F X Weill

Phylogeographical analysis of the dominant multidrug-resistant H58 clade of Salmonella Typhi identifies inter- and intracontinental transmission events

The emergence of multidrug-resistant (MDR) typhoid is a major global health threat affecting many countries where the disease is endemic. Here whole-genome sequence analysis of 1,832 Salmonella enterica serovar Typhi (S. Typhi) identifies a single dominant MDR lineage, H58, that has emerged and spread throughout Asia and Africa over the last 30 years. Our analysis identifies numerous transmissions of H58, including multiple transfers from Asia to Africa and an ongoing, unrecognized MDR epidemic within Africa itself. Notably, our analysis indicates that H58 lineages are displacing antibiotic-sensitive isolates, transforming the global population structure of this pathogen. H58 isolates can harbor a complex MDR element residing either on transmissible IncHI1 plasmids or within multiple chromosomal integration sites. We also identify new mutations that define the H58 lineage. This phylogeographical analysis provides a framework to facilitate global management of MDR typhoid and is applicable to similar MDR lineages emerging in other bacterial species.

Evaluation of the impact on human salmonellosis of control measures targeted to Salmonella Enteritidis and Typhimurium in poultry breeding using time-series analysis and intervention models in France.

In France, salmonellosis is the main cause of foodborne bacterial infection with serotypes Enteritis (SE) and Typhimurium (ST) accounting for 70% of all cases. French authorities implemented a national control programme targeting SE and ST in poultry and eggs from October 1998 onwards. A 33% decrease in salmonellosis has been observed since implementation. We designed an evaluation of the impact of this control programme on SE and ST human infections in France. Using monthly Salmonella human isolate reports to the National Reference Centre we defined two intervention series (SE and ST) and one control series comprising serotypes not know to be associated with poultry or eggs. The series, from 1992 to 2003, were analysed using autoregressive moving average models (ARMA). To test the hypothesis of a reduction of SE and ST human cases >0 after the programme started and to estimate its size, we introduced an intervention model to the ARMA modelling. In contrast to the control series, we found an annual reduction of 555 (95% CI 148-964) SE and of 492 (95% CI 0-1092) ST human infections, representing respectively a 21% and 18% decrease. For SE, the decrease occurred sharply after implementation while for ST, it followed a progressive decrease that started early in 1998. Our study, suggests a true relation between the Salmonella control programme and the subsequent decrease observed for the two targeted serotypes. For ST, however, the decrease prior to the intervention may also reflect control measures implemented earlier by the cattle and milk industry.

Distinct Salmonella Enteritidis lineages associated with enterocolitis in high-income settings and invasive disease in low-income settings

An epidemiological paradox surrounds Salmonella enterica serovar Enteritidis. In high-income settings, it has been responsible for an epidemic of poultry-associated, self-limiting enterocolitis, whereas in sub-Saharan Africa it is a major cause of invasive nontyphoidal Salmonella disease, associated with high case fatality. By whole-genome sequence analysis of 675 isolates of S. Enteritidis from 45 countries, we show the existence of a global epidemic clade and two new clades of S. Enteritidis that are geographically restricted to distinct regions of Africa. The African isolates display genomic degradation, a novel prophage repertoire, and an expanded multidrug resistance plasmid. S. Enteritidis is a further example of a Salmonella serotype that displays niche plasticity, with distinct clades that enable it to become a prominent cause of gastroenteritis in association with the industrial production of eggs and of multidrug-resistant, bloodstream-invasive infection in Africa.

Global phylogeography and evolutionary history of Shigella dysenteriae type 1.

Together with plague, smallpox and typhus, epidemics of dysentery have been a major scourge of human populations for centuries1. A previous genomic study concluded that Shigella dysenteriae type 1 (Sd1), the epidemic dysentery bacillus, emerged and spread worldwide after the First World War, with no clear pattern of transmission2. This is not consistent with the massive cyclic dysentery epidemics reported in Europe during the eighteenth and nineteenth centuries1,3,4 and the first isolation of Sd1 in Japan in 18975. Here, we report a whole-genome analysis of 331 Sd1 isolates from around the world, collected between 1915 and 2011, providing us with unprecedented insight into the historical spread of this pathogen. We show here that Sd1 has existed since at least the eighteenth century and that it swept the globe at the end of the nineteenth century, diversifying into distinct lineages associated with the First World War, Second World War and various conflicts or natural disasters across Africa, Asia and Central America. We also provide a unique historical perspective on the evolution of antibiotic resistance over a 100-year period, beginning decades before the antibiotic era, and identify a prevalent multiple antibiotic-resistant lineage in South Asia that was transmitted in several waves to Africa, where it caused severe outbreaks of disease.

An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

A Phylogenetic and Phenotypic Analysis of Salmonella enterica Serovar Weltevreden, an Emerging Agent of Diarrheal Disease in Tropical Regions

Salmonella enterica serovar Weltevreden (S. Weltevreden) is an emerging cause of diarrheal and invasive disease in humans residing in tropical regions. Despite the regional and international emergence of this Salmonella serovar, relatively little is known about its genetic diversity, genomics or virulence potential in model systems. Here we used whole genome sequencing and bioinformatics analyses to define the phylogenetic structure of a diverse global selection of S. Weltevreden. Phylogenetic analysis of more than 100 isolates demonstrated that the population of S. Weltevreden can be segregated into two main phylogenetic clusters, one associated predominantly with continental Southeast Asia and the other more internationally dispersed. Subcluster analysis suggested the local evolution of S. Weltevreden within specific geographical regions. Four of the isolates were sequenced using long read sequencing to produce high quality reference genomes. Phenotypic analysis in Hep-2 cells and in a murine infection model indicated that S. Weltevreden were significantly attenuated in these models compared to the classical S. Typhimurium reference strain SL1344. Our work outlines novel insights into this important emerging pathogen and provides a baseline understanding for future research studies.

Unusual increase in reported cases of Paratyphoid A fever among travellers returning from Cambodia, January to September 2013

From January to September 2013, a marked increase in notifications of Salmonella Paratyphi A infections among travellers returning from Cambodia occurred in France. An investigation revealed 35 cases without a common source: 21 in France, five in Germany, three in the Netherlands, one in Norway, one in the United Kingdom, four in New-Zealand. Data suggest an ongoing event that should trigger further investigation. Travellers to Cambodia should observe preventive measures including good personal hygiene and food handling practices.

Seroepidemiology of Helicobacter pylori infection in Guadeloupe.

854 sera collected from blood donors in Guadeloupe were screened for Helicobacter pylori immunoglobulin G antibodies by a commercial enzyme-linked immunosorbent assay kit. The overall prevalence was 55.2%; it increased significantly with age from 36.1% at 18-19 years to 63.7% at 50-59 years (P = 0.003).

The French human Salmonella surveillance system: evaluation of timeliness of laboratory reporting and factors associated with delays, 2007 to 2011

Given the regular occurrence of salmonellosis outbreaks in France, evaluating the timeliness of laboratory reporting is critical for maintaining an effective surveillance system. Laboratory-confirmed human cases of Salmonella infection from whom strains were isolated from 2007 to 2011 in France (n=38,413) were extracted from the surveillance database. Three delay intervals were defined: transport delay (strain isolation, transport from primary laboratory to national reference laboratory), analysis delay (serotyping, reporting) and total reporting delay. We calculated the median delay in days and generated the cumulative delay distribution for each interval. Variables were tested for an association with reporting delay using a multivariable generalised linear model. The median transport and analysis delays were 7 and 6 days respectively (interquartile range (IQR: 6-10 and 4-9 respectively), with a median total reporting delay of 14 days (IQR: 11-19). Timeliness was influenced by various external factors: decreasing serotype frequency, geographical zone of primary laboratory and strain isolation on Sundays were the variables most strongly associated with increased length of delay. The effect of season and day of the week of isolation was highly variable over the study period. Several areas for interventions to shorten delays are identified and discussed for both transport and analysis delays.

Serological reactivity and bacterial genotypes in Chlamydia trachomatis urogenital infections in Guadeloupe, French West Indies

Objectives To determine the prevalence and genotypes of Chlamydia trachomatis urogenital infection in Guadeloupe, French West Indies, and to compare C trachomatis direct detection to serological testing. Methods From March to November 2000, 971 consecutive patients (888 women and 83 men) who had been referred to the clinical laboratory of the Institut Pasteur de la Guadeloupe for routine testing for genital infection were recruited. Samples were subjected to a nucleic acid amplification assay (AMP CT, Gen-Probe, San Diego, California, USA). Genotypes were determined by omp1 PCR-restriction fragment length polymorphism analysis. Serological testing was carried out with the commercially available peptide-based ELISA assay (SERO-CT IgG/IgA, Savyon/BMD, Marne-La-Vallée, France). Results Positive AMP CT test results were obtained for 102 (10.5%) of the 971 samples. The prevalence of infection was 16.9% in men and 9.8% in women. The most common genotypes were E (34.3%), F (23.9%), Da (13.4%), I (9%) and Ia (7.5%). No relationship was found between genogroups and age, sex or clinical symptoms. With AMP CT used as a reference, the sensitivity, specificity, positive and negative predictive values of SERO-CT were 81.1%, 56%, 34.5% and 91.2%, respectively, for IgG and 55.4%, 76.8%, 59.4% and 85.8%, respectively, for IgA. IgG seroprevalence rates were very low (1/5, 20%) in patients infected with genotype Ia strains. Conclusions The prevalence found in Guadeloupe did not differ significantly from that found in mainland France. The genotypes Da, F, I and Ia were more prevalent in Guadeloupe; however, the SERO-CT assay was unable to detect serum antibodies in 80% of the patients infected with genotype Ia strains.