The Erice 58 Charter on 'The health of migrants. An equity challenge for the public health system'.

Abstract: The Erice 58 Charter titled "The Health of Migrants: a Challenge of Equity for the Public Health System", was unanimously approved at the conclusion of the 58th Residential Course of the School of Epidemiology and Preventive Medicine 'Giuseppe D'Alessandro' entitled "The Health of Migrants: a Challenge of Equity for the Public Health System. Epidemiological, clinical-relational, regulatory, organisational, training and public communication aspects at international, national and local level', which took place from 28 March to 2 April 2022 in Erice (Sicily, Italy), at the 'Ettore Majorana' Foundation and Centre for Scientific Culture. The Course was promoted by the Italian Society of Migration Medicine (S.I.M.M.) and the Italian Society of Hygiene, Preventive Medicine and Public Health (SItI), with the collaboration and patronage of the Istituto Superiore di Sanità (ISS). 72 learners participated (mainly resident doctors in 'Hygiene and Preventive Medicine' but also other health service professionals), whose average age was 37 years; on the basis of territorial origin, 13 of the 20 Italian regions were represented. During the intense learning experience, which consisted of 18 frontal lessons (with 20 lecturers from the bio-medical, socio-anthropological and journalistic fields) and 7 working group sessions (supported by 4 classroom tutors in addition to the lecturers) in 'blended learning' mode, the various dimensions and critical issues related to the possibility of guaranteeing truly inclusive health policies for foreigners/migrants, throughout the country, were identified and discussed from an 'Health Equity' perspective. This enabled a small editorial group to draw up the basic document that, in the last session of the Course, was discussed and modified by all participants into the version of the 'Erice 58 Charter' presented here.

Differences in the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals using routine data.

OBJECTIVES: This study was to compare the incidence and clinical outcomes of SARS-CoV-2 infection between Italian and non-Italian nationals. STUDY DESIGN: We retrospectively analysed data from the COVID-19 Italian integrated surveillance system (14 September 2020 to 17 October 2021). METHODS: We used multivariable Cox proportional hazards models to estimate the hazard ratio (HR) of infection and, among cases, the HRs of death, hospitalisation and subsequent admission to intensive care unit in non-Italian nationals relative to Italian nationals. Estimates were adjusted for differences in sociodemographic characteristics and in the week and region of diagnosis. RESULTS: Of 4,111,067 notified cases, 336,265 (8.2%) were non-Italian nationals. Compared with Italian nationals, non-Italians showed a lower incidence of SARS-CoV-2 infection (HR = 0.81, 95% confidence interval [CI]: 0.80-0.81). However, once diagnosed, they were more likely to be hospitalised (HR = 1.90, 95% CI: 1.87-1.92) and then admitted to intensive care unit (HR = 1.08, 95% CI: 1.04-1.13), with differences larger in those coming from countries with a lower human development index. Compared with Italian cases, an increased rate of death was observed in non-Italian cases from low-human development index countries (HR = 1.41, 95% CI: 1.23-1.62). The HRs of SARS-CoV-2 infection and severe outcomes slightly increased after the start of the vaccination campaign. CONCLUSIONS: Underdiagnosis and delayed diagnosis in non-Italian nationals could explain their lower incidence compared with Italians and, among cases, their higher probability to present clinical conditions leading to worse outcomes. Facilitating early access to vaccination, diagnosis and treatment would improve the control of SARS-CoV-2 transmission and health outcomes in this vulnerable group.

Clinical validity and utility of preconception expanded carrier screening for the management of reproductive genetic risk in IVF and general population.

STUDY QUESTION: What is the clinical validity and utility of preconception Expanded Carrier Screening (ECS) application on the management of prospective parents? SUMMARY ANSWER: The high detection rate of at-risk couples (ARCs) and the high proportion opting for IVF/preimplantation genetic testing (PGT) treatment demonstrate the clinical utility of ECS in the preconception space in IVF and general population. WHAT IS KNOWN ALREADY: About 2-4% of couples are at risk of conceiving a child with an autosomal recessive or X-linked genetic disorder. In recent years, the increasing cost-effectiveness of genetic diagnostic techniques has allowed the creation of ECS panels for the simultaneous detection of multiple recessive disorders. Comprehensive preconception genetic screening holds the potential to significantly improve couple's genetic risk assessment and reproductive planning to avoid detectable inheritable genetic offspring. STUDY DESIGN, SIZE, DURATION: A total of 3877 individuals without a family history of genetic conditions were analyzed between January 2017 and January 2020. Of the enrolled individuals, 1212 were gamete donors and 2665 were patients planning on conceiving from both the IVF and the natural conception group. From the non-donor cohort, 1133 were analyzed as individual patients, while the remaining ones were analyzed as couples, for a total of 766 couples. PARTICIPANTS/MATERIALS, SETTING, METHODS: A focused ECS panel was developed following American College of Obstetrics and Gynecology ACOG-recommended criteria (prevalence, carrier rate, severity), including highly penetrant severe childhood conditions. Couples were defined at-risk when both partners carried an autosomal recessive pathogenic/likely pathogenic variant (PLP) on the same gene or when the woman was a carrier of an X-linked PLP variant. ARC detection rate defined the clinical validity of the ECS approach. Clinical utility was evaluated by monitoring ARCs reproductive decision making. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 402 individuals (10.4%) showed PLP for at least one of the genes tested. Among the 766 couples tested, 173 showed one carrier partner (22.6%), whereas 20 couples (2.6%) were found to be at increased risk. Interestingly, one ARC was identified as a result of cascade testing in the extended family of an individual carrying a pathogenic variant on the Survival Of Motor Neuron 1SMN1 gene. Of the identified ARCs, 5 (0.7%) were at risk for cystic fibrosis, 5 (0.7%) for fragile X syndrome, 4 (0.5%) for spinal muscular atrophy, 4 (0.5%) for Beta-Thalassemia/Sickle Cell Anemia, 1 (0.1%) for Smith-Lemli-Opitz Syndrome and 1 (0.1%) for Duchenne/Becker Dystrophy. Fifteen ARCs were successfully followed up from both the IVF and the natural conception groups. All of these (15/15) modified their reproductive planning by undergoing ART with Preimplantation Genetic Testing for Monogenic disease and Aneuploidies (PGT-M and PGT-A). To date, 6/15 (40%) couples completed their PGT cycle with euploid/unaffected embryos achieving a pregnancy after embryo transfer and three of them have already had an unaffected baby. LIMITATIONS, REASONS FOR CAUTION: The use of a limited panel of core gene-disease pairs represents a limitation on the research perspective as it can underestimate the rate of detectable carriers and ARCs in this cohort of prospective parents. Expanding the scope of ECS to a larger panel of conditions is becoming increasingly feasible, thanks to a persistent technological evolution and progressive cataloging of gene-disease associations. WIDER IMPLICATIONS OF THE FINDINGS: These results highlight the potential clinical validity and utility of ECS in reducing the risk of a pregnancy affected by a detectable inheritable genetic condition. The steady reduction in the costs of genetic analyses enables the expansion of monogenic testing/screening applications at the preimplantation stage, thus, providing valid decisional support and reproductive autonomy to patients, particularly in the context of IVF. STUDY FUNDING/COMPETING INTEREST(S): No external funding was used for this study. A.C., M.F., S.C., M.P., L.G., and C.P. are employees of Igenomix Italy. C.S. is the head of the scientific board of Igenomix. TRIAL REGISTRATION NUMBER: N/A.

Early childhood vaccination coverage and timeliness by macro-area of origin in children born to foreign women residing in Italy.

OBJECTIVES: Country of origin might affect vaccine uptake in children born to immigrants. We aimed to evaluate differences in childhood vaccination coverage (VC) and timeliness by macro-area of origin of foreign mothers residing in Italy. STUDY DESIGN: Multicentre retrospective birth cohorts. METHODS: We analysed data of 23,287 children born in 2009-2014 to foreign women in the cities of Rome, Turin and Treviso. We retrieved data through record-linkage of the population, vaccination and birth registries. We estimated VCs at different ages for vaccines against tetanus, measles and meningococcal group-C, using the Kaplan-Meier method. Factors associated with vaccine uptake were evaluated using multilevel Poisson models. RESULTS: Estimates of VC at any age and for all antigens were significantly lower in children born to women from Asia and higher in children born to women from Africa, as compared to other macro-areas. Similar differences by area of origin were observed for timeliness; independently of mother's sociodemographic characteristics and neonatal outcomes, the probability of delay vaccination after 2 years of age for each antigen was highest in children born to women from Asia. The risk of missed vaccination for all antigens was significantly higher in children born to younger and unemployed women. CONCLUSIONS: Factors related to area of origin (e.g., cultural habits, language skills) are likely to affect parents' decision to vaccinate their children. These factors, as well as sociodemographic characteristics, should be adequately investigated and addressed to increase vaccine uptake in foreign children, especially those born to Asian women.

Efficacy of novel albendazole salt formulations against secondary cystic echinococcosis in experimentally infected mice.

In this study, we evaluated the efficacy, expressed as a mean weight decrease of the whole echinococcal cyst mass, of novel benzimidazole salt formulations in a murine Echinococcus granulosus infection model. BALB/c mice were intraperitoneally infected with protoscoleces of E. granulosus (genotype G1). At 9 months post-infection, treatment with albendazole (ABZ), ricobendazole (RBZ) salt formulations, and RBZ enantiomer salts (R)-(+)-RBZ-Na and (S)-(-)-RBZ-Na formulations were initiated. Drugs were orally applied by gavage at 10 mg kg-1 body weight per day during 30 days. Experimental treatments with benzimidazole sodium salts resulted in a significant reduction of the weight of cysts compared to conventional ABZ treatment, except for the (S)-(-)-RBZ-Na enantiomer formulation. Scanning electron microscopy and histological inspection revealed that treatments impacted not only the structural integrity of the parasite tissue in the germinal layer, but also induced alterations in the laminated layer. Overall, these results demonstrate the improved efficacy of benzimidazole salt formulations compared to conventional ABZ treatment in experimental murine cystic echinococcosis.

Trend of Legionella colonization in hospital water supply.

BACKGROUND: In many nosocomial Legionella outbreaks water distribution systems are the most frequent source of infection. OBJECTIVES: Considering the hospital waterline old age, an investigation on colonization by Legionella spp was carried out in order to evaluate the pipeline system weaknesses and to implement environmental preventive measures. METHODS: From 2004 to 2010, overall 97 samples from the water line were collected. The samples were analyzed according to the italian Legionella spp standard methods; water temperature, pH and residual free chlorine were determined at the time of collection. X2 test, exact-test and t-test were used to compare proportions and means. RESULTS: Overall 28 samples (23.7%) were positive for Legionella spp, and five of them (17.9%) exceeded the threshold level >104 cfu/L. The number of positive samples varied along the years, showing a significant increasing trend (X2 for trend = 11.5; p<0.01), but most occurred in 2008 (53,6%), when the hospital underwent major building reconstruction. Samples positive for Legionella spp by comparison to negative ones showed a lower free chlorine concentration (0.08 mg/L vs 0.15 mg/L) and a higher water temperature (46.1° vs 42.7°). Actually the percentage of positive samples decreased significantly with the increasing in free chlorine in the water (X2 for trend = 8.53; p<0.01). The samples collected at the connection between public water line with the hospital supply network were always free from Legionella. All hospital buildings were colonized by Legionella spp, although 80% of samples >104 cfu/L occurred in the C-building. No cases of nosocomial legionellosis were reported during the study period. CONCLUSIONS: Hospital water system showed a diffuse colonization by Legionella spp, although the degree of contamination reached the threshold level (>104 cfu/L) only in a small percentage of samples, showing a substantial effectiveness of the control measures applied.

Clinical and epidemiological features of HIV/AIDS infection among migrants at first access to healthcare services as compared to Italian patients in Italy: a retrospective multicentre study, 2000-2010.

PURPOSE: Migrants account for approximately 8.7% of the resident population in Italy. The immigration status deeply influences access to prevention and care, thus contributing to increase the burden of HIV/AIDS among such a fragile category. The aim of this study was to investigate socio-demographic and baseline clinical and immunological features of HIV-infected migrants, as compared to Italians. METHODS: We retrospectively analysed data for all the 1,611 HIV-infected migrant patients and a random sample of 4,230 HIV-infected Italian patients aged 18 or older who first accessed nine Italian clinical centres in 2000-2010 and were followed up at least 1 year. Differences in baseline characteristics between migrants and Italians were evaluated in univariate analysis, while factors associated with late presentation were evaluated in multivariate analysis using logistic regression models. RESULTS: The baseline profile differs between the HIV-infected migrant and Italian patients, substantially reflecting what reported by current statistics in terms of gender, age, risk category as well as clinical features. Late presenters were more frequent among migrants as compared to Italians (53.0 vs 45.8%; adjusted odds ratio [(AOR) = 1.55, 95% confidence interval (CI) 1.34-1.78]. Other factors associated with late presentation included increasing age, as well as undocumented legal status among foreign-born subjects (AOR = 1.41, 95% CI 0.97-2.04), though of borderline significance. CONCLUSIONS: Late presentation still represents a relevant problem despite the advances in the management of HIV infection. More efforts are needed to allow early diagnosis and access to care among the most vulnerable, such as undocumented foreign-born subjects in a country where migration flows are on the rise.

Critical review of the characteristics, interactions, and toxicity of micro/nanomaterials pollutants in aquatic environments.

A wide range of contaminants of emerging concern such as micro/nanoplastics (MPs/PNPs) and metal-nanoparticles (Me-NPs) from anthropogenic activities have been identified in aquatic environments. The hazardous effects of these micro/nanomaterials as pollutants in organisms and the lack of knowledge about their behavior in aquatic environments have generated growing concern in the scientific community. The nanomaterials have a colloidal-type behavior due to their size range but with differences in their physicochemical properties. This review comprises the behavior of micro/nanomaterials pollutants and the physicochemical interactions between MPs/PNPs and Me-NPs in aquatic environments, and their potential toxicological effects in organisms. Moreover, this article describes the potential use of Me-NPs to remove MPs/PNPs present in the water column due to their photocatalytic and magnetic properties. It also discusses the challenge to determine harmful effects of micro/nanomaterials pollutants in organisms and provides future research directions to improve integrated management strategies to mitigate their environmental impact.

Risk of hospitalization and death for healthcare workers with COVID-19 in nine European countries, January 2020-January 2021.

This article presents and compares coronavirus disease 2019 attack rates for infection, hospitalization, intensive care unit (ICU) admission and death in healthcare workers (HCWs) and non-HCWs in nine European countries from 31st January 2020 to 13th January 2021. Adjusted attack rate ratios in HCWs (compared with non-HCWs) were 3.0 [95% confidence interval (CI) 2.2-4.0] for infection, 1.8 (95% CI 1.2-2.7) for hospitalization, 1.9 (95% CI 1.1-3.2) for ICU admission and 0.9 (95% CI 0.4-2.0) for death. Among hospitalized cases, the case-fatality ratio was 1.8% in HCWs and 8.2% in non-HCWs. Differences may be due to better/earlier access to treatment, differential underascertainment and the healthy worker effect.

[Microbiological pollution of operating rooms: critical analysis of two decades of surveillance]. / Inquinamento microbiologico delle sale operatorie: analisi critica di due decenni di sorveglianza.

The objective of this study was to analyze the results of microbiological air sampling of operating rooms (OR) over the last two decades at the Sapienza University Hospital of Rome, in order to describe the time trends of contamination levels and to assess any significant changes. Microbiological air sampling carried out in 14 surgical units between 1992 and 2010 were examined. The sampling results have been aggregated into four time periods (prior to 1996, 1996-2000, 2001-2005, 2006-2010) and the time trend of sampling results was analyzed in comparison with the standard reported by ISPESL for OR at-rest (< or = 35 CFU/mc). The same analysis was repeated after stratification by risk level of the OR (high risk (AR) and low risk (BR)). To verify the significance level of the temporal variations in the distribution of results x2 test for trend was performed. There was a significant downward trend in the number of OR with contamination levels higher of the standard (x2 for trend = 8.94, P < 0.025). This reduction mainly regards AR-OR (x2 for trend = 7.33, P < 0.05). The results suggest that the preventive measures performed in AR-OR have been effective. More attention must be given to BR-OR.

Clinical and functional outcomes of the remplissage technique to repair anterior shoulder dislocation: average 7 years of follow-up.

PURPOSE: The purpose of this work is to report mid- to long-term clinical results, recurrence rates and instability following surgery to repair anterior dislocation of the shoulder by the remplissage technique. METHODS: This was a retrospective case series at a single center with patients with anterior shoulder instability that received surgery using the remplissage technique. Rowe questionnaire, instability complaints, recurrence episodes and return to sport were analyzed. RESULTS: Of all patients screened, 21 (92.3%) were enrolled and only 2 patients were lost to follow-up. The mean age of the patients at the time of surgery was 27.8y.o., and the mean number of dislocations before surgery was 3.2 episodes. The follow-up average was 83.8 months (range 28-126). No case of postoperative infection was observed. Two patients (9.5%) had recurrent shoulder instability and required reintervention after 18 and 48 months. The average final Rowe score was 92.9 (range 75-100). All patients that played sports before surgery returned to the sport, and 73.7% of them returned to the same activity level. CONCLUSION: The remplissage technique applied to repair anterior shoulder dislocation with humeral bone loss presents good results regarding clinical scores, shoulder stability and acceptable rates of return to sports, even in a mid- to long-term follow-up. LEVEL OF EVIDENCE: IV.

RHBDD2 overexpression promotes a chemoresistant and invasive phenotype to rectal cancer tumors via modulating UPR and focal adhesion genes.

The current standard of care for locally advanced rectal cancer (RC) is neoadjuvant radio-chemotherapy (NRC) with 5-fluorouracil (5Fu) as the main drug, followed by surgery and adjuvant chemotherapy. While a group of patients will achieve a pathological complete response, a significant percentage will not respond to the treatment. The Unfolding Protein Response (UPR) pathway is generally activated in tumors and results in resistance to radio-chemotherapy. We previously showed that RHBDD2 gene is overexpressed in the advanced stages of colorectal cancer (CRC) and that it could modulate the UPR pathway. Moreover, RHBDD2 expression is induced by 5Fu. In this study, we demonstrate that the overexpression of RHBDD2 in CACO2 cell line confers resistance to 5Fu, favors cell migration, adhesion and proliferation and has a profound impact on the expression of both, the UPR genes BiP, PERK and CHOP, and on the cell adhesion genes FAK and PXN. We also determined that RHBDD2 binds to BiP protein, the master UPR regulator. Finally, we confirmed that a high expression of RHBDD2 in RC tumors after NRC treatment is associated with the development of local or distant metastases. The collected evidence positions RHBDD2 as a promising prognostic biomarker to predict the response to neoadjuvant therapy in patients with RC.

EpiSouth: a network for communicable disease control in the Mediterranean region and the Balkans.

The countries around the Mediterranean Sea share epidemiological characteristics and public health problems. In 2006 the EpiSouth Project was started as a framework for collaboration for communicable diseases surveillance and training in the Mediterranean Basin. As of December 2008, 26 countries from southern Europe, the Balkans, North Africa and the Middle-East are members of EpiSouth and several international organisations and institutions collaborate: the European Commission (EC), the European Centre for Disease Prevention and Control (ECDC), the Italian Ministry of Work, Health and Social Policies and the World Health Organization (WHO). The project is coordinated by the Italian national public health institute and three work packages (WPs) Cross-border epidemic intelligence, vaccine preventable diseases and migrants and Cross-border emerging zoonoses are operated by the national institutes of France, Bulgaria and Greece. These WPs constitute technical pillars on which the project develops. Networking and Training are WPs dedicated to capacity building and are run by the Padua Teaching Hospital (Italy) and the Spanish national public health institute. A steering committee guides EpiSouth's activities while all countries collaborate through WP steering teams and focal points. A number of outcomes have been accomplished and documents with results are available from the EpiSouth website which hosts a public website and a restricted area for direct sharing of information among the participants. Five electronic bulletins were published, two trainings for 63 participants performed, national epidemic intelligence systems were evaluated, a preliminary survey on vaccine-preventable diseases and migrants performed, and a list of priorities for emerging zoonoses in the Mediterranean area was selected. Overall the network succeeded in creating cohesion, mutual trust and concrete collaboration on cross-border public health issues in a geographical area that is not addressed as a whole by any other initiative or organisation.

[Evaluation of cognitive requirements of parents consumers attending vaccination offices]. / Valutazione dei fabbisogni conoscitivi dei genitori utenti degli Uffici di Vaccinazione.

To vaccinate the majority of population it is essential a strong cooperation with parents (users) which have to be correctly informed through an efficient communication system. The present analysis aims at elucidating parental background knowledge and information sources on vaccination problems. We selected 387 parents from ASL vaccination offices in L'Aquila, Avezzano-Sulmona and Pescara. Two groups have been identified: the first group included parents dealing with the first vaccination of their child, parents in the second group already experienced the vaccination tool. The two groups have been tested with a 17 items questionnaire. Results analysis evidenced a reasonable trust in the validity of received information and a fair level of topic knowledge. Our results show that the organizative and cultural effort put on by Public health operators improved awareness and participation to vaccination program. Still a big effort has to be devoted to disadvantage group of population's mainly low-level education groups and new immigrants. Thus it would be wise to promote informative actions even through the media to increase the basic knowledge on vaccine strategies

The disease profile of poverty: morbidity and mortality in northern Uganda in the context of war, population displacement and HIV/AIDS.

The population of Gulu District (northern Uganda) has been severely incapacitated by war, epidemics and social disruption. This study is aimed at describing disease patterns and trends in this area through a retrospective analysis of discharge records for 155205 in-patients of Lacor Hospital in the period 1992-2002. The burden of infectious diseases in childhood is overwhelming, with malaria accounting for the steepest increase in admissions. Admissions for war-related injuries and malnutrition fluctuated with the intensity of the war and the severity of famine. Emerging and re-emerging infections, such as HIV/AIDS, tuberculosis and Ebola, accounted for a heavy disease burden; however, there has been a trend for admissions related to HIV/AIDS and tuberculosis to decrease since the implementation of community-based services. Vulnerable groups (infants, children and women) accounted for 79.8% of admissions. Long-term war, population displacement, the collapse of social structures and the breakdown of the health system place people at a much greater risk of persistent, emerging and re-emerging infectious diseases, malnutrition and war-related injuries, shaping the 'disease profile of poverty'. Most of the disease burden results from infectious diseases of childhood, whose occurrence could be dramatically reduced by low-cost and effective preventive and curative interventions.

Trend in HIV-1 prevalence in an antenatal clinic in North Uganda and adjusted rates for the general female population.

OBJECTIVES: To estimate HIV-1 prevalence among women attending an antenatal clinic in the Gulu District (North Uganda) and, based on these data, among the district's female population. METHODS: Anonymous HIV-1 screening was performed for 8555 antenatal clinic attendees aged 15-39 years in the period 1993-1997. The results were used to estimate the prevalence among the district's female population, accounting for differences in fertility rates by HIV-1 serostatus. RESULTS: Among antenatal clinic attendees, HIV-1 prevalence showed a significant linear decrease (P < 0.001), from 26.0% in 1993 [95% confidence Interval (CI), 23.2-29.0%] to 16.1% in 1997 (95% CI, 14.8-17.5%). This decrease was mostly due to a marked decrease until 1995 (14.3%; 95% Cl, 12.7-16.0%) and was more pronounced among women aged under 30 years (P < 0.001), from both urban and rural areas (P < 0.001). The risk of being infected was higher among women from urban areas (Gulu Municipality), both over the entire period (adjusted prevalence proportion ratio = 1.54; 95% CI, 1.40-1.68) and by individual year. The estimated prevalence for the 15-39-year-old female population, standardized by age and area of residence, decreased from 25.4% in 1993-1994 to 17.8% in 1996-1997; these rates were 1.22 and 1.28 times higher, respectively, than those among antenatal clinic attendees. CONCLUSIONS: The trend of decrease among young women, for whom changes in HIV-1 prevalence more closely reflect incidence, could be partially due to a reduction in risk behaviour and a consequent decreasing incidence. Differences in fertility rates by HIV-1 serostatus should be addressed when using antenatal clinic data to estimate prevalence among the general female population.

Immunological activation markers in the serum of African and European HIV-seropositive and seronegative individuals.

OBJECTIVE: The concentration of type 1 and type 2 cytokines and fibroblast-associated apoptosis-1 soluble receptor (sAPO-1/Fas) was analysed in the sera of Ugandan and Italian HIV-1-seropositive and seronegative individuals. The data were compared to determine whether the immunological status of these groups was different. METHODS: Sixty-seven Ugandan and 30 Italian HIV-positive patients were analysed and stratified according to CD4 counts (group 1, > 500 x 10(6)/l; group 2, 200-500 x 10(6)/l; group 3, < 200 x 10(6)/l). Sera from 15 Ugandan and 11 Italian HIV-negative blood donors were also analysed. Serum concentration of type 1 cytokines [interleukin (IL)-2, IL-12, and interferon (IFN)-gamma] and type 2 cytokines (IL-4 and IL-10), and sAPO-1/Fas were measured by enzyme-linked immunosorbent assay. RESULTS: Serum levels of IL-2, IFN-gamma and IL-10 but not of IL-4 and IL-12, were elevated in HIV-positive group 1 and 2 Africans compared with HIV-positive Italian individuals. IL-4 was mildly augmented in HIV-positive group 3 African patients. Serum concentration of sAPO-1/Fas was reduced in HIV-positive Africans compared with HIV-positive Italian individuals. Finally, serum levels of IL-2 and IL-10 were increased and sAPO-1/Fas reduced when sera of HIV-negative African healthy controls were compared with their Italian counterparts. The ratio of type 1/type 2 cytokines was roughly 1.0 in HIV-negative African controls, and much greater than 1.0 in HIV-negative Italian controls. CONCLUSIONS: These preliminary findings indicate that immune activation is present in African HIV infection. Furthermore, these data raise the possibility that abnormal immune activation and increased susceptibility to antigen-induced cell death is present even in HIV-negative African controls.

Immune activation in africa is environmentally-driven and is associated with upregulation of CCR5. Italian-Ugandan AIDS Project.

BACKGROUND: HIV infection in Africa is associated with immune activation and a cytokine profile that stimulates CCR5 expression. We investigated whether this immune activation is environmentally driven; if a dominant expression of CCR5 could indeed be detected in African individuals; and if R5 HIV strains would be prevalent in this population. METHODS: Freshly drawn peripheral blood mononuclear cells from HIV-uninfected African and Italian individuals living in rural Africa, from HIV-uninfected Africans and Italians living in Italy, and from HIV-infected African and Italian patients were analysed. Determinations of HIV coreceptor-specific mRNAs and immunophenotype analyses were performed in all samples. Virological analyses included virus isolation and characterization of plasma neutralizing activity. FINDINGS: Results showed that: immune activation is detected both in Italian and African HIV-uninfected individuals living in Africa but not in African subjects living in Italy; CCR5-specific mRNA is augmented and the surface expression of CCR5 is increased in African compared with Italian residents (CXCR4-specific mRNA is comparable); R5-HIV strains are isolated prevalently from lymphocytes of African HIV-infected patients; and plasma neutralizing activity in HIV-infected African patients is mostly specific for R5 strains. CONCLUSIONS: Immune activation in African residents is environmentally driven and not genetically predetermined. This immune activation results in a skewing of the CCR5 : CXCR4 ratio which is associated with a prevalent isolation of R5 viruses. These data suggest that the selection of the predominant virus strain within the population could be influenced by an immunologically driven pattern of HIV co receptor expression.