Didier Monchy

CTX-M β-lactamases in Escherichia coli from community-acquired urinary tract infections, Cambodia.

The prevalence of CTX-M β-lactamases has reached a critical level, which highlights the need for study of their spread in developing countries.

Evolutionary History of Helicobacter pylori Sequences Reflect Past Human Migrations in Southeast Asia

The human population history in Southeast Asia was shaped by numerous migrations and population expansions. Their reconstruction based on archaeological, linguistic or human genetic data is often hampered by the limited number of informative polymorphisms in classical human genetic markers, such as the hypervariable regions of the mitochondrial DNA. Here, we analyse housekeeping gene sequences of the human stomach bacterium Helicobacter pylori from various countries in Southeast Asia and we provide evidence that H. pylori accompanied at least three ancient human migrations into this area: i) a migration from India introducing hpEurope bacteria into Thailand, Cambodia and Malaysia; ii) a migration of the ancestors of Austro-Asiatic speaking people into Vietnam and Cambodia carrying hspEAsia bacteria; and iii) a migration of the ancestors of the Thai people from Southern China into Thailand carrying H. pylori of population hpAsia2. Moreover, the H. pylori sequences reflect iv) the migrations of Chinese to Thailand and Malaysia within the last 200 years spreading hspEasia strains, and v) migrations of Indians to Malaysia within the last 200 years distributing both hpAsia2 and hpEurope bacteria. The distribution of the bacterial populations seems to strongly influence the incidence of gastric cancer as countries with predominantly hspEAsia isolates exhibit a high incidence of gastric cancer while the incidence is low in countries with a high proportion of hpAsia2 or hpEurope strains. In the future, the host range expansion of hpEurope strains among Asian populations, combined with human motility, may have a significant impact on gastric cancer incidence in Asia.

Malignant pilomatrixoma of the scalp

&NA; A 33 yr old man with a history of pilomatrixoma of the scalp, presented 5 mths later with a metastatic undifferentiated carcinoma in a submandibular lymph node. The cutaneous and lymph node tumors showed close histological similarity and features of malignancy. Investigations over 30 mths excluded a primary neoplasm elsewhere and consequently led to the diagnosis of malignant pilomatrixoma. These tumors are rare and most often located on the scalp. Most of the affected patients are middle age males. Wide excision is advised to avoid recurrences.

Emergence of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae in the Central African Republic: genetic characterization

BackgroundCross-resistance to quinolones and beta-lactams is frequent in Enterobacteriaceae, due to the wide use of these antibiotics clinically and in the food industry. Prescription of one of these categories of antibiotic may consequently select for bacteria resistant to both categories. Genetic mechanisms of resistance may be secondary to a chromosomal mutation located in quinolone resistance determining region of DNA gyrase or topoisomerase IV or to a plasmid acquisition. The insertion sequence ISCR1 is often associated with qnr and may favour its dissemination in Gram-negative bacteria. The aim of this study was to determine the genetic mechanism of quinolone resistance among extended-spectrum beta-lactamase-producing Enterobacteriaceae strains in the Central African Republic.FindingsAmong seventeen ESBL-producing Enterobacteriaceae isolated from urine, pus or stool between January 2003 and October 2005 in the Central African Republic, nine were resistant to ciprofloxacin (seven from community patients and two from hospitalized patients). The ESBL were previously characterized as CTX-M-15 and SHV-12. Susceptibility to nalidixic acid, norfloxacin and ciprofloxacin, and the minimal inhibitory concentrations of these drugs were determined by disc diffusion and agar dilution methods, respectively. The presence of plasmid-borne ISCR1-qnrA region was determined by PCR and amplicons, if any, were sent for sequencing. Quinolone resistance determining region of DNA gyrase gyrA gene was amplified by PCR and then sequenced for mutation characterization. We found that all CTX-M-producing strains were resistant to the tested quinolones. All the isolates had the same nucleotide mutation at codon 83 of gyrA. Two Escherichia coli strains with the highest MICs were shown to harbour an ISCR1-qnrA1 sequence. This genetic association might favour dissemination of resistance to quinolone and perhaps other antibiotics among Enterobacteriaceae.ConclusionsThis study shows that at least two mechanisms might explain the emerging resistance of Enterobacteriaceae to quinolones in the CAR. Beside the classical topoisomerase mutation, the cause may be acquisition of a plasmid-borne qnrA1. Clinicians and bacteriologists should be made aware of possible dissemination of ISCR1-qnrA1 among Enterobacteriacae.

Pénicilliose au Laos

Resume Introduction La penicilliose est due a Penicillium marneffei . Ce champignon dimorphique est endemique dans le sud est asiatique et la Chine du sud. Depuis 1988, cette mycose profonde constitue une des infections opportunistes les plus frequentes des sujets infectes par le VIH vivant dans cette zone geographique. Nous rapportons la premiere observation de penicilliose chez un patient infecte par le VIH en RDP Lao. Observation Une patiente Lao, infectee par le VIH et traitee pour une tuberculose ganglionnaire, etait hospitalisee pour une toux febrile associee a des adenopathies cervicales. Une apposition ganglionnaire coloree au RAL 555 confirmait le diagnostic de penicilliose. L′examen histopathologique detectait les elements de P. marneffei colores au PAS et Gomori-Grocott. La patiente etait traitee avec succes par ketoconazole. Commentaires La penicilliose est endemique dans le sud-est asiatique. Elle constitue, notamment en Thailande, une des infections opportunistes les plus frequentes chez le sujet infecte par le VIH. Le cas rapporte confirme l′existence de la penicilliose au Laos. Elle est probablement une infection opportuniste sous estimee dans ce pays. La methode diagnostique (frottis colore au RAL 555) utilisee dans ce cas est simple, rapide et adaptee au pays aux ressources limitees pour le diagnostic de la penicillose notamment.

Cytokine and Chemokine Expression in Kidneys during Chronic Leptospirosis in Reservoir and Susceptible Animal Models.

Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. Humans can be infected after exposure to contaminated urine of reservoir animals, usually rodents, regarded as typical asymptomatic carriers of leptospires. In contrast, accidental hosts may present an acute form of leptospirosis with a range of clinical symptoms including the development of Acute Kidney Injury (AKI). Chronic Kidney Disease (CKD) is considered as a possible AKI-residual sequela but little is known about the renal pathophysiology consequent to leptospirosis infection. Herein, we studied the renal morphological alterations in relation with the regulation of inflammatory cytokines and chemokines, comparing two experimental models of chronic leptospirosis, the golden Syrian hamster that survived the infection, becoming carrier of virulent leptospires, and the OF1 mouse, a usual reservoir of the bacteria. Animals were monitored until 28 days after injection with a virulent L. borgpetersenii serogroup Ballum to assess chronic infection. Hamsters developed morphological alterations in the kidneys with tubulointerstitial nephritis and fibrosis. Grading of lesions revealed higher scores in hamsters compared to the slight alterations observed in the mouse kidneys, irrespective of the bacterial load. Interestingly, pro-fibrotic TGF-β was downregulated in mouse kidneys. Moreover, cytokines IL-1β and IL-10, and chemokines MIP-1α/CCL3 and IP-10/CXCL-10 were significantly upregulated in hamster kidneys compared to mice. These results suggest a possible maintenance of inflammatory processes in the hamster kidneys with the infiltration of inflammatory cells in response to bacterial carriage, resulting in alterations of renal tissues. In contrast, lower expression levels in mouse kidneys indicated a better regulation of the inflammatory response and possible resolution processes likely related to resistance mechanisms.

Expansion of European vacA and cagA alleles to East-Asian Helicobacter pylori strains in Cambodia.

Helicobacter pylori infection is associated with gastric cancer (GC). The highest incidence rates have been described in Asia, but regional variations exist that do not match the distribution of infection prevalence rates. The aim of the study was to examine the possible contribution of H. pylori virulence factors to geographic differences in the incidence of GC across East and Southeast Asia. We studied 66 isolates from Cambodian patients that had previously been assigned to two genetic populations based on sequences of seven housekeeping genes, namely hpEurope (n = 34, 51.5%) and hpEastAsia, subpopulation hspEAsia (n = 32, 48.5%). These strains were characterized with respect to vacA polymorphism and cagA status by PCR, and the CagA C-terminal region was sequenced. We also sequenced the complete cagA gene from 10 hpEurope and 10 hspEAsia strains chosen at random. The cagA gene was present in 92.4% of the 66 isolates and was mainly of Western type (n = 36, 59.0%). hspEAsia strains carrying East-Asian CagA and the m1-type vacA allele (15.2%) were less frequent among the 66 Cambodian isolates than reported in East Asian countries, a finding that might partly explain the intermediate incidence of GC in Cambodia, and by extension, in Southeast Asia (except for Vietnam). The observed high prevalence of s1a alleles (34.4%) and Western CagA (28.1%) among hspEAsia strains indicates frequent introgression of European vacA and cagA alleles into East Asian H. pylori strains. This expansion might have severe consequences for individual disease outcome.

Impact of human migrations on diversity of Helicobacter pylori in Cambodia and New Caledonia.

Helicobacter pylori is a major gastric bacterial pathogen, presumed to have established itself in the human stomach approximately 100,000 years ago. Helicobacter pylori co‐evolved with its host, and human migrations shaped the expansion and the diversity of strains around the world. Here, we investigated the population structure and the genomic diversity of H. pylori in New Caledonia and Cambodia, where humans of different origins are living.

In Vitro Antifungal-Drug Susceptibilities of Mycelial and Yeast Forms of Penicillium marneffei Isolates in Cambodia

ABSTRACT Penicillium marneffei infection is an important disease among human immunodeficiency virus patients in Southeast Asia. The in vitro antifungal-drug susceptibilities of 29 clinical isolates and 5 isolates from bamboo rats collected from 2002 to 2004 were determined. The P. marneffei yeast form is more susceptible than the mycelial form to amphotericin B and ketoconazole, while the mycelial and yeast forms displayed similar susceptibilities to flucytosine and itraconazole. The MICs of fluconazole were higher for both mycelial and yeast forms.

High level of IL-10 expression in the blood of animal models possibly relates to resistance against leptospirosis

HighlightsHigher IL‐10/TNF‐&agr; and IL‐10/IL‐1&bgr; expression ratios in mouse compared to hamster.Differential expression independently of the Leptospira strain.Neutralisation of IL‐10 led to increased susceptibility in Leptospira‐infected mouse.IL‐10 has a role in regulation of IL‐1&bgr; during leptospirosis.IL‐10 neutralization did not interact with TNF‐&agr; expression level. Abstract Leptospirosis is a severe zoonosis which immunopathogenesis is poorly understood. We evaluated correlation between acute form of the disease and the ratio of the anti‐inflammatory cytokine IL‐10 to the pro‐inflammatory TNF‐&agr; and IL‐1&bgr; expression during the early phase of infection comparing resistant mice and susceptible hamsters infected with two different species of virulent Leptospira. The IL‐10/TNF‐&agr; and IL‐10/IL‐1&bgr; expression ratios were higher in mouse compared to hamster independently of the Leptospira strain, suggesting a preponderant role of the host response and notably these cytokines in the clinical expression and survival to leptospirosis. Using an IL‐10 neutralization strategy in Leptospira‐infected mouse model, we also showed evidence of a possible role of this cytokine on host susceptibility, bacterial clearance and on regulation of cytokine gene expression.