models were constructed for the 'case-mix', 'operative' and the 'post-operative' periods in chronological order. Each model incorporated and adjusted for the risk estimated at the previous point in time, by forcing individual risk scores. RESULTS: Significant pre-operative risk factors for 30 days mortality, in the case-mix model included mainly severity of illness characteristics, such as, left ventricular dysfunction and emergency admission, (c-statistic 78.8%). Model 2 (the 'operation' model) included in addition to the case-mix score, excessive duration of the operation per graft, bleeding, etc. (c-statistic 85.3%). The post-operative model showed the added effect of the post-operative factors such as low haemoglobin, additional surgery, and excessive time on respirator, (c-statistic 92.4%). CONCLUSIONS: The sequential analysis was an efficient method for updating patients' risk over time, where the number of events was small, relative to the number of risk factors. The addition of peri-operative factors increased significantly the predictive power of the model, adding clinical insights to the role of the hospital experience on 30 days mortality.

Chronic immune activation associated with intestinal helminth infections results in impaired signal transduction and anergy.

Helminthic parasites cause widespread, persistent infections in humans. The immigration of Ethiopians to Israel (a group denoted here by "Eth."), many of them infested with helminths and in a chronic immune-activation state, enabled us to investigate the effects of such immune activation on immune responses. We studied the immune profile and immune functions of 190 Eth. and Israeli non-Eth. (Isr.) highly, partially, or non-immune-activated individuals. Immune cells from highly immune-activated individuals were defective in several signaling responses, all of which were restored gradually following anti-helminthic treatment. These cells showed poor transmembrane signaling, as seen by the phosphorylation of various tyrosine kinases and of the MAPK kinases, ERK1/2 and p38; deficient degradation of phosphorylated IkappaBalpha; increased expression of cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), which appears to block proliferative responses in these cells; decreased beta-chemokine secretion by CD8(+) cells after stimulation; and reduced proliferation to recall antigen stimulation. Highly immune-activated individuals also showed decreased delayed-type skin hypersensitivity responses to recall antigen before deworming. These findings support the notion that chronic helminthic infections cause persistent immune activation that results in hyporesponsiveness and anergy. Such impaired immune functions may diminish the capacity of these individuals to cope with infections and to generate cellular protective immunity after vaccination.