Search

Aspergillus fumigatus is a major airborne nosocomial pathogen that is responsible for severe mycosis in immunocompromised patients. We studied the efficacy of an innovative mobile air-treatment device in eliminating A. fumigatus from the air following experimental massive contamination in a high-security room. Viable mycological particles were isolated from sequential air samples in order to evaluate the device's effectiveness in removing the fungus. The concentration of airborne conidia was reduced by 95% in 18 min. Contamination was reduced below the detection threshold in 29 min, even when the machine was at the lowest airflow setting. In contrast, during spontaneous settling with no air treatment, conidia remained airborne for more than 1 h. This indoor air contamination model provided consistent and reproducible results. Because the air purifier proved to be effective at eliminating a major contaminant, it may prove useful in preventing air-transmitted disease agents. In an experimental space mimicking a hospital room, the AirLyse air purifier, which uses a combination of germicidal ultraviolet C irradiation and titanium photocatalysis, effectively eliminated Aspergillus conidia. Such a mobile device may be useful in routine practice for lowering microbiological air contamination in the rooms of patients at risk.

We investigated human immunodeficiency virus (HIV) type 1 RNA, proviral DNA, and antiretroviral drug-resistant variants in cervicovaginal secretions of HIV-1-infected women receiving antiretroviral therapy. The prevalence of detectable HIV-1 RNA in genital secretions was inversely related to the number of antiretroviral drugs taken by the patients. Proviral DNA was detected in approximately half of all samples of cervicovaginal secretions from HIV-1-infected women, regardless of the presence or absence of HIV-1 RNA in cervicovaginal secretions and of the antiretroviral regimen. In cervicovaginal secretions of most women with persisting genital viral replication, HIV variants exhibiting mutations associated with drug resistance against protease and reverse-transcriptase pol genes were found. Our observations indicate that antiretroviral therapy is not effective in purging the female genital tract of cell-associated provirus and that antiretroviral drugs that penetrate the female genital tract at suboptimal concentrations exert a potent selective pressure on genital HIV variants when local replication of free HIV-1 RNA persists.

International audience; Care-related infections are a major public health concern. Their transmission can be associated with environmental factors. This study looks at air contamination around 45 patients colonized with multidrug-resistant organisms (MDROs). We found that 30 hospital rooms (67%) were contaminated with MDRO species and 10 rooms (22%) were contaminated with at least 1 MDRO.

A CE method utilizing triple quadrupole electrospray (ES) MS (MS/MS) detection was developed and validated for the simultaneous measurement of nucleoside 5'-triphosphate and 5'-monophosphate anabolites of the anti-HIV (human immunodeficiency virus) didanosine (ddAMP, ddATP) and stavudine (d4TMP, d4TTP), among a pool of 14 endogenous 5'-mono-, di-, and triphosphate nucleosides. These compounds were spiked and extracted from peripheral blood mononuclear cells (PBMCs) which are the sites of HIV replication and drug action. An acetic acid/ammonia buffer (pH 10, ionic strength of 40 mM) was selected as running electrolyte, and the separation was performed by the simultaneous application of a CE voltage of +30 kV and an overimposed pressure of 28 mbar (0.4 psi). The application of pressure assistance was needed to provide stable ES conditions for successful coupling. The coupling was carried out with a modified sheath-flow interface, with one uninterrupted capillary (80 cmx 50 microm id; 192 microm od) in a dimension that fits into the ESI needle to get a stable ion spray. Some CE-MS parameters such as overimposed pressure, sheath-liquid composition, sheath-liquid and sheath-gas flow rates, ES voltage, and the CE capillary position were optimized in order to obtain an optimal sensitivity. The use of perfluorinated alcohols and acids in the coaxial sheath-liquid make-up (2,2,2-trifluoroethanol + 0.2 mM tridecafluoroheptanoic acid) appeared to provide the best MS sensitivity and improve the stability of spray. The linearity of the CE-MS and CE-MS/MS methods was checked under these conditions. Validation parameters such as accuracy, intraday and interday precision, and LOQs were determined in CE-MS/MS mode. Finally, the quantitation of d4T-TP and ddA-TP was validated in this CE-MS/MS system.

Signs and symptoms associated with the acute illness, also referred to as acute retroviral syndrome (ARS), are observed in approximately two-thirds of HIV-infected patients [1, 2]. Similar symptoms have been reported in patients infected through sexual intercourse and through the intravenous route except for mucosal lesions in the genital tract which are more frequently observed in patients contaminated through sexual intercourse. The ARS usually spontaneously resolves within 2 to 3 weeks but may last for months in rare cases. The ARS, originally described as an influenza or mononucleosis like illness is characterized by fever (the most common symptom), sore throat, pharyngitis, arthralgia, myalgia, weight loss and lymphadenopathy [3, 4]. Some signs and symptoms should araise a high degree of suspicion such as generalized lymphadenopathy accompanied by a mononucleosis-like illness and/or a cutaneous rash associated with mucocutaneous ulcers involving the oral cavity (buccal mucosa, gingival, palate) or the genital (penis, vagina) or anal mucosa [1, 2, 3, 4, 5]. The cutaneous rash presenting as a maculo-papular rash affecting predominantly the trunk is particularly suggestive and is present in 40 to 80% of persons with acute infection [1, 5, 6]. Some serious but rare complications including hepatitis, respiratory failure, rhabdomyolysis and HIV-1 encephalitis are also observed [6]. Other infections indicative of profound immunosuppression such as oral candidasis, oesophagitis due to candida albicans or cytomegalovirus and multidermal zoster are not uncommon during ARS [7].

An HIV-1–infected patient had a rebound in viremia when antiviral therapy was discontinued as part of a vaccine research protocol. Careful studies showed that this patient was infected initially with subtype AE of the virus but then became infected with subtype B. There was no evidence of dual infection, so the data indicate that this is a case of superinfection with a different strain of HIV-1. Natural infection does not necessarily produce cross-clade protection, a finding that may have implications for the development of a vaccine against HIV-1.

ObjectiveTo compare non-parametric tests and procedures of selection in building clinically validated genotypic scores.Design and patientsIn the Jaguar study, 111 patients on a stable antiretroviral regimen experiencing virological failure were randomized in the didanosine (ddI) arm to receive ddI for 4 weeks in addition to their current combination therapy.MethodsThe virological response was HIV-1 RNA reduction from baseline to week 4. The univariate impact of each mutation associated with resistance to ddI on virological response was quantified by comparing reduction in plasma HIV-1 RNA in patients with or without the specific mutation, using a Wilcoxon–Mann–Whitney test. The next step was to select the combination of mutations most strongly associated with the virological response. Two procedures and two tests were compared using either the set of resistance mutations or the set of resistance mutations and mutations providing a better virological response. The Kruskal–Wallis and the Jonckheere test for ordered alternatives were compared in order to build a genotypic score using the two distinct procedures.ResultsEight mutations were associated with a reduced virological response to ddI: M41L, D67N, T69D, L74V, V118I, L210W, T215Y/F and K219Q/E and two mutations with a better virological response: K70R and M184V/I. The Jonckheere–Terpstra test for trend provided the combination of mutations (M41L+T69D-K70R+L74V-M184V /I+T215Y/F+ K219A/E) that were the most predictive for the week 4 virological response, that is, leading to the lowest P value. The ‘removing’ procedure, starting from a set of mutations retained and removing mutations one by one to find the best combination, provides lower P values than the ‘adding’ procedure starting with a single mutation and adding mutations one by one. Whatever the set of mutations and the procedure used, the Jonckheere–Terpstra test selects combinations of mutations leading to lower P values than the Kruskal–Wallis test.ConclusionThe Jonckheere–Terpstra test for trend is recommended for building a genotypic score when compared with the Kruskal–Wallis. The choice of the selection procedure is discussed here and may be dependent on the objective of the score.

Objective. We investigated the relationship between human immunodeficiency virus (HIV) phenotypic susceptibility to didanosine and the antiviral activity of didanosine (ddI) in the JAGUAR study. Methods. Baseline plasma HIV phenotypic susceptibility to ddI was assessed using a phenotype assay of patients randomized to receive ddI or placebo for 4 weeks in addition to their current regimen. Phenotypic susceptibility scores (PSSs) were then calculated for each sample. Associations between PSS and week 4 reductions in plasma HIV-1 RNA load or virologic response were assessed using linear regression and Jonckherre’s test and the Wilcoxon and Cochran-Armitage tests, respectively. Results. In the ddI arm, a significant association between reduction in viral load and continuous PSS was observed ( ). Using distinct categories, an increasing fold change (FC) in susceptibility to ddI was strongly P ! .0001 associated with smaller reductions in plasma HIV-1 RNA load ( ). The proportion of virologic responders P ! .0001 was 83% (15/18) for patients with a ddI FC 1.3, 50% (33/66) for patients with an FC of 1.3‐2.2, and 29% (4/ 14) for patients with an FC 2.2 ( ). After we determined these findings, 3 ddI FC categories were P p .0008 defined using 1.3 and 2.2 as thresholds. Conclusions. The relationship between phenotypic susceptibility to ddI and reduction in plasma HIV-1 RNA load describes a continuum. The establishment of a lower clinical cutoff at 1.3 and an upper clinical cutoff at 2.2 are clinically relevant.