Cytokine profiles in adults with imported malaria.

The increase in worldwide travel is making imported malaria a growing health concern in non-endemic countries. Most data on the pathophysiology of malaria come from endemic areas. Little is known about cytokine profiles during imported malaria. This study aimed at deciphering the relationship between cytokine host response and malaria severity among imported cases in France. This study reports cytokine profiles in adults with Plasmodium falciparum malaria included in the PALUREA prospective study conducted between 2006 and 2010. The patients were classified as having uncomplicated malaria (UM) or severe malaria (SM), with this last further categorized as very severe malaria (VSM) or less severe malaria (LSM). At hospital admission, eight blood cytokines were assayed in duplicate using Luminex® technology: interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-10, tumor necrosis factor (TNF)α, interferon (IFN)γ, and macrophage migration inhibitory factor (MIF). These assays were repeated on days 1 and 2 in the SM group. Of the 278 patients, 134 had UM and 144 SM. At hospital admission, over half the patients had undetectable levels of IL-1α, IL-1ß, IL-2, IL-4, IFNγ, and TNFα, while IL-10 and MIF were significantly higher in the SM vs. the UM group. Higher IL-10 was significantly associated with higher parasitemia (R = 0.32 [0.16-0.46]; P = 0.0001). In the SM group, IL-10 elevation persisting from admission to day 2 was significantly associated with subsequent nosocomial infection. Of eight tested cytokines, only MIF and IL-10 were associated with disease severity in adults with imported P. falciparum malaria. At admission, many patients had undetectable cytokine levels, suggesting that circulating cytokine assays may not be helpful as part of the routine evaluation of adults with imported malaria. Persisting high IL-10 concentration was associated with subsequent nosocomial infection, suggesting its possible interest in immune monitoring of most severe patients.

A qualitative study on the educational needs of young people with chronic conditions transitioning from pediatric to adult care.

OBJECTIVES: Although patient education is recommended to facilitate the transition from pediatric to adult care, a consensus has not been reached for a particular model. The specific skills needed for the transition to help in facilitating the life plans and health of young people are still poorly understood. This study explored the educational needs of young people with diverse chronic conditions during their transition from pediatric to adult care. METHODS: Qualitative semi-structured interviews were conducted with 17 young people with chronic conditions. A thematic analysis was conducted to examine the data. RESULTS: Five themes emerged from the data, identified through the following core topics: learning how to have a new role, learning how to adopt a new lifestyle, learning how to use a new health care service, maintaining a dual relationship with pediatric and adult care, and having experience sharing with peers. CONCLUSION: A shift in perspective takes place when the transition is examined through the words of young people themselves. To them, moving from pediatric to adult care is not viewed as the heart of the process. It is instead a change among other changes. In order to encourage a transition in which the needs of young people are met, educational measures could focus on the acquisition of broad skills, while also being person-centered.

Autoimmune diseases in HIV-infected patients: 52 cases and literature review.

OBJECTIVES: 1) To describe autoimmune diseases (AD) in HIV-infected people; and 2) to perform a literature review concerning this issue. DESIGN: 52 HIV-infected patients that presented an AD in 14 medical departments in Paris and Ile-de-France area were retrospectively included in this study. RESULTS: The ADs were vasculitis (11), immune cytopenias (8), rheumatic diseases (8), lupus (7), sarcoidosis (7), thyroid diseases (6), hepatic diseases (5), and antiphospholipid syndrome (4). Four patients presented 2 ADs. In 5 patients the AD preceded HIV infection, in 14 HIV infection was diagnosed at the same time as the AD and 34 were HIV-infected when they developed an AD. 40 ADs (80%) occurred in patients with a CD4 T lymphocyte count of more than 200/mm(3). Cases of autoimmune hemolytic anemia occurred only in patients severely immunodepressed. In five patients (a vasculitis case, a sarcoidosis case, three thyroid disease cases) the AD presented as a form of immune restoration inflammatory syndrome (IRIS). Some ADs allowed HIV-infection diagnosis at a stage of moderate immune deficiency (vasculitis, antiphospholipid syndrome, immune thrombocytopenia). 37 patients received immunosuppressant treatments with good tolerance. These results confirm in a large series of patients previous data concerning autoimmune diseases occurrence in HIV-infected people. CONCLUSION: In the HAART era, when HIV-infected people are treated more and more early, autoimmune diseases can occur, mainly at the phase of immunological recovery. HIV infection should not limit immunosuppressant treatment use.

Changes in blood B cell phenotypes and Epstein-Barr virus load in chronically human immunodeficiency virus­infected patients before and after antiretroviral therapy.

BACKGROUND: Switched and nonswitched memory B cells, which usually constitute the main reservoirs of Epstein­Barr virus (EBV), are rapidly depleted in patients with chronic human immunodeficiency virus (HIV) infection. Because the EBV load is frequently increased in these patients, other B cell reservoirs might participate in EBV persistence. METHODS: We examined the combined expression of CD27, SIgD/G/M, CD38, CD10, CD5, CXCR5, CD62L, CD44, and CXCR3 on B cells from healthy donors (n = 30) and from HIV type 1-infected patients (n = 23) at diagnosis and after highly active antiretroviral therapy. The plasma HIV load and the DNA EBV load in peripheral blood mononuclear cells were assessed. RESULTS: Increased frequencies of CD38+SIgD+CD10+ B cells were found in patients with an EBV load >10(3)copies per 10(6)peripheral blood mononuclear cells and a strong depletion of memory B cells. This phenotype resembles that of transitional B cell subsets. Elevated percentages of these B cells were still found in 2 patients showing no decrease in EBV load after highly active antiretroviral therapy. CONCLUSIONS: Because transitional-like B cells persist concomitantly with high EBV load after highly active antiretroviral therapy, we suggest that this population might be an alternative EBV reservoir in patients with chronic HIV infection who have strongly reduced numbers of memory B cells. The consequences of EBV infection of immature B cells are discussed with regard to B cell maturation and a higher prevalence of B cell lymphoma in HIV­infected patients.

Risks factors of liver fibrosis in a cohort of intravenous drug users coinfected with HIV and HCV in the HAART era: the role of mixed steatosis.

Factors associated with the occurrence of severe liver fibrosis in HIV/HCV (hepatitis C virus) coinfected patients remain poorly understood. We thus questioned which factors influenced the occurrence of fibrosis in a cohort of HIV/HCV coinfected intravenous drug user patients. HIV/HCV coinfected intravenous drug user patients naive of anti-HCV therapy for whom a liver biopsy was performed between 1996 and 2003 were retrospectively studied in three University hospitals in Paris and the Parisian region. One hundred and fifty two patients (131 men and 21 women; mean age 39.3+/-4.9 years) were studied. Most of them (62%) were treated with HAART. HCV genotypes included type 1 (N=78), type 2 (N=1), type 3 (N=38) and type 4 (N=35). Mean duration of HCV infection was 19.0+/-5.2 years. Sixty-six percent had minimal to moderate fibrosis (F0/F1/F2) and 34% severe fibrosis (F3/F4). Multivariate analysis retained METAVIR activity score (OR=2.60, 95%CI [1.46-4.64]; P=0.001), mixed pattern of steatosis (OR=3.29, 95%CI [1.24-8.71]; P=0.017) and a CD4 cell count<200/mm3 (OR=4.04, 9%CI [1.47-11.12]; P=0.007) as independent factors associated with severe fibrosis. HAART did not influence the occurrence of liver fibrosis. In this cohort of HIV/HCV coinfected intravenous drug user patients, METAVIR activity score, mixed steatosis and a low CD4 cell count were independent factors associated with severe liver fibrosis.

Tuberculosis in adolescents: A French retrospective study of 52 cases.

BACKGROUND: The only available data about tuberculosis (TB) among adolescents date back to the 1980s, although the incidence of tuberculosis has been increasing in this age group. METHODS: Medical records were reviewed for all adolescents aged 12 to 18 years hospitalized with the diagnosis of TB in Avicenne/Jean Verdier Teaching hospital (Seine-Saint-Denis, suburb of Paris) between September 2000 and December 2004. RESULTS: Of the 52 patients identified, 52% were female. Median age at diagnosis was 15 years (range, 12-18 years). The proportion of adolescents known to be born abroad was 90%. Diagnoses resulted from the examination of a sick child in 79% of cases, a case contact investigation of an adult suspected of having TB in 19% and routine tuberculin skin test in 2%. Twenty-seven of 52 patients (52%) had isolated pulmonary disease. Sixteen patients (31%) had pulmonary and extrapulmonary TB and 8 cases (17%) had exclusively extrapulmonary disease. The site of extrapulmonary TB included pleural (n = 8), meningitis (n = 4), lymph node (n = 4), peritoneal (n = 5), osteoarticular (n = 3) and genitourinary (n = 1). TB was confirmed by the isolation of Mycobacterium tuberculosis from sputum (n = 21), gastric aspirate (n = 8), bone (n = 1) or cerebrospinal fluid (n = 2). No case had a relapse or recurrence of disease in median 3.2 years of follow up. CONCLUSIONS: Our results indicate that demographic and clinical characteristics of adolescents with TB differed from adults and children. A specific approach to the prevention and treatment of TB in adolescents is absolutely necessary.

Phylogenetic analyses confirm the high prevalence of hepatitis C virus (HCV) type 4 in the Seine-Saint-Denis district (France) and indicate seven different HCV-4 subtypes linked to two different epidemiological patterns.

Hepatitis C virus (HCV) has been classified into six clades as a result of high genetic variability. In the Seine-Saint-Denis district of north-east Paris, the prevalence of HCV-4, which usually infects populations from Africa or the Middle East, is twice as high as that recorded for the whole of continental France (10.2 versus 4.5%). Although the pathogenicity of HCV-4 remains unknown, resistance of HCV-4 to therapy appears to be similar to that observed for HCV-1. In order to characterize the epidemiology of HCV-4 in Paris, sequences of the non-structural 5B gene (332 bp) were obtained from 38 HCV-4-infected patients. Extensive phylogenetic analyses indicated seven different HCV-4 subtypes. Moreover, phylogenetic tree topologies clearly distinguished two epidemiological profiles. The first profile (52.6% of patients) reflects the intra-suburban emergence of two distinct HCV-4 subclades occurring mainly among intravenous drug users (65% of patients). The second profile shows six subclades [HCV-4a, -4f, -4h, -4k, -4a(B) and a new sequence] and accounts for patients from Africa (Egypt and sub-Saharan countries) who have unknown risk factors (77.8% of patients) and in whom no recent diffusion of HCV-4 is evident. This study indicates the high diversity of HCV-4 and the extension of HCV-4a and -4d subclades among drug users in FRANCE: