Severe Dysentery Research Articles

Historical gold mining infectious disease epidemics

Lethal infectious disease epidemics have historically occurred in military, refugee and mining camps where crowded conditions promote the spread of enteric, respiratory and insect-borne infections. The early history of gold mines around Palmer River, Queensland in the 1870s, Kalgoorlie, Western Australia in the 1890s and Papua on the island of New Guinea in the 1910s are recounted specifically as it relates to infectious disease deaths. Despite large diagnostic gaps, it is likely that malaria was the predominant problem in Palmer River, typhoid in Kalgoorlie and bacillary dysentery in Papua. Nearly two-thirds of all recorded deaths in the Palmer River district from 1873 to 1883 were due to infections, predominately 'fevers'. Typhoid fever likely killed >2000 Australians in the early phases of the Western Australian goldfields in the 1890s. Severe dysentery outbreaks killed up to a majority of the local workforce in the Lakekema goldfields of Papua resulting in the colonial authorities stopping mining activity in the second decade of the 20th century. In the absence of public health measures and specific chemotherapy, large mortality rates in miners reflected the over-riding economic drivers of gold miners and their lack of any understanding of microbial disease and its interruption by public health measures. Similar infectious disease epidemics are likely to reoccur when large numbers of impoverished miners use low-technology methods to work alluvial gold deposits in conflict areas as has been seen in modern Africa.

Target Product Profile and Development Path for Shigellosis Treatment with Antibacterials.

Enteric infection with Shigella spp. can lead to symptoms ranging from acute watery diarrhea to sudden, severe dysentery. Approximately 212 000 diarrheal deaths annually are attributed to Shigella with a disproportionate impact in low-resource countries. The impact in under-resourced countries was illustrated by a reanalysis of the Global Enteric Multicenter Study which found that Shigella was the leading pathogen associated with moderate-to severe diarrhea in children under 5 years old. While recent studies have highlighted the burden of the disease, there has been a concurrent reduction in therapeutic options for the treatment of shigellosis as drug resistant strains increase in prevalence. In addition, increasing reports of drug resistant shigellosis cases in the men who have sex with men community confirm that the impact is not limited to low-resource countries. Despite the urgent need for new treatments, a target product profile (TPP) has not been established, and there is no clear development path for antibacterial treatments. To address this troubling concern, this manuscript describes a TPP for antishigellosis small molecule therapeutics and a development path that integrates currently available preclinical and clinical models of Shigella infection.

<em>Shigella</em> pathogenesis: molecular and computational insights

Shigellosis, characterized by inflammation and ulceration of the large intestine, is caused by infection with Shigella species. It is a major public health problem in developing countries where filthy sanitation practices and restricted access to clean water encourage the spread of the disease. Shigellosis is spread by means of fecal-oral route. It is one of the most common disorders specially affecting children in West Bengal, India. Disease from Shigella species accounts for 165 million cases of diarrhoea culminating in one million deaths annually worldwide. Severe dysentery is treated still with antibiotics, with limited success because of the continuous development of multi drug resistance by the bacteria. WHO has identified Shigella as a potential target pathogen against which new drugs need to be formulated and in silico approach has the potential to identify drug targets. Molecular modeling of Shigella invasion proteins using computational tools may divulge novel therapeutic targets that can be used for future pharmacological intervention. Detailed annotation of previously unknown Hypothetical Proteins using an in-silico pipeline can identify crucial proteins in pathogenesis cascade, which can be explored further as effective drug targets, which may eventually enable us to combat the menace of shigellosis.

Shigillosis with Acute Appendicitis and Peritonitis: A Case Report

Shigellosis is a form of bacterial diarrhea caused by gram-negative bacteria Shigella species. It is common in developing countries and results from contaminated food, poor sanitation conditions, or direct person to person contact. Shigella can cause infection in all age groups. High-risk group include very young, elderly, and immunocompromised person. Shigella species is relatively resistant to acid in the stomach, and few organisms are required to cause the disease. Once ingested, it multiplies in the small intestine and enters the colon. In the colon, it produces shigella enterotoxins and serotype toxin 1, resulting in watery or bloody diarrhea. Clinical presentation of shigellosis may vary over a wide spectrum from mild diarrhea to severe dysentery. We report the case of 7 years old previously healthy boy, who presented to our hospital with abdominal pain, vomiting, and constipation. On examination, we noticed abdominal tenderness with guarding at the right lower quadrant. With the diagnosis of acute appendicitis, open appendectomy was performed. Exploration of the abdominal cavity revealed perforated appendicitis and generalized peritonitis. Shigella sonnei was isolated from the peritoneal fluid culture. The patient completely recovered without any complications. Surgical complications, including appendicitis, could have developed during shigellosis. There are few reported cases of perforated appendicitis associated with Shigella. Prompt surgical intervention can be beneficial to prevent morbidity and mortality if it is performed early in the course of the disease.

Acute Urinary Retention in a Young Man Secondary to Severe Dysentery: A Case Report

Acute Urinary Retention in a Young Man Secondary to Severe Dysentery: A Case Report

The Shigella Virulence Factor IcsA Relieves N-WASP Autoinhibition by Displacing the Verprolin Homology/Cofilin/Acidic (VCA) Domain

Shigella flexneri is a bacterial pathogen that invades cells of the gastrointestinal tract, causing severe dysentery. Shigella mediates intracellular motility and spreading via actin comet tail formation. This process is dependent on the surface-exposed, membrane-embedded virulence factor IcsA, which recruits the host actin regulator N-WASP. Although it is clear that Shigella requires N-WASP for this process, the molecular details of this interaction and the mechanism of N-WASP activation remain poorly understood. Here, we show that co-expression of full-length IcsA and the Shigella membrane protease IcsP yields highly pure IcsA passenger domain (residues 53–758). We show that IcsA is monomeric and describe the solution structure of the passenger domain obtained by small-angle X-ray scattering (SAXS) analysis. The SAXS-derived models suggest that IcsA has an elongated shape but, unlike most other autotransporter proteins, possesses a central kink revealing a distinctly curved structure. Pull-down experiments show direct binding of the IcsA passenger domain to both the WASP homology 1 (WH1) domain and the GTPase binding domain (GBD) of N-WASP and no binding to the verprolin homology/cofilin/acidic (VCA) region. Using fluorescence polarization experiments, we demonstrate that IcsA binding to the GBD region displaces the VCA peptide and that this effect is synergistically enhanced upon IcsA binding to the WH1 region. Additionally, domain mapping of the IcsA interaction interface reveals that different regions of IcsA bind to the WH1 and GBD domains of N-WASP. Taken together, our data support a model where IcsA and N-WASP form a tight complex releasing the N-WASP VCA domain to recruit the host cell machinery for actin tail formation.

Şigelozisin Nadir Bir Prezentasyonu: Akut Perfore Apendisit ve Peritonit

Shigella spp. is one of the most common agents that cause bacterial diarrhea and dysentery in developing countries. Clinical presentation of shigellosis may vary over a wide spectrum from mild diarrhea to severe dysentery. We report the case of 5.5-year-old previously healthy boy, who presented to our clinic with abdominal pain, vomiting, and constipation. On examination, we noticed abdominal tenderness with guarding at the right lower quadrant. With the diagnosis of acute appendicitis, open appendectomy was performed. Exploration of the abdominal cavity revealed perforated appendicitis and generalized peritonitis. Shigella sonnei was isolated from the peritoneal fluid culture. The patient completely recovered without any complications. Surgical complications, including appendicitis, could have developed during shigellosis. There are few reported cases of perforated appendicitis associated with Shigella. Prompt surgical intervention can be beneficial to prevent morbidity and mortality if it is performed early in the course of the disease. (J Pediatr Inf 2015; 9: 45-8)

Shigella: A Highly Virulent and Elusive Pathogen.

Despite a significant decrease in Shigella-related mortality, shigellosis continues to carry a significant burden of disease worldwide, particularly in Asia and Africa. Shigella is a highly virulent pathogen comprised of four major species with numerous subtypes. Shigella dysenteriae and Shigella flexneri infections are predominant in resource-limited settings. Clinical presentations range from mild watery diarrhea to severe dysentery with systemic complications such as electrolyte imbalance, seizures and hemolytic uremic syndrome. S. dysenteriae subtype 1, the producer of Shiga toxin, causes the most severe illness and highest mortality. Susceptible strains of Shigella may be effectively treated with inexpensive oral antibiotics such as ampicillin or trimethoprim-sulfamethoxazole. Unfortunately, multidrug resistant strains have emerged that have rendered most antibiotics, including fluoroquinolones and extended-spectrum cephalosporins, ineffective. Management and prevention of shigellosis represents a major public health challenge. The development of an effective vaccine is urgently needed to decrease its global impact.

Misdiagnosed amoebic colitis leading to severe dysentery and necrotizing colitis—Report of a case and review of the literature

We present a case of amoebic colitis, misdiagnosed as inflammatory bowel disease and treated with corticosteroids, leading to severe necrotizing enterocolitis. We review the literature on the epidemiology, pathogenesis, diagnosis, and treatment of amoebic dysentery, with special emphasis on the association between immunosuppressive treatment and the development of severe invasive amoebiasis.

Appendicial Entamoeba Histolytica Ulcer Mimicking Cancer

Purpose: A 58-year-old diabetic Lebanese male was evaluated for a screening colonoscopy. He had traveled to Lebanon two years ago, but was otherwise asymptomatic. During the colonoscopy, there was a 12-mm ulcerated lesion at the appendiceal orifice that was suggestive of a neoplasm. However, biopsy of the lesion showed colonic mucosa with cryptitis and mucosal erosions, with adherent amebae organisms. Moreover, ingested red blood cells were seen within the organisms, suggesting the lesion was most likely related to an Entamoeba histolytica infection. The patient was treated with Flagyl 500 mg tid and Paromomycin 250 mg tid times both for 10 days. He will have a repeat colonoscopy in a couple of months to evaluate if the ulcer healed. Entamoeba histolytica is an intestinal protozoan that is responsible for 40,000 deaths worldwide. It commonly infects people who live in underdeveloped countries, or individuals who travel to endemic areas. Roughly 90% of Entamoeba histolytica infections are asymptomatic, but the other 10% may have symptoms that can be quite profound, ranging from mild diarrhea to severe dysentery. Invasive infections, which are rare and occur in 0.5% of cases, include fulminant colitis with bowel necrosis, perforation, toxic megacolon, and spread to the liver, lungs, brain, and heart. The diagnosis and treatment is crucial, even in asymptomatic individuals like our patient, since it can quickly progress to invasive disease, especially in those who are diabetics, immunocompromised, alcoholics, or have the Entamoeba histolytica strain. It is best diagnosed by a combination of serology or antigen testing in conjunction with detection of the parasite in the stool. However, direct visualization of the colonic mucosa by colonoscopic biopsy can be of tremendous help, since these serological markers stay positive even if the infection has cleared in asymptomatic individuals. Classic findings on colononscopy and biopsy include diffuse, multiple areas of punctuate ulcerations that show non-specific inflammation or, as in severe disease, may appear necrotic. However, it is extremely rare to have focal, solitary ulcers present in asymptomatic patients who have Entamoeba histolytica strain infections, as these ulcers can be mistaken for a neoplasm. Our case demonstrates a diabetic, asymptomatic 58-year-old Lebanese male with such a case. Solitary Entamoeba histolytica-induced colonic ulcers, albeit rare, must be considered in any patient with a focal colonic ulcer or mass that mimics colonic neoplasm. Biopsy of the ulcer and histologic evaluation must be undertaken with prompt treatment with Flagyl and/or Parmomomycin, so as to prevent invasive Entamoeba histolytica infection and its complications.

Tyrosine kinases, drugs, and Shigella flexneri dissemination

Shigella flexneri is an enteropathogenic bacterium responsible for approximately 100 million cases of severe dysentery each year. S. flexneri colonization of the human colonic epithelium is supported by direct spread from cell to cell, which relies on actin-based motility. We have recently uncovered that, in intestinal epithelial cells, S. flexneri actin-based motility is regulated by the Bruton’s tyrosine kinase (Btk). Consequently, treatment with Ibrutinib, a specific Btk inhibitor currently used in the treatment of B-cell malignancies, effectively impaired S. flexneri spread from cell to cell. Thus, therapeutic intervention capitalizing on drugs interfering with host factors supporting the infection process may represent an effective alternative to treatments with antimicrobial compounds.

Evaluation of an intragastric challenge model forShigella dysenteriae1 in rhesus monkeys (Macaca mulatta) for the pre‐clinical assessment ofShigellavaccine formulations

Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains.

Cecal Mass, Ameboma

Introduction: The differential diagnosis of a cecal mass includes inflammatory, infections and neoplastic etiologies. In the U.S., we often fail to consider infectious causes in a patient who presents with CT evidence of a cecal mass and lymphoadenopathy. The aim of this case report is to present such a patient with an ameboma. Case: A 50-year-old Ecuadorian Male was seen for evaluation of findings on CT of the abdomen. The CT showed diffuse wall thickening of the cecum. The patient denied diarrhea, nausea, vomiting, or fever. Appetite was good and his weight was stable. He had daily formed stools denied BRBPR. His ROS was non contributory. He was not taking any medications. Physical Exam: was unremarkable.Work up included: CBC, BMP, LFT, O/P, all normal. Colonoscopy was normal until the cecum which had an ulcerated, friable on contact mass encompassing one third of the lumen of the cecum; a normal appearing Ileum; multiple biopsy were taken of the mass. The patient was started on metronidazole 500 mgs PO TID, while waiting for biopsies result. Biopsy of cecum mucosa revealed: acute and chronic inflammation and rare branched glands and organisms consistent with E. histolytica. Giemsa stain highlighted the organisms. Discussion: Intestinal amebiasis is caused by the protozoan E. histolytica. Most of Entamoeba infections are asymptomatic as in our patient but this depends on a multiplicity of factors. Clinically the infection will have a variety of symptoms that can range from mild diarrhea to severe dysentery, abdominal pain, bloody stools. Rarely patients with longstanding infection can develop a hyperplastic granulomatous lesion which can form a mass resembling colon cancer, and can present both with a palpable tender mass and as a mass seen on CT or on colonoscopy. These so called amebomas such as in our patient are usually solitary lesions, of variable size, affecting men between 20 and 60 years of age. These lesions most commonly develop in the cecum as in our patient. If biopsy proves that E. histolytica is present, then the duration of treatment with metronidazole should be 7 to 10 days to completely eliminate the intestinal infection. Summary: In patients who present for evaluation with a colonic mass, especially those that are localized in the cecum our main concern should be to rule out a malignancy, but when evaluating this patients we should take in consideration the epidemiology and prevalence of diseases, as in our case presentation, where the patient was living in a highly endemic area for Entamoeba. Once stool and multiple biopsies of the lesion have been accomplished patients should be started on a metronidazole, while waiting for biopsy results.

The structure of the Escherichia coli O148 lipopolysaccharide core region and its linkage to the O-specific polysaccharide

Recently it was demonstrated that Shigella dysenteriae type 1, a cause of severe dysentery epidemics, gained its O-specific polysaccharide (O-SP) from Escherichia coli O148. The O-SPs of these bacteria differ only by a galactose residue in the repeat unit of S. dysenteriae type 1 in place of a glucose residue in E. coli O148. Herein, we analyzed the core structure and its linkage to the O-SP in E. coli O148 LPS. Both were found to be identical to those of S. dysenteriae type 1 structures, further supporting the relatedness of these two bacteria. The following structure of the core with one repeat unit of the O-SP has been assigned (all have d-configuration except l-Rha): ▪

Subtype prevalence, plasmid profiles and growing fluoroquinolone resistance in Shigella from Kolkata, India (2001-2007): a hospital-based study

Shigellosis is a major public health problem, and increasing antimicrobial resistance has complicated its treatment. We report isolation frequency, plasmid profiles and antimicrobial resistance of Shigella subtypes in Kolkata, India, from a prospective hospital-based study. Fresh stool or rectal swabs were collected from children (<5 years) attending the Diarrhea Treatment Unit of a governmental paediatric referral hospital in Kolkata. Samples were processed following standard methods over a 7-year period from January 2001 to December 2007. Of 4478 samples collected, 516 (11.5%) were positive for Shigella spp. S. flexneri (312; 6.9%) was the most frequently isolated serogroup, ranking before S. sonnei (123, 2.7%), S. dysenteriae (48, 1.1%) and S. boydii (33, 0.7%). Although 10 subtypes of S. flexneri were identified, the common ones circulating locally were S. flexneri 2a (179), S. flexneri 6 (38) and S. flexneri 3a (36). Knowledge of Shigella subtypes is important for vaccine development. The majority of Shigella isolates (81.0%) were multidrug (two or more antimicrobial classes) resistant and showed high minimum inhibitory concentration (MIC) with commonly used drugs like ampicillin, tetracycline, co-trimoxazole and nalidixic acid. Emergence of fluoroquinolone (FQ)-resistant S. dysenteriae type 1 (100.0%) in 2002-2003 was followed by frequent isolation (>25.0%) of FQ-resistant S. flexneri 2a, and S. flexneri 3a in 2004, which restricted use of fluoroquinolones for treatment. A number of smaller plasmids (<20 kb) with distinct patterns have been observed for several years in predominant subtypes. Long-term surveillance of Shigellae and their antimicrobial resistance are mandatory in endemic areas to formulate treatment policy until any suitable candidate vaccine is available to control the disease.

Medics, Monarchs and Mortality, 1600-1800: Origins of the Knowledge-Driven Health Transition in Europe

Medical knowledge – defined broadly to include both its private and public forms – has been the driving force behind the historical transitions that have raised life expectancy in modern Europe. Advances in knowledge, rather than better nutrition (particularly the escape from caloric insufficiency) deserve greater emphasis because the very first groups to undergo anything recognizable as a secular rise in longevity were the rich and well fed, rather than the poor and chronically malnourished. At the beginning of the 16th century Europe’s ruling elites lacked virtually any reliable information about how best to use their ample material resources to prevent, manage and cure the ill-health that caused so many premature deaths among them.The advance of medical knowledge and practice accelerated in Western Europe after c. 1500, with a succession of discoveries that were quite useful (as judged by modern standards) in preventing disease, reducing “life-style” risks, managing illness and providing cures for a few debilitating and deadly diseases – severe dysentery, syphilis, malaria, scurvy and, finally, smallpox, being the principal diseases affected. Yet, access to most of the available innovative medical care remained closely restricted. Medical expertise was limited and highly priced, and many of the measures prescribed were unaffordable even to town-dwelling middling-income families in environments that exposed them to endemic and epidemic disease. Along with the poor, they therefore were left at a grave health disadvantage vis-a-vis adult members of the wealthy urban families to whose conditions the doctors were attending. The London-based ruling family of England in this epoch benefited to an exceptional degree among the European elites from the contemporary progress of medicine: their improved chances of survival in adulthood was the major factor raising royal life expectancy at birth (males and females, combined) from 24.7 years for the cohort born during the 1600s to 49.4 years for those born during the 1700s.

Ceftriaxone resistant Shigella Flexneri, an emerging problem

Shigellosis is a disease of public health importance in developing countries. It may cause self-limited diarrhea to severe dysentery. Emergence of multi drug resistant (MDR) strains is a growing concern globally. Ceftriaxone and ciprofloxacin are the drugs of choice for MDR cases. Here, we report a case of MDR Shigella flexneri from an immunocompromised patient. The strain was resistant to ceftriaxone [minimum inhibitory concentration (MIC) ≥ 64 μg/ml], limiting the treatment option. Simultaneously, the strain was also found to be resistant to ciprofloxacin (MIC ≥ 4 μg/ml). However, it was susceptible to ceftazidime (MIC 4 μg/ml). This is the first case of ceftriaxone resistant Shigella spp. reported from our hospital.

Site-specific modification of Shigella flexneri virF mRNA by tRNA-guanine transglycosylase in vitro.

Shigella flexneri is an enteropathogen responsible for severe dysentery in humans. VirF is a key transcriptional regulator that activates the expression of the downstream virulence factors required for cellular invasion and cell-to-cell spread of this pathogen. There are several environmental factors that induce the translation of VirF including temperature, pH, osmolarity and post-transcriptional RNA modification. Durand and colleagues (vacC, a virulence-associated chromosomal locus of Shigella flexneri, is homologous to tgt, a gene encoding tRNA-guanine transglycosylase of Escherichia coli K-12. J. Bacteriol., 176, 4627–4634) have demonstrated a correlation between VirF and tRNA-guanine transglycosylase (TGT), which catalyzes the exchange of the hypermodified base queuine for the guanine in the wobble position of certain tRNAs. They characterized tgt- mutant S. flexneri strains in which the translation of VirF is markedly reduced and the bacteria are unable to invade host cells. Although the function of TGT is to modify tRNA, we report that the virF mRNA is recognized by the Escherichia coli TGT (99% identity to the S. flexneri TGT) in vitro. Further, we show that this recognition results in the site-specific modification of a single base in the virF mRNA. In the context of previous reports that small molecule binding motifs (‘riboswitches’) in mRNAs modulate mRNA conformation and translation, our observations suggest that TGT may modulate the translation of VirF by base modification of the VirF encoding mRNA.

Reflections on my studies of the effects of sulphonamide drugs in bacillary dysentery in Egypt, 1943-1944

Reflections on my studies of the effects of sulphonamide drugs in bacillary dysentery in Egypt, 1943-1944

Enteroinvasive Escherichia coli severe dysentery complicated by rotavirus gastroenteritis

Enteroinvasive Escherichia coli (EIEC) is an important agent of pediatric diarrhea and dysentery in developing countries. We report a life-threatening severe dysentery case due to EIEC in a malnourished 4-month-old male, native Indian infant co-infected with rotavirus. The severe gastrointestinal bleeding anemia and hypovolemic shock was successfully treated with IV blood transfusions, rehydration and antibiotic therapy.