Fatal septic shock caused by Capnocytophaga canimorsus diagnosed by 16S rRNA gene sequencing.

Introduction: Capnocytophaga canimorsus is a commensal bacterium found in the saliva of dogs and cats. In most cases C. canimorsus causes local infection resulting from bite-wounds, scratches or licks but severe forms can occur. The following case describes a severe and rapidly fatal sepsis and disseminated intravascular coagulation with no evidence of bite in a patient without obvious cause of immunosuppression, diagnosed by polymerase chain reaction and 16S rRNA gene sequencing. Case report: Herein we present a rare case of a 39-year-old man who was taken care of by the emergency medical service for faintness, fever and chills associated with generalized mottling. Despite critical care management and broad-spectrum antibiotherapy, the patient presented an irrepressible shock with disseminated intravascular coagulation and multiple organ failure. He died during the night. The initial etiological assessment was negative but rod-shaped inclusions could be observed in his blood. A pan-bacterial polymerase chain reaction targeting part of the gene encoding 16S ribosomal ribonucleic acid (rRNA) was carried out directly on blood cultures; the sequencing identified Capnocytophaga canimorsus. Conclusions: This observation illustrates the potential severity of C. canimorsus infection even in a patient without neither obvious causes of immunosuppression nor evidence of bite. The presence of intracellular bacillary forms on the blood smear is an important information which should lead to performing a polymerase chain reaction and 16S rRNA gene sequencing.

Influence of geographic origin on AIDS and serious non-AIDS morbidity/mortality during cART among heterosexual HIV-infected men and women in France.

BACKGROUND: The influence of geographic origin on the risk of severe illness and death on cART has not been explored in European countries. METHOD: We studied antiretroviral-naïve heterosexual HIV-1-infected individuals enrolled in the FHDH-ANRS CO4 cohort in France who started cART between 2006 and 2011. Individuals originating from France (French natives), sub-Saharan Africa (SSA) and non-French West-Indies (NFW) were studied until 2012. Crude and adjusted rate ratios (aRR) of severe morbid events/deaths (AIDS-related and non-AIDS-related) were calculated using Poisson regression models stratified by sex, comparing each group of migrants to French natives. RESULTS: Among 2334 eligible men, 1379 (59.1%) originated from France, 838 (35.9%) from SSA and 117 (5.0%) from NFW. SSA male migrants had a higher aRR for non-AIDS infections, particularly bacterial infections (aRR 1.56 (95% CI 1.07-2.29), p = 0.0477), than French natives. Among 2596 eligible women, 1347 (51.9%) originated from France, 1131 (43.6%) from SSA, and 118 (4.5%) from NFW. SSA and NFW female migrants had a higher aRR for non-AIDS infections, particularly non-bacterial infections (respectively, 2.04 (1.18-3.53) and 7.87 (2.54-24.4), p = 0.0010), than French natives. We observed no other significant differences related to geographic origin as concerns the aRRs for AIDS-related infections or malignancies, or for other non-AIDS events/deaths such as cardiovascular disease, neurological/psychiatric disorders, non-AIDS malignancies and iatrogenic disorders, in either gender. CONCLUSION: Heterosexual migrants from SSA or NFW living in France have a higher risk of non-AIDS-defining infections than their French native counterparts. Special efforts are needed to prevent infectious diseases among HIV-infected migrants.

First Case of Actinomycetoma in France Due to a Novel Nocardia Species, Nocardia boironii sp. nov.

Bacterial mycetoma is a neglected disease mainly observed in tropical area countries and typically associated with rural conditions, making its presence in developed countries of temperate climate areas rare. However, we report the first case of an autochthonous mycetoma case in continental France that originated from a new Nocardia species. A Gram-positive filamentous bacterium (OFN 14.177T) was isolated from a pus sample from the mycetoma of a male French patient 92 years old suffering from chronic lymphocytic leukemia. The isolate was analyzed by a polyphasic taxonomic approach by coupling morphological, biochemical, physiological, and chemotaxonomic aspects to genomic and phylogenetic analyses. Multilocus sequence analysis (MLSA) using four housekeeping genes (16S rRNA gene, secA1, hsp65, and sod) combined with phylogenetic analysis revealed that the strain OFN 14.177T is phylogenetically closer not only to Nocardia altamirensis but also to all other species comprising the Nocardia brasiliensis clade (i.e., N. brasiliensis, N. altamirensis, N. vulneris, N. iowensis, and N. tenerifensis), some of which present cutaneous tropism. The G+C content of isolate OFN 14.177T was 68.2 mol%. DNA-DNA hybridization analyses demonstrated 38.25% relative reassociation with N. altamirensis. The strain OFN 14.177T is different from the closest species at genetic and phenotypical levels, and the data obtained indicate that it should be recognized as a new species, for which the name of Nocardia boironii sp. nov. is proposed. The type strain is OFN 14.177T (= EML 1451 = DSM 101696). IMPORTANCE Bacterial mycetoma is an endemic infection in areas with tropical and subtropical climates. Thus, its presence in temperate climate areas remains rare. We report here the first case of autochthonous actinomycetoma in continental France originating from a Nocardia species other than N. brasiliensis, namely, Nocardia boironii. Considering the history of the patient, the infection source of strain OFN 14.177T may be from frequent contact with the soil over many years because of his gardening activities. The discovery of a French autochthonous Nocardia species responsible for actinomycetoma reveals the importance of considering the possibility of having autochthonous infections of this type in nontropical countries, not only imported cases from tropical countries. However, further studies are needed to elucidate the real incidence of this new species.

Influence of geographic origin, sex, and HIV transmission group on the outcome of first-line combined antiretroviral therapy in France.

BACKGROUND: More data are needed on the influence of geographic origin, sex, and the HIV transmission group on biological and clinical outcomes after first-line combined antiretroviral therapy (cART) initiation. METHODS: We studied antiretroviral-naive HIV-1-infected adults enrolled in the French Hospital Database on HIV cohort in France and who started cART between 2006 and 2011. The censoring date of the study was 31 December 2012. According to geographic origin [French natives (FRA) or sub-Saharan Africa/non-French West Indies (SSA/NFW)], sex, and HIV transmission group, we assessed 2-year Kaplan-Meier probabilities and adjusted hazard ratios (aHRs) for plasma viral load undetectability and CD4 cell recovery, and 5-year cumulative incidences and aHRs for negative clinical outcomes (AIDS-defining event, serious non-AIDS events, or death). RESULTS: Of 9746 eligible individuals, 7297 (74.9%) were FRA and 2449 (25.1%) were sub-Saharan Africa/non-French West Indies migrants. More migrants (38.1%) than nonmigrants (27.5%) started cART with a CD4 cell count less than 200/µl (P < 0.0001). By comparison with FRA MSM, nonhomosexual men, whatever their geographic origin, had lower aHRs for viral undetectability; all patient groups, particularly migrants, had lower aHRs for CD4 cell recovery than FRA MSM; aHRs for negative clinical outcome (360 new AIDS-defining events, 1376 serious non-AIDS events, 38 deaths) were also higher in nonhomosexual men, regardless of geographic origin. Preexisting AIDS status, a lower CD4 cell count and older age at cART initiation had the biggest impact on changes between the crude and aHRs of clinical outcomes. CONCLUSION: Compared with FRA MSM, all migrants had a lower likelihood of CD4 cell recovery, and nonhomosexual men had a higher likelihood of negative virological and clinical outcomes.

Antimony to Cure Visceral Leishmaniasis Unresponsive to Liposomal Amphotericin B.

We report on 4 patients (1 immunocompetent, 3 immunosuppressed) in whom visceral leishmaniasis had become unresponsive to (or had relapsed after) treatment with appropriate doses of liposomal amphotericin B. Under close follow-up, full courses of pentavalent antimony were administered without life-threatening adverse events and resulted in rapid and sustained clinical and parasitological cure.

Later cART initiation in migrant men from sub-Saharan Africa without advanced HIV disease in France.

OBJECTIVE: To compare the time from entry into care for HIV infection until combination antiretroviral therapy (cART) initiation between migrants and non migrants in France, excluding late access to care. METHODS: Antiretroviral-naïve HIV-1-infected individuals newly enrolled in the FHDH cohort between 2002-2010, with CD4 cell counts >200/µL and no previous or current AIDS events were included. In three baseline CD4 cell count strata (200-349, 350-499, ≥ 500/µL), we examined the crude time until cART initiation within three years after enrollment according to geographic origin, and multivariable hazard ratios according to geographic origin, gender and HIV-transmission group, with adjustment for baseline age, enrollment period, region of care, plasma viral load, and HBV/HBC coinfection. RESULTS: Among 13338 individuals, 9605 (72.1%) were French natives (FRA), 2873 (21.4%) were migrants from sub-Saharan Africa/non-French West Indies (SSA/NFW), and 860 (6.5%) were migrants from other countries. Kaplan-Meier probabilities of cART initiation were significantly lower in SSA/NFW than in FRA individuals throughout the study period, regardless of the baseline CD4 stratum. After adjustment, the likelihood of cART initiation was respectively 15% (95%CI, 1-28) and 20% (95%CI, 2-38) lower in SSA/NFW men than in FRA men who had sex with men (MSM) in the 350-499 and ≥ 500 CD4 strata, while no difference was observed between other migrant groups and FRA MSM. CONCLUSION: SSA/NFW migrant men living in France with CD4 >350/µL at entry into care are more likely to begin cART later than FRA MSM, despite free access to treatment. Administrative delays in obtaining healthcare coverage do not appear to be responsible.

Is impaired kidney function an independent predictor of the risk of myocardial infarction in HIV-infected individuals?

We examined whether impaired kidney function is an independent risk factor for myocardial infarction in HIV-infected individuals without pre-existing coronary artery disease. The odds ratio for impaired kidney function fell from 1.22 (95% confidence interval 0.90-1.66) to 0.99 (95% confidence interval 0.69-1.41) after adjustment for cardiovascular risk factors and HIV-related parameters, with hypertension, high-density lipoprotein cholesterol, smoking and the CD4 T-cell nadir as most influential confounders. In this setting, no association was found between impaired kidney function and the risk of myocardial infarction.

Cohort Profile: French hospital database on HIV (FHDH-ANRS CO4).

The French Hospital Database on HIV (FHDH) is a hospital-based multicentre open cohort with inclusions ongoing since 1989. The research objectives focus mainly on mid- and long-term clinical outcomes and therapeutic strategies, as well as severe AIDS and non-AIDS morbidities, and public health issues relative to HIV infection. FHDH also serves to describe HIV-infected patients receiving hospital care in France. FHDH includes data on more than 120,000 HIV-infected patients from 70 French general or university hospitals distributed throughout France. Patients are eligible for inclusion if they are infected by HIV-1 or HIV-2 and give their written informed consent. Standardized variables are collected at each outpatient visit or hospital admission during which a new clinical manifestation is diagnosed, a new treatment is prescribed or a change in biological markers is noted, and/or at least every 6 months. Since its inception, variables collected in FHDH include demographic characteristics, HIV-related biological markers, the date and type of AIDS and non AIDS-defining events, antiretroviral treatments and the date and causes of death, as reported in the medical records. Since 2005, data have also been collected on: co-infection with hepatitis B or C virus; alcohol and tobacco use; and non HIV-related biomarkers. Anyone can submit a research project by completing a standardized form available on the FHDH website (http://www.ccde.fr/_fold/fl-1385734776-429.pdf) or from the corresponding author, describing the context and objectives of the study. All projects are reviewed by the scientific committee.

HIV replication and immune status are independent predictors of the risk of myocardial infarction in HIV-infected individuals.

BACKGROUND: Individuals infected by human immunodeficiency virus (HIV) have a higher risk of cardiovascular disease than the general population. The specific effects of virological and immunological parameters on the risk of myocardial infarction (MI) in HIV-infected individuals are debated. METHODS: We conducted a nested case-control study within the French Hospital Database on HIV. Case patients (n = 289) were patients who, between January 2000 and December 2006, had a prospectively recorded and validated first MI. Up to 5 HIV-infected controls (n = 884) matched for age, sex, and clinical center were selected, at random with replacement, among patients with no history of MI. Conditional logistic regression models were used to identify predictors of the risk of MI. RESULTS: Plasma HIV-1 RNA levels >50 copies/mL, a low CD4 T-cell nadir, and a high CD8 T-cell count were independently associated with an increased risk of MI, with respective odds ratios of 1.51 (95% confidence interval, 1.09-2.10), 0.90 (.83-.97) per log(2) unit, and 1.48 (1.01-2.18) for the highest tertile of CD8 T-cell counts (>1150 cells/mm(3)) compared with the lowest (≤760 cells/mm(3)). CONCLUSIONS: Independently of cardiovascular risk factors and antiretroviral therapy, HIV replication, a low CD4 T-cell nadir and a high current CD8 T-cell count are associated with an increased risk of MI in HIV-infected individuals. This suggests new paths for interventions to diminish the risk of MI in HIV-infected patients.

Recurrent Mycobacterium avium infection after seven years of latency in a HIV-infected patient receiving efficient antiretroviral therapy.

We report the first case of Mycobacterium avium reactivation, after prolonged latency, in a HIV-infected patient receiving highly active antiretroviral therapy with undetectable viral replication and normal CD4 cell count. The patient presented with a painful swollen shoulder seven years after initial M. avium bacteriaemia. Articular puncture grew M. avium. The isolates of the first and second infection were identical using repetitive-sequence-based Polymerase Chain Reaction analyses.

Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4.

BACKGROUND: The role of exposure to specific antiretroviral drugs on risk of myocardial infarction in human immunodeficiency virus (HIV)-infected patients is debated in the literature. METHODS: To assess whether we confirmed the association between exposure to abacavir and risk of myocardial infarction (MI) and to estimate the impact of exposure to other nucleoside reverse transcriptase inhibitors (NRTIs), protease inhibitors (PIs), and non-NRTIs on risk of MI, we conducted a case-control study nested within the French Hospital Database on HIV. Cases (n = 289) were patients who, between January 2000 and December 2006, had a prospectively recorded first definite or probable MI. Up to 5 controls (n = 884), matched for age, sex, and clinical center, were selected at random with replacement among patients with no history of MI already enrolled in the database when MI was diagnosed in the corresponding case. Conditional logistic regression models were used to adjust for potential confounders. RESULTS: Short-term/recent exposure to abacavir was associated with an increased risk of MI in the overall sample (odds ratios [ORs], 2.01; 95% confidence interval [CI], 1.11-3.64) but not in the subset of matched cases and controls (81%) who did not use cocaine or intravenous drugs (1.27; 0.64-2.49). Cumulative exposure to all PIs except saquinavir was associated with an increased risk of MI significant for amprenavir/fosamprenavir with or without ritonavir (OR, 1.53; 95% CI, 1.21-1.94 per year) and lopinavir with ritonavir (1.33; 1.09-1.61 per year). Exposure to all non-NRTIs was not associated with risk of MI. CONCLUSION: The risk of MI was increased by cumulative exposure to all the studied PIs except saquinavir and particularly to amprenavir/fosamprenavir with or without ritonavir and lopinavir with ritonavir, whereas the association with abacavir cannot be considered causal.

Increased risk of myocardial infarction in HIV-infected patients in France, relative to the general population.

The incidence of myocardial infarction (MI) is lower in France than in English-speaking and northern European countries. We estimated the incidence of MI in the HIV-infected population in France, on the basis of the data from the FHDH-ANRS CO4 cohort, by comparison with the general population. The sex- and age-standardized morbidity ratio was estimated as 1.5 [95% confidence interval (CI) 1.3-1.7] overall, 1.4 (95% CI 1.3-1.6) in men and 2.7 (95% CI 1.8-3.9) in women.

Defective interleukin-2-dependent STAT5 signalling in CD8 T lymphocytes from HIV-positive patients: restoration by antiretroviral therapy.

BACKGROUND: CD8 T lymphocytes are critical in the control of HIV replication and disease progression. Our previous studies demonstrated that CD8 T cells from chronically infected patients with high virus load proliferated poorly in response to interleukin-2 (IL-2), a cytokine critical in CD8 T cell growth and differentiation, even though relatively high levels of IL-2 receptor (IL-2R) were expressed. This suggested that signal transduction defects in response to IL-2 might be involved. The STAT5 transcription factor is important in IL-2-dependent biological responses and it is known that there are defects in unstimulated CD3 and CD4 cells in HIV-infected patients. OBJECTIVE: To investigate whether the induction of STAT5 by IL-2 is altered in the CD8 T cells from HIV-positive individuals and the impact of highly active antiretroviral therapy (HAART) on its status. METHODS: CD8 T lymphocytes were purified from the peripheral blood mononuclear cells of HIV-positive patients before and after HAART. Ex vivo IL-2-induced STAT5 activation was evaluated by immunoblotting and electrophoretic mobility shift assays. RESULTS: CD8 T cells from a subset of untreated HIV-positive patients were unable to activate STAT5a and STAT5b proteins functionally in response to IL-2. This defect was not a result of alterations in IL-2R expression but correlated with an impaired activation of the upstream kinase Jak-3, known to mediate STAT5 activation. Overall, HAART restored Jak/STAT signalling in such patients. CONCLUSIONS: These results further uncover a potential mechanism by which CD8 T cell function is impaired in HIV-infected patients.

Failure of antibiotic therapy in Staphylococcus epidermidis infection of implantable venous access devices in patients with AIDS, as documented by molecular typing.

OBJECTIVE: To study the efficacy and safety of high-concentration antibiotic locks in association with systemic antibiotherapy in Staphylococcus epidermidis infections of totally implantable venous access devices (TIVADs) in patients with AIDS. METHODS: Thirty-one episodes of S. epidermidis TIVAD infection were observed in nine patients. Locks consisted of high concentrations of aminoglycosides or vancomycin according to antibiogram results (susceptibility results obtained with the disk diffusion technique). Genotyping of bacterial strains was performed by pulsed-field gel electrophoresis (PFGE) in 26 of the 31 infectious episodes. RESULTS: The infections occurred within a median period of 62 catheter-days. The median duration of systemic antibiotic therapy was 17.5 days in association with a median of three antibiotic locks. Failure as defined by the occurrence of a novel episode within 2 months was observed in 17 of the 31 infections (58%). According to the PFGE results, relapse with the same strain of S. epidermidis or reinfection with a different strain of S. epidermidis could be assigned to 10 episodes which failed to respond to therapy. Relapse was observed in six of 10 episodes. Four episodes were followed by the occurrence of a novel infection with a different S. epidermidis strain. In one patient, a relapse occurred despite TIVAD removal. CONCLUSION: Our observations further document the poor efficacy of associating antibiotic locks with systemic antibiotic therapy for the treatment of TIVAD infections in patients with AIDS.