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1.
Proc Natl Acad Sci U S A ; 120(33): e2305465120, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37549252

RESUMEN

Microbes evolve rapidly by modifying their genomes through mutations or through the horizontal acquisition of mobile genetic elements (MGEs) linked with fitness traits such as antimicrobial resistance (AMR), virulence, and metabolic functions. We conducted a multicentric study in India and collected different clinical samples for decoding the genome sequences of bacterial pathogens associated with sepsis, urinary tract infections, and respiratory infections to understand the functional potency associated with AMR and its dynamics. Genomic analysis identified several acquired AMR genes (ARGs) that have a pathogen-specific signature. We observed that blaCTX-M-15, blaCMY-42, blaNDM-5, and aadA(2) were prevalent in Escherichia coli, and blaTEM-1B, blaOXA-232, blaNDM-1, rmtB, and rmtC were dominant in Klebsiella pneumoniae. In contrast, Pseudomonas aeruginosa and Acinetobacter baumannii harbored blaVEB, blaVIM-2, aph(3'), strA/B, blaOXA-23, aph(3') variants, and amrA, respectively. Regardless of the type of ARG, the MGEs linked with ARGs were also pathogen-specific. The sequence type of these pathogens was identified as high-risk international clones, with only a few lineages being predominant and region-specific. Whole-cell proteome analysis of extensively drug-resistant K. pneumoniae, A. baumannii, E. coli, and P. aeruginosa strains revealed differential abundances of resistance-associated proteins in the presence and absence of different classes of antibiotics. The pathogen-specific resistance signatures and differential abundance of AMR-associated proteins identified in this study should add value to AMR diagnostics and the choice of appropriate drug combinations for successful antimicrobial therapy.


Asunto(s)
Antibacterianos , Escherichia coli , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Escherichia coli/genética , beta-Lactamasas/genética , beta-Lactamasas/farmacología , Proteómica , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple/genética , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana
3.
Nature ; 565(7738): 230-233, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30602788

RESUMEN

Yemen is currently experiencing, to our knowledge, the largest cholera epidemic in recent history. The first cases were declared in September 2016, and over 1.1 million cases and 2,300 deaths have since been reported1. Here we investigate the phylogenetic relationships, pathogenesis and determinants of antimicrobial resistance by sequencing the genomes of Vibrio cholerae isolates from the epidemic in Yemen and recent isolates from neighbouring regions. These 116 genomic sequences were placed within the phylogenetic context of a global collection of 1,087 isolates of the seventh pandemic V. cholerae serogroups O1 and O139 biotype El Tor2-4. We show that the isolates from Yemen that were collected during the two epidemiological waves of the epidemic1-the first between 28 September 2016 and 23 April 2017 (25,839 suspected cases) and the second beginning on 24 April 2017 (more than 1 million suspected cases)-are V. cholerae serotype Ogawa isolates from a single sublineage of the seventh pandemic V. cholerae O1 El Tor (7PET) lineage. Using genomic approaches, we link the epidemic in Yemen to global radiations of pandemic V. cholerae and show that this sublineage originated from South Asia and that it caused outbreaks in East Africa before appearing in Yemen. Furthermore, we show that the isolates from Yemen are susceptible to several antibiotics that are commonly used to treat cholera and to polymyxin B, resistance to which is used as a marker of the El Tor biotype.


Asunto(s)
Cólera/epidemiología , Cólera/microbiología , Genoma Bacteriano/genética , Genómica , Vibrio cholerae/genética , Vibrio cholerae/aislamiento & purificación , Humanos , Filogenia , Vibrio cholerae/clasificación , Yemen/epidemiología
4.
J Infect Dis ; 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637321

RESUMEN

BACKGROUND: Quantitative molecular assays are increasingly used for detection of enteric viruses. METHODS: We compared the clinical severity using modified Vesikari score (mVS) of enteric viruses detected by conventional assays (enzyme immunoassays [EIA] for rotavirus and adenovirus 40/41 and conventional polymerase chain reaction for astrovirus, sapovirus, and norovirus) and a quantitative molecular assay (TaqMan Array Card [TAC]) among children aged 0-59 months in the Global Enteric Multicenter Study. For rotavirus and adenovirus 40/41, we compared severity between EIA-positive and TAC-positive cases assigned etiologies using different cycle threshold (CT) cutoffs. RESULTS: Using conventional assays, the median (interquartile range) mVS was 10 (8, 11) for rotavirus, 9 (7, 11) for adenovirus 40/41, 8 (6, 10) for astrovirus, sapovirus, and norovirus GII, and 7 (6, 9) for norovirus GI. Compared to rotavirus EIA-positive cases, the median mVS was 2 and 3 points lower for EIA-negative/TAC-positive cases with CT<32.6 and 32.6≤CT<35, respectively (p-value<.0001). Adenovirus 40/41 EIA-positive and EIA-negative/TAC-positive cases were similar, regardless of CT cutoff. CONCLUSIONS: Quantitative molecular assays compared to conventional assays, such as EIA, may influence severity of identified cases, especially for rotavirus. Cutoffs to assign etiology for quantitative assays should be considered in the design and interpretation of enteric virus studies.

5.
Crit Rev Microbiol ; : 1-22, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38441045

RESUMEN

Vibrio cholerae is a cholera-causing pathogen known to instigate severe contagious diarrhea that affects millions globally. Survival of vibrios depend on a combination of multicellular responses and adapt to changes that prevail in the environment. This process is achieved through a strong communication at the cellular level, the process has been recognized as quorum sensing (QS). The severity of infection is highly dependent on the QS of vibrios in the gut milieu. The quorum may exist in a low/high cell density (LCD/HCD) state to exert a positive or negative response to control the regulatory pathogenic networks. The impact of this regulation reflects on the transition of pathogenic V. cholerae from the environment to infect humans and cause outbreaks or epidemics of cholera. In this context, the review portrays various regulatory processes and associated virulent pathways, which maneuver and control LCD and HCD states for their survival in the host. Although several treatment options are existing, promotion of therapeutics by exploiting the virulence network may potentiate ineffective antibiotics to manage cholera. In addition, this approach is also useful in resource-limited settings, where the accessibility to antibiotics or conventional therapeutic options is limited.

6.
Indian J Med Res ; 160(1): 87-94, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39382492

RESUMEN

Background & objectives Food and waterborne illnesses remain a neglected public health issue in India. Events with large gatherings frequently witness outbreaks of acute diarrheal diseases due to consumption of contaminated food or water or poor food handling practices. In the present study, an outbreak of acute diarrhoeal disease (ADD) occurring among the attendees of a birthday party in rural Dibrugarh district in the northeastern Indian State of Assam was investigated. Methods Sociodemographic information along with details of ADD outbreak that included information about source of foods, food handlers, illness details, etc., were collected using an outbreak investigation form for descriptive and analytical epidemiology. Rectal swabs from affected individuals and food handlers were collected along with bore-well water samples and tested in the laboratory by performing bacterial culture, biochemical analysis and polymerase chain reaction. Due to the delayed report on the outbreak, collecting leftover food for laboratory testing and analysis was impossible. Results A total of 25 cases of ADD had similar signs and symptoms. The mean incubation period for developing acute diarrhoea was 26.36±8.76 (± standard deviation) hours from food consumption. The overall attack rate was 60.04 per cent (25/41); 20 per cent (5/25) required hospitalization. Thirteen rectal swab samples were tested for pathogens and found positive for Shigella sonnei. Antibiotic susceptibility test of isolated S. sonnei showed resistance to nalidixic acid, ciprofloxacin and cefotaxime. Consumption of one of the food items - chicken curry was significantly associated with illness (Odds Ratio=14.8; 95% Confidence Interval: 2.75-85.11); P value<0.05 and Population Attributable Fraction (PAF) was 70.18 per cent. The water samples were found satisfactory for human consumption. Interpretation & conclusions The findings suggested that S. sonnei infection could be implicated in the investigated food-borne diarrhoeal disease outbreak and that there was a potential for human-poultry cross-infection. Additionally, the study revealed concerning levels of S. sonnei resistance to recommended antibiotics and drew attention to their public health relevance.


Asunto(s)
Diarrea , Brotes de Enfermedades , Disentería Bacilar , Shigella sonnei , Humanos , Shigella sonnei/patogenicidad , Shigella sonnei/aislamiento & purificación , India/epidemiología , Masculino , Disentería Bacilar/epidemiología , Disentería Bacilar/microbiología , Diarrea/microbiología , Diarrea/epidemiología , Femenino , Adulto , Adolescente , Persona de Mediana Edad , Niño , Antibacterianos/uso terapéutico , Antibacterianos/farmacología , Enfermedad Aguda , Preescolar
7.
BMC Public Health ; 24(1): 451, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38347565

RESUMEN

BACKGROUND: Food safety is a critical factor in promoting public health and nutrition, especially in developing countries like India, which experience several foodborne disease outbreaks, often with multidrug-resistant pathogens. Therefore, implementing regular surveillance of enteric pathogens in the human-animal-environment interface is necessary to reduce the disease burden in the country. OBJECTIVE: To establish a network of laboratories for the identification of major food and waterborne pathogens prevailing in the northeast region of India through integrated surveillance of animal, food, human, and environment and investigate the antimicrobial susceptibility pattern of the pathogens of public health significance. METHODS: The Indian Council of Medical Research (ICMR) has identified FoodNet laboratories; based on their geographical location, inclination to undertake the study, preparedness, proficiency, and adherence to quality assurance procedures, through an 8-step process to systematically expand to cover the Northeastern Region (NER) with comprehensive diagnostic capacities for foodborne pathogens and diarrhea outbreak investigations. Network initiated in the NER given the unique food habits of the ethnic population. FINDINGS: This surveillance network for foodborne enteric pathogens was established in Assam, Arunachal Pradesh, Tripura, and Sikkim, and expanded to other four states, i.e., Manipur, Mizoram, Meghalaya, and Nagaland, thereby covering the entire NER by including nine medical and three veterinary centers. All these centers are strengthened with periodic training, technical support, funding, capacity building, quality assurance, monitoring, centralized digital data management, and website development. RESULTS: The ICMR-FoodNet will generate NER-specific data with close to real-time reporting of foodborne disease and outbreaks, and facilitate the updating of food safety management protocols, policy reforms, and public health outbreak response. During 2020-2023, 13,981 food samples were tested and the detection of enteric pathogens ranged from 3 to 4%. In clinical samples, the detection rate of the pathogens was high in the diarrheal stools (8.9%) when 3,107 samples were tested. Thirteen outbreaks were investigated during the study period. CONCLUSION: Foodborne diseases and outbreaks are a neglected subject. Given the frequent outbreaks leading to the deaths of children, it is crucial to generate robust data through well-established surveillance networks so that a strong food safety policy can be developed for better public health.


Asunto(s)
Enfermedades Transmitidas por los Alimentos , Salud Única , Niño , Animales , Humanos , Estados Unidos , Salud Pública , India/epidemiología , Enfermedades Transmitidas por los Alimentos/epidemiología , Enfermedades Transmitidas por los Alimentos/prevención & control , Diarrea/epidemiología , Brotes de Enfermedades/prevención & control
8.
Lancet ; 399(10333): 1429-1440, 2022 04 09.
Artículo en Inglés | MEDLINE | ID: mdl-35397865

RESUMEN

Cholera was first described in the areas around the Bay of Bengal and spread globally, resulting in seven pandemics during the past two centuries. It is caused by toxigenic Vibrio cholerae O1 or O139 bacteria. Cholera is characterised by mild to potentially fatal acute watery diarrhoeal disease. Prompt rehydration therapy is the cornerstone of management. We present an overview of cholera and its pathogenesis, natural history, bacteriology, and epidemiology, while highlighting advances over the past 10 years in molecular epidemiology, immunology, and vaccine development and deployment. Since 2014, the Global Task Force on Cholera Control, a WHO coordinated network of partners, has been working with several countries to develop national cholera control strategies. The global roadmap for cholera control focuses on stopping transmission in cholera hotspots through vaccination and improved water, sanitation, and hygiene, with the aim to reduce cholera deaths by 90% and eliminate local transmission in at least 20 countries by 2030.


Asunto(s)
Cólera , Vibrio cholerae , Cólera/epidemiología , Cólera/prevención & control , Diarrea/epidemiología , Humanos , Epidemiología Molecular , Saneamiento
9.
Proc Natl Acad Sci U S A ; 117(38): 23762-23773, 2020 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-32873641

RESUMEN

Bacterial species are hosts to horizontally acquired mobile genetic elements (MGEs), which encode virulence, toxin, antimicrobial resistance, and other metabolic functions. The bipartite genome of Vibrio cholerae harbors sporadic and conserved MGEs that contribute in the disease development and survival of the pathogens. For a comprehensive understanding of dynamics of MGEs in the bacterial genome, we engineered the genome of V. cholerae and examined in vitro and in vivo stability of genomic islands (GIs), integrative conjugative elements (ICEs), and prophages. Recombinant vectors carrying the integration module of these GIs, ICE and CTXΦ, helped us to understand the efficiency of integrations of MGEs in the V. cholerae chromosome. We have deleted more than 250 acquired genes from 6 different loci in the V. cholerae chromosome and showed contribution of CTX prophage in the essentiality of SOS response master regulator LexA, which is otherwise not essential for viability in other bacteria, including Escherichia coli In addition, we observed that the core genome-encoded RecA helps CTXΦ to bypass V. cholerae immunity and allow it to replicate in the host bacterium in the presence of similar prophage in the chromosome. Finally, our proteomics analysis reveals the importance of MGEs in modulating the levels of cellular proteome. This study engineered the genome of V. cholerae to remove all of the GIs, ICEs, and prophages and revealed important interactions between core and acquired genomes.


Asunto(s)
Genoma Bacteriano/genética , Islas Genómicas/genética , Vibrio cholerae/genética , Proteínas Bacterianas/genética , Conjugación Genética/genética , Ingeniería Genética , Secuencias Repetitivas Esparcidas/genética , Profagos/genética , Serina Endopeptidasas/genética , Vibrio cholerae/patogenicidad
10.
J Appl Microbiol ; 133(6): 3605-3616, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36000378

RESUMEN

AIMS: The present study aimed to document the comparative analysis of differential hypervirulent features of Vibrio cholerae O1 strains isolated during 2018 from cholera endemic regions in Gujarat and Maharashtra (Western India) and West Bengal (Eastern India). METHODS AND RESULTS: A total of 87 V. cholerae O1 clinical strains from Western India and 48 from Eastern India were analysed for a number of biotypic and genotypic features followed by antimicrobial resistance (AMR) profile. A novel polymerase chain reaction was designed to detect a large fragment deletion in the Vibrio seventh pandemic island II (VSP-II) genomic region, which is a significant genetic feature of the V. cholerae strains that have caused Yemen cholera outbreak. All the strains from Western India belong to the Ogawa serotype, polymyxin B-sensitive, hemolytic, had a deletion in VSP-II (VSP-IIC) region and carried Haitian genetic alleles of ctxB, tcpA and rtxA. Conversely, 14.6% (7/48) of the strains from Eastern India belonged to the Inaba serotype, polymyxin B-resistant, nonhemolytic, harboured VSP-II other than VSP-IIC type, classical ctxB, Haitian tcpA and El Tor rtxA alleles. Resistance to tetracycline and chloramphenicol has been observed in strains from both regions. CONCLUSIONS: This study showed hypervirulent, polymyxin B-sensitive epidemic causing strains in India along with the strains with polymyxin B-resistant and nonhemolytic traits that may spread and cause serious disease outcomes in future. SIGNIFICANCE AND IMPACT OF THE STUDY: The outcomes of this study can help to improve the understanding of the hyperpathogenic property of recently circulating pandemic Vibrio cholerae strains in India. Special attention is also needed for the monitoring of AMR surveillance because V. cholerae strains are losing susceptibility to many antibiotics used as a second line of defence in the treatment of cholera.


Asunto(s)
Cólera , Vibrio cholerae O1 , Humanos , Vibrio cholerae O1/genética , Cólera/epidemiología , Cólera/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Polimixina B/farmacología , Haití , Farmacorresistencia Bacteriana/genética , India/epidemiología , Genotipo , Brotes de Enfermedades , Toxina del Cólera/genética , Toxina del Cólera/uso terapéutico
11.
J Appl Microbiol ; 132(6): 4544-4554, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-35338762

RESUMEN

AIMS: This study analyses the prevalence and antimicrobial resistance (AMR) of major diarrhoeagenic Escherichia coli (DEC) pathotypes detected in hospitalized diarrhoeal patients in Kolkata, India, during 2012-2019. METHODS AND RESULTS: A total of 8891 stool samples were collected from the Infectious Diseases Hospital, Kolkata and screened for the presence of enteric pathogens. Multiplex PCR identified the presence of DEC in 7.8% of the samples, in which ETEC was most common (47.7%) followed by EAEC (38.4%) and EPEC (13.9%). About 54% cases were due to sole DEC infections. Majority of the mixed DEC infections were caused by the Vibrio spp. (19.1%) followed by Rotavirus (14.1%) and Campylobacter spp. (8.4%). ETEC and EAEC were associated significantly with diarrhoea in children <5 years of age, whereas EPEC and also ETEC were prevalent in patients aged between 5 and 14 years. AMR profile showed high prevalence of multidrug resistance (MDR) among DEC (56.9%) in which 9% were resistant to antibiotics of six different antimicrobial classes. Screening of the AMR conferring genes of DEC showed the presence of blaCTX-M3 (30.2%) in highest number followed by blaTEM (27.5%), tetB (18%), sul2 (12.6%), strA (11.8%), aadA1 (9.8%), blaOXA-1 (9%), dfrA1 (1.6%) and blaSHV (1.2%). CONCLUSIONS: These findings highlighted the high prevalence of MDR in major DEC pathotypes that could be considered as the leading aetiological bacterial agent responsible for diarrhoea and suggests a significant public health threat. SIGNIFICANCE AND IMPACT OF THE STUDY: The results of this study can help to improve the understanding of the epidemiology of DEC infections in patients with diarrhoea. Monitoring of AMR surveillance needs special attention because the DEC isolates were highly resistant to commonly used antimicrobials in the treatment of diarrhoea.


Asunto(s)
Antiinfecciosos , Coinfección , Infecciones por Escherichia coli , Adolescente , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Niño , Preescolar , Diarrea/epidemiología , Diarrea/microbiología , Farmacorresistencia Bacteriana/genética , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Heces/microbiología , Humanos , Pruebas de Sensibilidad Microbiana
12.
Proc Natl Acad Sci U S A ; 116(13): 6226-6231, 2019 03 26.
Artículo en Inglés | MEDLINE | ID: mdl-30867296

RESUMEN

The Bay of Bengal is known as the epicenter for seeding several devastating cholera outbreaks across the globe. Vibrio cholerae, the etiological agent of cholera, has extraordinary competency to acquire exogenous DNA by horizontal gene transfer (HGT) and adapt them into its genome for structuring metabolic processes, developing drug resistance, and colonizing the human intestine. Antimicrobial resistance (AMR) in V. cholerae has become a global concern. However, little is known about the identity of the resistance traits, source of AMR genes, acquisition process, and stability of the genetic elements linked with resistance genes in V. cholerae Here we present details of AMR profiles of 443 V. cholerae strains isolated from the stool samples of diarrheal patients from two regions of India. We sequenced the whole genome of multidrug-resistant (MDR) and extensively drug-resistant (XDR) V. cholerae to identify AMR genes and genomic elements that harbor the resistance traits. Our genomic findings were further confirmed by proteome analysis. We also engineered the genome of V. cholerae to monitor the importance of the autonomously replicating plasmid and core genome in the resistance profile. Our findings provided insights into the genomes of recent cholera isolates and identified several acquired traits including plasmids, transposons, integrative conjugative elements (ICEs), pathogenicity islands (PIs), prophages, and gene cassettes that confer fitness to the pathogen. The knowledge generated from this study would help in better understanding of V. cholerae evolution and management of cholera disease by providing clinical guidance on preferred treatment regimens.


Asunto(s)
Cólera/microbiología , Farmacorresistencia Bacteriana Múltiple/genética , Transferencia de Gen Horizontal , Genoma Bacteriano/genética , Vibrio cholerae/genética , Antibacterianos/farmacología , Conjugación Genética/genética , Elementos Transponibles de ADN/genética , Diarrea/microbiología , Evolución Molecular , Heces/microbiología , Variación Genética , Islas Genómicas/genética , Humanos , Imipenem/farmacología , India , Secuencias Repetitivas Esparcidas/genética , Fenotipo , Plásmidos/genética , Profagos/genética , Proteoma , Vibrio cholerae/efectos de los fármacos , Vibrio cholerae/aislamiento & purificación , Vibrio cholerae/patogenicidad , Vibrio cholerae O1/genética , Vibrio cholerae O1/aislamiento & purificación , Vibrio cholerae O1/patogenicidad , Secuenciación Completa del Genoma
13.
J Infect Dis ; 224(12 Suppl 2): S848-S855, 2021 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-34528677

RESUMEN

BACKGROUND: The association between childhood diarrheal disease and linear growth faltering in developing countries is well described. However, the impact attributed to specific pathogens has not been elucidated, nor has the impact of recommended antibiotic treatment. METHODS: The Global Enteric Multicenter Study enrolled children with moderate to severe diarrhea (MSD) seeking healthcare at 7 sites in sub-Saharan Africa and South Asia. At enrollment, we collected stool samples to identify enteropathogens. Length/height was measured at enrollment and follow-up, approximately 60 days later, to calculate change in height-for-age z scores (ΔHAZ). The association of pathogens with ΔHAZ was tested using linear mixed effects regression models. RESULTS: Among 8077 MSD cases analyzed, the proportion with stunting (HAZ below -1) increased from 59% at enrollment to 65% at follow-up (P < .0001). Pathogens significantly associated with linear growth decline included Cryptosporidium (P < .001), typical enteropathogenic Escherichia coli (P = .01), and untreated Shigella (P = .009) among infants (aged 0-11 months) and enterotoxigenic E. coli encoding heat-stable toxin (P < .001) and Cryptosporidium (P = .03) among toddlers (aged 12-23 months). Shigella-infected toddlers given antibiotics had improved linear growth (P = .02). CONCLUSIONS: Linear growth faltering among children aged 0-23 months with MSD is associated with specific pathogens and can be mitigated with targeted treatment strategies, as demonstrated for Shigella.


Asunto(s)
Antibacterianos/uso terapéutico , Criptosporidiosis/tratamiento farmacológico , Cryptosporidium/patogenicidad , Diarrea/tratamiento farmacológico , Escherichia coli/patogenicidad , Trastornos del Crecimiento/etiología , Shigella/patogenicidad , Estudios de Casos y Controles , Niño , Cryptosporidium/aislamiento & purificación , Diarrea/epidemiología , Diarrea/microbiología , Escherichia coli/aislamiento & purificación , Femenino , Humanos , Lactante , Masculino , Shigella/aislamiento & purificación
14.
Clin Infect Dis ; 73(3): e569-e579, 2021 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-33044509

RESUMEN

BACKGROUND: Shigella is a leading cause of childhood diarrhea and target for vaccine development. Microbiologic and clinical case definitions are needed for pediatric field vaccine efficacy trials. METHODS: We compared characteristics of moderate to severe diarrhea (MSD) cases in the Global Enteric Multicenter Study (GEMS) between children with culture positive Shigella to those with culture-negative, quantitative polymerase chain reaction (qPCR)-attributable Shigella (defined by an ipaH gene cycle threshold <27.9). Among Shigella MSD cases, we determined risk factors for death and derived a clinical severity score. RESULTS: Compared to culture-positive Shigella MSD cases (n = 745), culture-negative/qPCR-attributable Shigella cases (n = 852) were more likely to be under 12 months, stunted, have a longer duration of diarrhea, and less likely to have high stool frequency or a fever. There was no difference in dehydration, hospitalization, or severe classification from a modified Vesikari score. Twenty-two (1.8%) Shigella MSD cases died within the 14-days after presentation to health facilities, and 59.1% of these deaths were in culture-negative cases. Age <12 months, diarrhea duration prior to presentation, vomiting, stunting, wasting, and hospitalization were associated with mortality. A model-derived score assigned points for dehydration, hospital admission, and longer diarrhea duration but was not significantly better at predicting 14-day mortality than a modified Vesikari score. CONCLUSIONS: A composite severity score consistent with severe disease or dysentery may be a pragmatic clinical endpoint for severe shigellosis in vaccine trials. Reliance on culture for microbiologic confirmation may miss a substantial number of Shigella cases but is currently required to measure serotype specific immunity.


Asunto(s)
Disentería Bacilar , Shigella , Vacunas , Estudios de Casos y Controles , Niño , Diarrea/epidemiología , Disentería Bacilar/diagnóstico , Disentería Bacilar/epidemiología , Humanos , Lactante , Reacción en Cadena de la Polimerasa , Shigella/genética
15.
Epidemiol Infect ; 149: e148, 2021 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-34096499

RESUMEN

Cholera is one of the major public health problems in the state of Odisha, India since centuries. The current paper is a comprehensive report on epidemiology of cholera in Odisha, which was documented from 1993. PubMed and Web of Knowledge were searched for publications reporting cholera in Odisha during the period 1993-2015. The search was performed using the keywords 'Odisha' and/or 'Orissa' and 'Cholera'. In addition, manual search was undertaken to find out relevant papers. During the study period, a total of 37 cholera outbreaks were reported with an average of >1.5 cholera outbreaks per year and case fatality ratio was 0.3%. Vibrio cholerae O1 Ogawa serotype was the major causative agent in most of the cholera cases. The recent studies demonstrated the prevalence of V. cholerae O1, El Tor variants carrying ctxB1, ctxB7 and Haitian variant tcpA allele associated with polymyxin B sensitivity and these variants are replacing the proto type El Tor. The first report of variant ctxB7 in Odisha during super-cyclone 1999 predicted its emergence and subsequent spread causing cholera outbreaks. The prevalence of multidrug-resistant V. cholerae at different time periods created alarming situation. The efficacy trial of oral cholera vaccine (OCV, Shanchol) in a public health set-up in Odisha has shown encouraging results which should be deployed for community level vaccination among the vulnerable population. This paper has taken an effort to disseminate the valuable information of epidemiology of cholera that will influence the policy-makers and epidemiologists for constant surveillance in other parts of Odisha, India and around the globe.


Asunto(s)
Cólera/epidemiología , Cólera/prevención & control , Antibacterianos/farmacología , Cólera/microbiología , Toxina del Cólera/genética , Vacunas contra el Cólera/administración & dosificación , Brotes de Enfermedades/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Farmacorresistencia Bacteriana Múltiple , Proteínas Fimbrias/genética , Variación Genética , Genotipo , Humanos , India/epidemiología , Pruebas de Sensibilidad Microbiana , Prevalencia , Serogrupo , Vibrio cholerae/efectos de los fármacos , Vibrio cholerae/genética , Vibrio cholerae/inmunología , Vibrio cholerae/aislamiento & purificación
16.
Infect Immun ; 88(5)2020 04 20.
Artículo en Inglés | MEDLINE | ID: mdl-32094260

RESUMEN

Antimicrobial peptides play an important role in host defense against Vibrio cholerae Generally, the V. cholerae O1 classical biotype is polymyxin B (PB) sensitive and El Tor is relatively resistant. Detection of classical biotype traits like the production of classical cholera toxin and PB sensitivity in El Tor strains has been reported in recent years, including in the devastating Yemen cholera outbreak during 2016-2018. To investigate the factor(s) responsible for the shift in the trend of sensitivity to PB, we studied the two-component system encoded by carRS, regulating the lipid A modification of El Tor vibrios, and found that only carR contains a single nucleotide polymorphism (SNP) in recently emerged PB-sensitive strains. We designated the two alleles present in PB-resistant and -sensitive strains carRr and carRs alleles, respectively, and replaced the carRs allele of a sensitive strain with the carRr allele, using an allelic-exchange approach. The sensitive strain then became resistant. The PB-resistant strain N16961 was made susceptible to PB in a similar fashion. Our in silico CarR protein models suggested that the D89N substitution in the more stable CarRs protein brings the two structural domains of CarR closer, constricting the DNA binding cleft. This probably reduces the expression of the carR-regulated almEFG operon, inducing PB susceptibility. Expression of almEFG in PB-sensitive strains was found to be downregulated under natural culturing conditions. In addition, the expression of carR and almEG decreased in all strains with increased concentrations of extracellular Ca2+ but increased with a rise in pH. The downregulation of almEFG in CarRs strains confirmed that the G265A mutation is responsible for the emergence of PB-sensitive El Tor strains.


Asunto(s)
Mutación Puntual/genética , Polimixina B/farmacología , Transcripción Genética/genética , Vibrio cholerae O1/efectos de los fármacos , Vibrio cholerae O1/genética , Alelos , Antibacterianos/farmacología , Calcio/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo/genética , Escherichia coli/genética , Polimorfismo de Nucleótido Simple/genética , Vibrio cholerae O1/metabolismo
17.
BMC Microbiol ; 20(1): 62, 2020 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-32293257

RESUMEN

BACKGROUND: V. parahaemolyticus is autochthonous to the marine environment and causes seafood-borne gastroenteritis in humans. Generally, V. parahaemolyticus recovered from the environment and/or seafood is thought to be non-pathogenic and the relationship between environmental isolates and acute diarrhoeal disease is poorly understood. In this study, we explored the virulence potential of environmental V. parahaemolyticus isolated from water, plankton and assorted seafood samples collected from the Indian coast. RESULTS: Twenty-two V. parahaemolyticus isolates from seafood harboured virulence associated genes encoding the thermostable-direct haemolysin (TDH), TDH-related haemolysin (TRH), and Type 3 secretion systems (T3SS) and 95.5% of the toxigenic isolates had pandemic strain attributes (toxRS/new+). Nine serovars, with pandemic strain traits were newly identified and an O4:K36 tdh-trh+V. parahaemolyticus bearing pandemic marker gene was recognised for the first time. Results obtained by reverse transcription PCR showed trh, T3SS1 and T3SS2ß to be functional in the seafood isolates. Moreover, the environmental strains were cytotoxic and could invade Caco-2 cells upon infection as well as induce changes to the tight junction protein, ZO-1 and the actin cytoskeleton. CONCLUSION: Our study provides evidence that environmental isolates of V. parahaemolyticus are potentially invasive and capable of eliciting pathogenic characteristics typical of clinical strains and present a potential health risk. We also demonstrate that virulence of this pathogen is highly complex and hence draws attention for the need to investigate more reliable virulence markers in order to distinguish the environmental and clinical isolates, which will be crucial for the pathogenomics and control of this pathogen.


Asunto(s)
Plancton/microbiología , Alimentos Marinos/microbiología , Vibriosis/microbiología , Vibrio parahaemolyticus/patogenicidad , Factores de Virulencia/genética , Citoesqueleto de Actina/genética , Proteínas Bacterianas/genética , Toxinas Bacterianas/genética , Células CACO-2 , Proteínas Hemolisinas/genética , Humanos , India , Filogenia , Sistemas de Secreción Tipo III/genética , Vibriosis/genética , Vibriosis/metabolismo , Vibrio parahaemolyticus/clasificación , Vibrio parahaemolyticus/genética , Vibrio parahaemolyticus/aislamiento & purificación , Microbiología del Agua , Proteína de la Zonula Occludens-1/genética
18.
Microbiol Immunol ; 64(6): 435-444, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32222116

RESUMEN

Non-O1/non-O139 nontoxigenic Vibrio cholerae associated with cholera-like diarrhea has been reported in Kolkata, India. However, the property involved in the pathogenicity of these strains has remained unclear. The character of 25 non-O1/non-O139 nontoxigenic V. cholerae isolated during 8 years from 2007 to 2014 in Kolkata was examined. Determination of the serogroup showed that the serogroups O6, O10, O35, O36, O39, and O70 were represented by two strains in each serogroup, and the remaining isolates belonged to different serogroups. To clarify the character of antibiotic resistance of these isolates, an antibiotic resistance test and the gene analysis were performed. According to antimicrobial drug susceptibility testing, 13 strains were classified as drug resistant. Among them, 10 strains were quinolone resistant and 6 of the 13 strains were resistant to more than three antibiotics. To define the genetic background of the antibiotic character of these strains, whole-genome sequences of these strains were determined. From the analysis of these sequences, it becomes clear that all quinolone resistance isolates have mutations in quinolone resistance-determining regions. Further research on the genome sequence showed that four strains possess Class 1 integrons in their genomes, and that three of the four integrons are found to be located in their genomic islands. These genomic islands are novel types. This indicates that various integrons containing drug resistance genes are spreading among V. cholerae non-O1/non-O139 strains through the action of newly generated genomic islands.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Islas Genómicas/genética , Integrones/genética , Vibriosis , Vibrio cholerae no O1 , Humanos , India , Pruebas de Sensibilidad Microbiana/métodos , Serotipificación/métodos , Vibriosis/epidemiología , Vibriosis/microbiología , Vibrio cholerae no O1/clasificación , Vibrio cholerae no O1/efectos de los fármacos , Vibrio cholerae no O1/genética , Secuenciación Completa del Genoma/métodos
19.
Microb Ecol ; 77(2): 546-557, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30009332

RESUMEN

Antimicrobial resistance (AMR) among bacterial species that resides in complex ecosystems is a natural phenomenon. Indiscriminate use of antimicrobials in healthcare, livestock, and agriculture provides an evolutionary advantage to the resistant variants to dominate the ecosystem. Ascendency of resistant variants threatens the efficacy of most, if not all, of the antimicrobial drugs commonly used to prevent and/or cure microbial infections. Resistant phenotype is very common in enteric bacteria. The most common mechanisms of AMR are enzymatic modifications to the antimicrobials or their target molecules. In enteric bacteria, most of the resistance traits are acquired by horizontal gene transfer from closely or distantly related bacterial population. AMR traits are generally linked with mobile genetic elements (MGEs) and could rapidly disseminate to the bacterial species through horizontal gene transfer (HGT) from a pool of resistance genes. Although prevalence of AMR genes among pathogenic bacteria is widely studied in the interest of infectious disease management, the resistance profile and the genetic traits that encode resistance to the commensal microbiota residing in the gut of healthy humans are not well-studied. In the present study, we have characterized AMR phenotypes and genotypes of five dominant commensal enteric bacteria isolated from the gut of healthy Indians. Our study revealed that like pathogenic bacteria, enteric commensals are also multidrug-resistant. The genes encoding antibiotic resistance are physically linked with MGEs and could disseminate vertically to the progeny and laterally to the distantly related microbial species. Consequently, the AMR genes present in the chromosome of commensal gut bacteria could be a potential source of resistance functions for other enteric pathogens.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Microbioma Gastrointestinal/genética , Genes Bacterianos/genética , Fenotipo , Simbiosis , Antibacterianos/farmacología , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/aislamiento & purificación , Elementos Transponibles de ADN/genética , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Transferencia de Gen Horizontal/genética , Genoma Bacteriano , Genotipo , Humanos , Secuencias Repetitivas Esparcidas/genética , Metagenoma/genética , Pruebas de Sensibilidad Microbiana , Transformación Genética/genética , Vibrio cholerae/genética , Secuenciación Completa del Genoma
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