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In the HTML version of this Letter, the affiliations for authors Andrew S. Azman, Dhirendra Kumar and Thandavarayan Ramamurthy were inverted (the PDF and print versions of the Letter were correct); the affiliations have been corrected online.
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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.
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Cólera/epidemiología , Cólera/microbiología , Genoma Bacteriano/genética , Genómica , Vibrio cholerae/genética , Vibrio cholerae/aislamiento & purificación , Humanos , Filogenia , Vibrio cholerae/clasificación , Yemen/epidemiologíaRESUMEN
Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.
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Cólera , Vibrio cholerae O1 , Humanos , Vibrio cholerae O1/genética , Tanzanía , Lagos , Cólera/epidemiología , GenómicaRESUMEN
After a lull of >20 years, Algeria experienced a cholera outbreak in 2018 that included 291 suspected cases. We found that outbreak isolates were Vibrio cholerae O1 serotype Ogawa from seventh pandemic El Tor sublineage AFR14, which corresponds to a new introduction of cholera into Africa from South Asia.
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Cólera , Vibrio cholerae O1 , Argelia/epidemiología , Cólera/epidemiología , Brotes de Enfermedades , Humanos , Pandemias , Vibrio cholerae O1/genéticaRESUMEN
Four cholera outbreaks were reported in the Central African Republic during 1997-2016. We show that the outbreak isolates were Vibrio cholerae O1 serotype Inaba from 3 seventh pandemic El Tor sublineages originating from West Africa (sublineages T7 and T9) or the African Great Lakes Region (T10).
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Cólera , Vibrio cholerae O1 , África Occidental , República Centroafricana/epidemiología , Cólera/epidemiología , Brotes de Enfermedades , Humanos , Pandemias , Vibrio cholerae O1/genéticaRESUMEN
Combining the official cholera line list data and outbreak investigation reports from the ministries of health in Uganda and South Sudan with molecular analysis of Vibrio cholerae strains revealed the interrelatedness of the epidemics in both countries in 2014. These results highlight the need for collaboration to control cross-border outbreaks.
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Cólera/epidemiología , Cólera/prevención & control , Epidemias , Cooperación Internacional , Humanos , Sudán del Sur/epidemiología , Factores de Tiempo , Uganda/epidemiologíaRESUMEN
OBJECTIVE: To assess the performance of the SD Bioline Cholera Ag O1/O139 rapid diagnostic test (RDT) compared to a reference standard combining culture and PCR for the diagnosis of cholera cases during an outbreak. METHODS: RDT and bacterial culture were performed on site using fresh stools collected from cholera suspected cases, and from stools enriched in alkaline peptone water. Dried stool samples on filter paper were tested for V. cholerae by PCR in Lusaka (as part of a laboratory technology transfer project) and at a reference laboratory in Paris, France. A sample was considered positive for cholera by the reference standard if any of the culture or PCR tests was positive for V. cholerae O1 or O139. RESULTS: Among the 170 samples tested with SD Bioline and compared to the reference standard, the RDT showed a sensitivity of 90.9% (95% CI: 81.3-96.6) and specificity of 95.2% (95% CI: 89.1-98.4). After enrichment, the sensitivity was 95.5% (95% CI: 87.3-99.1) and specificity 100% (95% CI: 96.5-100). CONCLUSION: The observed sensitivity and specificity were within recommendations set by the Global Task Force for Cholera Control on the use of cholera RDT (sensitivity = 90%; specificity = 85%). Although the sample size was small, our findings suggest that the SD Bioline RDT could be used in the field to rapidly alert public health officials to the likely presence of cholera cases when an outbreak is suspected.
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Cólera/diagnóstico , Pruebas Diagnósticas de Rutina/métodos , Heces/microbiología , Vibrio cholerae/aislamiento & purificación , Humanos , Reacción en Cadena de la Polimerasa , Juego de Reactivos para Diagnóstico , ZambiaRESUMEN
BACKGROUND: The use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa. METHODS: We conducted a matched case-control study in Guinea between May 20 and October 19, 2012. Suspected cholera cases were confirmed by means of a rapid test, and controls were selected among neighbors of the same age and sex as the case patients. The odds of vaccination were compared between case patients and controls in bivariate and adjusted conditional logistic-regression models. Vaccine effectiveness was calculated as (1-odds ratio)×100. RESULTS: Between June 8 and October 19, 2012, we enrolled 40 case patients and 160 controls in the study for the primary analysis. After adjustment for potentially confounding variables, vaccination with two complete doses was associated with significant protection against cholera (effectiveness, 86.6%; 95% confidence interval, 56.7 to 95.8; P=0.001). CONCLUSIONS: In this study, Shanchol was effective when used in response to a cholera outbreak in Guinea. This study provides evidence supporting the addition of vaccination as part of the response to an outbreak. It also supports the ongoing efforts to establish a cholera vaccine stockpile for emergency use, which would enhance outbreak prevention and control strategies. (Funded by Médecins sans Frontières.).
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Vacunas contra el Cólera/administración & dosificación , Cólera/prevención & control , Brotes de Enfermedades/prevención & control , Vibrio cholerae , Administración Oral , Adolescente , Adulto , Estudios de Casos y Controles , Cólera/epidemiología , Vacunas contra el Cólera/economía , Factores de Confusión Epidemiológicos , Almacenaje de Medicamentos , Femenino , Guinea/epidemiología , Humanos , Modelos Logísticos , Masculino , Vigilancia de la Población , Adulto JovenRESUMEN
OBJECTIVES: Vibrio cholerae non-O1/non-O139 (NOVC) bacteremia is infrequently reported in Western countries and is associated with unfavorable outcome. PATIENT/METHOD: We describe here the case of a diabetic patient with hepatic cytolysis and NOVC bacteremia following an episode of diarrhea. RESULT: The patient was paucisymptomatic and had a favorable resolution with oral ciprofloxacin. CONCLUSION: NOVC should be systematically sought in stool samples, particularly in immunocompromised patients, due to an increased risk of infection occurrence.
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Antibacterianos , Bacteriemia , Vibrio cholerae no O1 , Humanos , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Francia/epidemiología , Vibrio cholerae no O1/aislamiento & purificación , Vibrio cholerae no O1/genética , Vibrio cholerae no O1/clasificación , Antibacterianos/uso terapéutico , Masculino , Ciprofloxacina/uso terapéutico , Hepatitis/microbiología , Hepatitis/complicaciones , Vibriosis/microbiología , Vibriosis/diagnóstico , Vibriosis/tratamiento farmacológico , Diarrea/microbiología , Cólera/microbiología , Cólera/complicaciones , Persona de Mediana Edad , Heces/microbiología , Anciano , FemeninoRESUMEN
Cholera is a life-threatening gastrointestinal infection caused by a toxigenic bacterium, Vibrio cholerae. After a lull of almost 30 years, a first case of cholera was detected in Lebanon in October 2022. The outbreak lasted three months, with 8007 suspected cases (671 laboratory-confirmed) and 23 deaths. In this study, we use phenotypic methods and microbial genomics to study 34 clinical and environmental Vibrio cholerae isolates collected throughout this outbreak. All isolates are identified as V. cholerae O1, serotype Ogawa strains from wave 3 of the seventh pandemic El Tor (7PET) lineage. Phylogenomic analysis unexpectedly reveals the presence of two different strains of the seventh pandemic El Tor (7PET) lineage. The dominant strain has a narrow antibiotic resistance profile and is phylogenetically related to South Asian V. cholerae isolates and derived African isolates from the AFR15 sublineage. The second strain is geographically restricted and extensively drug-resistant. It belongs to the AFR13 sublineage and clusters with V. cholerae isolates collected in Yemen. In conclusion, the 2022-2023 Lebanese cholera outbreak is caused by the simultaneous introduction of two different 7PET strains. Genomic surveillance with cross-border collaboration is therefore crucial for the identification of new introductions and routes of circulation of cholera, improving our understanding of cholera epidemiology.
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Cólera , Brotes de Enfermedades , Filogenia , Líbano/epidemiología , Humanos , Cólera/epidemiología , Cólera/microbiología , Genoma Bacteriano/genética , Genómica/métodos , Vibrio cholerae/genética , Vibrio cholerae/aislamiento & purificación , Vibrio cholerae/clasificación , Masculino , Antibacterianos/farmacología , Femenino , Vibrio cholerae O1/genética , Vibrio cholerae O1/aislamiento & purificación , Vibrio cholerae O1/clasificación , Adolescente , Adulto , Adulto Joven , Persona de Mediana Edad , Niño , Epidemiología MolecularRESUMEN
Since 2016, Yemen has been experiencing the largest cholera outbreak in modern history. Multidrug resistance (MDR) emerged among Vibrio cholerae isolates from cholera patients in 2018. Here, to characterize circulating genotypes, we analysed 260 isolates sampled in Yemen between 2018 and 2019. Eighty-four percent of V. cholerae isolates were serogroup O1 belonging to the seventh pandemic El Tor (7PET) lineage, sub-lineage T13, whereas 16% were non-toxigenic, from divergent non-7PET lineages. Treatment of severe cholera with macrolides between 2016 and 2019 coincided with the emergence and dominance of T13 subclones carrying an incompatibility type C (IncC) plasmid harbouring an MDR pseudo-compound transposon. MDR plasmid detection also in endemic non-7PET V. cholerae lineages suggested genetic exchange with 7PET epidemic strains. Stable co-occurrence of the IncC plasmid with the SXT family of integrative and conjugative element in the 7PET background has major implications for cholera control, highlighting the importance of genomic epidemiological surveillance to limit MDR spread.
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Cólera , Vibrio cholerae O1 , Humanos , Cólera/epidemiología , Vibrio cholerae O1/genética , Yemen/epidemiología , Plásmidos/genética , GenómicaRESUMEN
In 2022, the burden of cholera-an acute watery diarrheal disease caused by Vibrio cholerae serogroup O1 (or more rarely O139) bacteria, which produce cholera toxin-remains high in many African and Asian countries. In the last few years, microbial genomics has made it possible to define the bacterial populations responsible for cholera more precisely. It has been shown that the current, seventh pandemic is due to a single lineage with a reservoir in the countries of the Bay of Bengal (India and Bangladesh). There have been several transmissions of the causal agent of cholera from this region to Africa, Asia and Latin America, suggesting a human-to-human transmission of the disease. Microbial genetics can help to fight this scourge by providing insight into cholera epidemiology and through its use in disease monitoring, thereby contributing to the achievement of the World Health Organization's goal of reducing cholera deaths by 90% by 2030.
En 2022, de nombreux pays d'Afrique et d'Asie restent des foyers épidémiques de choléra, maladie diarrhéique causée par la bactérie Vibrio cholerae de sérogroupe O1 (ou plus rarement O139) produisant la toxine cholérique. La génomique microbienne a permis ces dernières années de mieux définir les populations bactériennes responsables du choléra. Il a ainsi été montré qu'il n'existait qu'une seule lignée génétique de Vibrio cholerae O1 responsable de la septième pandémie dont le réservoir se situe dans la région du golfe du Bengale (Inde et Bangladesh). Plusieurs évènements de transmission de l'agent du choléra vers l'Afrique, l'Europe ou l'Amérique latine ont été identifiés et suggèrent une transmission interhumaine de la maladie. Les données issues des travaux de génomique microbienne ainsi que son utilisation pour la surveillance globale du choléra vont permettre de mieux lutter contre ce fléau et participer à l'objectif de l'Organisation mondiale de la Santé de réduire de 90 % les décès dus à cette maladie en 2030.
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Cólera , Vibrio cholerae , Asia/epidemiología , Bangladesh/epidemiología , Cólera/etiología , Cólera/microbiología , Genómica , Humanos , Vibrio cholerae/genéticaRESUMEN
Confirmation of a cholera epidemic is based on bacteriological identification of the agent and requires the sending of samples to a culture laboratory, often in countries with limited resources. Comparison of the use of filter paper with the use of Cary-Blair reference medium for stool transport showed that this simple transport medium is appropriate for the recovery of Vibrio cholerae.
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Técnicas Bacteriológicas/métodos , Cólera/diagnóstico , Papel , Manejo de Especímenes/métodos , Vibrio cholerae/aislamiento & purificación , Adulto , Cólera/microbiología , Heces/microbiología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 70-year-old woman with no relevant medical history presented banal clinical signs of infectious gastroenteritis on her return from a trip to the Republic of the Union of Myanmar. The appearance of her stools and clinical findings were not suggestive of a typical case of cholera, but Vibrio cholerae was nevertheless isolated from her stools in the laboratory. The National reference center (NRC) for vibrios and cholera identified a Vibrio cholerae serogroup O1 (serotype Inaba) strain. The health authorities were notified of an imported case of cholera, identified on the basis of clinical, biological and epidemiological data. The diagnostic strategy used in the laboratory was based on a two-step algorithm involving molecular biological screening followed by culture on selective media for species identification. It was this approach, benefiting from the complementarity of the different techniques, that made it possible to reach a reliable rapid biological diagnosis of this atypical, but frequent form of the disease. The diagnosis of imported cases is of the utmost importance, because the mandatory signaling and notification of cases trigger investigations to check for additional cases among other exposed individuals or contacts of the patient, even though the risk of secondary transmission appears to be low in France. It also supplies data to international surveillance networks for cholera, which remains a serious disease and a major problem globally. This case highlights the importance of interactions between the various biological personnel and clinicians.
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Cólera/diagnóstico , Gastroenteritis/diagnóstico , Enfermedad Relacionada con los Viajes , Anciano , Diagnóstico Diferencial , Femenino , Francia , Humanos , Pruebas de Sensibilidad Microbiana , Mianmar , Fenotipo , Síndrome , Vibrio cholerae O1/aislamiento & purificaciónRESUMEN
In 1970, the seventh pandemic of cholera (7 P) reached both Africa and Europe. Between 1970 and 2011, several European countries reported cholera outbreaks of a few to more than 2,000 cases. We report here a whole-genome analysis of 1,324 7 P V. cholerae El Tor (7 PET) isolates, including 172 from autochthonous sporadic or outbreak cholera cases occurring between 1970 and 2011 in Europe, providing insight into the spatial and temporal spread of this pathogen across Europe. In this work, we show that the 7 PET lineage was introduced at least eight times into two main regions: Eastern and Southern Europe. Greater recurrence of the disease was observed in Eastern Europe, where it persisted until 2011. It was introduced into this region from Southern Asia, often circulating regionally in the countries bordering the Black Sea, and in the Middle East before reaching Eastern Africa on several occasions. In Southern Europe, the disease was mostly seen in individual countries during the 1970s and was imported from North and West Africa, except in 1994, when cholera was imported into Albania and Italy from the Black Sea region. These results shed light on the geographic course of cholera during the seventh pandemic and highlight the role of humans in its global dissemination.
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Cólera/historia , Pandemias/historia , Cólera/epidemiología , Cólera/microbiología , Farmacorresistencia Bacteriana/genética , Europa (Continente)/epidemiología , Evolución Molecular , Genoma Bacteriano , Genómica , Historia del Siglo XX , Historia del Siglo XXI , Migración Humana/historia , Humanos , Filogenia , Ribotipificación , Análisis Espacio-Temporal , Vibrio cholerae/clasificación , Vibrio cholerae/genética , Vibrio cholerae/aislamiento & purificaciónRESUMEN
BACKGROUND: Between 2014 and 2017, successive cholera epidemics occurred in South Sudan within the context of civil war, population displacement, flooding, and drought. We aim to describe the spatiotemporal and molecular features of the three distinct epidemic waves and explore the role of vaccination campaigns, precipitation, and population movement in shaping cholera spread in this complex setting. METHODS: In this descriptive epidemiological study, we analysed cholera linelist data to describe the spatiotemporal progression of the epidemics. We placed whole-genome sequence data from pandemic Vibrio cholerae collected throughout these epidemics into the global phylogenetic context. Using whole-genome sequence data in combination with other molecular attributes, we characterise the relatedness of strains circulating in each wave and the region. We investigated the association of rainfall and the instantaneous basic reproduction number using distributed lag non-linear models, compared county-level attack rates between those with early and late reactive vaccination campaigns, and explored the consistency of the spatial patterns of displacement and suspected cholera case reports. FINDINGS: The 2014 (6389 cases) and 2015 (1818 cases) cholera epidemics in South Sudan remained spatially limited whereas the 2016-17 epidemic (20 438 cases) spread among settlements along the Nile river. Initial cases of each epidemic were reported in or around Juba soon after the start of the rainy season, but we found no evidence that rainfall modulated transmission during each epidemic. All isolates analysed had similar genotypic and phenotypic characteristics, closely related to sequences from Uganda and Democratic Republic of the Congo. Large-scale population movements between counties of South Sudan with cholera outbreaks were consistent with the spatial distribution of cases. 21 of 26 vaccination campaigns occurred during or after the county-level epidemic peak. Counties vaccinated on or after the peak incidence week had 2·2 times (95% CI 2·1-2·3) higher attack rates than those where vaccination occurred before the peak. INTERPRETATION: Pandemic V cholerae of the same clonal origin was isolated throughout the study period despite interepidemic periods of no reported cases. Although the complex emergency in South Sudan probably shaped some of the observed spatial and temporal patterns of cases, the full scope of transmission determinants remains unclear. Timely and well targeted use of vaccines can reduce the burden of cholera; however, rapid vaccine deployment in complex emergencies remains challenging. FUNDING: The Bill & Melinda Gates Foundation.
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Cólera/epidemiología , Epidemias , Conflictos Armados , Cólera/prevención & control , Sequías/estadística & datos numéricos , Estudios Epidemiológicos , Femenino , Inundaciones/estadística & datos numéricos , Humanos , Programas de Inmunización/métodos , Incidencia , Masculino , Dinámicas no Lineales , Filogenia , Lluvia , Sudán del Sur/epidemiología , Análisis Espacio-Temporal , Vibrio cholerae/genética , Secuenciación Completa del Genoma/métodosRESUMEN
We studied the evolution of Vibrio cholerae O1 during the 1991 to 2000 cholera epidemic in Mexico by biochemical, serological, and molecular characterization of strains collected during this period. Strains were divided into toxigenic and nontoxigenic groups according to the presence or absence of genes encoding cholera toxin. As previously reported, we characterized two populations among toxigenic strains, which were present from the first year of the epidemic. BglI rRNA analysis revealed that these strains had ribotype profiles, denoted M5 and M6 in our study, that were identical to those previously designated Koblavi B5 or Popovic 5 and Popovic 6a or Tamayo B21a, respectively. Ribotype M5 was isolated between 1991 and 1993. This ribotype had a low level of genetic variation as detected by pulsed-field gel electrophoresis (PFGE). Ribotype M6 persisted from 1991 to 2000. However, PFGE profiles suggested that two epidemiologically unrelated strains coexisted within this single ribotype from 1995 until the end of the epidemic. We identified three new BglI ribotypes, Mx1, Mx2, and Mx3, from nontoxigenic V. cholerae O1 strains isolated between 1998 and 2000; one of them grouped strains positive for the toxin-coregulated pilus island. They differed from nontoxigenic clones isolated in Latin America and on the U.S. Gulf Coast and are probably autochthonous Mexican V. cholerae O1 variants. Most of these new variants were isolated from states surrounding the Gulf of Mexico, where the highest incidence of cholera in the country was recorded. Thus, the Mexican Gulf Coast, like the U.S. Gulf Coast, may act as an environmental reservoir of V. cholerae O1.
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Cólera/epidemiología , Cólera/microbiología , Vibrio cholerae O1/clasificación , Vibrio cholerae O1/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Toxina del Cólera/genética , Análisis por Conglomerados , Dermatoglifia del ADN , ADN Bacteriano/genética , Electroforesis en Gel de Campo Pulsado , Genotipo , Humanos , México/epidemiología , Polimorfismo Genético , Ribotipificación , Serotipificación , Vibrio cholerae O1/genéticaRESUMEN
There was an outbreak of cholera in Cameroon during 2004 and 2005; the epidemic began in Douala in January 2004 and spread throughout the south of the country. The World Health Organization (WHO) reported 8005 cases in 2004 and 2847 cases in 2005. Five hundred eighty-nine stool samples were received in the Pasteur Centre of Cameroon and 352 were microbiologically confirmed to be positive for Vibrio cholerae O1. Isolated strains were tested for their antimicrobial susceptibilities. All the strains were multidrug resistant and predominantly showed a common resistance pattern at the beginning of the outbreak. Tetracycline, recommended by the WHO for treating cholera in adults, was effective against all the strains tested. Cotrimoxazole (trimethoprim/sulfamethoxazole), previously a first-line treatment in children, was ineffective in vitro for all the clinical isolates and was quickly replaced by amoxicillin. Ampicillin resistance emerged at the end of 2004 and was the leading resistance pattern observed in the second half of 2005. This therefore represented the second major resistance pattern. These two major resistance profiles were not associated with patient characteristics (sex and age) or to the geographic origin of strains. However, there was a highly significant relationship between resistance patterns and the year of isolation (p < 0.001). The strains possessed genes ctxA and ctxB encoding the two cholera toxin subunits and were very closely related, irrespective of their antimicrobial resistance patterns. They were not differentiated by molecular typing methods and gave similar ribotyping and pulsed-field gel electrophoresis patterns.
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Antibacterianos/farmacología , Cólera/microbiología , ADN Bacteriano/análisis , Farmacorresistencia Bacteriana Múltiple , Vibrio cholerae O1/efectos de los fármacos , Camerún/epidemiología , Cólera/epidemiología , Recuento de Colonia Microbiana , Brotes de Enfermedades , Electroforesis en Gel de Campo Pulsado , Heces/microbiología , Microbiología de Alimentos , Humanos , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Ribotipificación , Vibrio cholerae O1/genética , Vibrio cholerae O1/aislamiento & purificaciónRESUMEN
This is a case report about a 54-year-old man with hypovolemic shock, due to diarrhea and major vomiting after his return from India. The isolation of Vibrio cholerae serogroup O1 (Ogawa serotype) explains this typical clinical presentation of cholera, seen in 10% of cholera cases only. The patient had co-infection with Vibrio cholerae and Campylobacter coli. Co-infections appear to be frequent in endemic areas. The purpose of this case report is to recall the relevance of Vibrio isolation when the clinical context is evocative (diarrhea on travel return, raw sea food consumption).