Vibrio cholerae O1 Variant with Reduced Susceptibility to Ciprofloxacin, Western Africa

International audienceLetter

Fatal Vibrio vulnificus Infection Associated with Eating Raw Oysters, New Caledonia

International audienceTo the Editor: The bacterium Vi-brio vulnifi cus is a marine fl ora sap-rophyte that can cause necrotic skin infection and septicemia in humans who eat shellfi sh. Symptoms of sep-ticemia (mortality rate >50%) have been described mostly in Florida and Japan among persons who ate raw fi lter-feeding shellfi sh when seawater temperatures are >20°C (1). V. vulnifi cus–related septicemia introduced through the digestive system appears within 7 days after inges-tion (2). Clinical signs and symptoms include fever, collapse, and metastatic necrotic skin lesions. We report 3 patients from New Caledonia who died after V. vulnifi cus infection, which they probably acquired by eating contaminated oysters. These patients were hospitalized during February–May 2008 at Noumea Hospital (Noumea, New Caledonia). Patient 1 was a 51-year-old man with fever, muscle pains, bleeding gums, and a history of alcohol abuse; within 48 hours after symptom onset, he died of septic shock, with diffuse ecchymoses and purpura. Patient 2 was a 67-year-old woman with no known concurrent conditions who was admitted to the hospital with chills, diarrhea, and vomiting; septic shock developed, with painful erythematous plaques on the lower limbs becoming foamy, confl uent, and necrotic. Patient 3 was a 74-year-old woman with untreated lupus who was hospitalized with lower-limb edema, hypotension, hypothermia, and erythematous skin lesions. All 3 patients received cepha-losporins but died of multiple organ failure within 12 hours after hospital admission. Peripheral blood aerobic–anaer-obic samples were taken from all patients , stored in BacT/Alert FA vials (bioMérieux, Marcy-l'Etoile, France), and incubated in the BacT/Alert 3D system (bioMérieux). Curved mobile gram-negative bacilli were isolated from blood samples cultured on conventional media without additional salt within 24 h after incubation at 37°C in a 5% CO 2-enriched atmosphere. V. vulnifi cus was identifi ed through the Vitek2 system (bioMérieux) and con-fi rmed by using the Api 20E system (bioMérieux). Strains were sent to the Centre National de Reference des Vibrions et du Choléra, (Institut Pasteur, Paris, France), which by PCR confi rmed the gene encoding virulence-associated hemolysin, a species-specifi c marker (3). Molecular typing by pulsed-fi eld gel electrophoresis was performed to assess possible clonality of the strains. Several studies have shown the genomic diversity among environmental and clinical V. vulnifi cus isolates. The use of genotyping methods has identifi ed >100 V. vulnifi cus strains in a single oyster (4) and notable hetero-geneity among clinical isolates from multiple patients, even if a unique pathogenic strain causes the infection in each patient. Thus, V. vulnifi cus infections within a large population at risk may result from rare events controlled more by the host than by the bacterial strain (5). Pulsed-fi eld gel electrophoresis genotype analysis enabled us to divide the strains into 2 groups. One group included the isolate from patient 1, and the other group included isolates from patients 2 and 3, which despite having slightly different NotI and Sfi I patterns refl ecting genetic rearrangement , clearly belonged to a single clone. Isolation of strains with such a high degree of homogeneity is not common, raising the question of the existence of V. vulnifi cus clones that are particularly virulent or adapted to humans. Currently, however, reliable markers for determining V. vulnifi cus virulence do not exist. Thus, no geno-typing system is likely to be useful for rapidly identifying strains that affect public health (6). V. vulnifi cus–related analysis requires the assumption that all strains are virulent. Epidemiologic information collected from patients' families indicated recent consumption of raw oysters. Two of the 3 cases occurred within a short time frame and were associated with eating local oysters harvested on the west coast of New Caledonia. The literature mentions few cases of V. vulnifi cus infection in the South Pacifi c. Cases described were isolated, rarely fatal, and involved infection through the skin (7–10). The V. vulnifi-cus infections we report may be related to the emergence of a new clone or to changes in the climate or environmental conditions. New Caledonia experienced unusual weather conditions during the fi rst half of 2008 (heavy rains and exceptionally high temperatures). These specifi c conditions may have favored higher sea surface temperatures, lower salinity, increased turbidity, and subsequent multiplication of V. vulnifi-cus in seawater. A range of projects were implemented to train practitioners to recognize potential V. vulnifi cus infections. Local health authorities issued criteria for defi ning suspected cases of V. vulnifi cus infection and recommendations for early medical care of patients with clinical symptoms. Methods of detecting the bacterium in human and animal health laboratories were improved , particularly by the systematic use of selective media in the event of suspected clinical V. vulnifi cus infection and standardized reporting of V. vulnifi cus isolation. Preventive measures , such as improving microbial surveillance and warning consumers about risks associated with eating raw seafood, are essential to help reduce the risk for V. vulnifi cus–induced illness. 136 Emerging Infectious Diseases • www.cdc.gov/eid • Vol. 17, No. 1, January 2011 LETTERS Acknowledgments We thank Jacob Kool, Martha Iwa-moto, Rajal Mody, and Dominique Hervio-Heath for help in investigating these cases and for formulating recommendations

Use of Vibrio cholerae Vaccine in an Outbreak in Guinea

Producción CientíficaThe 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

Single-dose cholera vaccine in response to an outbreak in Zambia

Producción CientíficaKilled oral cholera vaccines (OCVs) are part of the standard response package to a cholera outbreak, although the two-dose regimen of vaccines that has been prequalified by the World Health Organization (WHO) poses challenges to timely and efficient reactive vaccination campaigns.1 Recent data suggest that the first dose alone provides short-term protection, similar to that of two doses, which may largely dictate the effect of OCVs during epidemic

Use of a Cholera Rapid Diagnostic Test during a Mass Vaccination Campaign in Response to an Epidemic in Guinea, 2012

During the 2012 cholera outbreak in the Republic of Guinea, the Ministry of Health, supported by Médecins Sans Frontières - Operational Center Geneva, used the oral cholera vaccine Shanchol as a part of the emergency response. The rapid diagnostic test (RDT) Crystal VC, widely used during outbreaks, detects lipopolysaccharide antigens of Vibrio cholerae O1 and O139, both included in Shanchol. In the context of reactive use of a whole-cell cholera vaccine in a region where cholera cases have been reported, it is essential to know what proportion of vaccinated individuals would be reactive to the RDT and for how long after vaccination

Eff ectiveness of one dose of oral cholera vaccine in response to an outbreak: a case-cohort study

Background Oral cholera vaccines represent a new eff ective tool to fi ght cholera and are licensed as two-dose regimens with 2–4 weeks between doses. Evidence from previous studies suggests that a single dose of oral cholera vaccine might provide substantial direct protection against cholera. During a cholera outbreak in May, 2015, in Juba, South Sudan, the Ministry of Health, Médecins Sans Frontières, and partners engaged in the fi rst fi eld deployment of a single dose of oral cholera vaccine to enhance the outbreak response. We did a vaccine eff ectiveness study in conjunction with this large public health intervention. Methods We did a case-cohort study, combining information on the vaccination status and disease outcomes from a random cohort recruited from throughout the city of Juba with that from all the cases detected. Eligible cases were those aged 1 year or older on the fi rst day of the vaccination campaign who sought care for diarrhoea at all three cholera treatment centres and seven rehydration posts throughout Juba. Confi rmed cases were suspected cases who tested positive to PCR for Vibrio cholerae O1. We estimated the short-term protection (direct and indirect) conferred by one dose of cholera vaccine (Shanchol, Shantha Biotechnics, Hyderabad, India). Findings Between Aug 9, 2015, and Sept 29, 2015, we enrolled 87 individuals with suspected cholera, and an 898-person cohort from throughout Juba. Of the 87 individuals with suspected cholera, 34 were classifi ed as cholera positive, 52 as cholera negative, and one had indeterminate results. Of the 858 cohort members who completed a follow-up visit, none developed clinical cholera during follow-up. The unadjusted single-dose vaccine eff ectiveness was 80·2% (95% CI 61·5–100·0) and after adjusting for potential confounders was 87·3% (70·2–100·0). Interpretation One dose of Shanchol was eff ective in preventing medically attended cholera in this study. These results support the use of a single-dose strategy in outbreaks in similar epidemiological settings

Genomic history of the seventh pandemic of cholera in Africa.

The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa

Cholera epidemic in Yemen, 2016–18: an analysis of surveillance data

Summary: Background: In war-torn Yemen, reports of confirmed cholera started in late September, 2016. The disease continues to plague Yemen today in what has become the largest documented cholera epidemic of modern times. We aimed to describe the key epidemiological features of this epidemic, including the drivers of cholera transmission during the outbreak. Methods: The Yemen Health Authorities set up a national cholera surveillance system to collect information on suspected cholera cases presenting at health facilities. Individual variables included symptom onset date, age, severity of dehydration, and rapid diagnostic test result. Suspected cholera cases were confirmed by culture, and a subset of samples had additional phenotypic and genotypic analysis. We first conducted descriptive analyses at national and governorate levels. We divided the epidemic into three time periods: the first wave (Sept 28, 2016, to April 23, 2017), the increasing phase of the second wave (April 24, 2017, to July 2, 2017), and the decreasing phase of the second wave (July 3, 2017, to March 12, 2018). We reconstructed the changes in cholera transmission over time by estimating the instantaneous reproduction number, Rt. Finally, we estimated the association between rainfall and the daily cholera incidence during the increasing phase of the second epidemic wave by fitting a spatiotemporal regression model. Findings: From Sept 28, 2016, to March 12, 2018, 1 103 683 suspected cholera cases (attack rate 3·69%) and 2385 deaths (case fatality risk 0·22%) were reported countrywide. The epidemic consisted of two distinct waves with a surge in transmission in May, 2017, corresponding to a median Rt of more than 2 in 13 of 23 governorates. Microbiological analyses suggested that the same Vibrio cholerae O1 Ogawa strain circulated in both waves. We found a positive, non-linear, association between weekly rainfall and suspected cholera incidence in the following 10 days; the relative risk of cholera after a weekly rainfall of 25 mm was 1·42 (95% CI 1·31–1·55) compared with a week without rain. Interpretation: Our analysis suggests that the small first cholera epidemic wave seeded cholera across Yemen during the dry season. When the rains returned in April, 2017, they triggered widespread cholera transmission that led to the large second wave. These results suggest that cholera could resurge during the ongoing 2018 rainy season if transmission remains active. Therefore, health authorities and partners should immediately enhance current control efforts to mitigate the risk of a new cholera epidemic wave in Yemen. Funding: Health Authorities of Yemen, WHO, and Médecins Sans Frontières

Genomic insights into the 2016-2017 cholera epidemic in Yemen.

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