Search

This review surveys some of the areas in which nutrients have been shown to have an impact on specific immune functions, the use of molecular and genetic tools to study molecular responses to dietary factors,and the metabolic consequences of food. It also explores the relationships between nutrient molecules, genetic polymorphisms, and the biological system as a whole, while providing a short introduction to nutrition immunology, nutrient-gene interactions and the novel technologies employed in nutrigenomics and nutrigenetics research. [ABSTRACT FROM AUTHOR]

This paper briefly reviews the current situation of Latin American medical schools and the search to improve the quality and professionalism of medical education through the region. Institutional evaluation and accreditation programs based on nationally ongoing developing standards have been accepted, now optimized and complemented by the framework of the Global & International Standards of Medical Education working jointly with the WFME. More recently, the process has evolved to look into the quality of the outcomes of the medicals as seen by examinations implemented at the end of medical studies and the initiation of medical practice. In addition, there is vision for the application of new programs such as the global minimum essential requirements advanced by the Institute for International Medical Education (IIME). The PanAmerican Federation of Associations of Medical Schools (PAFAMS), an academic, non-governmental organization, is fostering the exchange of ideas and experiences among members, associations and affiliated medical schools geared to focus on the quality and professionalism of the graduates of medical schools in Latin America. These actions also aim to consolidate databases of information on medical education and innovative endeavors in continuing professional education and development through e-learning projects in the region. [ABSTRACT FROM AUTHOR]

Sesame bran (SB) is a by-product of the food industry. The objective of the present study was to characterize SB for its content of bioactive compounds (individual phenolic and lignan compounds, fiber, minerals, and calcium bioaccessibility), antioxidant capacity and proximate analysis. SB presented high levels of insoluble fiber, free calcium (~1400 mg/kg), protein (~90 g/kg), and free ferulic acid (~1950 mg/kg). Likewise, sesamol was identified as one of the major lignans (~550 mg/kg) in SB, which has been regarded as a promising antimutagenic antioxidant compound. Results indicate that SB can be considered an adequate source of bioactive compounds and used in the formulation of low calorie and high fiber foods. [ABSTRACT FROM AUTHOR]

Currently, no formal mechanisms or systematic approaches exist to inform developers of new vaccines of the evidence anticipated to facilitate global policy recommendations, before a vaccine candidate approaches regulatory approval at the end of pre-licensure efficacy studies. Consequently, significant delays may result in vaccine introduction and uptake, while post-licensure data are generated to support a definitive policy decision. To address the uncertainties of the evidence-to-recommendation data needs and to mitigate the risk of delays between vaccine recommendation and use, WHO is evaluating the need for and value of a new strategic alignment tool: Evidence Considerations for Vaccine Policy (ECVP). EVCPs aim to fill a critical current gap by providing early (pre-phase 3 study design) information on the anticipated clinical trial and observational data or evidence that could support WHO and/or policy decision making for new vaccines in priority disease areas. The intent of ECVPs is to inform vaccine developers, funders, and other key stakeholders, facilitating stakeholder alignment in their strategic planning for late stage vaccine development. While ECVPs are envisaged as a tool to support dialogue on evidence needs between regulators and policy makers at the national, regional and global level, development of an ECVP will not preclude or supersede the independent WHO's Strategic Advisory Group of Experts on Immunization (SAGE) evidence to recommendation (EtR) process that is required for all vaccines seeking WHO policy recommendation. Tuberculosis (TB) vaccine candidates intended for use in the adolescent and adult target populations comprise a portfolio of priority vaccines in late-stage clinical development. As such, TB vaccines intended for use in this target population provide a 'test case' to further develop the ECVP concept, and develop the first WHO ECVP considerations guidance. [ABSTRACT FROM AUTHOR]

The article discusses impact of Covid-19 on infants and adolescent vaccine supplies. Topics including immunization coverage of infants dropped in 2020 as a result of the pandemic; the emergency production of Covid-19 vaccine has is affecting the global supply of key infant and adolescent vaccines; and manufacturers report that they are facing difficulties in timely access to consumable components such as bioprocessing bags, filters, tubing, and laboratory supplies.

The purpose of this commentary is to provide an overview of the growing interest in global health education at ICDDR,B and to review examples of how this has grown from public-health research and education to include clinical education (medical and nursing) as well. This parallels the growth of the institution, with an increased focus on educational linkages within and beyond Bangladesh and the rise in interest in global health at western medical schools. Specific collaborations, their setup and structure are described. This is presented as a model for other centres of excellence in developing countries to engage their partners in the South and North on matters of education and research for mutual cooperation and benefit. [ABSTRACT FROM AUTHOR]

Nicotine replacement therapies (NRT) are powerful tools for the successful treatment of nicotine addiction and tobacco use. The medicines are clinically effective, supported by the Framework Convention on Tobacco Control, and are now World Health Organization-approved essential medicines. Enabling global access to NRT remains a challenge given ongoing confusion and misperceptions about their efficacy, cost-effectiveness, and availability with respect to other tobacco control and public health opportunities. In this commentary, we review existing evidence and guidelines to make the case for global access to NRT highlighting the smoker's right to access treatment to sensibly address nicotine addiction. [ABSTRACT FROM AUTHOR]

Oedematous malnutrition, represented by its most severe form kwashiorkor, is rampant in many parts of the world and is associated with a high case fatality rate. Despite being first described more than a century ago, the pathogenesis of kwashiorkor is still not clear. The traditional thinking is that it results from a deficiency of dietary protein and is usually associated with an infection. This has now been challenged by the finding that there is no difference in diets of children developing marasmus or kwashiorkor. Nutritional oedema is associated with an increased secretion of anti-diuretic substance (probably anti-diuretic hormone) which prevents the normal excretory response to water administration. Experimental studies have shown that feeding low-protein, low-calorie diets results in delayed and incomplete response to a water load, and that the livers of the animals show a reduced capacity for inactivating anti-diuretic hormone. There is now evidence that links generation of free radicals and depletion of anti-oxidants with the development of oedema in kwashiorkor. [ABSTRACT FROM AUTHOR]

Diarrhoeal disease attributable to enterotoxigenic Escherichia coli (ETEC) causes substantial morbidity and mortality predominantly in paediatric populations in low- and middle-income countries. In addition to acute illness, there is an increasing appreciation of the long-term consequences of enteric infections, including ETEC, on childhood growth and development. Provision of potable water and sanitation and appropriate clinical care for acute illness are critical to reduce the ETEC burden. However, these interventions are not always practical and may not achieve equitable and sustainable coverage. Vaccination may be the most cost-effective and equitable means of primary prevention; however, additional data are needed to accelerate the investment and guide the decision-making process for ETEC vaccines. First, to understand and quantify the ETEC disease burden, additional data are needed on the association between ETEC infection and physical and cognitive stunting as well as delayed educational attainment. Furthermore, the role of inappropriate or inadequate antibiotic treatment of ETEC-attributable diarrhoea may contribute to the development of antimicrobial resistance (AMR) and needs further elucidation. An ETEC vaccine that mitigates acute diarrhoeal illness and minimizes the longer-term disease manifestations could have significant public health impact and be a cost-effective countermeasure. Herein we review the ETEC vaccine pipeline, led by candidates compatible with the general parameters of the Preferred Product Characteristics (PPC) recently developed by the World Health Organization. Additionally, we have developed an ETEC Vaccine Development Strategy to provide a framework to underpin priority activities for researchers, funders and vaccine manufacturers, with the goal of addressing globally unmet data needs in the areas of research, product development, and policy, as well as commercialization and delivery. The strategy also aims to guide prioritization and co-ordination of the priority activities needed to minimize the timeline to licensure and use of ETEC vaccines, especially in in low- and middle-income countries, where they are most urgently needed. [ABSTRACT FROM AUTHOR]

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely – and at times uniquely – affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group – a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy – in consultation with a variety of external experts and stakeholders. [ABSTRACT FROM AUTHOR]

Although enteroaggregative E. coli (EAEC) has been implicated as a common cause of diarrhea in multiple settings, neither its essential genomic nature nor its role as an enteric pathogen are fully understood. The current definition of this pathotype requires demonstration of cellular adherence; a working molecular definition encompasses E. coli which do not harbor the heat-stable or heat-labile toxins of enterotoxigenic E. coli (ETEC) and harbor the genes aaiC, aggR, and/or aatA. In an effort to improve the definition of this pathotype, we report the most definitive characterization of the pan-genome of EAEC to date, applying comparative genomics and functional characterization on a collection of 97 EAEC strains isolated in the course of a multicenter case-control diarrhea study (Global Enteric Multi-Center Study, GEMS). Genomic analysis revealed that the EAEC strains mapped to all phylogenomic groups of E. coli. Circa 70% of strains harbored one of the five described AAF variants; there were no additional AAF variants identified, and strains that lacked an identifiable AAF generally did not have an otherwise complete AggR regulon. An exception was strains that harbored an ETEC colonization factor (CF) CS22, like AAF a member of the chaperone-usher family of adhesins, but not phylogenetically related to the AAF family. Of all genes scored, sepA yielded the strongest association with diarrhea (P = 0.002) followed by the increased serum survival gene, iss (p = 0.026), and the outer membrane protease gene ompT (p = 0.046). Notably, the EAEC genomes harbored several genes characteristically associated with other E. coli pathotypes. Our data suggest that a molecular definition of EAEC could comprise E. coli strains harboring AggR and a complete AAF(I-V) or CS22 gene cluster. Further, it is possible that strains meeting this definition could be both enteric bacteria and urinary/systemic pathogens. Author summary: Enteroaggregative E. coli (EAEC) has been implicated as a common cause of diarrhea in multiple settings and associated with linear growth faltering among children in low-income countries. Unlike other E. coli pathotypes EAEC stands alone in employing a phenotypic, rather than genotypic, definition. Therefore, the lack of a formally recognized genetic definition for EAEC serves to complicate its epidemiologic investigation. In an effort to improve the definition of this pathotype, we generated the most definitive characterization of the pan-genome of EAEC by performing whole genome sequencing on a collection of strains isolated from different geographic settings. We identified a genetic signature of EAEC which could comprise of E. coli strains harboring the EAEC transcriptional activator and its adhesin dependent factors. Further, we found that EAEC strains harbor additional putative virulence genes previously reported in extraintestinal pathogenic E. coli (ExPEC) and, therefore, strains meeting the re-definition could be both enteric bacteria and urinary/systemic pathogens. [ABSTRACT FROM AUTHOR]

• GVAP provided a comprehensive and coherent global framework for immunization. • Much progress was achieved under GVAP, although most GVAP goals will not be met. • GVAP was perceived as top-down, with too little consideration of country context. • GVAP was only partially implemented, and it had limited levers to influence country actions. • Many targets were seen as unrealistic, particularly in the absence of additional funding. • Lessons learned from GVAP can inform the Immunization Agenda 2030. The Global Vaccine Action Plan 2011–2020 (GVAP) was developed to realize the ambitions of the Decade of Vaccines – that all individuals and communities enjoy lives free from vaccine-preventable diseases. It included a comprehensive monitoring and evaluation/accountability framework to assess progress towards global targets with recommendations for corrective actions. While many of the GVAP targets are very unlikely to be met by the end of 2020, substantial progress has nevertheless been made, establishing a strong foundation for a successor global immunization strategy, the Immunization Agenda 2030 (IA2030). The Strategic Advisory Group of Experts on immunization has made a series of recommendations to ensure that the lessons learned from GVAP inform the development and implementation of IA2030. [ABSTRACT FROM AUTHOR]

Helicobacter pylori is a Gram-negative bacterium that causes chronic atrophic gastritis and peptic ulcers and it has been associated with the development of gastric adenocarcinoma and mucosa-associated lymphoid tissue (MALT). One of the more remarkable characteristics of H. pylori is its ability to survive in the hostile environment of the stomach. H. pylori regulates the expression of specific sets of genes allowing it to survive high acidity levels and nutrient scarcity. In the present study, we determined the expression of virulence associated protein D (VapD) of H. pylori inside adenocarcinoma gastric (AGS) cells and in gastric biopsies. Using qRT-PCR, VapD expression was quantified in intracellular H. pylori-AGS cell cultures at different time points and in gastric mucosa biopsies from patients suffering from chronic atrophic gastritis, follicular gastritis, peptic ulcers, gastritis precancerous intestinal metaplasia and adenocarcinoma. Our results show that vapD of H. pylori presented high transcription levels inside AGS cells, which increased up to two-fold above basal values across all assays over time. Inside AGS cells, H. pylori acquired a coccoid form that is metabolically active in expressing VapD as a protection mechanism, thereby maintaining its permanence in a viable non-cultivable state. VapD of H. pylori was expressed in all gastric biopsies, however, higher expression levels (p = 0.029) were observed in gastric antrum biopsies from patients with follicular gastritis. The highest VapD expression levels were found in both antrum and corpus gastric biopsies from older patients (>57 years old). We observed that VapD in H. pylori is a protein that is only produced in response to interactions with eukaryotic cells. Our results suggest that VapD contributes to the persistence of H. pylori inside the gastric epithelial cells, protecting the microorganism from the intracellular environment, reducing its growth rate, enabling long-term infection and treatment resistance. [ABSTRACT FROM AUTHOR]

The Strategic Advisory Group of Experts (SAGE) on Immunization advises WHO on global policies for vaccines. In April, 2016, SAGE issued recommendations on the use of the first licenced dengue vaccine, CYD-TDV. In November, 2017, a retrospective analysis of clinical trial data, stratifying participants according to their dengue serostatus before the first vaccine dose, showed that although in high seroprevalence settings the vaccine provides overall population benefit, there was an excess risk of severe dengue in seronegative vaccinees. SAGE's working group on dengue vaccines met to discuss the new data and mainly considered two vaccination strategies: vaccination of populations with dengue seroprevalence rates above 80% or screening of individuals before vaccination, and vaccinating only seropositive individuals. We report on the deliberations that informed the recommendation of the pre-vaccination screening strategy, in April, 2018. Important research and implementation questions remain for CYD-TDV, including the development of a highly sensitive and specific rapid diagnostic test to determine serostatus, simplified immunisation schedules, and assessment of the need for booster doses. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is one of the most common, yet manageable, risks for life-threatening events like stroke and myocardial infarction in the world. Bangladesh adults experience high rates of hypertension, with one in three women and one in five men meeting the condition's clinical definition. In the midst of an epidemiological transition, Bangladesh has the opportunity to slow the growth of hypertension prevalence through increased coverage of anti-hypertensive drugs for high-risk patients.Methods: Using economic cost-benefit analysis and a societal perspective, we model the return on investment of providing blood-pressure lowering drugs to 60% of hypertensive adults by 2021 and 2030. We stratify the projections on both gender and income quintile.Results: If the government of Bangladesh is proactive about hypertension management now, they could see a 12.7: 1 annual return on investment by 2021 and an 8.6: 1 annual return on investment by 2030. The return on investment is higher for providing medication for women than for men in both time horizons.Conclusion: Bangladesh has a unique opportunity to address hypertension now in order to prevent thousands of premature deaths and to accrue substantial net economic benefits within 6years. [ABSTRACT FROM AUTHOR]

Background: Information on the impact of hygiene interventions on severe outcomes is limited. As a pre-specified secondary outcome of a cluster-randomized controlled trial among >400 000 low-income residents in Dhaka, Bangladesh, we examined the impact of cholera vaccination plus a behaviour change intervention on diarrhoea-associated hospitalization.Methods: Ninety neighbourhood clusters were randomly allocated into three areas: cholera-vaccine-only; vaccine-plus-behaviour-change (promotion of hand-washing with soap plus drinking water chlorination); and control. Study follow-up continued for 2 years after intervention began. We calculated cluster-adjusted diarrhoea-associated hospitalization rates using data we collected from nearby hospitals, and 6-monthly census data of all trial households.Results: A total of 429 995 people contributed 500 700 person-years of data (average follow-up 1.13 years). Vaccine coverage was 58% at the start of analysis but continued to drop due to population migration. In the vaccine-plus-behaviour-change area, water plus soap was present at 45% of hand-washing stations; 4% of households had detectable chlorine in stored drinking water. Hospitalization rates were similar across the study areas [events/1000 person-years, 95% confidence interval (CI), cholera-vaccine-only: 9.4 (95% CI: 8.3-10.6); vaccine-plus-behaviour-change: 9.6 (95% CI: 8.3-11.1); control: 9.7 (95% CI: 8.3-11.6)]. Cholera cases accounted for 7% of total number of diarrhoea-associated hospitalizations.Conclusions: Neither cholera vaccination alone nor cholera vaccination combined with behaviour-change intervention efforts measurably reduced diarrhoea-associated hospitalization in this highly mobile population, during a time when cholera accounted for a small fraction of diarrhoea episodes. Affordable community-level interventions that prevent infection from multiple pathogens by reliably separating faeces from the environment, food and water, with minimal behavioural demands on impoverished communities, remain an important area for research. [ABSTRACT FROM AUTHOR]

Latin America has experienced two of the largest cholera epidemics in modern history; one in 1991 and the other in 2010. However, confusion still surrounds the relationships between globally circulating pandemic Vibrio cholerae clones and local bacterial populations. We used whole-genome sequencing to characterize cholera across the Americas over a 40-year time span. We found that both epidemics were the result of intercontinental introductions of seventh pandemic El Tor V. cholerae and that at least seven lineages local to the Americas are associated with disease that differs epidemiologically from epidemic cholera. Our results consolidate historical accounts of pandemic cholera with data to show the importance of local lineages, presenting an integrated view of cholera that is important to the design of future disease control strategies. [ABSTRACT FROM AUTHOR]

Background: Rotavirus vaccines are now globally recommended by the World Health Organization (WHO), but in early 2009 WHO's Strategic Advisory Group of Experts on Immunization reviewed available data and concluded that there was no evidence for the efficacy or effectiveness of a two-dose schedule of the human rotavirus vaccine (HRV; Rotarix) given early at 6 and 10 wk of age. Additionally, the effectiveness of programmatic rotavirus vaccination, including possible indirect effects, has not been assessed in low-resource populations in Asia.Methods and Findings: In Bangladesh, we cluster-randomized (1:1) 142 villages of the Matlab Health and Demographic Surveillance System to include two doses of HRV with the standard infant vaccines at 6 and 10 wk of age or to provide standard infant vaccines without HRV. The study was initiated November 1, 2008, and surveillance was conducted concurrently at Matlab Diarrhoea Hospital and two community treatment centers to identify children less than 2 y of age presenting with acute rotavirus diarrhea (ARD) through March 31, 2011. Laboratory confirmation was made by enzyme immunoassay detection of rotavirus antigen in stool specimens. Overall effectiveness of the HRV vaccination program (primary objective) was measured by comparing the incidence rate of ARD among all children age-eligible for vaccination in villages where HRV was introduced to that among such children in villages where HRV was not introduced. Total effectiveness among vaccinees and indirect effectiveness were also evaluated. In all, 6,527 infants were age-eligible for vaccination in 71 HRV villages, and 5,791 in 71 non-HRV villages. In HRV villages, 4,808 (73.7%) infants received at least one dose of HRV. The incidence rate of ARD was 4.10 cases per 100 person-years in non-HRV villages compared to 2.8 per 100 person-years in HRV villages, indicating an overall effectiveness of 29.0% (95% CI, 11.3% to 43.1%). The total effectiveness of HRV against ARD among vaccinees was 41.4% (95% CI, 23.2% to 55.2%). The point estimate for total effectiveness was higher against ARD during the first year of life than during the second (45.2% versus 28.9%), but estimates for the second year of life lacked precision and did not reach statistical significance. Indirect effects were not detected. To check for bias in presentation to treatment facilities, we evaluated the effectiveness of HRV against acute diarrhea associated with enterotoxigenic Escherichia coli; it was 4.0% (95% CI, -46.5% to 37.1%), indicating that bias likely was not introduced. Thirteen serious adverse events were identified among recipients of HRV, but none were considered related to receipt of study vaccine. The main limitation of this study is that it was an open-label study with an observed-only control group (no placebo).Conclusions: The two-dose HRV rotavirus vaccination program significantly reduced medically attended ARD in this low-resource population in Asia. Protection among vaccinees was similar to that in other low-resource settings. In low-resource populations with high rotavirus incidence, large-scale vaccination across a wide population may be required to obtain the full benefit of rotavirus vaccination, including indirect effects.Trial Registration: ClinicalTrials.gov NCT00737503. [ABSTRACT FROM AUTHOR]

Background Pregnant women are vulnerable to complications of cholera. Killed oral cholera vaccines (OCV) are not recommended for pregnant women though there is no evidence of harmful effects during pregnancy. We evaluated the effect of a killed OCV, Shanchol™, on pregnancy outcomes during an effectiveness trial of the vaccine in urban Bangladesh. Methodology Individuals ⩾1 year were invited to participate in the trial, conducted in 2011 in Dhaka, Bangladesh. Pregnancy by history was an exclusion criterion and all women of reproductive age (15–49 years) were verbally questioned about pregnancy at enrollment and prior to vaccination. Out of 48,414 women of reproductive age 286 women received the OCV unknowingly while pregnant. Out of these, we could recruit 69 women defined as exposed to OCV. Accordingly, we selected 69 pregnant women randomly from those who did not take the OCV (non-exposed to OCV). We evaluated adverse pregnancy outcome (spontaneous miscarriages, still births, or congenital malformations) between those who were exposed to OCV and those who were not exposed to OCV. Results About 16% of pregnant women exposed to OCV had pregnancy loss, as compared to 12% of unvaccinated pregnant women (P = 0.38). One congenital anomaly was observed and occurred in women non-exposed to OCV group. Models that adjusted for baseline characteristics that were unbalanced between the exposed and non-exposed groups, revealed a no elevation of risk of adverse pregnancy outcomes in vaccinees versus non-vaccinees (Adj. OR (95% CI): 0.45 (0.11–1.88). Conclusions No excess of adverse fetal outcomes associated with receipt of OCV was observed in this study. Trial registration: Clinical Trials.gov number NCT01339845 . [ABSTRACT FROM AUTHOR]

Escherichia coli O157:H7 is a subtype of Shiga toxin-producing E. coli that is associated with haemorrhagic colitis and haemolytic uremic syndrome (HUS). Studies of populations in endemic areas have reported that the presence of specific antibodies against the O157 lipopolysaccharide (LPS) is associated with a lower incidence of diarrhoea and HUS. Phage display and IgG anti-O157 LPS antibodies were used in the present study to select peptide mimotopes of O157 LPS expressed in protein III of the M13 phage. Synthetic peptides (SP) were designed using the derived amino acid sequences obtained from DNA nucleotides of 63 selected phagotopes. The LxP/YP/SxL motif was identified in five of the phagotope amino acid sequences. Antibody responses against the phagotopes and their corresponding SPs were evaluated. SP12, one of the designed SP, induced the production of antibodies against the homologous peptide (1:800) and O157 LPS (1:200). The specificity of anti-SP12 antiserum was confirmed by analyzing its response to SP3, an SP with a different amino acid sequence than that of SP12, as well as against an E. coli LPS different from O157. Competitive studies with SP12 and O157 LPS showed a significant decrease in anti-SP12 and anti-LPS O157 antiserum responses against SP12 and O157 LPS, respectively. Eighteen (82%) of the 22 human serum samples with positive reactivity against E. coli O157 LPS reacted with SP12 SP (cutoff >0.4). These results support the idea that SP12 is an immunogenic mimotope of O157 LPS. [ABSTRACT FROM AUTHOR]

Introduction: Any microorganism is capable of causing urinary tract infections (UTI). However, Uropathogenic Escherichia coli (UPEC) is responsible for the majority of UTI. A variety of virulence genes have been identified in UPEC. Diverse epidemiological studies support that specific subsets of genes are characteristic of each E. coli uropathogenic subtype involved in the development of cystitis, pyelonephritis, and urosepsis. Methodology: Twenty-three E. coli strains isolated from women with cystitis, 25 from men with prostatitis were characterized according to serotype, virulence genes, PFGE profile and susceptibility antimicrobials. Results: E. coli O25:H4-ST131 was more frequently isolated from cystitis than prostatitis. The majority of cystitis strains presented almost all the virulence genes, contrary to 60% of prostatitis strains. The strains characterized by serology, PFGE and MLST and virulence profile showed that cystitis strains shared a lineage with their own genomic fingerprint, indicating that these strains derived from a common ancestor. The prostatitis strains showed serotypes diverse and much higher degree of genetic diversity, indicating that they are an unrelated group. More than 50% of isolates were resistant to at least 7 of the antimicrobials tested. Antibiotic-tolerant cells were observed, presenting with more frequency in response chloramphenicol, tetracycline, trimethoprim-sulfometoxazole and dicloxicillin. Conclusions: Persister cells can be detected from the beginning of the infection. The importance of these persister cells that exhibit multidrug tolerance is that a single surviving bacterium can initiate again an infection making it clinical relevant in the chronic urinary tract infection. [ABSTRACT FROM AUTHOR]

Background The oral cholera vaccine (OCV), Shanchol™ has shown protective efficacy lasting up to 5 years, however, requirement for a cold chain limits its use in resource poor settings. The study was conducted to determine the safety and immunogenicity of Shanchol in adult participants in Bangladesh when stored at elevated temperatures. Methods The study was conducted in Mirpur, Dhaka. Four groups of healthy adult participants received two doses of Shanchol™, kept under standard storage temperature (Group A; 2–8 °C) or at elevated temperatures (Group B, 25 °C; Group C, 37 °C; Group D, 42 °C) for 14 days, respectively. Vaccine specific antibody responses were determined. Findings 145 participants were assigned to each group. Adverse events were mild not differing among groups. Vaccine stored at elevated temperatures remained stable with cumulative LPS content within admissible limits. Vibriocidal antibody responses were observed in all groups after each dose of vaccine at day 7 and 21 compared to pre-immune levels ( P < 0.001). Four-fold increases to Vibrio cholerae O1 Ogawa were observed at day 7 and/or day 21 after vaccination in the standard temperature and the three elevated temperature groups, with responder rates of; 76% (95% CI LB; 70%), 80% (95% CI LB; 74%), 69% (95% CI LB; 63%), and 74% (95% CI LB; 68%) in Groups A–D, respectively ( P = 0.240). Responses were also seen in all groups to V. cholerae O1 Inaba and V. cholerae O139 and in LPS specific IgA response to V. cholerae O1 antigens. Interpretation This is the first report to show that the OCV is stable at elevated temperatures, and the safety and immunogenicity profiles are not altered. This information will help formulate global policies for use of the vaccine at higher temperatures, resulting in easier distribution and vaccination costs and decrease logistical challenges to vaccine delivery. Funding Bill & Melinda Gates Foundation. Trial registration Clinical Trials.gov number NCT01762930 . [ABSTRACT FROM AUTHOR]

Cholera is a major global public health problem that causes both epidemic and endemic disease. The World Health Organization recommends oral cholera vaccines as a public health tool in addition to traditional prevention practices and treatments in both epidemic and endemic settings. In many developing countries like Bangladesh, the major issue concerns the affordability of this vaccine. In February 2011, a feasibility study entitled, “Introduction of Cholera Vaccine in Bangladesh (ICVB)”, was conducted for a vaccination campaign using inactivated whole-cell cholera vaccine (Shanchol) in a high risk area of Mirpur, Dhaka. Empirical data obtained from this trial was used to determine the vaccination cost for a fully immunized person from the societal perspective. A total of 123,661 people were fully vaccinated receiving two doses of the vaccine, while 18,178 people received one dose of the same vaccine. The total cost for vaccine delivery was US$ 492,238 giving a total vaccination cost per fully-vaccinated individual of US$ 3.98. The purchase cost of the vaccine accounted for 58% of the overall cost of vaccination. Attempts to reduce the per-dose cost of the vaccine are likely to have a large impact on the cost of similar vaccination campaigns in the future. [ABSTRACT FROM AUTHOR]

The article discusses a study which examines the natural history of Shigella flexneri, a common cause of bacterial dysentery, by integrating whole genome sequencing and geographical and temporal data.

Diarrhea remains one of the major causes of death in Bangladesh. We studied diarrheal disease risk and healthcare seeking behavior among populations at high risk for diarrhea in Dhaka, Bangladesh. Data were obtained from a cross-sectional survey conducted during April and September 2010. The prevalence of diarrhea was calculated by age-group and sex. A generalized estimating equation with logit link function was used to predict diarrheal disease risk and seeking care from a professional healthcare provider. Of 316,766 individuals, 10% were young children (<5 years). The prevalence of diarrhea was 16 per 1000 persons among all ages; young children accounted for 44 per 1000 persons. Prevalence of diarrhea was significantly higher (p=.003) among younger males (<15 years) compared to that among younger females. In contrast, prevalence of diarrhea was significantly higher (p<.0001) among older females (≥15 years) compared to that among older males. An increased risk for diarrhea was observed in young children, males, and those staying in rented houses, lower family members in the house, using non-sanitary toilets, living in the area for short times, living in a community with less educated persons, living in a community with less use of safe water source for drinking, or living close to the hospital. About 80% of those with diarrhea sought care initially from a non-professional healthcare provider. Choice of the professional healthcare provider was driven by age of the patient, educational status of the household head, and hygienic practices by the household. The study reaffirms that young children are at greater risk for diarrhea. Like other developing countries most people in this impoverished setting of Dhaka are less likely to seek care from a professional healthcare provider than from a non-professional healthcare provider, which could be attributed to a higher number of diarrheal deaths among young children in Bangladesh. Dissemination of information on health education, increasing the supply of skilled healthcare providers, and low-cost and quality healthcare services may encourage more people to seek care from professional healthcare providers, thus may help reduce child mortality in the country. Further studies are warranted to validate the results. [ABSTRACT FROM AUTHOR]

Background: Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. Methods: As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. Principal Findings: We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. Conclusions: This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children. Author Summary: The highest disease burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) is seen in children under five years of age in endemic areas. We investigated both mucosal and systemic immune responses in S. Typhi bacteremic young children (aged, 1 to 5 years) by measuring S. Typhi membrane preparation (MP) specific IgA response in lymphocyte culture secretion and plasma IgA, IgG and IgM responses using ELISA. We also measured T cell proliferation responses using 3H-thymidine incorporation assay. We compared the responses to S. Typhi bacteremic older children (6 to 17 years) and adults (18 to 59 years) and with age-matched healthy controls (HC). Younger children, older children and adults show comparable responses in lymphocyte secretions after onset of illness. Plasma antibody responses to MP vary between young children and other age groups. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts. Emergence of MDR S. Typhi strains is seen in young children which does not impact on the clinical symptoms or the immune responses. The results of this study show that natural infections do induce immune response in young children as well as in adults. [ABSTRACT FROM AUTHOR]

Background: Children bear a large burden of typhoid fever caused by Salmonella enterica serotype Typhi (S. Typhi) in endemic areas. However, immune responses and clinical findings in children are not well defined. Here, we describe clinical and immunological characteristics of young children with S. Typhi bacteremia, and antimicrobial susceptibility patterns of isolated strains. Methods: As a marker of recent infection, we have previously characterized antibody-in-lymphocyte secretion (TPTest) during acute typhoid fever in adults. We similarly assessed membrane preparation (MP) IgA responses in young children at clinical presentation, and then 7-10 days and 21-28 days later. We also assessed plasma IgA, IgG and IgM responses and T cell proliferation responses to MP at these time points. We compared responses in young children (1-5 years) with those seen in older children (6-17 years), adults (18-59 years), and age-matched healthy controls. Principal Findings: We found that, compared to age-matched controls patients in all age cohorts had significantly more MP-IgA responses in lymphocyte secretion at clinical presentation, and the values fell in all groups by late convalescence. Similarly, plasma IgA responses in patients were elevated at presentation compared to controls, with acute and convalescent IgA and IgG responses being highest in adults. T cell proliferative responses increased in all age cohorts by late convalescence. Clinical characteristics were similar in all age cohorts, although younger children were more likely to present with loss of appetite, less likely to complain of headache compared to older cohorts, and adults were more likely to have ingested antibiotics. Multi-drug resistant strains were present in approximately 15% of each age cohort, and 97% strains had resistance to nalidixic acid. Conclusions: This study demonstrates that S. Typhi bacteremia is associated with comparable clinical courses, immunologic responses in various age cohorts, including in young children, and that TPTest can be used as marker of recent typhoid fever, even in young children. [ABSTRACT FROM AUTHOR]

Enteroaggregative E. coli (EAEC) is an established diarrhoeagenic pathotype. The association with virulence gene content and ability to cause disease has been studied but little is known about the population structure of EAEC and how this pathotype evolved. Analysis by Multi Locus Sequence Typing of 564 EAEC isolates from cases and controls in Bangladesh, Nigeria and the UK spanning the past 29 years, revealed multiple successful lineages of EAEC. The population structure of EAEC indicates some clusters are statistically associated with disease or carriage, further highlighting the heterogeneous nature of this group of organisms. Different clusters have evolved independently as a result of both mutational and recombination events; the EAEC phenotype is distributed throughout the population of E. coli. [ABSTRACT FROM AUTHOR]

Background: Resistance to cephalosporins in Enterobacteriaceae is mainly due to the production of extended-spectrum beta-lactamase (ESBL). Little is known about ESBL-producing bacteria in Bangladesh. Therefore, the study presents results of phenotypic and molecular characterization of ESBL-producing Escherichia coli from hospitals in Bangladesh. Methods: A total of 339 E. coli isolated from patients with urinary tract and wound infections attending three different medical hospitals in urban and rural areas of Bangladesh between 2003–2007 were screened for ESBL-production by the double disk diffusion test. Isolates with ESBL-phenotype were further characterized by antibiotic susceptibility testing, PCR and sequencing of different β-lactamase and virulence genes, serotyping, and XbaI-macrorestriction followed by pulsed-field gel electrophoresis (PFGE). Results: We identified 40 E. coli with ESBL phenotype. These isolates were resistant to ceftriaxone, ceftazidime, cefotaxime, aztreonam, cefepime, and nalidixic acid but remained susceptible to imipenem. All but one isolate were additionally resistant to ciprofloxacin, and 3 isolates were resistant to cefoxitin. ESBL genes of blaCTX-M-1-group were detected in all isolates; blaTEM-type and blaOXA-1-type genes were detected in 33 (82.5%) and 19 (47.5%) isolates, respectively. Virulence genes that are present in diarrhoeagenic E. coli were not found. Class-1 integron was present in 20 (50%) isolates. All the ESBL-producing E. coli isolates harbored plasmids ranging between 1.1 and 120 MDa. PFGE-typing revealed 26 different pulsotypes, but identical pulsotype showed 6 isolates of serotype O25:H4. Conclusion: The prevalence of multidrug-resistant ESBL-producing E. coli isolates appears to be high and the majority of the isolates were positive for blaCTX-M. Although there was genetic heterogeneity among isolates, presence of a cluster of isolates belonging to serotype O25:H4 indicates dissemination of the pandemic uropathogenic E. coli clone in Bangladesh. [ABSTRACT FROM AUTHOR]

Background: There has been no population-based study on human papillomavirus (HPV) prevalence or its genotypes in Bangladesh; a country eligible for GAVI funding for HPV vaccine. Methods: We used baseline survey data of a prospective cohort study that was conducted in one urban and one rural area of Bangladesh. A total of 997 urban and 905 rural married women, aged 13 to 64 years, were enrolled in the baseline during July-December, 2011. Information was collected on socio-demographic characteristics and potential risk factors for HPV infection followed by gynecological examination and collection of endocervical samples using the cervical cytobrush (Digene cervical sampler). HPV DNA testing was done by Polymerase Chain Reaction (PCR) using a consensus primer set. Results: Prevalence of any HPV infection was 7.7% with no significant difference between urban and rural women. Most common high-risk genotypes were HPV16, HPV66, HPV18, HPV45, HPV31 and HPV53. Urban women working as housemaids or garment workers were at higher risk of any HPV infection (OR = 2.15, 95% CI: 1.13–4.11) compared to housewives. Rural women whose husband lived overseas were almost two times more likely to have any HPV infection (OR = 1.93; 95% CI 1.05–3.55) compared to women whose husbands lived with them. Conclusion: The prevalence of HPV infection among Bangladeshi women is similar to other regions of Asia. However, type-specific patterns are different. The study findings will inform the formulation of HPV vaccination policies in Bangladesh, monitoring the impact of vaccination programmes, and the identification of target populations for screening. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of bacterial diarrhea. Over the last decade, from 1996 to 2012, changes in the virulence antigen properties of ETEC such as heat labile (LT) and heat stable (ST) toxins, colonization factors (CFs), and 'O'-serogroups have been observed. The aim of this prospective study was to compare changes in antigenic profiles of ETEC strains isolated from a 2% surveillance system at the icddr,b hospital in Dhaka, Bangladesh between 2007–2012 and an earlier time period of 1996–1998 conducted at the same surveillance site. Methodology: In the surveillance system every 50th patient attending the hospital was screened for major enteric pathogens including ETEC, Vibrio cholerae, Shigella spp. and Salmonella spp. from January 2007 to December 2012. Principal Findings: Of the 15,152 diarrheal specimens tested between 2007–2012, the overall rate of ETEC isolation was 11%; of these, 43% were LT/ST, 27% LT and 30% ST positive. Isolation rate of ST-ETEC (p<0.009) and LT/ST ETEC (p<0.011) during 2007–2012 period differed significantly compared to those seen between 1996–1998. In comparison to the 1996–1998 period, difference in CF profile of ETEC isolates during 2007–2012 was observed particularly for strains expressing CS7 (12.4%), CS14 (9.5%) and CS17 (10.0%). The predominant CF types were CS5+CS6, CFA/I, CS7, CS17, CS1+CS3, CS6 and CS14. The most common serogroups among the CF positive ETEC isolates were O115, O114, O6, O25 and O8. A strong association was found between CFs and 'O' serogroups i.e. between CS5+CS6 and (O115 and O126); CS7 and (O114), CFA/I and (O78 and O126), CS17 and (O8 and O167) and CS1/CS2+CS3 and (O6). Conclusion: The analyses show a shift in prevalence of antigenic types of ETEC over the study period; the information is important in designing effective ETEC vaccines with broad protective coverage. Author Summary: Diarrheal diseases constitute a major health problem in Bangladesh, where Vibrio cholerae and enterotoxigenic Escherichia coli (ETEC) are two most important causes of bacterial diarrhea. Prevention through vaccination is helpful to reduce the incidence and severity of diarrheal disease due to ETEC, particularly among children in low-resource settings. In this context, we collected stool and/or rectal swab (RS) specimens from patients with diarrhea between 2007 to 2012 under the 2% systematic routine surveillance system at the icddr,b hospital in Dhaka, Bangladesh and screened for ETEC infection. We tested the specimens for two major virulence factors of ETEC: toxins and colonization factors. In this research article, we have focused on changes in toxin as well as colonization factor profiles of ETEC strains isolated from diarrheal patients seeking care at the icddr,b hospital between 2007–2012 and an earlier time period of 1996–1998. We concluded that, such shift in antigenic profile of ETEC over the study period is important in designing effective ETEC vaccines with broad protective coverage. [ABSTRACT FROM AUTHOR]

The seventh cholera pandemic caused by Vibrio cholerae O1 El Tor (ET) has been superseded in Asia and Africa by altered ET possessing the cholera toxin (CTX) gene of classical (CL) biotype. The CL biotype of V. cholerae was isolated, along with prototypic and altered ET, during the 1991 cholera epidemic in Mexico and subsequently remained endemic until 1997. Microbiological, molecular, and phylogenetic analyses of clinical and environmental V. cholerae isolated in Mexico between 1998 and 2008 revealed important genetic events favoring predominance of ET over CL and altered ET. V. cholerae altered ET was predominant after 1991 but not after 2000. 7. cholerae strains isolated between 2001 and 2003 and a majority isolated in 2004 lacked CTX prophage (Φ) genes encoding CTX subunits A and B and repeat sequence transcriptional regulators of ET and CL biotypes: i.e., CTXΦ-. Most CTXΦ-V. cholerae isolated in Mexico between 2001 and 2003 also lacked toxin coregulated pili tcpA whereas some carried either tcpAET or a variant tcpA with noticeable sequence dissimilarity from tcpACL. The tcpA variants were not detected in 2005 after CTXΦ+ ET became dominant. All clinical and environmental V. cholerae 01 strains isolated during 2005-2008 in Mexico were CTXΦ+ ET, carrying an additional truncated CTXΦ instead of RS1 satellite phage. Despite V. cholerae CTXΦ- ET exhibiting heterogeneity in pulsed-field gel electrophoresis patterns, CTXΦ+ ET isolated during 2004-2008 displayed homogeneity and clonal relationship with V. cholerae ET N16961 and V. cholerae ET isolated in Peru. [ABSTRACT FROM AUTHOR]

Background: Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of bacterial diarrhea. Over the last decade, from 1996 to 2012, changes in the virulence antigen properties of ETEC such as heat labile (LT) and heat stable (ST) toxins, colonization factors (CFs), and ‘O’-serogroups have been observed. The aim of this prospective study was to compare changes in antigenic profiles of ETEC strains isolated from a 2% surveillance system at the icddr,b hospital in Dhaka, Bangladesh between 2007–2012 and an earlier time period of 1996–1998 conducted at the same surveillance site. Methodology: In the surveillance system every 50th patient attending the hospital was screened for major enteric pathogens including ETEC, Vibrio cholerae, Shigella spp. and Salmonella spp. from January 2007 to December 2012. Principal Findings: Of the 15,152 diarrheal specimens tested between 2007–2012, the overall rate of ETEC isolation was 11%; of these, 43% were LT/ST, 27% LT and 30% ST positive. Isolation rate of ST-ETEC (p<0.009) and LT/ST ETEC (p<0.011) during 2007–2012 period differed significantly compared to those seen between 1996–1998. In comparison to the 1996–1998 period, difference in CF profile of ETEC isolates during 2007–2012 was observed particularly for strains expressing CS7 (12.4%), CS14 (9.5%) and CS17 (10.0%). The predominant CF types were CS5+CS6, CFA/I, CS7, CS17, CS1+CS3, CS6 and CS14. The most common serogroups among the CF positive ETEC isolates were O115, O114, O6, O25 and O8. A strong association was found between CFs and ‘O’ serogroups i.e. between CS5+CS6 and (O115 and O126); CS7 and (O114), CFA/I and (O78 and O126), CS17 and (O8 and O167) and CS1/CS2+CS3 and (O6). Conclusion: The analyses show a shift in prevalence of antigenic types of ETEC over the study period; the information is important in designing effective ETEC vaccines with broad protective coverage. [ABSTRACT FROM AUTHOR]

Rates of childhood mortality due to diarrhoea remain unacceptably high and call for renewed global focus and commitment. Affordable, simple and effective diarrhoeal treatments have already been available for many years, yet a shift in international health priorities has seen coverage of recommended treatments slow to a nearstandstill since 1995. This article reviews coverage of recommended childhood diarrhoeal treatments (lowosmolarity oral rehydration solution (ORS) and zinc), globally and regionally, and provides an overview of the major barriers to wide-scale coverage. It is argued that to ensure smooth supply and equitable distribution of ORS and zinc, adequate financing, relevant policy changes, strong public, private and non-government organisation (NGO) collaboration, local manufacturing of pharmaceuticals, mass media awareness and campaigning, in conjunction with strong government support, are necessary for successful treatment scale-up. [ABSTRACT FROM AUTHOR]

Eighty-nine T4-like phages from our phage collection were tested against four collections of childhood diarrhoea-associated Escherichia coli isolates representing different geographical origins (Mexico versus Bangladesh), serotypes (69 O, 27 H serotypes), pathotypes (ETEC, EPEC, EIEC, EAEC, VTEC, Shigella), epidemiological settings (community and hospitalized diarrhoea) and years of isolation. With a cocktail consisting of 3 to 14 T4-like phages, we achieved 54% to 69% coverage against predominantly EPEC isolates from Mexico, 30% to 53% against mostly ETEC isolates from a prospective survey in Bangladesh, 24% to 61% against a mixture of pathotypes isolated from hospitalized children in Bangladesh, and 60% coverage against Shigella isolates. In comparison a commercial Russian phage cocktail containing a complex mixture of many different genera of coliphages showed 19%, 33%, 50% and 90% coverage, respectively, against the four above-mentioned collections. Few O serotype-specific phages and no broad-host range phages were detected in our T4-like phage collection. Interference phenomena between the phage isolates were observed when constituting larger phage cocktails. Since the coverage of a given T4-like phage cocktail differed with geographical area and epidemiological setting, a phage composition adapted to a local situation is needed for phage therapy approaches against E. coli pathogens. [ABSTRACT FROM AUTHOR]

Background: Although endemic cholera causes significant morbidity and mortality each year in Nepal, lack of information about the causal bacterium often hinders cholera intervention and prevention. In 2012, diarrheal outbreaks affected three districts of Nepal with confirmed cases of mortality. This study was designed to understand the drug response patterns, source, and transmission of Vibrio cholerae associated with 2012 cholera outbreaks in Nepal. Methods: V. cholerae (n = 28) isolated from 2012 diarrhea outbreaks {n = 22; Kathmandu (n = 12), Doti (n = 9), Bajhang (n = 1)}, and surface water (n = 6; Kathmandu) were tested for antimicrobial response. Virulence properties and DNA fingerprinting of the strains were determined by multi-locus genetic screening employing polymerase chain reaction, DNA sequencing, and pulsed-field gel electrophoresis (PFGE). Results: All V. cholerae strains isolated from patients and surface water were confirmed to be toxigenic, belonging to serogroup O1, Ogawa serotype, biotype El Tor, and possessed classical biotype cholera toxin (CTX). Double-mismatch amplification mutation assay (DMAMA)-PCR revealed the V. cholerae strains to possess the B-7 allele of ctx subunit B. DNA sequencing of tcpA revealed a point mutation at amino acid position 64 (N→S) while the ctxAB promoter revealed four copies of the tandem heptamer repeat sequence 5′-TTTTGAT-3′. V. cholerae possessed all the ORFs of the Vibrio seventh pandemic island (VSP)-I but lacked the ORFs 498–511 of VSP-II. All strains were multidrug resistant with resistance to trimethoprim-sulfamethoxazole (SXT), nalidixic acid (NA), and streptomycin (S); all carried the SXT genetic element. DNA sequencing and deduced amino acid sequence of gyrA and parC of the NAR strains (n = 4) revealed point mutations at amino acid positions 83 (S→I), and 85 (S→L), respectively. Similar PFGE (NotI) pattern revealed the Nepalese V. cholerae to be clonal, and related closely with V. cholerae associated with cholera in Bangladesh and Haiti. Conclusions: In 2012, diarrhea outbreaks in three districts of Nepal were due to transmission of multidrug resistant V. cholerae El Tor possessing cholera toxin (ctx) B-7 allele, which is clonal and related closely with V. cholerae associated with cholera in Bangladesh and Haiti. [ABSTRACT FROM AUTHOR]

The article examines the efficacy of quadrivalent influenza vaccine (QIV) in preventing mild and moderate-to-severe influenza in children. It mentions that the vaccine efficacy and the impact of vaccination on daily activities and utilization of health care resources were determine in the total vaccinated cohort, and the per-protocol cohort. It notes that 62 children in the QIV group, and 148 in the control group had real-time polymerase chain reaction (rt-PCR) with 59.3% of QIV efficacy.

Highlights: [•] Largest feasibility study to reach high-risk endemic urban population with OCV. [•] 82% were reached with first dose and 87% of those received two doses. [•] Coverage in children was 81% and it was significantly higher in females than males. [•] Two doses cost per-person was US$3.93 and delivering cost of single dose was US$0.76. [•] Mass OCV delivery with existing national immunization system is feasible. [ABSTRACT FROM AUTHOR]

Abstract: Treatment of shigellosis in rabbits with phenylbutyrate reduces clinical severity and counteracts down-regulation of cathelicidin (CAP-18) in the large intestinal epithelia. We aimed to further evaluate whether in a rabbit model of enteropathogenic Escherichia coli (EPEC) diarrhea, CAP-18 is down-regulated in the small intestine and if oral phenylbutyrate treatment affects CAP-18 expression, clinical recovery, shedding of EPEC in stool and virulence properties of the isolated colonies. EPEC-induced diarrhea down-regulated CAP-18 in the small intestinal epithelia as revealed by immunohistochemistry. Phenylbutyrate treatment reduced clinical illness, improved histological features of inflammation and up-regulated CAP-18 in the epithelia. Active CAP-18 peptide was also released in the stool as noted in Western blot analysis. Multiplex PCR analysis of total bacterial DNA in the stool showed absence of EPEC specific genes eae and bfpA. Treated rabbits shed rough strains still harboring eae and bfpA genes, which were less potent in binding to HeLa cells and induced delayed onset of diarrhea in new rabbits. In conclusion, EPEC-mediated down-regulation of CAP-18 in the small intestinal epithelia was restored by phenylbutyrate treatment. Upregulation of CAP-18 in the epithelia was accompanied by healing of the epithelial lining, reduced shedding and virulence of EPEC and recovery from diarrhea. [Copyright &y& Elsevier]

The ability of a bacterial population to survive in different niches, as well as in stressful and rapidly changing environmental conditions, depends greatly on its genetic content. To survive such fluctuating conditions, bacteria have evolved different mechanisms to modulate phenotypic variations and related strategies to produce high levels of genetic diversity. Laboratories working in microbiological diagnosis have shown that Citrobacter freundii is very versatile in its colony morphology, as well as in its biochemical, antigenic and pathogenic behaviours. This phenotypic versatility has made C. freundii difficult to identify and it is frequently confused with both Salmonella enterica and Escherichia coli. In order to determine the genomic events and to explain the mechanisms involved in this plasticity, six C. freundii isolates were selected from a phenotypic variation study. An I-CeuI genomic cleavage map was created and eight housekeeping genes, including 16S rRNA, were sequenced. In general, the results showed a range of both phenotypes and genotypes among the isolates with some revealing a greater similarity to C. freundii and some to S. enterica, while others were identified as phenotypic and genotypic intermediary states between the two species. The occurrence of these events in natural populations may have important implications for genomic diversification in bacterial evolution, especially when considering bacterial species boundaries. In addition, such events may have a profound impact on medical science in terms of treatment, course and outcomes of infectious diseases, evading the immune response, and understanding host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Background: Rapid and reliable diagnostic assays for enteric (typhoid and paratyphoid) fever are urgently needed. We report the characterization of novel approach utilizing lymphocyte secretions, for diagnosing patients with enteric fever by the TPTest procedure. Methodology: TPTest detects Salmonella-specific IgA responses in lymphocyte culture supernatant. We utilized TPTest in patients with suspected enteric fever, patients with other illnesses, and healthy controls. We also evaluated simplified modifications of TPTest for adaptation in laboratories with limited facilities and equipment. Principal Findings: TPTest was positive in 39 (27 typhoid and 12 paratyphoid A) patients confirmed by blood culture and was negative in 74 healthy individuals. Among 32 individuals with other illnesses, 29 were negative by TPTest. Of 204 individuals with suspected enteric fever who were negative by blood culture, 44 were positive by TPTest and the patients were clinically indistinguishable from patients with confirmed bacteremia, except they were more likely to be under 5 years of age. We evaluated simplifications in TPTest, including showing that lymphocytes could be recovered using lysis buffer or buffy coat method as opposed to centrifugation, that incubation of cells at 37°C did not require supplemental CO2, and that results were available for majority of samples within 24 hours. Positive results by TPTest are transient and revert to negative during convalescence, supporting use of the test in endemic areas. The results can also be read using immunodot blot approach as opposed to ELISA. Since no true gold standard currently exists, we used a number of definitions of true positives and negatives. TPTest had sensitivity of 100% compared to blood culture, and specificity that ranged from 78–97% (73–100, 95% CI), depending on definition of true negative. Conclusion: The TPTest is useful for identification of patients with enteric fever in an endemic area, and additional development of simplified TPTest is warranted. Author Summary: Salmonella enterica serotype Typhi and Paratyphi A are responsible for typhoid and paratyphoid fever respectively and the disease caused is known generally as enteric fever. Appropriate and early diagnosis of the disease is important for initiation of treatment of the patient with a suitable antibiotic. The performance of the available diagnostic methods take time and as well as have low sensitivity and specificity. We describe here an immunodiagnostic assay, the TPTest, which is based on the use of secretions of antibodies from peripheral blood lymphocytes. We describe simplifications of the procedure and show that the assay has as a sensitivity of 100% with a specificity that ranges from 78–97% (73–100, 95% CI) for detecting patients with typhoid and paratyphoid fever in an enteric fever endemic zone. The TPTest uses a small blood volume, and reverts to negative by convalescence, supporting its further development as a relatively low cost assay to diagnose patients with enteric fever in endemic zones. [ABSTRACT FROM AUTHOR]

Background: Rapid and reliable diagnostic assays for enteric (typhoid and paratyphoid) fever are urgently needed. We report the characterization of novel approach utilizing lymphocyte secretions, for diagnosing patients with enteric fever by the TPTest procedure. Methodology: TPTest detects Salmonella-specific IgA responses in lymphocyte culture supernatant. We utilized TPTest in patients with suspected enteric fever, patients with other illnesses, and healthy controls. We also evaluated simplified modifications of TPTest for adaptation in laboratories with limited facilities and equipment. Principal Findings: TPTest was positive in 39 (27 typhoid and 12 paratyphoid A) patients confirmed by blood culture and was negative in 74 healthy individuals. Among 32 individuals with other illnesses, 29 were negative by TPTest. Of 204 individuals with suspected enteric fever who were negative by blood culture, 44 were positive by TPTest and the patients were clinically indistinguishable from patients with confirmed bacteremia, except they were more likely to be under 5 years of age. We evaluated simplifications in TPTest, including showing that lymphocytes could be recovered using lysis buffer or buffy coat method as opposed to centrifugation, that incubation of cells at 37°C did not require supplemental CO2, and that results were available for majority of samples within 24 hours. Positive results by TPTest are transient and revert to negative during convalescence, supporting use of the test in endemic areas. The results can also be read using immunodot blot approach as opposed to ELISA. Since no true gold standard currently exists, we used a number of definitions of true positives and negatives. TPTest had sensitivity of 100% compared to blood culture, and specificity that ranged from 78–97% (73–100, 95% CI), depending on definition of true negative. Conclusion: The TPTest is useful for identification of patients with enteric fever in an endemic area, and additional development of simplified TPTest is warranted. [ABSTRACT FROM AUTHOR]