Shigellosis

Intestinal and extra-intestinal complications are associated with inflammatory bowel disease (IBD) but their exact incidence is not well known. In order to improve our understanding of their incidence and impact, we assessed the complications associated with ulcerative colitis (UC) and Crohn's disease (CD) in a population-based study in Medicaid patients. We utilized a retrospective cohort design and identified cases of UC and CD using Medi-Cal, the Medicaid program for the State of California. The disease cohort was age- and gender-matched to four controls each and the intestinal and extra-intestinal complications of CD and UC (analyzed separately) were studied over a period of 5 years following the initial diagnosis. For UC, the total number of intestinal complications, per 100 cases, was 92 observed compared to 21 expected; the total number of extra-intestinal complications was 42 observed compared to 30 expected. For CD, the number of intestinal complications was 81 observed compared to 20 expected and for extra-intestinal complications, 37 observed compared to 26 expected (all p < 0.001). For both UC and CD, bleeding was the most frequently seen intestinal complication, while the most common extra-intestinal complication was osteoporosis. IBD is associated with several intestinal and extra-intestinal complications of variable incidence and risk. Success of therapeutic regimens should be measured by decreases in incidence, risks, and costs of these complications, in addition to the usual impact on disease activity.

This Month in Gastroenterology

INTRODUCTION: Medical management of Inflammatory Bowel Diseases is complex and tailored to disease activity. The primary goal is the induction of remission and maintenance of remission with longterm prevention of disease progression. AIM: to describe current drug treatment practices in Inflammatory Bowel Diseases in Dobrogea. MATERIAL AND METHOD: The retrospective and descriptive study included 128 patients: group 1 = Crohn’s Disease (79), group 2 = Ulcerative Colitis (46) and group 3 = Unclassified Colitis (3). RESULTS: The phenotypic distribution was: 62% with Crohn’s Disease, 36% with Ulcerative Colitis and 3 patients with Unclassified Colitis. CROHN’S DISEASE: According to Montreal Classification, the majority of patients were diagnosed after 40 years (58%); the most frequent involvement was ileo-colonic (47%) and the most frequent phenotype was inflammatory (60%). 40% patients had intestinal complications and 7% had extraintestinal complications. 16.4% required surgical interventions. 67% were treated at some point with aminosalicylates, 44% with immunosuppressive drugs (thiopurines), 80% with corticosteroids for the induction of remission (inaugural flare) and 50% of them received again corticosteroidssteroids in the evolution of the disease, and 29% with biologic therapy. ULCERATIVE COLITIS: Most common location was left colitis in 47% cases. One patient had intestinal complications and no extraintestinal complications were reported in this group. No patients required surgical interventions. 82.5% were treated at some point with aminosalicylates, 37% with immunosuppressive drugs (thiopurines), 17% with corticosteroids and 11% with biologic therapy. UNCLASSIFIED COLITIS: In this group were not reported intestinal and extraintestinal complications and also no patient required surgical interventions. 2 patients were treated at some point with aminosalicylates, all patients were treated with immunomodulators and only one patient was administered biologic therapy. CONCLUSIONS: Particularities of Crohn’s Disease in our region are: widespread use of aminosalicylates, overuse of corticosteroids overtime, underprescribed biologic therapy.

Crohn's disease (CD) may have some severe complications that pose an increasing health burden and negatively impact the quality of life. There are two major types - intestinal and extraintestinal complications, in which immune and non-immune mechanisms take place. We aimed to search for some associations between specific extraintestinal manifestation and intestinal complications in CD patients with some clinicallaboratory findings, immunological markers, and the therapy administered. We examined retrospectively medical files of 26 patients with CD at mean age 42 ± 13 years, including the laboratory results. The immunological markers fecal calprotectin (FC) and fecal lactoferrin (FL) were assessed in frozen fecal samples of the chosen patients. Seventy-three percent of the investigated CD patients had some extraintestinal manifestation and/or intestinal complications, at least 13/26 had intestinal complications. All three patients with extraintestinal signs were positive for FC and 2/3 were positive for FL. We observed a higher serum level of CRP (24.49 mg/l vs. 3.13 mg/l, p = 0.010), slightly lowered serum level of hemoglobin (120 g/l vs. 145 g/l, p = 0.044) and about 2-fold lower iron level (7.23 μmol/l vs. 14.0 μmol/l, p = 0.019) in patients with intestinal complications compared to patients without complications, respectively. Four out of thirteen patients with intestinal complications were without immunosuppressive therapy at the time of our study, and nine out of thirteen - on immunosuppressive drugs. Routine laboratory and immunology testing could be beneficial for gastroenterologists in identifying patients at high risk for the development of complications and in the decision making for more aggressive therapy early after diagnosis.

There are no licensed vaccines against Shigella, a leading cause of children's diarrhea and travelers' diarrhea. To develop a cross-protective vaccine against heterogeneous Shigella species and serotypes, we attempted to apply an epitope- and structure-based vaccinology platform, multiepitope fusion antigen, to construct an optimal polyvalent chimeric immunogen with functional epitopes from the key Shigella virulence determinants. With Shigella invasion plasmid antigens B and D functional epitopes identified in recent studies, in this study, we focused on Shigella intracellular spread protein A (IcsA; also known as virulence gene G, VirG), a multifunctional virulence factor that plays roles in bacterial adherence, invasion, and particularly intracellular and intercellular spread. We in silico predicted continuous B-cell immunodominant epitopes from the IcsA functional passenger domain, and we fused each epitope to a non-homologous carrier protein, Escherichia coli adhesin CS4 subunit CsaB, for epitope fusions. We then immunized mice with each epitope fusion and examined antibody functions against Shigella bacterial invasion and adherence. Eleven IcsA B-cell epitopes were identified and fused to CsaB. Mice intramuscularly immunized with each epitope fusion developed IgG responses. Mouse serum antibodies significantly reduced Shigella sonnei or Shigella flexneri 2a bacterial invasion or adherence in vitro, particularly from the fusion with epitope #2 (122GDNNDGNSCGGNG134), #3 (156GGSGADHNGDGGE168), #7 (309YIISGKEDDGTQNV325), #9 (485WNDTDGDSHG494), or #10 (507TILADNLSHHNIN523). These IcsA epitopes are more effective in inducing functional antibodies, suggesting their antigenic utility in constructing an optimal polyvalent Shigella immunogen and developing a cross-protective vaccine, and perhaps in better understanding their role in IcsA biogenesis.IMPORTANCEAn effective Shigella vaccine is urgently needed to reduce Shigella-associated diarrhea and dysentery. Shigella IcsA (or VirG) plays a crucial role in Shigella bacterial pathogenesis and is conserved across Shigella species and serotypes, thus making IcsA an excellent antigen target in Shigella vaccine development. Identification of the functional epitopes of the IcsA passenger domain from this study enables us to construct an optimal epitope- and structure-based polyvalent immunogen for a cross-protective multivalent Shigella vaccine. Unlike the lipopolysaccharide-based whole-cell or subunit vaccine candidates that are serotype-specific, a multivalent vaccine carrying functional epitopes of conserved virulence determinants would be cross-protective against the heterogeneous Shigella species and serotypes, effectively preventing shigellosis and dysentery. Data from this study may also provide insightful information for a better understanding of IcsA biogenesis.

The Shigella species are Gram-negative, facultative intracellular pathogens that invade the colonic epithelium and cause significant diarrheal disease. Despite extensive research on the pathogen, a comprehensive understanding of how Shigella initiates contact with epithelial cells remains unknown. Shigella maintains many of the same Escherichia coli adherence gene operons; however, at least one critical gene component in each operon is currently annotated as a pseudogene in reference genomes. These annotations, coupled with a lack of structures upon microscopic analysis following growth in laboratory media, have led the field to hypothesize that Shigella is unable to produce fimbriae or other traditional adherence factors. Nevertheless, our previous analyses have demonstrated that a combination of bile salts and glucose induces both biofilm formation and adherence to colonic epithelial cells. The goal of this study was to perform transcriptomic and genetic analyses to demonstrate that adherence gene operons in Shigella flexneri strain 2457T are functional, despite the gene annotations. Our results demonstrate that at least three structural genes facilitate S. flexneri 2457T adherence for epithelial cell contact and biofilm formation. Furthermore, our results demonstrate that host factors, namely, glucose and bile salts at their physiological concentrations in the small intestine, offer key environmental stimuli required for adherence factor expression in S. flexneri This research may have a significant impact on Shigella vaccine development and further highlights the importance of utilizing in vivo-like conditions to study bacterial pathogenesis.IMPORTANCE Bacterial pathogens have evolved to regulate virulence gene expression at critical points in the colonization and infection processes to successfully cause disease. The Shigella species infect the epithelial cells lining the colon to result in millions of cases of diarrhea and a significant global health burden. As antibiotic resistance rates increase, understanding the mechanisms of infection is vital to ensure successful vaccine development. Despite significant gains in our understanding of Shigella infection, it remains unknown how the bacteria initiate contact with the colonic epithelium. Most pathogens harbor multiple adherence factors to facilitate this process, but Shigella was thought to have lost the ability to produce these factors. Interestingly, we have identified conditions that mimic some features of gastrointestinal transit and that enable Shigella to express adherence structural genes. This work highlights aspects of genetic regulation for Shigella adherence factors and may have a significant impact on future vaccine development.

Study Background and Purpose: Chronic intestinal diseases (CIDs) are often associated with intestinal complications (fistulas, abscesses, stricture-obstruction, toxic megacolon) and extraintestinal complications. The aim of this work is to evaluate the efficacy and safety of biological therapy in IBD.Materials and Methods: Between 2018-2023, 89 patients (51 M; 38 F) with Crohn's disease (30 patients) and ulcerative colitis (59 patients) were enrolled, with a mean age of 38 years. The biological drugs used were: infliximab (31 patients), adalimumab (44 patients), vedolizumab (2 patients), ustekinumab (9 patients), and upadacitinib (3 patients).Results: Biological therapy resulted in remission of symptoms and complications in 70% of cases, normalization of ESR, CRP, and calprotectin, and mucosal healing. The safety of biological drugs has been excellent. Switch therapy and swap therapy were performed in 15 patients due to an inadequate response to the medication.Conclusions: Biological therapy provides effective control of IBD, leading to a reduction in both intestinal and extraintestinal complications. Mucosal healing is the ideal endpoint for controlling the natural history of IBD and is the exclusive domain of biological therapy.

New and Off-Label Uses of Tranexamic Acid.

To investigate the epidemiologic and clinical characteristics of inflammatory bowel disease (IBD) patients in a large multicenter, countrywide, hospital-based study in Turkey. Twelve centers uniformly distributed throughout Turkey reported through a questionnaire the new IBD cases between 2001 and 2003. The incidence of ulcerative colitis (UC) and Crohn's disease (CD) has been reported per 100,000 people. Epidemiologic features and clinical characteristics of both diseases were analyzed. During the study period, 661 patients of UC and 216 patients of CD were identified. The incidence in the referral population was 4.4/100,000 and 2.2/100,000 for UC and CD, respectively. The age of the patients showed the characteristic biphasic distribution with 2 peaks between 20 and 30 and 50 and 70 years. A male predominance was observed in both diseases. A history of smoking was detected in 15.5% of UC patients and 49.3% of patients with CD. Family history was positive in 4.4% in UC and 8.3% in CD patients. Concomitant amebiasis was observed in 17.3% of patients with UC and 1.3% of patients with CD. A history of appendectomy was reported in 15% of patients with CD and only 3% of patients with UC. Both extraintestinal and local complications were more frequent in CD patients, whereas arthritis was most common in both diseases. IBDs are frequently encountered in Turkey. IBD incidence is lower than North and West Europe but close to Middle East in our country. The majority of IBD cases are diagnosed in young people (20 to 40 y) with predominance in males. The rate of both intestinal and extraintestinal complications in our population was low when compared with the data reported in the literature. IBD and especially UC, can coexist with amebiasis or become manifest with amebic infestation. The presence of concomitant ameba may create confusion and cause dilemmas in the diagnosis and treatment of UC.

BackgroundMalaria vector control using long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), with pyrethroids and DDT, to reduce malaria transmission has been expansively implemented in Zambia. The impact of these interventions on malaria morbidity and mortality has not previously been formally assessed at the population level in Zambia.MethodsThe impact of IRS (15 urban districts) and LLINs (15 rural districts) implementation on severe malaria cases, deaths and case fatality rates in children below the age of five years were compared. Zambian national Health Management Information System data from 2007 to 2008 were retrospectively analysed to assess the epidemiological impact of the two interventions using odds ratios to compare the pre-scaling up year 2007 with the scaling-up year 2008.ResultsOverall there were marked reductions in morbidity and mortality, with cases, deaths and case fatality rates (CFR) of severe malaria decreasing by 31%, 63% and 62%, respectively between 2007 and 2008. In urban districts with IRS introduction there was a significant reduction in mortality (Odds Ratio [OR] = 0.37, 95% CI = 0.31-0.43, P = 0.015), while the reduction in mortality in rural districts with LLINs implementation was not significant (OR = 0.83, 95% CI = 0.67-1.04, P = 0.666). A similar pattern was observed for case fatality rates with a significant reduction in urban districts implementing IRS (OR = 0.34, 95% CI = 0.33-0.36, P = 0.005), but not in rural districts implementing LLINs (OR = 0.96, 95% CI = 0.91-1.00, P = 0.913). No substantial difference was detected in overall reduction of malaria cases between districts implementing IRS and LLINs (P = 0.933).ConclusionRoutine surveillance data proved valuable for determining the temporal effects of malaria control with two strategies, IRS and LLINs on severe malaria disease in different types of Zambian districts. However, this analysis did not take into account the effect of artemisinin-based combination therapy (ACT), which were being scaled up countrywide in both rural and urban districts.

Reduction in mortality from cardiac causes in Goldman class IV patients

Chlorhexidine cord cleansing to reduce neonatal mortality

Severe meningococcal disease in childhood

Sudden cardiac death (SCD) is among the most common causes of death in developed countries throughout the world. It is estimated that more than 3 million people die yearly from SCD, with a survival rate of less than 1%. In the United States, the Center for Disease Control recently estimated an annual incidence of 450 000 sudden deaths,1 with a survival rate of approximately 5%, although this probably is an overestimation. Although there has been a reduction in total cardiac mortality from 728 115 in 1989 to 719 456 in 1999, the percentage of deaths that are sudden has actually increased from 38% to 47%. The increase was greatest in women older than 65 years of age, from 56.3% to 63.9%. This has resulted primarily from an increase in out-of-hospital sudden deaths. There is a comparable incidence of SCD and survival rate in Western Europe.2 The magnitude of this problem can be understood by noting that SCD accounts for more deaths each year than the total number of deaths from AIDS, breast cancer, lung cancer, and stroke (Figure 1). Unfortunately, it is the first presentation of cardiac disease in 33% to 50% of patients and is 3 times as common in men than in women. Figure 1. Magnitude of the problem of sudden cardiac arrest. Coronary artery disease, with or without myocardial infarction, is by far the most common underlying disease for SCD in the western world, being responsible for approximately 75% of all SCDs.3,4 Cardiomyopathies (dilated and hypertrophic) and primary electrical heart disease account for most of the remainder. The two most important risk factors for SCD (ie, those with highest predictive value) are left ventricular ejection fraction (LVEF) less than 40% and clinical congestive heart failure.3,4 These are followed by significant ventricular arrhythmias (particularly …

The worldwide incidence and prevalence of Inflammatory Bowel Diseases (IBD) continues to increase, recent studies showing a future global spread of Inflammatory Bowel Diseases. Epidemiological data coming for Romania are scarce. The aim is to describe epidemiological features of Inflammatory Bowel Diseases in an adult population in the South-East side of Romania. The retrospective and descriptive study included 128 patients: group 1=Crohn’s Disease (CD) (79), group 2=Ulcerative Colitis (UC) (46) and group 3=Unclassified Colitis (Unclassified C) (3). We calculated the prevalence of Inflammatory Bowel Diseases in Constanţa in 2016. The phenotypic distribution was: 62% with Crohn’s Disease, 36% with Ulcerative Colitis and 3 patients with Unclassified Colitis. Crohn’s Disease: The prevalence was 0.11/100000 inhabitants. 51% were female and 49% were male. The age distribution showed a uniform model of the frequency of Crohn’s Disease in patients aged between 21 and 50 years. According to Montreal Classification, ileo-colonic involvement L3 was the most frequent in 47% and 60% patients presented inflammatory phenotype B1. 44% had intestinal complications. 9% had extraintestinal complications. 16.4% required surgical interventions. Ulcerative Colitis: The prevalence was 0.06/100000 inhabitants. We noticed a slight male predominance: 57% were male and 43% female. The age distribution showed a bimodal peak of incidence in patients aged between 21-30 years and 41-50 years. The most common disease extension was left colitis E2 in 47% cases. One patient had an enterovesical fistula. Extraintestinal complications were not reported in this group. No patient required surgical intervention. Unclassified Colitis: 3 male patients with ages between 31-50 years were diagnosed with Unclassified Colitis. Complications or need for surgery were not reported in this group. We noticed the predominance of Crohn’s Disease in our region while in other parts of Romania Ulcerative Colitis is predominant. We suppose that the predominance of Crohn’s Disease in Dobrogea can be due to environmental factors, diet or ethnics, but additional epidemiological studies to define better the association with environmental factors and risk factors for Crohn Disease or Ulcerative Colitis in our region are needed.