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1.
J Clin Microbiol ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611794

RESUMO

A fundamental, clinical and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR for V. cholerae (n=78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (OR 0.108; 95%CI 0.002-0.872) and 87% (OR 0.130; 95%CI 0.022-0.649) when lytic bacteriophage were detected, respectively. The odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by more than 99% (OR 0.00; 95% CI: 0.00-0.28) and 89% (OR 0.11; 95% CI: 0.03-0.44) when azithromycin was detected, respectively. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

3.
Ecohealth ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32705577

RESUMO

The reduced species richness typical of oceanic islands provides an interesting environmental setup to examine in natura the epidemiological dynamics of infectious agents with potential implications for public health and/or conservation. On Amsterdam Island (Indian Ocean), recurrent die-offs of Indian yellow-nosed albatross (Thalassarche carteri) nestlings have been attributed to avian cholera, caused by the bacterium Pasteurella multocida. In order to help implementing efficient measures for the control of this disease, it is critical to better understand the local epidemiology of P. multocida and to examine its inter- and intra-annual infection dynamics. We evaluated the infection status of 264 yellow-nosed albatrosses over four successive breeding seasons using a real-time PCR targeting P. multocida DNA from cloacal swabs. Infection prevalence patterns revealed an intense circulation of P. multocida throughout the survey, with a steady but variable increase in infection prevalence within each breeding season. These epizootics were associated with massive nestling dies-offs, inducing very low fledging successes (≤ 20%). These results suggest important variations in the transmission dynamics of this pathogen. These findings and the developed PCR protocol have direct applications to guide future research and refine conservation plans aiming at controlling the disease.

4.
Int J Antimicrob Agents ; : 106097, 2020 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-32697966

RESUMO

Cholera caused by the Gram negative bacterium Vibrio cholerae has been a serious threat in under developed countries. Though rehydration therapy has been the mainstay of the disease management, antibiotics are also being used as an adjunct in the treatment regime causing an increase in the circulation of antibiotic resistant V. cholerae strains. In the present study, adaptive laboratory evolution, whole genome sequencing and molecular docking studies were carried out to identify putative mutations related to doxycycline resistance in V. cholerae. rpsJ (V57L) was identified to be important in conferring doxycycline resistance as the mutationwas identified to alter the ribosome structure near the doxycycline binding site as revealed by the molecular docking studies. Dxycycline stress also induced co-resistance to colistin antibiotic, a last resort drug to treat extensively drug resistant bacteria. The study illustrates a possible mechanism of doxycycline selected resistance in V. cholerae for the first time and doxycycline selected co-resistance which warrants strict restrictions on the indiscriminate use of antibiotics.

5.
J Bacteriol ; 2020 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-32661076

RESUMO

Vibrio cholerae biofilm biogenesis, which is important for survival, dissemination, and persistence, requires multiple genes in the Vibrio polysaccharides (vps) operons I and II as well as the cluster of ribomatrix (rbm) genes. Transcriptional control of these genes is a complex process that requires several activators/repressors and the ubiquitous signaling molecule, cyclic di-GMP (c-di-GMP). Previously, we demonstrated that VpsR directly activates RNA polymerase containing σ70 (σ70-RNAP) at the vpsL promoter (P vpsL ), which precedes the vps-II operon, in a c-di-GMP-dependent manner by stimulating formation of the transcriptionally active, open complex. Using in vitro transcription, electrophoretic mobility shift assays, and DNase I footprinting, we show here that VpsR also directly activates σ70-RNAP transcription from other promoters within the biofilm formation cluster: P vpsU , at the beginning of the vps-I operon; P rbmA , at the start of the rbm cluster; and P rbmF , which lies upstream of the divergent rbmF/E genes. In this capacity, we find that VpsR is able to behave both as a Class II activator, which functions immediately adjacent/overlapping the core promoter sequence (P vpsL and P vpsU ), and as a Class I activator, which functions farther upstream (P rbmA and P rbmF ). Because these promoters vary in VpsR-DNA binding affinity in the absence and presence of c-di-GMP, we speculate that VpsR's mechanism of activation is dependent on both the concentration of VpsR and the level of c-di-GMP to increase transcription, resulting in finely tuned regulation.Importance Vibrio cholerae, the bacterial pathogen that is responsible for the disease cholera, uses biofilms to aid in survival, dissemination, and persistence. VpsR, which directly senses the second messenger c-di-GMP, is a major regulator of this process. Together with c-di-GMP, VpsR directly activates transcription by RNA polymerase containing σ70 from the vpsL biofilm biogenesis promoter. Using biochemical methods, we demonstrate for the first time that VpsR/c-di-GMP directly activates σ70-RNA polymerase at the first genes of the vps and ribomatrix operons. In this regard, it functions as either a Class I or Class II activator. Our results broaden the mechanism of c-di-GMP-dependent transcription activation and the specific role of VpsR in biofilm formation.

6.
BMC Public Health ; 20(1): 1128, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32680495

RESUMO

BACKGROUND: Water is the most abundant resource on earth, however water scarcity affects more than 40% of people worldwide. Access to safe drinking water is a basic human right and is a United Nations Sustainable Development Goal (SDG) 6. Globally, waterborne diseases such as cholera are responsible for over two million deaths annually. Cholera is a major cause of ill-health in Africa and Uganda. This study aimed to determine the physicochemical characteristics of the surface and spring water in cholera endemic communities of Uganda in order to promote access to safe drinking water. METHODS: A longitudinal study was carried out between February 2015 and January 2016 in cholera prone communities of Uganda. Surface and spring water used for domestic purposes including drinking from 27 sites (lakes, rivers, irrigation canal, springs and ponds) were tested monthly to determine the vital physicochemical parameters, namely pH, temperature, dissolved oxygen, conductivity and turbidity. RESULTS: Overall, 318 water samples were tested. Twenty-six percent (36/135) of the tested samples had mean test results that were outside the World Health Organization (WHO) recommended drinking water range. All sites (100%, 27/27) had mean water turbidity values greater than the WHO drinking water recommended standards and the temperature of above 17 °C. In addition, 27% (3/11) of the lake sites and 2/5 of the ponds had pH and dissolved oxygen respectively outside the WHO recommended range of 6.5-8.5 for pH and less than 5 mg/L for dissolved oxygen. These physicochemical conditions were ideal for survival of Vibrio. cholerae. CONCLUSIONS: This study showed that surface water and springs in the study area were unsafe for drinking and had favourable physicochemical parameters for propagation of waterborne diseases including cholera. Therefore, for Uganda to attain the SDG 6 targets and to eliminate cholera by 2030, more efforts are needed to promote access to safe drinking water. Also, since this study only established the vital water physicochemical parameters, further studies are recommended to determine the other water physicochemical parameters such as the nitrates and copper. Studies are also needed to establish the causal-effect relationship between V. cholerae and the physicochemical parameters.

7.
Einstein (Sao Paulo) ; 18: eRW5774, 2020.
Artigo em Português, Inglês | MEDLINE | ID: mdl-32667418

RESUMO

Coronavirus disease 2019 (COVID-19) is a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has spread globally in pandemic proportions. Accumulative evidence suggests SARS-CoV-2 can be transmitted through the digestive system, the so-called fecal-oral route of transmission, and may induce several gastrointestinal manifestations. MEDLINE® and Embase databases were extensively searched for major clinical manifestations of gastrointestinal involvement in children and adolescents with COVID-19 reported in medical literature, and for nutritional therapy-related data. Findings and recommendations were pragmatically described to facilitate overall pediatric approach. A total of 196 studies addressing gastrointestinal or nutritional aspects associated with the global COVID-19 pandemic were found. Of these, only 17 focused specifically on pediatric patients with regard to aforementioned gastrointestinal or nutritional aspects. Most articles were descriptive and six addressed guidelines, established protocols, or expert opinions. Children and adolescents with gastrointestinal symptoms, such as nausea, vomiting and diarrhea, should be seriously suspected of COVID-19. Gastrointestinal signs and symptoms may occur in 3% to 79% of children, adolescents and adults with COVID-19, and are more common in severe cases. These include diarrhea (2% to 50%), anorexia (40% to 50%), vomiting (4% to 67%), nausea (1% to 30%), abdominal pain (2% to 6%) and gastrointestinal bleeding (4% to 14%). Patients with inflammatory bowel disease or chronic liver disease are not at greater risk of infection by SARS-CoV-2 relative to the general population. Nutritional support plays an important role in treatment of pediatric patients, particularly those with severe or critical forms of the disease. The digestive system may be a potential route of COVID-19 transmission. Further research is needed to determine whether the fecal-oral route may be involved in viral spread. Nutritional therapy is vital to prevent malnutrition and sarcopenia in severe cases.


Assuntos
Infecções por Coronavirus/terapia , Gastroenteropatias/virologia , Apoio Nutricional , Pneumonia Viral/terapia , Adolescente , Betacoronavirus , Criança , Infecções por Coronavirus/complicações , Humanos , Pandemias , Pediatras , Pneumonia Viral/complicações
8.
Med Decis Making ; 40(5): 693-709, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32639859

RESUMO

Background. Published data on a disease do not always correspond directly to the parameters needed to simulate natural history. Several calibration methods have been applied to computer-based disease models to extract needed parameters that make a model's output consistent with available data. Objective. To assess 3 calibration methods and evaluate their performance in a real-world application. Methods. We calibrated a model of cholera natural history in Bangladesh, where a lack of active surveillance biases available data. We built a cohort state-transition cholera natural history model that includes case hospitalization to reflect the passive surveillance data-generating process. We applied 3 calibration techniques: incremental mixture importance sampling, sampling importance resampling, and random search with rejection sampling. We adapted these techniques to the context of wide prior uncertainty and many degrees of freedom. We evaluated the resulting posterior parameter distributions using a range of metrics and compared predicted cholera burden estimates. Results. All 3 calibration techniques produced posterior distributions with a higher likelihood and better fit to calibration targets as compared with prior distributions. Incremental mixture importance sampling resulted in the highest likelihood and largest number of unique parameter sets to better inform joint parameter uncertainty. Compared with naïve uncalibrated parameter sets, calibrated models of cholera in Bangladesh project substantially more cases, many of which are not detected by passive surveillance, and fewer deaths. Limitations. Calibration cannot completely overcome poor data quality, which can leave some parameters less well informed than others. Calibration techniques may perform differently under different circumstances. Conclusions. Incremental mixture importance sampling, when adapted to the context of high uncertainty, performs well. By accounting for biases in data, calibration can improve model projections of disease burden.

9.
JMIR Public Health Surveill ; 6(3): e19354, 2020 07 17.
Artigo em Inglês | MEDLINE | ID: mdl-32640418

RESUMO

BACKGROUND: Coronavirus disease (COVID-19) is a novel viral illness that has rapidly spread worldwide. While the disease primarily presents as a respiratory illness, gastrointestinal symptoms such as diarrhea have been reported in up to one-third of confirmed cases, and patients may have mild symptoms that do not prompt them to seek medical attention. Internet-based infodemiology offers an approach to studying symptoms at a population level, even in individuals who do not seek medical care. OBJECTIVE: This study aimed to determine if a correlation exists between internet searches for gastrointestinal symptoms and the confirmed case count of COVID-19 in the United States. METHODS: The search terms chosen for analysis in this study included common gastrointestinal symptoms such as diarrhea, nausea, vomiting, and abdominal pain. Furthermore, the search terms fever and cough were used as positive controls, and constipation was used as a negative control. Daily query shares for the selected symptoms were obtained from Google Trends between October 1, 2019 and June 15, 2020 for all US states. These shares were divided into two time periods: pre-COVID-19 (prior to March 1) and post-COVID-19 (March 1-June 15). Confirmed COVID-19 case numbers were obtained from the Johns Hopkins University Center for Systems Science and Engineering data repository. Moving averages of the daily query shares (normalized to baseline pre-COVID-19) were then analyzed against the confirmed disease case count and daily new cases to establish a temporal relationship. RESULTS: The relative search query shares of many symptoms, including nausea, vomiting, abdominal pain, and constipation, remained near or below baseline throughout the time period studied; however, there were notable increases in searches for the positive control symptoms of fever and cough as well as for diarrhea. These increases in daily search queries for fever, cough, and diarrhea preceded the rapid rise in number of cases by approximately 10 to 14 days. The search volumes for these terms began declining after mid-March despite the continued rises in cumulative cases and daily new case counts. CONCLUSIONS: Google searches for symptoms may precede the actual rises in cases and hospitalizations during pandemics. During the current COVID-19 pandemic, this study demonstrates that internet search queries for fever, cough, and diarrhea increased prior to the increased confirmed case count by available testing during the early weeks of the pandemic in the United States. While the search volumes eventually decreased significantly as the number of cases continued to rise, internet query search data may still be a useful tool at a population level to identify areas of active disease transmission at the cusp of new outbreaks.


Assuntos
Infecções por Coronavirus/diagnóstico , Gastroenteropatias/epidemiologia , Pandemias , Pneumonia Viral/diagnóstico , Vigilância em Saúde Pública/métodos , Ferramenta de Busca/estatística & dados numéricos , Infecções por Coronavirus/epidemiologia , Humanos , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia
10.
Vaccine ; 38(36): 5803-5813, 2020 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-32684498

RESUMO

Listeria monocytogenes is a facultative intracellular pathogen responsible for the life-threatening disease listeriosis. The pore-forming toxin listeriolysin O (LLO) is a critical virulence factor that plays a major role in the L. monocytogenes intracellular lifecycle and is indispensable for pathogenesis. LLO is also a dominant antigen for T cells involved in sterilizing immunity and it was proposed that LLO acts as a T cell adjuvant. In this work, we generated a novel full-length LLO toxoid (LLOT) in which the cholesterol-recognition motif, a threonine-leucine pair located at the tip of the LLO C-terminal domain, was substituted with two glycine residues. We showed that LLOT lost its ability to bind cholesterol and to form pores. Importantly, LLOT retained binding to the surface of epithelial cells and macrophages, suggesting that it could efficiently be captured by antigen-presenting cells. We then determined if LLOT can be used as an antigen and adjuvant to protect mice from L. monocytogenes infection. Mice were immunized with LLOT alone or together with cholera toxin or Alum as adjuvants. We found that mice immunized with LLOT alone or in combination with the Th2-inducing adjuvant Alum were not protected against L. monocytogenes. On the other hand, mice immunized with LLOT along with the experimental adjuvant cholera toxin, were protected against L. monocytogenes, as evidenced by a significant decrease in bacterial burden in the liver and spleen three days post-infection. This immunization regimen elicited mixed Th1, Th2, and Th17 responses, as well as the generation of LLO-neutralizing antibodies. Further, we identified T cells as being required for immunization-induced reductions in bacterial burden, whereas B cells were dispensable in our model of non-pregnant young mice. Overall, this work establishes that LLOT is a promising vaccine antigen for the induction of protective immunity against L. monocytogenes by subunit vaccines containing Th1-driving adjuvants.

11.
J Neurosci Methods ; 344: 108872, 2020 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-32693000

RESUMO

BACKGROUND: The introduction of viral transneuronal tracers in the toolbox of neural tract-tracing methods has been an important addition in the field of connectomics for deciphering circuit-level architecture of the nervous system. One of the added values of viral compared to conventional retrograde tracers, in particular of rabies virus, is to provide a Golgi staining-like view of the infected neurons, revealing the thin dendritic arborizations and the spines that are major post-synaptic seats of neuronal connections. NEWMETHOD: Here, we comparatively illustrate the characteristics of the labeling obtained in the same model system, the basal ganglia circuitry, by different retrograde viral tracing approaches, using the Bartha strain of pseudorabies virus, the SAD and CVS strains of rabies virus and by the conventional retrograde tracer cholera toxin B. To best contrast the differences in the capacity of these tracers to reveal the dendritic morphology in details, we focused on one population of first-order infected neurons in the striatum, which exhibit high spine density, after tracer injection in the substantia nigra. RESULTS AND CONCLUSION: None of the viruses tested allowed to detect as many neurons as with cholera toxin B, but the SAD and CVS strains of rabies virus had the advantage of enabling detailed Golgi-like visualisation of the dendritic trees, the best numerical detection being offered by the transneuronal rCVS-N2c-P-mCherry while poor labeling was provided by rCVS-N2c-M-GFP. Results also suggest that, besides different viral properties, technical issues about constructs and detection methods contribute to apparently different efficiencies among the viral approaches.

12.
J Hazard Mater ; 402: 123514, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32717546

RESUMO

We selected ruthenium (Ru) to improve the photocatalytic activity of a WO3/ZrO2 composite. The synthesized Ru/WO3/ZrO2 was then compared to a benchmark photocatalyst (S-TiO2) in terms of photocatalytic disinfection of raw surface waters collected from the Nile Delta region, Egypt. The photocatalysts were immobilized on aluminum plates with polysiloxane to test them in repetitive cycles under the irradiation of a metal-halide lamp. Bacterial concentrations in the raw waters ranged from 300 to 5000 CFU/mL (CFU: colony-forming units) and different species and genus were detected including gram-negative (e.g., shigella, salmonella, vibrio parahaemolyticus, and vibrio cholera) and gram-positive bacteria (e.g., enterococcus). Ru/WO3/ZrO2 deactivated over 90 % of the bacterial content within 120 min for most sources, whereas S-TiO2 did not perform as highly. The bacterial count after 240 min of irradiation was below the detection limit for all different water sources. Moreover, the inhabitation of photocatalytic disinfection by natural organic matter (NOM) was investigated. Ru/WO3/ZrO2 was stable for four continuous cycles (960 min in total), suggesting the viability for practical application.

13.
Sci Total Environ ; 745: 140795, 2020 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-32731065

RESUMO

BACKGROUND: Non-cholera Vibrio bacteria are a major cause of foodborne illness in the United States. Raw oysters are commonly implicated in gastroenteritis caused by pathogenic Vibrio parahaemolyticus. In response to outbreaks in 1997-1998, the US Food and Drug Administration developed a nation-wide quantitative microbial risk assessment (QMRA) of V. parahaemolyticus in raw oysters in 2005. The QMRA identified information gaps that new research may address. Incidence of sporadic V. parahaemolyticus illness has recently increased and, as oyster consumption increases and sea temperatures rise, V. parahaemolyticus outbreaks may become more frequent, posing health concerns. Updated and region-specific QMRAs will improve the accuracy and precision of risk of infection estimates. OBJECTIVES: We identify research to support an updated QMRA of V. parahaemolyticus from oysters harvested in Chesapeake Bay and Puget Sound, focusing on observational and experimental research on post-harvest practices (PHPs) published from 2004 to 2019. METHODS: A predefined search strategy was applied to PubMed, Embase, Scopus, Science.gov, NAL Agricola, and Google Scholar. Study eligibility criteria were defined using a population, intervention, comparator, and outcome statement. Reviewers independently coded abstracts for inclusion/exclusion using predefined criteria. Data were extracted and study quality and relevance evaluated based on published guidance for food safety risk assessments. Findings were synthesized using a weight of evidence approach. RESULTS: Of 12,174 articles retrieved, 93 were included for full-text review. Twenty-seven studies were found to be high quality and high relevance, including studies on cold storage, high hydrostatic pressure, depuration, and disinfectant, and other PHPs. High hydrostatic pressure consistently emerged as the most effective PHP in reducing abundance of V. parahaemolyticus. DISCUSSION: Limitations of the knowledge base and review approach involve the type and quantity of data reported. Future research should focus on PHPs for which few or no high quality and high relevance studies exist, such as irradiation and relaying.

14.
J Infect Dis ; 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32610345

RESUMO

BACKGROUND: Susceptibility to Vibrio cholerae infection is impacted by blood group, age, and pre-existing immunity, but these factors only partially explain who becomes infected. A recent study used 16S rRNA amplicon sequencing to quantify the composition of the gut microbiome and identify predictive biomarkers of infection with limited taxonomic resolution. METHODS: To achieve increased resolution of gut microbial factors associated with V. cholerae susceptibility and identify predictors of symptomatic disease, we applied deep shotgun metagenomic sequencing to a cohort of household contacts of patients with cholera. RESULTS: Using machine learning, we resolved species, strains, gene families, and cellular pathways in the microbiome at the time of exposure to V. cholerae to identify markers that predict infection and symptoms. Use of metagenomic features improved the precision and accuracy of prediction relative to 16S sequencing. We also predicted disease severity, although with greater uncertainty than our infection prediction. Species within the genera Prevotella and Bifidobacterium predicted protection from infection, and genes involved in iron metabolism also correlated with protection. CONCLUSION: Our results highlight the power of metagenomics to predict disease outcomes and suggest specific species and genes for experimental testing to investigate mechanisms of microbiome-related protection from cholera.

15.
FEMS Microbiol Lett ; 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32672823

RESUMO

Vibrio cholerae (V. cholerae) is an etiological cause of cholera implicated in several pandemics. Antibacterial activity of plant extracts has been established. However, these extracts exhibit activity at a concentration which may alter organoleptic attributes of water and food, hence limiting their application. In this light, there is need to device ways of reducing plant extracts effective levels in order to widen their application. Thus, this study was conducted to improve activities of plant ethanolic extracts through combination with other generally recognized as safe (GRAS) antimicrobials. Combination of plant extracts with sodium acetate (NaOAc) 0.4%, at pH 7.0 reduced Minimum Inhibitory Concentrations (MICs) of clove, lemon eucalyptus, rosemary and sage from 0.2% to 0.025%. At pH 6.4, combinations were more effective reducing MICs of clove, lemon eucalyptus, rosemary and sage from 0.2% to 0.0125% with NaOAc at 0.2%. At pH 7.0, the combination resulted in additive effect. Nevertheless, at pH 6.4, synergic effect was established. No interactive effect was observed with combinations involving glycine. Combination of plant extracts with NaOAc at mildly acidic pH creates a hurdle effect which may have potential application to control the growth of V. cholerae.

16.
PLoS One ; 15(7): e0235440, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32614915

RESUMO

BACKGROUND: Cholera remains a significant public health problem in more than one-third of the countries of the world. Cholera outbreak has become more common in Addis Ababa particularly in the rainy seasons; however, there is a paucity of data on risk factors associated with cholera outbreaks rendering interventions difficult. We investigated the outbreak to identify its etiology, source, risk factors and in order to control the outbreak. METHODS: We compared cases with health center-based unmatched controls (1:2). Cases were patients aged ≥5 years with acute watery diarrhea, with or without vomiting while controls were persons aged ≥5 years without history of acute watery diarrhea. We interviewed our study participants using structured questionnaire to collect demographic and cholera risk factors data. We described the outbreak over time, and then tested our hypotheses using unconditional logistic regression. RESULTS: The outbreak began on 7 September, 2017 reaching its peak on 23 September, 2017 and ended on 01 October, 2017. We identified a total of 25 cases (Median age: 38 years; IQR: 20 years) and recruited 50 controls (Median age: 35 years; IQR: 29 years). All case-patients had acute watery diarrhea and dehydration requiring intravenous fluids. All cases were admitted to cholera treatment center but there were no deaths. Stool and water samples yielded isolates of Vibrio cholerae O1 of serological subtype Ogawa. Consumption of contaminated holy water (AOR: 20.5, 95%CI: 3.50, 119.61) and raw vegetables (AOR: 15.3, 95%CI: 3, 81.51) were independent risk factors whereas washing hands with soap after visiting latrine (AOR: 0.04, 95%CI: 0.01, 0.25) was independent protective factor. CONCLUSION: Our findings demonstrated cholera foodborne transmission via consumption of raw vegetables, and its waterborne transmission via consumption of contaminated holy water. Washing hands with soap after visiting latrine was protective. We recommended cooking of vegetables and promoting hand washing.

17.
Mol Cell ; 2020 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-32681820

RESUMO

Sister-chromatid cohesion describes the orderly association of newly replicated DNA molecules behind replication forks. It plays an essential role in the maintenance and faithful transmission of genetic information. Cohesion is created by DNA topological links and proteinaceous bridges, whose formation and deposition could be potentially affected by many processes. Current knowledge on cohesion has been mainly gained by fluorescence microscopy observation. However, the resolution limit of microscopy and the restricted number of genomic positions that can be simultaneously visualized considerably hampered progress. Here, we present a high-throughput methodology to monitor sister-chromatid contacts (Hi-SC2). Using the multi-chromosomal Vibrio cholerae bacterium as a model, we show that Hi-SC2 permits to monitor local variations in sister-chromatid cohesion at a high resolution over a whole genome.

18.
Lancet Glob Health ; 8(8): e1081-e1089, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710864

RESUMO

BACKGROUND: Cholera was introduced into Haiti in 2010. Since then, more than 820 000 cases and nearly 10 000 deaths have been reported. Oral cholera vaccine (OCV) is safe and effective, but has not been seen as a primary tool for cholera elimination due to a limited period of protection and constrained supplies. Regionally, epidemic cholera is contained to the island of Hispaniola, and the lowest numbers of cases since the epidemic began were reported in 2019. Hence, Haiti may represent a unique opportunity to eliminate cholera with OCV. METHODS: In this modelling study, we assessed the probability of elimination, time to elimination, and percentage of cases averted with OCV campaign scenarios in Haiti through simulations from four modelling teams. For a 10-year period from January 19, 2019, to Jan 13, 2029, we compared a no vaccination scenario with five OCV campaign scenarios that differed in geographical scope, coverage, and rollout duration. Teams used weekly department-level reports of suspected cholera cases from the Haiti Ministry of Public Health and Population to calibrate the models and used common vaccine-related assumptions, but other model features were determined independently. FINDINGS: Among campaigns with the same vaccination coverage (70% fully vaccinated), the median probability of elimination after 5 years was 0-18% for no vaccination, 0-33% for 2-year campaigns focused in the two departments with the highest historical incidence, 0-72% for three-department campaigns, and 35-100% for nationwide campaigns. Two-department campaigns averted a median of 12-58% of infections, three-department campaigns averted 29-80% of infections, and national campaigns averted 58-95% of infections. Extending the national campaign to a 5-year rollout (compared to a 2-year rollout), reduced the probability of elimination to 0-95% and the proportion of cases averted to 37-86%. INTERPRETATION: Models suggest that the probability of achieving zero transmission of Vibrio cholerae in Haiti with current methods of control is low, and that bolder action is needed to promote elimination of cholera from the region. Large-scale cholera vaccination campaigns in Haiti would offer the opportunity to synchronise nationwide immunity, providing near-term population protection while improvements to water and sanitation promote long-term cholera elimination. FUNDING: Bill & Melinda Gates Foundation, Global Good Fund, Institute for Disease Modeling, Swiss National Science Foundation, and US National Institutes of Health.

19.
Lancet Glob Health ; 8(8): e984, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32710871
20.
Eur J Pharmacol ; : 173393, 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32712094

RESUMO

Secretory diarrhea is one of the most common types of diarrhea with high morbidity and mortality. Previous studies showed that inhibition of cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels alleviated fluid loss in secretory diarrheas. This study aimed to identify novel CFTR inhibitors from fungal metabolites and explore its underlying mechanisms and potential utility in secretory diarrheas. Electrophysiological analyses in human intestinal epithelial (T84) cells were performed to investigate the effect and mechanism of fungal metabolites on CFTR-mediated Cl- secretion. Anti-diarrheal efficacy and the effect of compound on fluid absorption were investigated in mouse closed-loop models. We found that the screening identified arthropsolide A, a fungal metabolite from an endophytic fungus Roussoella sp. PSU-H51, as an inhibitor of CFTR-mediated Cl- secretion in T84 cells (IC50 ∼0.8 µM). Arthropsolide A inhibited both CFTR and cAMP-activated basolateral K+ channels. Arthropsolide A had no effect on Na+-K+ ATPase activity. Interestingly, the inhibitory effect of arthropsolide A on CFTR was attenuated by cell depolarization and AMPK inhibition independent of multi-drug resistance protein 4, phosphodiesterases, and protein phosphatases. Importantly, arthropsolide A suppressed cholera toxin (CT)-induced Cl- secretion in T84 cells and CT-induced intestinal fluid secretion in mice by ∼75% without affecting intestinal fluid absorption. Taken together, arthropsolide A represents a novel class of fungal metabolites that acts as a potent CFTR inhibitor. Further development of this class of compounds may provide a therapy for secretory diarrheas.

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