Olivier Patey

Seven years of recurrent severe strongyloidiasis in an HTLV-I-infected man who developed adult T-cell leukaemia

ObjectiveHuman T-cell leukaemia/lymphoma virus type I (HTLV-I) is endemic in Japan, the Caribbean basin and Africa, where it has been aetiologically linked to certain chronic myelopathies and adult T-cell leukamia (ATL). We sought to investigate whether strongyloidiasis, a parasitic disease common in these areas, might be a cofactor in the pathogenesis of ATL, as some reports have suggested. Patients, participantsOne 35-year-old HTLV-l-seropositive French West Indian man with a 7-year history of recurrent strongyloidiasis associated with episodic hyperinfestation presenting at the Centre Hospitalier Intercommunal, Villeneuve St Georges, France. InterventionsTreatment with various chemotherapeutic agents and symptomatic therapy for hypercalcaemia and antiviral therapy (zidovudine and interferon). ResultsThe patient developed ATL and died shortly after, despite chemotherapy. Immunological and virological studies performed during the last 15 months of his life showed an increase of the percentage of peripheral ATL cells, and progression from a polyclonal to a monoclonal integration of HTLV-I proviral DNA in the peripheral blood mononuclear and lymph-node cells. ConclusionsRecurrent strongyloidiasis appears to have been a possible cofactor associated with progression from healthy carrier state to ATL in our patient.

Lack of control of T cell apoptosis under HAART. Influence of therapy regimen in vivo and in vitro.

Background Increased and premature T cell apoptosis is recognized as a feature of HIV infection, and its normalization during highly active antiretroviral therapy (HAART) is thought to contribute to quantitative CD4 T cell restoration. Design Cross-sectional study of spontaneous, CD3- and CD95-mediated apoptosis in lymphocytes from 53 HIV-infected individuals taking HAART. Methods Overnight stimulation of peripheral blood mononuclear cells (PBMC) with coated anti-CD3 or anti-CD95 monoclonal antibodies or incubation overnight in medium. Apoptosis in CD4 and CD8 T cells was measured by flow cytometry. For in vitro assay of antiretroviral drugs, normal PBMC were prestimulated with anti-CD3 monoclonal antibodies and apoptosis was induced by ligation of CD95. The expression of active caspase-8 and caspase-3 was examined by flow cytometry. Results We report for the first time that important levels of T cell apoptosis may persist under HAART, in spite of a rise in CD4 T cells from baseline and a sustained suppression of plasmatic viral load. Spontaneous CD3- or CD95-induced apoptosis levels were inversely correlated with the in vivo number of CD4 T cells and the CD4/CD8 ratio, but not with the viral load or duration of antiretroviral therapy. Regimens including lamivudine are associated with persistent T cell apoptosis, particularly following CD95 ligation. Lamivudine was also found to stimulate in vitro CD95-induced apoptosis and caspase activation in pre-activated T lymphocytes from healthy donors. Conclusion The immunomodulatory effect of lamivudine may be one of the contributing factor to increased levels of T cell apoptosis under HAART. The data suggest that there is a requirement for physiological apoptosis during HAART.

Changing patterns of disseminated gonococcal infection in France: cross-sectional data 2009–2011

Objectives Disseminated gonococcal infections (DGIs) are rare. We describe the characteristics of DGIs in France. Methods This is a 3-year retrospective analysis of DGI cases collected through two networks of microbiologists and infectious disease specialists in France between 2009 and 2011. DGI was defined either by the isolation of Neisseria gonorrhoeae from blood and synovial fluid or by the existence of a clinical syndrome consistent with DGI and the isolation of N gonorrhoeae from any site. We describe the epidemiological, clinical and microbiological characteristics and outcomes of DGIs. Results 21 patients (9 women, 12 men; 18–62 years old) were diagnosed with DGI. The number of DGI cases increased between 2009 and 2011. Two men who had sex with men were coinfected with HIV. We found 28 extragenital locations, including arthritis (14 cases), tenosynovitis (7), skin lesions (4), endocarditis (1), prostatitis (1) and pelvic inflammatory disease (1). Genital signs were present in five patients. The diagnosis was confirmed by cultures in 20 patients—blood (4), synovial fluid (11), genital (3), throat (1), urine (1)—and by molecular biology on a pharyngeal swab in 1 patient. Seven cases were resistant to fluoroquinolones. The patients were treated with ceftriaxone, associated with corticosteroids (two cases) and surgery (six cases). Four patients had joint sequelae. Conclusions DGIs are increasing. Men seem to be at higher risk than women. Joint involvement was common. Microbiological diagnosis was based on culture, however molecular biology using pharyngeal swabs was helpful when cultures were negative.

Mother-to-child transmission of human immunodeficiency virus type 1 and type 2 and dual infection: a cohort study in Banfora, Burkina Faso.

A prospective cohort study on the mother-to-child transmission of human immunodeficiency virus type 1 (HIV1), type 2 (HIV2) and dual positivity (HIV1 + HIV2) was carried out in Banfora, West Burkina Faso. The study samples consist of 117 newborns of HTV-seropositive women matched to 234 newborns of HIV-seronegative women. Among cases, 91 were born of HIV1-seropositive mothers, 15 were born of HTV2-seropositive mothers and 11 were born of HTV1 and HTV2 dual-seropositive mothers and were included in an 18-month follow-up. Calculation of the mother-to-child transmission rate was according to the recommendations of the European Economic Community working group. The HTV1 mother-to-child transmission rate was estimated to be 27.8% (95% confidence interval (CD 24.5 to 32.4) with one method and 25.5% (95% CI 13.5 to 37.5) with a second method. For HIV2, this rate was estimated to be 29.5% (95% CI 26.0 to 39.8) and was not statistically different from the HIV1 mother-to-child transmission rate. No case of transmission was observed in children born of dual seropositive mothers. Survival rate at month 18 was significantly lower for children born of HIV1 mothers: 83.7% (95% CI 78.2 to 92.2). Survival rates were similar between children born of HIV2-seroposi-tive (86.7), dual HIV1 + 2-positive (100) and sero-negative mothers (92.0%). Findings suggest a …

Endemic level of Lyme borreliosis in a region of Central France: A sero-epidemiologic examination involving blood donors

[1] which revealed a high incidence of Lyme disease in a region in central France, a sero-epidemiologic investigation was performed with blood donor sera to evaluate the level of contact among the general population of the region. Ten-ml samples were obtained from bona fide blood donations on 17 and 24 May 1995, and on 19 June 1995, in 3 towns in central France: Ste Sévère, La Châtre, Châteaumeillant. These sera (without any anticoagulant) were stored at –80 °C. The method of analysis was as follows: qualitative detection of anti-Borrelia antibodies IgM and IgG (VIDAS LYME IgM/IgG – BioMérieux, Lyon, France); then confirmation by quantitative titration of IgG (note that a positive value is indicated at 35 UGLD/ml for IgG anti-Borrelia antibodies, were UGLD represents a Diagast IgG Lyme unit in terms of the activity of 0.1 μg IgG/ml serum) and qualitative detection of IgM (ELILYME-G/M – Diagast, Lille, France), and by TPHA (TPHA PHASYL DIAGAST – Diagast). Polymerase chain reaction (PCR) was then performed when blood samples were positive for IgM or IgG using a method published elsewhere [4]: (i) extraction of DNA (GENECLEAN kit – BIO 101 Inc., La Jolla, California, USA) before (ii) specific OspA-SL amplification; (iii) solid phase sandwich hybridation of the PCR products (PROBLYME kit – Biocode, Brussels, BELGIUM). Consultations were arranged for those patients whose serologic test results were definitely positive. The samples from a 182 blood donors were included in the study: 84 women and 98 men (sex ratio 0.86), mean age 44.7 ± 10.8 (range 20–66). Six sera were found positive for anti-Borrelia antibodies (four with IgG patients 1, 2, 3, 4-, two with IgM -patients 5, 6-). The patients resided in Ste Sévère and La Châtre (Table 1). The four patients with IgG were asymptomatic (no memory of tick-bite or previous history of Lyme disease, no treatment received). Paired serum sample of patients 5 and 6 gave a negative result with IgG in one case and then a positive result for the other after 2 weeks. PCR test was negative. Only patients 5 and 6 complained of rheumatoid symptoms (arthralgia, fatigue, headache), without memory of a tick-bite. Immediate treatment of patient 6 (amoxicillin 3 g per diem for 14 days, commencing European Journal of Epidemiology 13: 361–362, 1997.  1997 Kluwer Academic Publishers. Printed in the Netherlands.

Epidemiology of lyme disease in France: Lyme borreliosis in the region of Berry sud: A six year retrospective

The purpose of this epidemiologic retrospective is to recognize the endemic nature of Lyme borreliosis in ‘Berry’, region of France. Fifty-nine cases have been reported here during the past six years (1988–1994). An erythema migrans (EM), or a late manifestation concurrent with positive ELISA-test represents the main inclusion criterion (case definition used by the CDC). The results reveal a high incidence considering the limited information available in France. The farmer has been found to be mainly at risk, with EM being observed in 49% of cases. In general, late manifestations are rarely described. Peripheral neurological manifestations occur more frequently than those reported in the USA. The steps taken as a result of our study of Lyme disease are in accordance with the recommendations of the World Health Organization.

Fluconazole. Review and situation among antifungal drugs in the treatment of opportunistic mycoses of human immuno-deficiency virus infections.

Fluconazole is a novel triazole antifungal drug chiefly used in the treatment of opportunistic mycoses in immuno-compromised patients, particularly those with the acquired immuno-deficiency syndrome (AIDS). In comparison with other antifungal drugs, fluconazole has outstanding physical and pharmacokinetic properties, such as an excellent aqueous solubility allowing a parenteral formulation, high bioavailability by the oral route, even distribution throughout the tissues, including the central nervous system and the cerebro-spinal fluid, a long half-life (permitting once daily administration), and low binding to plasma proteins. It is excreted mainly as unchanged drug in the urine. Fluconazole is a broad-spectrum antifungal agent, especially effective against Candida spp., Cryptococcus neoformans and dermatophytes. Its antifungal efficacy was mainly proved by testing in animal models, since there is no relationship between in vitro and in vivo activities. It possesses a low toxicity and it is well-tolerated. Fluconazole is currently marketed for the treatment of oropharyngeal candidiasis in immuno-compromised patients and of atrophic oral candidiasis. Its place in the treatment of opportunistic mycoses in human immuno-deficiency virus-positive patients, in particular cryptococcal meningitis, is still under investigation but is promising.

Week 96 efficacy of lopinavir/ritonavir monotherapy in virologically suppressed patients with HIV: a randomized non-inferiority trial (ANRS 140 DREAM)

Background Sparing of antiretroviral drug classes could reduce the toxicity and cost of maintenance treatment for HIV infection. Objectives To evaluate the non-inferiority of efficacy and the safety of lopinavir/ritonavir (r) monotherapy versus a single-tablet regimen of efavirenz, emtricitabine and tenofovir (EFV/FTC/TDF) over 2 years. Methods Adults on stable ART with plasma HIV-1 RNA viral load <50 copies/mL for the past 12 months and no documented treatment failure were randomized to receive either lopinavir/r or EFV/FTC/TDF for 2 years. The primary endpoint was the proportion of patients without treatment failure at week 96 (viral load <50 copies/mL at week 96, confirmed at week 98), without study treatment discontinuation, a new AIDS-defining illness, or death. Results In the ITT analysis, the primary endpoint was reached by, respectively, 64% and 71% of patients in the lopinavir/r (n = 98) and EFV/FTC/TDF arms (n = 97), yielding a difference of -6.8% (lower limit of the 95% two-sided CI: -19.9%). Sanger and UltraDeep sequencing showed the occurrence of PI mutations in the lopinavir/r arm (n = 4) and of NNRTI and/or NRTI mutations in the EFV/FTC/TDF arm (n = 2). No unexpected serious clinical events occurred. Conclusions Lopinavir/r monotherapy cannot be considered non-inferior to EFV/FTC/TDF. PI resistance rarely emerged in the lopinavir/r arm and did not undermine future PI options. Two years of lopinavir/r monotherapy had no deleterious clinical impact when compared with EFV/FTC/TDF.

Tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients treated for tuberculosis: the ANRS 129 BKVIR trial.

BACKGROUND HIV-infected patients with TB need simplified, effective and well-tolerated antiretroviral regimens. METHODS The French ANRS 129 BKVIR open trial evaluated the once-daily tenofovir DF/emtricitabine and efavirenz combination, started within 12 weeks after TB treatment initiation, in antiretroviral-naive HIV-1-infected patients. Success was defined as an HIV-1 RNA <50 copies/mL and TB cure at 48 weeks. RESULTS TB was confirmed microbiologically (90%) or histologically (10%) in 69 patients (71% male; median age 43 years; 54% born in Africa). The median time between TB treatment initiation and antiretroviral therapy was 8 weeks (range 1-22 weeks). At baseline, median HIV-1 RNA was 5.4 log10 copies/mL and median CD4 cell count 74 cells/mm(3). In the ITT analysis, combined success at week 48 was achieved in 57/69 patients (83%, 95% CI 74-92). Twelve patients did not achieve virological success, and TB was not cured in one of them. Among the 47 patients who fully adhered to the strategy, the success rate was 96% (95% CI 90-100) and was not affected by low rifampicin and isoniazid serum concentrations. Forty-nine serious adverse events were reported in 31 patients (45%), and 11 led to antiretroviral drug interruption. All adverse events resolved. The immune reconstitution inflammatory syndrome occurred in 23 patients (33%, 95% CI 22-44), and was associated with a low baseline BMI (P = 0.03) and a low haemoglobin level (P = 0.02). CONCLUSION These results support the use of tenofovir DF/emtricitabine and efavirenz combination therapy for HIV infection in patients with TB.