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Modeling the role of bacteriophage in the control of cholera outbreaks.

ABSTRACT: Cholera is a waterborne diarrheal disease that continues to plague the developing world. Individuals become infected by consuming water from reservoirs contaminated by virulent strains of the bacterium Vibrio cholerae. Epidemiological and environmental observations of a cholera outbreak in Dhaka, Bangladesh, suggest that lytic bacteriophage specific for V. cholerae may limit the severity of cholera outbreaks by killing bacteria present in the reservoir and in infected individuals. To quantify this idea and generate testable hypotheses, we analyzed a mathematical model that combines the epidemiology of cholera with the population dynamics of the bacteria and phage. Under biologically reasonable conditions, we found that vibriophage can ameliorate cholera outbreaks. If phage predation limits bacterial density before an outbreak, a transient reduction in phage density can disrupt that limitation, and subsequent bacterial growth can initiate a cholera outbreak. The severity of the outbreak depends on the density of phage remaining in the reservoir. If the outbreak is initiated instead by a rise in bacterial density, the introduction of phage can reduce the severity of the outbreak and promote its decline. In both situations, the magnitude of the phage effect depends mainly on vibrio growth and phage mortality rates; the lower the rates, the greater the effect. Our analysis also suggests that either bacteria in the environmental reservoir are hyperinfectious or most victims ingest bacteria amplified in food or drinking water contaminated by environmental water carrying few viable V. cholerae. Our theoretical results make a number of empirically testable predictions.

SUBMITTER: Jensen MA

PROVIDER: S-EPMC1450226 | biostudies-other | 2006 Mar

REPOSITORIES: biostudies-other

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Modeling the role of bacteriophage in the control of cholera outbreaks.

Jensen Mark A MA Faruque Shah M SM Mekalanos John J JJ Levin Bruce R BR

Proceedings of the National Academy of Sciences of the United States of America 20060314 12

Cholera is a waterborne diarrheal disease that continues to plague the developing world. Individuals become infected by consuming water from reservoirs contaminated by virulent strains of the bacterium Vibrio cholerae. Epidemiological and environmental observations of a cholera outbreak in Dhaka, Bangladesh, suggest that lytic bacteriophage specific for V. cholerae may limit the severity of cholera outbreaks by killing bacteria present in the reservoir and in infected individuals. To quantify th ...[more]

PMID: 16537404

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Project description:BACKGROUND:Cholera prevention and control interventions targeted to neighbors of cholera cases (case-area targeted interventions [CATIs]), including improved water, sanitation, and hygiene, oral cholera vaccine (OCV), and prophylactic antibiotics, may be able to efficiently avert cholera cases and deaths while saving scarce resources during epidemics. Efforts to quickly target interventions to neighbors of cases have been made in recent outbreaks, but little empirical evidence related to the effectiveness, efficiency, or ideal design of this approach exists. Here, we aim to provide practical guidance on how CATIs might be used by exploring key determinants of intervention impact, including the mix of interventions, "ring" size, and timing, in simulated cholera epidemics fit to data from an urban cholera epidemic in Africa. METHODS AND FINDINGS:We developed a micro-simulation model and calibrated it to both the epidemic curve and the small-scale spatiotemporal clustering pattern of case households from a large 2011 cholera outbreak in N'Djamena, Chad (4,352 reported cases over 232 days), and explored the potential impact of CATIs in simulated epidemics. CATIs were implemented with realistic logistical delays after cases presented for care using different combinations of prophylactic antibiotics, OCV, and/or point-of-use water treatment (POUWT) starting at different points during the epidemics and targeting rings of various radii around incident case households. Our findings suggest that CATIs shorten the duration of epidemics and are more resource-efficient than mass campaigns. OCV was predicted to be the most effective single intervention, followed by POUWT and antibiotics. CATIs with OCV started early in an epidemic focusing on a 100-m radius around case households were estimated to shorten epidemics by 68% (IQR 62% to 72%), with an 81% (IQR 69% to 87%) reduction in cases compared to uncontrolled epidemics. These same targeted interventions with OCV led to a 44-fold (IQR 27 to 78) reduction in the number of people needed to target to avert a single case of cholera, compared to mass campaigns in high-cholera-risk neighborhoods. The optimal radius to target around incident case households differed by intervention type, with antibiotics having an optimal radius of 30 m to 45 m compared to 70 m to 100 m for OCV and POUWT. Adding POUWT or antibiotics to OCV provided only marginal impact and efficiency improvements. Starting CATIs early in an epidemic with OCV and POUWT targeting those within 100 m of an incident case household reduced epidemic durations by 70% (IQR 65% to 75%) and the number of cases by 82% (IQR 71% to 88%) compared to uncontrolled epidemics. CATIs used late in epidemics, even after the peak, were estimated to avert relatively few cases but substantially reduced the number of epidemic days (e.g., by 28% [IQR 15% to 45%] for OCV in a 100-m radius). While this study is based on a rigorous, data-driven approach, the relatively high uncertainty about the ways in which POUWT and antibiotic interventions reduce cholera risk, as well as the heterogeneity in outbreak dynamics from place to place, limits the precision and generalizability of our quantitative estimates. CONCLUSIONS:In this study, we found that CATIs using OCV, antibiotics, and water treatment interventions at an appropriate radius around cases could be an effective and efficient way to fight cholera epidemics. They can provide a complementary and efficient approach to mass intervention campaigns and may prove particularly useful during the initial phase of an outbreak, when there are few cases and few available resources, or in order to shorten the often protracted tails of cholera epidemics.

Project description:BackgroundThe monkeypox outbreak in non-endemic countries in recent months has led the World Health Organization (WHO) to declare a public health emergency of international concern (PHEIC). It is thought that festivals, parties, and other gatherings may have contributed to the outbreak.MethodsWe considered a hypothetical metropolitan city and modeled the transmission of the monkeypox virus in humans in a high-risk group (HRG) and a low-risk group (LRG) using a Susceptible-Exposed-Infectious-Recovered (SEIR) model and incorporated gathering events. Model simulations assessed how the vaccination strategies combined with other public health measures can contribute to mitigating or halting outbreaks from mass gathering events.ResultsThe risk of a monkeypox outbreak was high when mass gathering events occurred in the absence of public health control measures. However, the outbreaks were controlled by isolating cases and vaccinating their close contacts. Furthermore, contact tracing, vaccinating, and isolating close contacts, if they can be implemented, were more effective for the containment of monkeypox transmission during summer gatherings than a broad vaccination campaign among HRG, when accounting for the low vaccination coverage in the overall population, and the time needed for the development of the immune responses. Reducing the number of attendees and effective contacts during the gathering could also prevent a burgeoning outbreak, as could restricting attendance through vaccination requirements.ConclusionMonkeypox outbreaks following mass gatherings can be made less likely with some restrictions on either the number and density of attendees in the gathering or vaccination requirements. The ring vaccination strategy inoculating close contacts of confirmed cases may not be enough to prevent potential outbreaks; however, mass gatherings can be rendered less risky if that strategy is combined with public health measures, including identifying and isolating cases and contact tracing. Compliance with the community and promotion of awareness are also indispensable to containing the outbreak.

Project description:Infectious diseases may be particularly critical for the conservation of endangered species. A striking example is the recurrent outbreaks that have been occurring in seabirds on Amsterdam Island for the past 30 years, threatening populations of three Endangered seabird species and of the endemic, Critically Endangered Amsterdam albatross Diomedea amsterdamensis. The bacteria Pasteurella multocida (avian cholera causative agent), and to a lesser extent Erysipelothrix rhusiopathiae (erysipelas causative agent), were both suspected to be responsible for these epidemics. Despite this critical situation, demographic trends were not available for these threatened populations, and the occurrence and characterization of potential causative agents of epizootics remain poorly known. The aims of the current study were to (i) provide an update of population trends for four threatened seabird species monitored on Amsterdam Island, (ii) assess the occurrence of P. multocida, and E. rhusiopathiae in live birds from five species, (iii) search for other infectious agents in these samples and, (iv) isolate and genotype the causative agent(s) of epizooties from dead birds. Our study shows that the demographic situation has worsened substantially in three seabird species during the past decade, with extremely low reproductive success and declining populations for Indian yellow-nosed albatrosses Thalassarche carteri, sooty albatrosses Phoebetria fusca, and northern rockhopper penguins Eudyptes moseleyi. Pasteurella multocida or E. rhusiopathiae were detected by PCR in live birds of all five investigated species, while results were negative for eight additional infectious agents. A single strain of P. multocida was repeatedly cultured from dead birds, while no E. rhusiopathiae could be isolated. These results highlight the significance of P. multocida in this particular eco-epidemiological system as the main agent responsible for epizootics. The study stresses the urgent need to implement mitigation measures to alter the course of avian cholera outbreaks threatening the persistence of seabird populations on Amsterdam Island.

Project description:Fecal contamination of water sources and open defecation have been linked to cholera outbreaks in India. However, a systematic review on the drivers responsible for these outbreaks has yet to be published. Here, we systematically review the published literature on cholera outbreaks in India between 2011 and 2020. We searched studies in English in three databases (MEDLINE, EMBASE, and Web of Science) and the Integrated Disease Surveillance Program that tracks cholera outbreaks throughout India. Two authors independently extracted data and assessed the quality of the included studies. Quantitative data on the modes of transmission reviewed in this study were assessed for any change over time between 2011-2015 and 2016-2020. Our search retrieved 10823 records initially, out of which 81 full-text studies were assessed for eligibility. Among these 81 studies, 20 were eligible for inclusion in this review. There were 565 reported outbreaks between 2011 and 2020 that led to 45,759 cases and 263 deaths. Outbreaks occurred throughout the year; however, they exploded with monsoons (June through September). In Tamil Nadu, a typical peak of cholera outbreaks was observed from December to January. Seventy-two percent (33,089/45,759) of outbreak-related cases were reported in five states, namely Maharashtra, West Bengal, Punjab, Karnataka, and Madhya Pradesh. Analysis of these outbreaks highlighted the main drivers of cholera including contaminated drinking water and food, inadequate sanitation and hygiene (including open defecation), and direct contact between households. The comparison between 2011-2015 and 2016-2020 showed a decreasing trend in the outbreaks that arose due to damaged water pipelines. Many Indians still struggle with open defecation, sanitation, and clean water access. These issues should be addressed critically. In addition, it is essential to interrupt cholera short-cycle transmission (mediated by households, stored drinking water and foodstuffs) during an outbreak. As cholera is associated with deprivation, socio-economic development is the only long-term solution.

Dataset Information

Modeling the role of bacteriophage in the control of cholera outbreaks.

Publications

Modeling the role of bacteriophage in the control of cholera outbreaks.

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