Person: Jacqueline Forget, Camille
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First Name
Camille
Last Name
Jacqueline Forget
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ISCIII
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ISCIII::Centro Nacional de Microbiología (CNM)
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CNIO Organization
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Publication Integración de la información molecular y epidemiológica en la vigilancia del sarampión. Aplicación en el estudio de los brotes en España, 2017-2020(2023-06-15) Jacqueline Forget, CamilleSe valora la situación epidemiológica en España con el objetivo de fortalecer el sistema de vigilancia y la actuación en brotes, implementando rápidamente las medidas de control de aquellos brotes que supongan un evento de salud pública de importancia nacional o internacional. A través de la vigilancia molecular, se evalúa la circulación del virus, estableciendo el origen de los casos, cadenas de trnsmisión, etc. La recogida de información genómica adicional sirve para aumentar la resolución molecular.Publication Utility of MF-non coding region for measles molecular surveillance during post-elimination phase, Spain, 2017-2020(Frontiers Media, 2023-05) Jacqueline Forget, Camille; Gavilán, Ana M; Lopez-Perea, Noemi; Penedos, Ana Raquel; Masa-Calles, Josefa; Echevarria, Juan Emilio; Fernandez-Garcia, Aurora; MMR Study Group; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERESP (Epidemiología y Salud Pública); Unión Europea. European Centre for Disease Prevention and Control (ECDC)Background: In countries entering the post-elimination phase for measles, the study of variants by sequencing of 450 nucleotides of the N gene (N450) does not always allow the tracing of chains of transmission. Indeed, between 2017 and 2020, most measles virus sequences belonged to either the MVs/Dublin.IRL/8.16 (B3-Dublin) or the MVs/Gir Somnath.IND/42.16 (D8-Gir Somnath) variants. We evaluated the additional use of a non-coding region (MF-NCR) as a tool to enhance resolution and infer case origin, chains of transmission and characterize outbreaks. Methods: We obtained 115 high-quality MF-NCR sequences from strains collected from Spanish patients infected with either B3-Dublin or D8-Gir Somnath variants between 2017 and 2020, performed epidemiological, phylogenetic and phylodynamic analyses and applied a mathematical model to determine relatedness among identified clades. Results: Applying this model allowed us to identify phylogenetic clades potentially derived from concomitant importations of the virus rather than single chain of transmission, inferred based on only N450 and epidemiology data. In a third outbreak, we found two related clades that corresponded to two chains of transmission. Discussion: Our results show the ability of the proposed method to improve identification of simultaneous importations in the same region which could trigger enhanced contact tracing. Moreover, the identification of further transmission chains indicates that the size of import-related outbreaks was smaller than previously found, supporting the interpretation that endemic measles transmission was absent in Spain between 2017 and 2020. We suggest considering the use of the MF-NCR region in conjunction with the study of N450 variants in future WHO recommendations for measles surveillance.Publication Comparative whole-genome sequence analysis of Mycobacterium tuberculosis isolated from pulmonary tuberculosis and tuberculous lymphadenitis patients in Northwest Ethiopia(Frontiers Media, 2023-06) Mekonnen, Daniel; Munshea, Abaineh; Nibret, Endalkachew; Adnew, Bethlehem; Herrera-León, Silvia; Amor Aramendia, Aranzazu; Benito, Agustin; Abascal, Estefanía; Jacqueline Forget, Camille; Aseffa, Abraham; Herrera-Leon, Laura; Bahir Dar University (Etiopía); Amhara National Regional State Public Health Institute (Etiopía); Instituto de Salud Carlos IIIBackground: Tuberculosis (TB), caused by the Mycobacterium tuberculosis complex (MTBC), is a chronic infectious disease with both pulmonary and extrapulmonary forms. This study set out to investigate and compare the genomic diversity and transmission dynamics of Mycobacterium tuberculosis (Mtb) isolates obtained from tuberculous lymphadenitis (TBLN) and pulmonary TB (PTB) cases in Northwest Ethiopia. Methods: A facility-based cross-sectional study was conducted using two groups of samples collected between February 2021 and June 2022 (Group 1) and between June 2020 and June 2022 (Group 2) in Northwest Ethiopia. Deoxyribonucleic acid (DNA) was extracted from 200 heat-inactivated Mtb isolates. Whole-genome sequencing (WGS) was performed from 161 isolates having ≥1 ng DNA/μl using Illumina NovaSeq 6000 technology. Results: From the total 161 isolates sequenced, 146 Mtb isolates were successfully genotyped into three lineages (L) and 18 sub-lineages. The Euro-American (EA, L4) lineage was the prevailing (n = 100; 68.5%) followed by Central Asian (CAS, L3, n = 43; 25.3%) and then L7 (n = 3; 2.05%). The L4.2.2.ETH sub-lineage accounted for 19.9%, while Haarlem estimated at 13.7%. The phylogenetic tree revealed distinct Mtb clusters between PTB and TBLN isolates even though there was no difference at lineages and sub-lineages levels. The clustering rate (CR) and recent transmission index (RTI) for PTB were 30 and 15%, respectively. Similarly, the CR and RTI for TBLN were 31.1 and 18 %, respectively. Conclusion and recommendations: PTB and TBLN isolates showed no Mtb lineages and sub-lineages difference. However, at the threshold of five allelic distances, Mtb isolates obtained from PTB and TBLN form distinct complexes in the phylogenetic tree, which indicates the presence of Mtb genomic variation among the two clinical forms. The high rate of clustering and RTI among TBLN implied that TBLN was likely the result of recent transmission and/or reactivation from short latency. Hence, the high incidence rate of TBLN in the Amhara region could be the result of Mtb genomic diversity and rapid clinical progression from primary infection and/or short latency. To validate this conclusion, a similar community-based study with a large sample size and better sampling technique is highly desirable. Additionally, analysis of genomic variants other than phylogenetic informative regions could give insightful information. Combined analysis of the host and the pathogen genome (GXG) together with environmental (GxGxE) factors could give comprehensive co-evolutionary information.Publication Mycobacterium tuberculosis Sub-Lineage 4.2.2/SIT149 as Dominant Drug-Resistant Clade in Northwest Ethiopia 2020-2022: In-silico Whole-Genome Sequence Analysis(Dove Medical Press, 2023-10) Mekonnen, Daniel; Munshea, Abaineh; Nibret, Endalkachew; Adnew, Bethlehem; Getachew, Hailu; Kebede, Amiro; Gebrewahid, Ananya; Herrera-León, Silvia; Aramendia, Aranzazu Amor; Benito, Agustin; Abascal, Estefanía; Jacqueline Forget, Camille; Aseffa, Abraham; Herrera-Leon, Laura; Bahir Dar University (Etiopía); Instituto de Salud Carlos III; International Federation of Clinical Chemistry and Laboratory Medicine (IFCC)Introduction: Drug resistance (DR) in Mycobacterium tuberculosis complex (MTBC) is mainly associated with certain lineages and varies across regions and countries. The Beijing genotype is the leading resistant lineage in Asia and western countries. M. tuberculosis (Mtb) (sub) lineages responsible for most drug resistance in Ethiopia are not well described. Hence, this study aimed to identify the leading drug resistance sub-lineages and characterize first-line anti-tuberculosis drug resistance-associated single nucleotide polymorphisms (SNPs). Methods: A facility-based cross-sectional study was conducted in 2020-2022 among new and presumptive multidrug resistant-TB (MDR-TB) cases in Northwest Ethiopia. Whole-genome sequencing (WGS) was performed on 161 isolates using Illumina NovaSeq 6000 technology. The SNP mutations associated with drug resistance were identified using MtbSeq and TB profiler Bioinformatics softwares. Results: Of the 146 Mtb isolates that were successfully genotyped, 20 (13.7%) harbored one or more resistance-associated SNPs. L4.2.2.ETH was the leading drug-resistant sub-lineage, accounting for 10/20 (50%) of the resistant Mtb. MDR-TB isolates showed extensive mutations against first-line anti-TB drugs. Ser450Leu/(tcg/tTg) for Rifampicin (RIF), Ser315Thr/(agc/aCc) for Isoniazid (INH), Met306Ile/(atg/atA(C)) for Ethambutol (EMB), and Gly69Asp for Streptomycin (STR) were the leading resistance associated mutations which accounted for 56.5%, 89.5%, 47%, and 29.4%, respectively. The presence of both clustered and non-clustered drug resistance (DR) isolates indicated that the epidemics is driven by both new DR development and acquired resistance. Conclusion: The high prevalence of drug-resistant TB due to geographically restricted sub-lineages (L4.2.2.ETH) indicates the ongoing local micro epidemics. The Mtb drug resistance surveillance system must be improved. Further evolutionary analysis of L4.2.2.ETH strain is highly desirable to understand evolutionary forces that leads L4.2.2.ETH in to high level DR and transmissible sub-lineage.Publication Phenotypic and genetic characterization of antimicrobial resistance in Salmonella enterica serovar Choleraesuis isolates from humans and animals in Spain from 2006 to 2021(Oxford University Press, 2024) Jacqueline Forget, Camille; Samper-Cativiela, Clara; Monzon-Fernandez, Sara; Ugarte-Ruiz, María; Cuesta de la Plaza, Isabel; Alvarez, Julio; Herrera-León, Silvia; Unión Europea. European Centre for Disease Prevention and Control (ECDC); Complutense University of Madrid (España); Banco Santander; Ministerio de Economía y Competitividad (España); Instituto de Salud Carlos IIIObjectives: While an increase in the levels of MDR in Salmonella enterica sevorar Choleraesuis has been reported in Europe, little is known about the situation in Spain. Therefore, we first aimed to assess the phenotypic resistance profile and to determine the presence of genetic determinants of resistance of S. Choleraesuis isolates collected in animal and human. Our second objective was to identify and characterize clusters of highly related isolates. Methods: We analysed 50 human and 45 animal isolates retrieved from 2006 to 2021 using the disc diffusion method and performed WGS followed by analyses of genetic determinants and phylogenetic analysis. Results: All isolates were of ST145 and corresponded to the variant Kunzendorf. Swine isolates harboured a significantly higher number of antimicrobial resistance genes than human isolates, and often carried plasmid replicons of the IncHI2/IncHI2A type (42% of all animal isolates). In addition, we identified several MDR S. Choleraesuis strains circulating in humans and swine between 2006 and 2021. The phylogenetic analyses identified four clades associated with specific patterns of resistance genes and plasmid replicons. The clades also included isolates that differed in terms of year and region of isolation as well as host of origin. Conclusions: This One Health approach highlights that reducing human MDR S. Choleraesuis infections may require the adoption of strategies that not only seek to prevent cases in humans but also to characterize and reduce the infection burden in swine.Publication Genetic Characterization of Extensively Drug-Resistant Shigella sonnei Infections, Spain, 2021-2022(Centers for Disease Control and Prevention (CDC), 2023-11) Jacqueline Forget, Camille; Ruiz-Carrascoso, Guillermo; Gutiérrez-Fernández, José; Vicente Rangel, Teresa; Goterris, Lidia; Vázquez-Valdés, Fernando; Vecilla, Domingo Fernández; Elía-López, Matilde; Martinez Ruiz, Maria Rocío; Aspiroz Sancho, Carmen; Pérez-Tanoira, Ramón; Sirvent Quílez, Elia; la Rica Martínez, Alba de; Gonzalo Jiménez, Nieves; García Salguero, Cristina; González-Barberá, Eva; Sánchez Florez, Maria Reyes; Merino, Francisco J; Sagardia Redondo, Begoña; Rodriguez Guerrero, Enrique; Sanz González, Claudia; Herrera-León, Silvia; Instituto de Salud Carlos IIIIn 2022, the United Kingdom reported an increase in drug resistance in Shigella sonnei isolates. We report 33 cases in Spain genetically related to the UK cases and 4 cases with similar antimicrobial resistance profiles infected with genetically distant strains. Our results suggest circulation of multiple genetic clusters of multidrug-resistant S. sonnei in Spain.Publication Norovirus GII.3[P12] Outbreak Associated with the Drinking Water Supply in a Rural Area in Galicia, Spain, 2021(American Society for Microbiology (ASM), 2022-08-31) Jacqueline Forget, Camille; Del Valle Arrojo, Manuel; Bellver Moreira, Paloma; Rodríguez Feijóo, Maria Asunción; Cabrerizo, Maria; Fernandez-Garcia, Maria Dolores; Instituto de Salud Carlos IIIOn 30 September 2021, the city council of Muxia, Spain (population of 4,564 inhabitants), reported an unusual increase of patients with acute gastroenteritis (AGE). Because geographically widespread villages belonging to the same water supply were affected, a waterborne outbreak was suspected. Overall, 115 probable cases were ascertained during epidemiological investigations carried out by the local health authority (attack rate, 5.7%); the age range was 0 to 92 years, and 54% were female. The main symptoms were vomiting (78.1%) and diarrhea (67.5%). Primary cases peaked on 29 September and subsided on 1 October, compatible with a point-source outbreak followed by possible secondary cases until 7 October. We conducted an unmatched case-control study using phone surveys. The case-control study included 62 cases and 46 controls. Univariate analysis showed that cases had a higher exposure to tap water through direct consumption (odds ratio [OR] = 86; 95% confidence interval [CI], 18 to 409) or vegetable washing (OR = 27; 95% CI, 7 to 98). Norovirus GII was detected in two terminal points of the water supply system, and 14 cases were laboratory confirmed after detection of GII in stool samples. A unique genotype (GII.3[P12]) was identified in stool samples. On 1 October, a tap water ban was put in place and the water was purged and chlorinated. The rapid increase in the number of cases and its decline after implementing control measures suggested a waterborne point-source outbreak among the residents of Muxia sharing the same water distribution system. IMPORTANCE: Noroviruses are likely to be underrecognized in most suspected waterborne outbreaks. Therefore, effective norovirus detection and the early recognition of water as a possible source of infection are important to reduce morbidity as appropriate steps are taken to control the source. In our study, we combined epidemiological, environmental, and microbiological investigations to demonstrate that it was a waterborne outbreak caused by norovirus. Metagenomic sequencing in one norovirus-positive stool sample confirmed norovirus etiology and the absence of other potential pathogens. Detection of fecal indicator bacteria and the fact that the drinking water was not chlorinated suggest a breakdown in chlorination as the cause of the outbreak. This outbreak investigation also demonstrated the importance of timely communication to the public about the risk linked to tap water consumption.