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1.  Modeling the Epidemiology of Cholera to Prevent Disease Transmission in Developing Countries 
Microbiology spectrum  2015;3(3):10.1128/microbiolspec.VE-0011-2014.
Cholera remains an important global cause of morbidity and mortality, which is capable of causing periodic epidemic disease. A number of mathematical models have been developed to help in understanding the dynamics of cholera outbreaks and for use as a tool in planning interventions, including vaccination campaigns. We have explored the utility of models in assessing the spread of cholera in the recent epidemics in Zimbabwe and Haiti. In both instances, a mathematical model was formulated and fitted to cumulative cholera cases to estimate the basic reproductive number ℜ0, and the partial reproductive numbers reflecting potential differences in environmental-to-human versus human-to-human transmission were quantified. In Zimbabwe, estimated ℜ0 for the epidemic using aggregated data at the national level was 1.15; in Haiti, it was 1.55. However, when calculated at a provincial/departmental level, estimated basic reproductive numbers were highly heterogeneous, with a range of 1.11 to 2.72 in Zimbabwe and 1.06 to 2.63 in Haiti. Our models suggest that the underlying patterns of cholera transmission varied widely from region to region, with a corresponding variation in the amenability of outbreaks to control measures such as immunization. These data underscore the heterogeneity of transmission dynamics, potentially linked to differences in environment, socio-economic conditions, and cultural practices. They also highlight the potential utility of these types of models in guiding development of public health intervention strategies.
PMCID: PMC4634708  PMID: 26185087
2.  Spectrum of Outpatient Illness in a School-Based Cohort in Haiti, with a Focus on Diarrheal Pathogens 
Currently, there are only limited data available on rates of major diagnostic categories of illnesses among Haitian children. We have established a cohort of 1,245 students attending schools run by the Christianville Foundation in the Gressier/Leogane region of Haiti, for whom our group provides primary medical care. Among 1,357 clinic visits during the 2012–2013 academic year, the main disease categories (with rates per 1,000 child years of observation) included acute respiratory infection (ARI) (385.6 cases/1,000 child years of observation), gastrointestinal complaints (277.8 cases/1,000 child years), febrile illness (235.0 cases/1,000 child years), and skin infections (151.7 cases/1,000 child years). The most common diarrheal pathogen was enteroaggregative Escherichia coli (present in 17% of children with diarrhea); Vibrio cholerae O1 and norovirus were the next most common. Our data highlight the importance of better defining etiologies for ARI and febrile illnesses and continuing problems of diarrheal illness in this region, including mild cases of cholera, which would not have been diagnosed without laboratory screening.
PMCID: PMC4385768  PMID: 25732684
3.  Hemagglutinin Gene Clade 3C.2a Influenza A(H3N2) Viruses, Alachua County, Florida, USA, 2014–15 
Emerging Infectious Diseases  2016;22(1):121-123.
Influenza A(H3N2) strains isolated during 2014–15 in Alachua County, Florida, USA, belonged to hemagglutinin gene clade 3C.2a. High rates of influenza-like illness and confirmed influenza cases in children were associated with a decrease in estimated vaccine effectiveness. Illnesses were milder than in 2013–14; severe cases were concentrated in elderly patients with underlying diseases.
PMCID: PMC4696699  PMID: 26692074
influenza; viruses; Florida; hemagglutinin; vaccines; influenza A(H3N2); respiratory infections
4.  Water-Related Infrastructure in a Region of Post-Earthquake Haiti: High Levels of Fecal Contamination and Need for Ongoing Monitoring 
We inventoried non-surface water sources in the Leogane and Gressier region of Haiti (approximately 270 km2) in 2012 and 2013 and screened water from 345 sites for fecal coliforms and Vibrio cholerae. An international organization/non-governmental organization responsible for construction could be identified for only 56% of water points evaluated. Sixteen percent of water points were non-functional at any given time; 37% had evidence of fecal contamination, with spatial clustering of contaminated sites. Among improved water sources (76% of sites), 24.6% had fecal coliforms versus 80.9% in unimproved sources. Fecal contamination levels increased significantly from 36% to 51% immediately after the passage of Tropical Storm Sandy in October of 2012, with a return to 34% contamination in March of 2013. Long-term sustainability of potable water delivery at a regional scale requires ongoing assessment of water quality, functionality, and development of community-based management schemes supported by a national plan for the management of potable water.
PMCID: PMC4183406  PMID: 25071005
5.  Feasibility of the Hydrogen Sulfide Test for the Assessment of Drinking Water Quality in Post-Earthquake Haiti 
Environmental monitoring and assessment  2014;186(12):8509-8516.
In 2010 a magnitude 7.0 earthquake struck Haiti, severely damaging the drinking and waste water infrastructure and leaving millions homeless. Compounding this problem, the introduction of Vibrio cholera resulted in a massive cholera outbreak that infected over 700,000 people and threatened the safety of Haiti’s drinking water. To mitigate this public health crisis, non-government organizations installed thousands of wells to provide communities with safe drinking water. However, despite increased access, Haiti currently lacks the monitoring capacity to assure the microbial safety of any of its water resources. For these reasons, this study was designed to assess the feasibility of using a simple, low cost method to detect indicators of fecal contamination of drinking water that could be implemented at the community level. Water samples from 358 sources of drinking water in the Léogâne flood basin were screened with a commercially available hydrogen sulfide test and a standard membrane method for the enumeration of thermotolerant coliforms. When compared with the gold standard method, the hydrogen sulfide test had a sensitivity of 65% and a specificity of 93%. While the sensitivity of the assay increased at higher fecal coliform concentrations, it never exceeded 88%, even with fecal coliform concentrations greater than 100 colony forming units per 100 milliliters. While its simplicity makes the hydrogen sulfide test attractive for assessing water quality in low resource settings, the low sensitivity raises concerns about its use as the sole indicator of the presence or absence of fecal coliforms in individual or community water sources.
PMCID: PMC4213301  PMID: 25182685
hydrogen sulfide test; water quality assessment; fecal coliforms; Haiti
6.  Phylodynamic Analysis of Clinical and Environmental Vibrio cholerae Isolates from Haiti Reveals Diversification Driven by Positive Selection 
mBio  2014;5(6):e01824-14.
Phylodynamic analysis of genome-wide single-nucleotide polymorphism (SNP) data is a powerful tool to investigate underlying evolutionary processes of bacterial epidemics. The method was applied to investigate a collection of 65 clinical and environmental isolates of Vibrio cholerae from Haiti collected between 2010 and 2012. Characterization of isolates recovered from environmental samples identified a total of four toxigenic V. cholerae O1 isolates, four non-O1/O139 isolates, and a novel nontoxigenic V. cholerae O1 isolate with the classical tcpA gene. Phylogenies of strains were inferred from genome-wide SNPs using coalescent-based demographic models within a Bayesian framework. A close phylogenetic relationship between clinical and environmental toxigenic V. cholerae O1 strains was observed. As cholera spread throughout Haiti between October 2010 and August 2012, the population size initially increased and then fluctuated over time. Selection analysis along internal branches of the phylogeny showed a steady accumulation of synonymous substitutions and a progressive increase of nonsynonymous substitutions over time, suggesting diversification likely was driven by positive selection. Short-term accumulation of nonsynonymous substitutions driven by selection may have significant implications for virulence, transmission dynamics, and even vaccine efficacy.
Cholera, a dehydrating diarrheal disease caused by toxigenic strains of the bacterium Vibrio cholerae, emerged in 2010 in Haiti, a country where there were no available records on cholera over the past 100 years. While devastating in terms of morbidity and mortality, the outbreak provided a unique opportunity to study the evolutionary dynamics of V. cholerae and its environmental presence. The present study expands on previous work and provides an in-depth phylodynamic analysis inferred from genome-wide single nucleotide polymorphisms of clinical and environmental strains from dispersed geographic settings in Haiti over a 2-year period. Our results indicate that even during such a short time scale, V. cholerae in Haiti has undergone evolution and diversification driven by positive selection, which may have implications for understanding the global clinical and epidemiological patterns of the disease. Furthermore, the continued presence of the epidemic strain in Haitian aquatic environments has implications for transmission.
PMCID: PMC4278535  PMID: 25538191
7.  Mapping to Support Fine Scale Epidemiological Cholera Investigations: A Case Study of Spatial Video in Haiti 
The cartographic challenge in many developing world environments suffering a high disease burden is a lack of granular environmental covariates suitable for modeling disease outcomes. As a result, epidemiological questions, such as how disease diffuses at intra urban scales are extremely difficult to answer. This paper presents a novel geospatial methodology, spatial video, which can be used to collect and map environmental covariates, while also supporting field epidemiology. An example of epidemic cholera in a coastal town of Haiti is used to illustrate the potential of this new method. Water risks from a 2012 spatial video collection are used to guide a 2014 survey, which concurrently included the collection of water samples, two of which resulted in positive lab results “of interest” (bacteriophage specific for clinical cholera strains) to the current cholera situation. By overlaying sample sites on 2012 water risk maps, a further fifteen proposed water sample locations are suggested. These resulted in a third spatial video survey and an additional “of interest” positive water sample. A potential spatial connection between the “of interest” water samples is suggested. The paper concludes with how spatial video can be an integral part of future fine-scale epidemiological investigations for different pathogens.
PMCID: PMC4772207  PMID: 26848672
spatial video; geographic information systems; cholera; Haiti; bacteriophage
8.  Ciguatera Incidence in the US Virgin Islands Has Not Increased over a 30-Year Time Period Despite Rising Seawater Temperatures 
Ciguatera fish poisoning is the most common marine food poisoning worldwide. It has been hypothesized that increasing seawater temperature will result in increasing ciguatera incidence. In St. Thomas, US Virgin Islands, we performed an island-wide telephone survey (N = 807) and a medical record review of diagnosed ciguatera cases at the emergency department of the sole hospital and compared these data with comparable data sources collected in 1980. Annual incidence from both recent data sources remained high (12 per 1,000 among adults in the telephone survey). However, the combined data sources suggest that incidence has declined by 20% or more or remained stable over 30 years, whereas seawater temperatures were increasing. Illness was associated with lower education levels, higher levels of fish consumption, and having previous episodes of ciguatera; population shifts from 1980 to 2010 in these factors could explain an incidence decline of approximately 3 per 1,000, obscuring effects from rising seawater temperature.
PMCID: PMC3752756  PMID: 23400575
10.  Vibrio cholerae Persisted in Microcosm for 700 Days Inhibits Motility but Promotes Biofilm Formation in Nutrient-Poor Lake Water Microcosms 
PLoS ONE  2014;9(3):e92883.
Toxigenic Vibrio cholerae, ubiquitous in aquatic environments, is responsible for cholera; humans can become infected after consuming food and/or water contaminated with the bacterium. The underlying basis of persistence of V. cholerae in the aquatic environment remains poorly understood despite decades of research. We recently described a “persister” phenotype of V. cholerae that survived in nutrient-poor “filter sterilized” lake water (FSLW) in excess of 700-days. Previous reports suggest that microorganisms can assume a growth advantage in stationary phase (GASP) phenotype in response to long-term survival during stationary phase of growth. Here we report a V. cholerae GASP phenotype (GASP-700D) that appeared to result from 700 day-old persister cells stored in glycerol broth at −80°C. The GASP-700D, compared to its wild-type N16961, was defective in motility, produced increased biofilm that was independent of vps (p<0.005) and resistant to oxidative stress when grown specifically in FSLW (p<0.005). We propose that V. cholerae GASP-700D represents cell populations that may better fit and adapt to stressful survival conditions while serving as a critical link in the cycle of cholera transmission.
PMCID: PMC3965490  PMID: 24667909
11.  Cholera Transmission in Ouest Department of Haiti: Dynamic Modeling and the Future of the Epidemic 
PLoS Neglected Tropical Diseases  2015;9(10):e0004153.
In the current study, a comprehensive, data driven, mathematical model for cholera transmission in Haiti is presented. Along with the inclusion of short cycle human-to-human transmission and long cycle human-to-environment and environment-to-human transmission, this novel dynamic model incorporates both the reported cholera incidence and remote sensing data from the Ouest Department of Haiti between 2010 to 2014. The model has separate compartments for infectious individuals that include different levels of infectivity to reflect the distribution of symptomatic and asymptomatic cases in the population. The environmental compartment, which serves as a source of exposure to toxigenic V. cholerae, is also modeled separately based on the biology of causative bacterium, the shedding of V. cholerae O1 by humans into the environment, as well as the effects of precipitation and water temperature on the concentration and survival of V. cholerae in aquatic reservoirs. Although the number of reported cholera cases has declined compared to the initial outbreak in 2010, the increase in the number of susceptible population members and the presence of toxigenic V. cholerae in the environment estimated by the model indicate that without further improvements to drinking water and sanitation infrastructures, intermittent cholera outbreaks are likely to continue in Haiti.
Author Summary
Based on the model-fitted trend and the observed incidence, there is evidence that after an initial period of intense transmission, the cholera epidemic in Haiti stabilized during the third year of the outbreak and became endemic. The model estimates indicate that the proportion of the population susceptible to infection is increasing and that the presence of toxigenic V. cholerae in the environment remains a potential source of new infections. Given the lack of adequate improvements to drinking water and sanitation infrastructure, these conditions could facilitate ongoing, seasonal cholera epidemics in Haiti.
PMCID: PMC4619523  PMID: 26488620
12.  Southeastern Center for Emerging Biologic Threats Tabletop Exercise: Foodborne Toxoplasmosis Outbreak on College Campuses 
The use of tabletop exercises as a tool in emergency preparedness and response has proven to be an effective means of assessing readiness for unexpected events. Whereas most exercise developers target a population in a defined space (eg, state, county, metropolitan area, hospital), the Southeastern Center for Emerging Biologic Threats (SECEBT) conducted an innovative tabletop exercise involving an unusual foodborne outbreak pathogen, targeting public health agencies and academic institutions in 7 southeastern states. The exercise tested the ability of participants to respond to a simulated foodborne disease outbreak affecting the region. The attendees represented 4 federal agencies, 9 state agencies, 6 universities, 1 nonprofit organization, and 1 private corporation. The goals were to promote collaborative relationships among the players, identify gaps in plans and policies, and identify the unique contributions of each organization—and notably academic institutions—to outbreak recognition, investigation, and control. Participants discussed issues and roles related to outbreak detection and management, risk communication, and coordination of policies and responsibilities before, during, and after an emergency, with emphasis on assets of universities that could be mobilized during an outbreak response. The exercise generated several lessons and recommendations identified by participants and evaluators. Key recommendations included a need to establish trigger points and protocols for information sharing and alerts among public health, academic, and law enforcement; to establish relationships with local, state, and federal stakeholders to facilitate communications during an emergency; and to catalogue and leverage strengths, assets, and priorities of academic institutions to add value to outbreak responses.
A tabletop exercise simulated a foodborne outbreak and involved representatives from federal and state agencies, universities, a nonprofit organization, and a corporation. The exercise pointed up the need to establish working relationships before an emergency and suggested that the resources of academic institutions could be used to good advantage.
PMCID: PMC3316480  PMID: 22283568
13.  Stx-Producing Shigella Species From Patients in Haiti: An Emerging Pathogen With the Potential for Global Spread 
Open Forum Infectious Diseases  2015;2(4):ofv134.
Shiga toxins (Stx) are commonly produced by Shigella dysenteriae serotype 1 and Stx-producing Escherichia coli. However, the toxin genes have been detected in additional Shigella species. We recently reported the emergence of Stx-producing Shigella in travelers in the United States and France who had recently visited Hispaniola (Haiti and the Dominican Republic). In this study, we confirm this epidemiological link by identifying Stx-producing Shigella from Haitian patients attending clinics near Port-au-Prince. We also demonstrate that the bacteriophage encoding Stx is capable of dissemination to stx-negative Shigella species found in Haiti, suggesting that Stx-producing Shigella may become more widespread within that region.
PMCID: PMC4606844  PMID: 26484357
bacteriophage; Haiti; Shiga toxin; Shigella
14.  Cholera—Modern Pandemic Disease of Ancient Lineage 
Emerging Infectious Diseases  2011;17(11):2099-2104.
Environmental triggers may lead to increases in Vibrio cholerae in environmental reservoirs, with spillover into human populations.
Cholera has affected humans for at least a millennium and persists as a major cause of illness and death worldwide, with recent epidemics in Zimbabwe (2008–2009) and Haiti (2010). Clinically, evidence exists of increasing severity of disease linked with emergence of atypical Vibrio cholerae organisms that have incorporated genetic material from classical biotype strains into an El Tor biotype background. A key element in transmission may be a recently recognized hyperinfectious phase, which persists for hours after passage in diarrheal feces. We propose a model of transmission in which environmental triggers (such as temperature) lead to increases in V. cholerae in environmental reservoirs, with spillover into human populations. However, once the microorganism is introduced into a human population, transmission occurs primary by “fast” transmission from person to person (taking advantage of the hyperinfectious state), without returning to the aquatic environment.
PMCID: PMC3310593  PMID: 22099113
cholera; Vibrio cholerae; bacteria; hyperinfectious; mathematical models; reservoir; synopsis; pandemic; environmental; triggers; human; lineage
15.  Recent Clonal Origin of Cholera in Haiti 
Emerging Infectious Diseases  2011;17(4):699-701.
Altered El Tor Vibrio cholerae O1, with classical cholera toxin B gene, was isolated from 16 patients with severe diarrhea at St. Mark’s Hospital, Arbonite, Haiti, <3 weeks after onset of the current cholera epidemic. Variable-number tandem-repeat typing of 187 isolates showed minimal diversity, consistent with a point source for the epidemic.
PMCID: PMC3377427  PMID: 21470464
Cholera; Haiti; Vibrio cholerae; bacteria; variable-number tandem-repeat; molecular epidemiology; clonal origin; expedited; dispatch
16.  How Safe Is Our Food? 
Emerging Infectious Diseases  2011;17(1):7-15.
PMCID: PMC3375763  PMID: 21192873
Foodborne disease; disease burden; food attribution; United States; commentary
17.  Severity of Influenza A(H1N1) Illness and Emergence of D225G Variant, 2013–14 Influenza Season, Florida, USA 
Emerging Infectious Diseases  2015;21(4):664-667.
Despite a regional decline in influenza A(H1N1)pdm09 virus infections during 2013–14, cases at a Florida hospital were more severe than those during 2009–10. Examined strains had a hemagglutinin polymorphism associated with enhanced binding to lower respiratory tract receptors. Genetic changes in this virus must be monitored to predict the effect of future pandemic viruses.
PMCID: PMC4378462  PMID: 25811540
influenza virus; H1N1 subtype; pandemic; hemagglutinin; influenza; acute respiratory distress syndrome; respiratory tract disease; sialic acid; viruses; Florida; D225G polymorphism; genetic changes
18.  Distribution of Virulence-Associated Genes and Genetic Relationships in Non-O1/O139 Vibrio cholerae Aquatic Isolates from China 
Applied and Environmental Microbiology  2014;80(16):4987-4992.
Non-O1/O139 Vibrio cholerae is naturally present in aquatic ecosystems and has been linked with cholera-like diarrhea and local outbreaks. The distribution of virulence-associated genes and genetic relationships among aquatic isolates from China are largely unknown. In this study, 295 aquatic isolates of V. cholerae non-O1/O139 serogroups from different regions in China were investigated. Only one isolate was positive for ctxB and harbored a rare genotype; 10 (3.4%) isolates carried several types of rstR sequences, eight of which carried rare types of toxin-coregulated pili (tcpA). Furthermore, 16 (5.4%) isolates carried incomplete (with partial open reading frames [ORFs]) vibrio seventh pandemic island I (VSP-I) or VSP-II clusters, which were further classified as 11 novel types. PCR-based analyses revealed remarkable variations in the distribution of putative virulence genes, including mshA (95.6%), hlyA (95.3%), rtxC (89.8%), rtxA (82.7%), IS1004 (52.9%), chxA (30.2%), SXT (15.3%), type III secretion system (18.0%), and NAG-ST (3.7%) genes. There was no correlation between the prevalence of putative virulence genes and that of CTX prophage or TCP genes, whereas there were correlations among the putative virulence genes. Further multilocus sequence typing (MLST) placed selected isolates (n = 70) into 69 unique sequence types (STs), which were different from those of the toxigenic O1 and O139 counterparts, and each isolate occupied a different position in the MLST tree. The V. cholerae non-O1/O139 aquatic isolates predominant in China have high genotypic diversity; these strains constitute a reservoir of potential virulence genes, which may contribute to evolution of pathogenic isolates.
PMCID: PMC4135755  PMID: 24907334
19.  School-Located Influenza Vaccination Reduces Community Risk for Influenza and Influenza-Like Illness Emergency Care Visits 
PLoS ONE  2014;9(12):e114479.
School-located influenza vaccination (SLIV) programs can substantially enhance the sub-optimal coverage achieved under existing delivery strategies. Randomized SLIV trials have shown these programs reduce laboratory-confirmed influenza among both vaccinated and unvaccinated children. This work explores the effectiveness of a SLIV program in reducing the community risk of influenza and influenza-like illness (ILI) associated emergency care visits.
For the 2011/12 and 2012/13 influenza seasons, we estimated age-group specific attack rates (AR) for ILI from routine surveillance and census data. Age-group specific SLIV program effectiveness was estimated as one minus the AR ratio for Alachua County versus two comparison regions: the 12 county region surrounding Alachua County, and all non-Alachua counties in Florida.
Vaccination of ∼50% of 5–17 year-olds in Alachua reduced their risk of ILI-associated visits, compared to the rest of Florida, by 79% (95% confidence interval: 70, 85) in 2011/12 and 71% (63, 77) in 2012/13. The greatest indirect effectiveness was observed among 0–4 year-olds, reducing AR by 89% (84, 93) in 2011/12 and 84% (79, 88) in 2012/13. Among all non-school age residents, the estimated indirect effectiveness was 60% (54, 65) and 36% (31, 41) for 2011/12 and 2012/13. The overall effectiveness among all age-groups was 65% (61, 70) and 46% (42, 50) for 2011/12 and 2012/13.
Wider implementation of SLIV programs can significantly reduce the influenza-associated public health burden in communities.
PMCID: PMC4260868  PMID: 25489850
20.  Circulation and Transmission of Clones of Vibrio cholerae During Cholera Outbreaks 
Cholera is still a major public health problem. The underlying bacterial pathogen Vibrio cholerae (V. cholerae) is evolving and some of its mutations have set the stage for outbreaks. After V. cholerae acquired the mobile elements VSP I & II, the El Tor pandemic began and spread across the tropics. The replacement of the O1 serotype encoding genes with the O139 encoding genes triggered an outbreak that swept across the Indian subcontinent. The sxt element generated a third selective sweep and most recently a fourth sweep was associated with the exchange of the El Tor ctx allele for a classical ctx allele in the El Tor background. In Kenya, variants of this fourth selective sweep have differentiated and become endemic residing in and emerging from environmental reservoirs. On a local level, studies in Bangladesh have revealed that outbreaks may arise from a nonrandom subset of the genetic lineages in the environment and as the population of the pathogen expands, many novel mutations may be found increasing the amount of genetic variation, a phenomenon known as a founder flush. In Haiti, after the initial invasion and expansion of V. cholerae in 2010, a second outbreak occurred in the winter of 2011–2012 driven by natural selection of specific mutations.
PMCID: PMC4243509  PMID: 24407776
21.  Modeling cholera outbreaks 
Mathematical modeling can be a valuable tool for studying infectious disease outbreak dynamics and simulating the effects of possible interventions. Here, we describe approaches to modeling cholera outbreaks and how models have been applied to explore intervention strategies, particularly in Haiti. Mathematical models can play an important role in formulating and evaluating complex cholera outbreak response options. Major challenges to cholera modeling are insufficient data for calibrating models and the need to tailor models for different outbreak scenarios.
PMCID: PMC4238032  PMID: 23412687
22.  High-Frequency Rugose Exopolysaccharide Production by Vibrio cholerae Strains Isolated in Haiti 
PLoS ONE  2014;9(11):e112853.
In October, 2010, epidemic cholera was reported for the first time in Haiti in over 100 years. Establishment of cholera endemicity in Haiti will be dependent in large part on the continued presence of toxigenic V. cholerae O1 in aquatic reservoirs. The rugose phenotype of V. cholerae, characterized by exopolysaccharide production that confers resistance to environmental stress, is a potential contributor to environmental persistence. Using a microbiologic medium promoting high-frequency conversion of smooth to rugose (S–R) phenotype, 80 (46.5%) of 172 V. cholerae strains isolated from clinical and environmental sources in Haiti were able to convert to a rugose phenotype. Toxigenic V. cholerae O1 strains isolated at the beginning of the epidemic (2010) were significantly less likely to shift to a rugose phenotype than clinical strains isolated in 2012/2013, or environmental strains. Frequency of rugose conversion was influenced by incubation temperature and time. Appearance of the biofilm produced by a Haitian clinical rugose strain (altered biotype El Tor HC16R) differed from that of a typical El Tor rugose strain (N16961R) by confocal microscopy. On whole-genome SNP analysis, there was no phylogenetic clustering of strains showing an ability to shift to a rugose phenotype. Our data confirm the ability of Haitian clinical (and environmental) strains to shift to a protective rugose phenotype, and suggest that factors such as temperature influence the frequency of transition to this phenotype.
PMCID: PMC4229229  PMID: 25390633
23.  Agricultural Antibiotics and Human Health 
PLoS Medicine  2005;2(8):e232.
Smith and colleagues discuss evidence suggesting that antibiotic use in agriculture has contributed to antibiotic resistance in the pathogenic bacteria of humans.
Does antibiotic use in agriculture have a greater impact than hospital use?
PMCID: PMC1167557  PMID: 15984910
24.  A Molecular Surveillance Reveals the Prevalence of Vibrio cholerae O139 Isolates in China from 1993 to 2012 
Journal of Clinical Microbiology  2014;52(4):1146-1152.
Vibrio cholerae serogroup O139 was first identified in 1992 in India and Bangladesh, in association with major epidemics of cholera in both countries; cases were noted shortly thereafter in China. We characterized 211 V. cholerae O139 isolates that were isolated at multiple sites in China between 1993 and 2012 from patients (n = 92) and the environment (n = 119). Among clinical isolates, 88 (95.7%) of 92 were toxigenic, compared with 47 (39.5%) of 119 environmental isolates. Toxigenic isolates carried the El Tor CTX prophage and toxin-coregulated pilus A gene (tcpA), as well as the Vibrio seventh pandemic island I (VSP-I) and VSP-II. Among a subset of 42 toxigenic isolates screened by multilocus sequence typing (MLST), all were in the same sequence type as a clinical isolate (MO45) from the original Indian outbreak. Nontoxigenic isolates, in contrast, generally lacked VSP-I and -II, and fell within13 additional sequence types in two clonal complexes distinct from the toxigenic isolates. In further pulsed-field gel electrophoresis (PFGE) (with NotI digestion) studies, toxigenic isolates formed 60 pulsotypes clustered in one group, while the nontoxigenic isolates formed 43 pulsotypes which clustered into 3 different groups. Our data suggest that toxigenic O139 isolates from widely divergent geographic locations, while showing some diversity, have maintained a relatively tight clonal structure across a 20-year time span. Nontoxigenic isolates, in contrast, exhibited greater diversity, with multiple clonal lineages, than did their toxigenic counterparts.
PMCID: PMC3993493  PMID: 24452176
25.  Household-Level Spatiotemporal Patterns of Incidence of Cholera, Haiti, 2011 
Emerging Infectious Diseases  2014;20(9):1516-1519.
A cholera outbreak began in Haiti during October, 2010. Spatiotemporal patterns of household-level cholera in Ouest Department showed that the initial clusters tended to follow major roadways; subsequent clusters occurred further inland. Our data highlight transmission pathway complexities and the need for case and household-level analysis to understand disease spread and optimize interventions.
PMCID: PMC4178390  PMID: 25148590
Cholera; bacteria; Vibrio cholerae; Haiti; spatiotemporal; SaTScan; GIS; GPS; foodborne; waterborne; diarrhea

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