Pulmonary melioidosis in CAMBODIA: a prospective study

<p>Abstract</p> <p>Background</p> <p>Melioidosis is a disease caused by <it>Burkholderia pseudomallei </it>and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes.</p> <p>Methods</p> <p>We characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. <it>B. pseudomallei </it>was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome.</p> <p>Results</p> <p>During April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against <it>B. pseudomallei</it>. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US$65 (range$25-$5000). Almost two-thirds (61.5%) incurred debt and 28.2% sold land or other belongings to pay illness-related costs.</p> <p>Conclusions</p> <p>The observed high fatality rate is likely explained by the lack or limited access to efficient antibiotics and under-recognition of the disease among clinicians, which led to inappropriate therapy.</p

Molecular Demonstration of a Pneumocystis Outbreak in Stem Cell Transplant Patients: Evidence for Transmission in the Daycare Center

Pneumocystis jirovecii pneumonia (PCP) is a life-threatening infection in hematology. Although occasionally reported, the role of interhuman transmission of P. jirovecii in PCP, compared to that of reactivation, remains an unresolved question; the recommendation to isolate PCP patients in the hematology ward are not well evidence-based. Following an unexpected increase in the number of febrile pneumonia patients with P. jirovecii DNA detected in respiratory samples in our hematology ward, we explored 12 consecutive patients from November 2015 to May 2016. Genotyping of P jirovecii was performed using microsatellite markers. The frequency of simultaneous occupancy of these 12 patients in the same unit on the same day from 4 months prior to the first diagnosis was recorded. In three patients, the P. jirovecii genotype could not be determined because DNA was insufficient. One rare single genotype (Gt2) was found in four of the other nine, all allogeneic stem cell transplant recipients. The transmission map showed that these 4 patients had multiple opportunities to meet on the same day (median, 6.5; range, 4–10) at the daycare center. It was much less among the eight non-Gt2 patients (median, 1; range, 0–9; P = 0.048). This study, based on modern molecular technics, strongly suggests that interhuman transmission of P. jirovecii between allogeneic stem cell transplant recipients is possible. P. jirovecii DNA detected in respiratory specimens supports that isolation and respiratory precautions be recommended in such cases in the hematology ward

Assessment of the Anthelmintic Efficacy of Albendazole in School Children in Seven Countries Where Soil-Transmitted Helminths Are Endemic

Soil-transmitted helminths (roundworms, whipworms and hookworms) infect millions of children in (sub)tropical countries, resulting in malnutrition, growth stunting, intellectual retardation and cognitive deficits. Currently, there is a need to closely monitor anthelmintic drug efficacy and to develop standard operating procedures, as highlighted in a World Health Organization–World Bank meeting on “Monitoring of Drug Efficacy in Large Scale Treatment Programs for Human Helminthiasis” in Washington DC at the end of 2007. Therefore, we have evaluated the efficacy of a commonly used treatment against these parasitic infections in school children in Africa, Asia and South-America using a standardized protocol. In addition, different statistical approaches to analyzing the data were evaluated in order to develop standardized procedures for data analysis. The results demonstrate that the applied treatment was highly efficacious against round- and hookworms, but not against whipworms. However, there was large variation in efficacy across the different trials which warrants further attention. This study also provides new insights into the statistical analysis of efficacy data, which should be considered in future monitoring and evaluation studies of large scale anthelmintic treatment programs. Finally, our findings emphasize the need to update the World Health Organization recommended efficacy threshold for the treatment of STH

Combined bacterial and fungal targeted amplicon sequencing of respiratory samples: Does the DNA extraction method matter?

International audienceBackground: High-throughput sequencing techniques are used to analyse the diversity of the respiratory microbiota in health and disease. Although extensive data are available regarding bacterial respiratory microbiota, its fungal component remains poorly studied. This is partly due to the technical issues associated with fungal metagenomics analyses. In this study, we compared two DNA extraction protocols and two fungal amplification targets for combined bacterial and fungal targeted amplicon sequencing analyses of the respiratory microbiota.Methods: Six sputa, randomly selected from routine samples in Mondor Hospital (Creteil, France) and treated anonymously, were tested after bacterial and fungal routine culture. Two of which were spiked with Aspergillus Fumigati and Aspergillus Nigri (105 conidia/mL). After mechanical lysis, DNA was extracted using automated QIAsymphony® extraction (AQE) or manual PowerSoil® MoBio extraction (MPE). DNA yield and purity were compared. DNA extracted from spiked sputa was subjected to (i) real-time PCR for Aspergillus DNA detection and (ii) combined metagenomic analyses targeting barcoded primers for fungal ITS1 and ITS2, and bacterial V1-V2 and V3-V4 16S regions. Amplicon libraries were prepared using MiSeq Reagent V3 kit on Illumina platform. Data were analysed using PyroMIC© and SHAMAN software, and compared with culture results.Results: AQE extraction provided a higher yield of DNA (AQE/MPE DNA ratio = 4.5 [1.3-11]) in a shorter time. The yield of Aspergillus DNA detected by qPCR was similar for spiked sputa regardless of extraction protocol. The extraction moderately impacted the diversity or relative abundances of bacterial communities using targeted amplicon sequencing (2/43 taxa impacted). For fungi, the relative abundances of 4/11 major taxa were impacted and AQE results were closer to culture results. The V1-V2 or V3-V4 and ITS1 or ITS2 targets assessed similarly the diversity of bacterial and fungal major taxa, but ITS2 and V3-V4 detected more minor taxa.Conclusion: Our results showed the importance of DNA extraction for combined bacterial and fungal targeted metagenomics of respiratory samples. The extraction protocol can affect DNA yield and the relative abundances of few bacterial but more fungal taxa. For fungal analysis, ITS2 allowed the detection of a greater number of minor taxa compared with ITS1

ER stress disturbs SR/ER-mitochondria Ca2+transfer: Implications in Duchenne muscular dystrophy

International audienc

Prospective evaluation of serum beta-glucan in patients with invasive fungal diseases

International audienceObjectives : The incidence of invasive fungal diseases (IFD) is currently increasing as a consequence of the growing population of immunocompromised patients. A key to IFD prognosis relies on early diagnosis, allowing early initiation of antifungal therapy. Over past years, the detection of the fungal (1-3)-β-D-glucan (BG) antigen has been increasingly used as an early IFD marker. However, different studies evaluating the performances of the BG assay in different target populations found contradictory results. In the present study, we assessed BG serum concentrations (Fungitell®, Associates of Cape Cod) in patients with documented IFD at time of diagnosis (TOD) and during antifungal treatment. Methods : We included 118 adults and 23 children with candidemia, invasive aspergillosis (IA) or rare IFD. Patients with two concomitant IFD or a possible cause of false-positive BG results were excluded. For candidemia and IA, serial sera were prospectively collected. The first serum was sampled respectively within [-3;+7] or [-7;+7] days toward mycological diagnosis. The follow-up period was of 2 and 6 months, respectively. Patients with rare IFD were included when at least one BG dosage was available within [-7;+15] days toward diagnosis. Whenever possible, a BG follow-up was performed until the IFD was controlled. Results: Thirty-three patients with candidemia and 31 with IA (28 probable and 3 proven IA) were included. They were patients with hematological diseases, solid organ transplant or patients hospitalized in ICU. Serum BG at TOD was negative in 44% of patients with candidemia and 52% with IA. No correlation was observed between negative BG at TOD and particular Candida species, catheter use, IA type, category of patients or recent administration of antifungals. Overall, for 18% and 14% of patients with candidemia and IA, BG remained not detected during the entire follow-up period. Among patients with candidemia or IA who had positive BG at TOD, >80% reached their peak value within the subsequent 2 weeks. Afterwards, the decrease of BG concentrations was rapid (half-concentration 3 weeks) in 20%, while 30% had persistently high BG. Thirty-three percent of patients with IA had a rapid decrease (half-concentration in 2 months). Regarding rare IFD, we included 77 patients with 26 different infections. While some IFD (scedosporiosis or cryptococcosis) had variable patterns toward BG at TOD, other were associated in all our cases with negative BG (fusariosis, microsporidiosis) or moderate to high (≥ 200 pg/ml) BG (hepatosplenic candidiasis, eumycotic mycetoma, subcutaneous phaehypho- or dermatophytomycosis, trichosporonosis). Conclusion: Altogether, our results offer valuable information for the clinical use of BG assay in various IFD and highlight the high percentage of patients with documented IFD, mainly candidemia and IA, for whom BG are negative at TOD

Mucor irregularis-associated cutaneous mucormycosis: Case report and review

Solid organ transplant recipients are at risk for invasive fungal diseases, and are also exposed to healthcare-associated mucormycosis. Mainly causing localized cutaneous mucormycosis, Mucor irregularis infection is reported for the first time in a kidney-transplant recipient. A healthcare-associated origin was highly suspected in this case. We performed a literature review and highlight the characteristics of this very rare fungus

Azole Resistance in Clinical and Environmental Aspergillus Isolates from the French West Indies (Martinique)

The emergence of azole resistant Aspergillus spp., especially Aspergillus fumigatus, has been described in several countries around the world with varying prevalence depending on the country. To our knowledge, azole resistance in Aspergillus spp. has not been reported in the West Indies yet. In this study, we investigated the antifungal susceptibility of clinical and environmental isolates of Aspergillus spp. from Martinique, and the potential resistance mechanisms associated with mutations in cyp51A gene. Overall, 208 Aspergillus isolates were recovered from clinical samples (n = 45) and environmental soil samples (n = 163). They were screened for resistance to azole drugs using selective culture media. The Minimum Inhibitory Concentrations (MIC) towards voriconazole, itraconazole, posaconazole and isavuconazole, as shown by the resistant isolates, were determined using the European Committee on Antimicrobial Susceptibility Testing (EUCAST) microdilution broth method. Eight isolates (A. fumigatus, n = 6 and A. terreus, n = 2) had high MIC for at least one azole drug. The sequencing of cyp51A gene revealed the mutations G54R and TR34/L98H in two A. fumigatus clinical isolates. Our study showed for the first time the presence of azole resistance in A. fumigatus and A. terreus isolates in the French West Indies

Toxoplasmosis as an Early Complication of Allogeneic Hematopoietic Cell Transplantation

International audienceAmong 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial

Ecology of the Scedosporium apiospermum species complex and species distribution in Morocco

National audienc