Infection with enterohemorrhagic Escherichia coli (EHEC) serogroup O157 is one of the significant emerging diseases globally, which causes a variety of symptoms such as abdominal cramps, diarrhea and hemorrhagic colitis. As a serious complication, the haemolytic uremic syndrome (HUS) sometimes occurrs, which can lead to the death of the patient (1). Since the bacteria were first found in the North America in 1982, they have been isolated in many places around the world, especially in developed countries (2). Although our knowledge of the virulence mechanisms of this pathogen is still limited, the pathogenic factors of EHEC seem to consist of at least three independent elements: Shiga toxin (Stx) (3), which is cytotoxic for Vero cells and presently classified in two broad types, Stx1 and Stx2, is encoded by a temperent phage and associated with hemolytic uremic syndrome (1); the chromosomal LEE locus (4), which is a 35kb element also present in enteropathogenic E. coli and encodes genetic factors involved in the attaching and effacing process; a large plasmid carrying the hemolysin genes, of which role during infection is still unknow, but a correlation between the occurrence of the HUS and the presence of the hemolysin genes has been observed (5). In Japan, since an EHEC O157:H7 outbreak in which two out of 268 patients died of HUS occurred in a kindergarten at Urawa City of Saitama Prefecture in 1990, which cause was attributed to well water contaminated by the pathogen, a great attention has been drawn to this disease. We then established reporting system of EHEC isolates by the cooperation with prefectural and manucipal public health institutes (PHIs) and every report of EHEC isolation has been collected to IASR (Infectious Agents Surveillance Report) in NIID (National Institute of Infectious Diseases) since 1991. Until 1995, such reports of isolation
Shigellosis is an infectious disease of global importance, and also an important cause of traveler's diarrhea (1). Although improved public health measures have greatly reduced its incidence in the developed countries where the disease is now sporadic, it continues to be a major cause of childhood morbidity, deaths and growth-faltering in the developing world where epidemic form of the disease is associated with increased morbidity and deaths (1-5). S. dysenteriae, S. flexneri, S. boydii and S. sonnei are the four species of Shigella which together have over 45 serotypes. S. dysenteriae type 1, the epidemic serotype in the developing countries, causes the most severe form of the disease as well as more complications, and is also the most efficient in acquiring antimicrobial resistance (1, 6, 7). S. flexneri, endemic in many developing countries, causes a disease of intermediate severity, and S. sonnei, prevalent in the developed countries, generally causes a milder, non-dysenteric form of illness, however, is also efficient in acquiring antimicrobial resistance (1, 8, 9).
INTRODUCTION Shiga-toxin (stx)-producing Escherichia coil (STEC), also referred to as Verocytotoxin (VT)-producing E. coil (VTEC) (25) are causes of a major zoonotic food-borne illness (12, 20) whose spectrum includes non-specific diarrhea, hemorrhagic colitis (42), and the hemolytic uremic syndrome (HUS) (21, 24) which is the leading cause of acute renal failure in children. Not only do VTEC rival non-typhoidal Salmonella spp. and Campylobacter spp. as the commonest agents of sporadic bacterial diarrhea (12, 37), they have also been responsible for massive outbreaks of illness with significant morbidity and mortality. Examples include the lunch-foodassociated Japanese outbreak in Sakai in 1996 (9) which affected over 6,000 children with 102 cases of HUS and 3 deaths and the food-borne outbreak in the U.S. in 1993 (8) which affected 500 cases with 171 hospitalizations, 43 HUS cases, and 4 deaths. HUS, the most serious complication of VTEC infection, is associated with significant long-term morbidity, with renal dysfunction in up to 40% of the patients, and a mortality rate of 3%-5% (27, 50). The syndrome occurs most frequently in young children with an annual incidence, in North America, of about 2-3 cases per 100,000 children under 5 years of age (12) in contrast to a roughly 10-fold higher incidence in this age group in Argentina (29). Given that no specific treatment is currently available for HUS, immunization against VTEC infection may be the only practical option for limiting the serious morbidity and mortality associated with this condition. Unfortunately knowledge about the nature of protective immunity associated with VTEC infection is still in its infancy.
The program of the National Epidemiological Surveillance of Infectious Diseases under the auspices of the Ministry of Health and Welfare started in 1981 apprehended in 1995 emergence of adenovirus type 7 in Japan. We analyzed the reported data of type 7 comparing with those of type 3, both belonging to the same subgenus B, and the following results were obtained:After 1981, the main serotypes in the reports of adenovirus isolation/detection were types 3, 2, and 1 in this order. The reports of isolation of adenovirus type 7 used to be extremely few, however, suddenly increased in 1995. In 1997, reports of isolation of adenovirus type 3 decreased and those of type 7 acquired the third place after those of types 2 and 3. Type 7 infection occur almost every month, but most frequently during May-September. The ages of cases from which type 7 was isolated were 0-4 years accounting for 55%, 5-9 years 35%, teens 6.3% and adults 4.0%, being similar proportions to those yielding type 3.Clinical diagnoses of cases yielding adenovirus type 7 were pharyngoconjunctival fever (PCF) and influenza-like illness, these two accounting for half. The symptoms were severe, being characterized by higher maximum body temperature during the feverish period and severe pneumonia. Encephalitis and arthro-muscular pain were seen in only type 7-infected cases, although such cases were few.
Atayal aborigines, living at an altitude of 1,500-1,600 m in northeastern Taiwan, still hunt for wild animals with the help of hunting dogs. In this study, the latex agglutination test (LAT) was used to detect sera anti-toxoplasma antibodies in this community as a measure of their exposure to Toxoplasma gondii. The positive rates for sera anti-toxoplasma antibodies were 21.8% and 19.6%, respectively, in 422 Atayal and 51 hunting dogs tested. Neither of the positive rates were found to be significantly different between male (22.1%) and female Atayal (21.4%), or between humans (21.8%) and dogs (19.6%) (P > 0.05) when compared by the Chi-Squared test (chi 2-test). A significant difference was observed between the positive rates in adults (28.3%) and children (18.7%) (P < 0.05), and the age pattern of prevalence is consistent with an increasing duration of exposure to Toxoplasma gondii with age. The consumption of raw liver of wild animals or insufficiently cooked meat may be the major mode of transmission of toxoplasmosis in Atayal.
INTRODUCTION Shiga toxin-producing E. coil (STEC) O157:H7 and enteropathogenic E. coil (EPEC) produce a characteristic histopathology on intestinal epithelial cells known as attaching and effacing (AlE). The characteristics of this pattern includes effacement of epithelial cell microvilli and intimate adherence between the bacterium and the epithelial cell membrane. Marked cytoskeletal changes are seen directly beneath the adherent bacterium, including accumulation of polymerized actin, and the development of pedestal-like structures upon which the bacteria sit. Tzipori et al. (20) first reported the attaching and effacing histopathology in gnotobiotic piglets infected with STEC O157: H7 and it has since been reported in variety of animal species as well as with cultured epithelial cells infected with O157: H7 (reviewed in (14)). This pattern was first described for EPEC and it has been best characterized in this pathogen.
INTRODUCTION Salmonella typhi triggers a microfilament-dependent entry into cultured cells. Kinetic studies have revealed a strict physical limitation on S. typhi Ty2W invation into INT407 human epithelial cells at MOIs•†40. Analyses of time course-infected monolayers showed that all host cells were susceptible to S. typhi entry and that internalized bacteria were typically located in 2-3 foci of infection per host cell. Scanning EM/TEM revealed that the host cell apical surface contained 2-3 focal aggregates containing 1 or few bacteria bound to shortened microvilli. At 10-30 min postinfection, the host cell undergoes surface-detectable, cytoskeletal rearrangements resulting in the macropinocytosis of bound bacteria. These data indicate that S. typhi are internalized at 2-3 entry sites/receptors on infected INT407 cells, after which further entry is limited. Competitive inhibition assays showed that a KmR Ty2W strain was inhibited 2-3 logs in entry efficiency by monolayer pretreatment for 30 min with Ty2W, but did not reduce the microfilament-dependent, Yersinia invasin-mediated entry pathway. S. typhimurium entry was efficiently and competitively inhibited by Ty2W, indicating that these two serovars recognize the same major INT407 cell receptors. Preincubation of INT407 monolayers with mouse monoclonal antibodies to the ƒÀ1 integrin reduced invasion ability of E. coli HB 101
quently spread within and between the cells are a prerequisite for causing dysentery. The capacity of the bacteria to spread in the cytoplasm and then move into adjacent epithelial cells is know as intra / intercellular spreading, respectively, and requires the bacterial functions encoded by the virG (icsA) gene (1, 2, 3). After invasion of epithelial cells, Shigella become surrounded by F-actin. This F-actin •hclot•hthen rearranges into a tail which remains stationary in the cytoplasm and is left behind by bacteria moving ahead, in which the VirG protein recruits host components and mediate actin polymerization, which is thought to serve as the propulsive force (4, 5). The movement of S. flexneri within the host cells resembles the formation of filopodium of locomoting cells, since those are mediated by actin polymerization and cause membrane protrusions (2, 5). However, so far no known protein has been reported to be specifically involved in both phenomena. Several host proteins such as vinculin, plastin (fimbrin), filamin, ƒ¿ -actinin, profilin (6), VASP (7) have been identified as being associated with the F-actin tail generated by intracellular S. flexneri (8, 9, 10). Amongst these proteins, only vinculin can directly interact with VirG, in which the 95 kDa vinculin head domain interacting with the VirG a-domain is involved in promoting the formation of actin tail from intracellular Shigella (10). However, vinculin is not only associated with Shigella actin tail but is also widely distributed in focal adhesions, filopodia and lamellipodia (11). Recently, N-WASP was identified as the Ash/Grb2 binding protein in brain, but its expression was also noted in other tissues including the colon (12, 13). The sequence of N-WASP is
INTRODUCTION In 1896, Shiga isolated the causative organism from the feces and the intestinal walls of patients suffering from clinical dysentery in Tokyo, which is Shigella dysenteriae type 1. He confirmed the proof of pathogenicity of the organism by the finding of specific agglutimins against the organism in the blood of patients suffering, convalescing or recently recovered from the disease. Six yeas later, also in Tokyo, Kenzo Futaki isolated another type of Shigella from dysentery patients which is known as Sh. flexneri, isolated in Philippine in 1900 by Flexner. In Japan, since then for about sixty years, for notified dysentery cases the statistics indicated the morbidity 50 to 100 per one hundred thousand people every years; namely each year several ten thousands were notified. The predominating serotype of these dysentery patients were mostly Sh. flexneri, partially Sh. sonnei, seldom Sh. ambigua. Sh. dysenteriae 1 were never isolated.
INTRODUCTION Shigellosis, or bacillary dysentery, is a bloody diarrhea caused by the invasion of the human colonic and rectal mucosa by Shigella, a gramnegative microorganism belonging to the family enterobacteriaceae. In the developing world, children are the major victims with 600,000 deaths every year. The symptoms are characterized by early watery diarrhea rapidly followed by fever, intestinal cramps, and emission of mucopurulent and bloody stools. Immediate complications may occur, such as hypoglykemia, seizure, toxic megacolon, and the hemolytic uremic syndrome (HUS). A chronic enteropathy may also be observed with delayed thriving of affected children. There are four species of Shigella (Shigella sonnei, Shigella flexneri, Shigella dysenteriae and Shigella boydii). The worldwide endemic form of the disease is caused by S. sonnei and S. flexneri. The epidemic form, which accounts for deadly outbreaks in developing areas, is caused by S. dysenteriae 1. The latter, which was discovered in 1898 by the Japanese microbiologist Shiga, is still often referred to as the Shiga bacillus. It is characterized by the production of Shiga toxin, a potent cytotoxin accounting for the particular severity of the cases the Shiga bacillus usually causes. Shigella is a highly contagious microorganism which is transmitted directly from person to person by hand contact, or indirectly by contaminated food or water. High infectious capacity and rapid occurrence of multiple resistance to antibiotics make prevention and treatment of shigellosis a difficult task. No vaccine is yet available.
The program of the National Epidemiological Surveillance of Infectious Diseases under the auspices of the Ministry of Health and Welfare started in 1981 apprehended in 1995 emergence of adenovirus type 7 in Japan. We analyzed the reported data of type 7 comparing with those of type 3, both belonging to the same subgenus B, and the following results were obtained: After 1981, the main serotypes in the reports of adenovirus isolation/detection were types 3, 2, and 1 in this order. The reports of isolation of adenovirus type 7 used to be extremely few, however, suddenly increased in 1995. In 1997, reports of isolation of adenovirus type 3 decreased and those of type 7 acquired the third place after those of types 2 and 3. Type 7 infection occur almost every month, but most frequently during May-September. The ages of cases from which type 7 was isolated were 0-4 years accounting for 55%, 5-9 years 35%, teens 6.3% and adults 4.0%, being similar proportions to those yielding type 3. Clinical diagnoses of cases yielding adenovirus type 7 were pharyngo-conjunctival fever (PCF) and influenza-like illness, these two accounting for half. The symptoms were severe, being characterized by higher maximum body temperature during the feverish period and severe pneumonia. Encephalitis and arthro-muscular pain were seen in only type 7-infected cases, although such cases were few.
Iron is an important nutrient required by bacteria for optimal growth. Acquisition of iron from the host where iron is restricted is an important mediator of bacterial pathogenesis. In iron deplete chemically defined medium (CDM-Fe) growth of Acinetobacter baumannii was restricted as compared to iron replete medium (CDM + Fe). Bacteria developed four high molecular weight outer membrane proteins (OMPs) of 88, 84, 80 and 77 kDa in CDM-Fe medium which were absent in CDM + Fe medium, and are known iron regulated outer membrane proteins (IROMPs). A. baumannii secreted siderophores extracellularly into the medium which act as iron chelators which had been demonstrated in the supernatants of CDM-Fe media. The siderophore was of catechol type. This shows that A. baumannii under iron restricted conditions express IROMPs along with production of catechol type siderophore in order to acquire iron from the external milieu.
INTRODUCTION Since Shiga's bacilli were discovered 100 years ago, Shigella dysenteriae type I (SD 1) has been implicated in large-scale epidemics world-wide with many thousands of deaths. Its infectivity and virulence, protean manifestations and propensity to develop multi-drug resistance, has meant that as a cause of disease it has not been conquered despite all advances. Epidemic Shigella has been termed a disease of wars (1). The historian Herodotus attributed the defeat of the Persian army in 380 BC to dysentery. It also follows droughts in arid climates, when contamination of meagre water sources can result in significant outbreaks. In other instances epidemics have followed the breakdown of waste disposal and sanitation as a result of flooding. Indeed, the history of SD1 and its spread through Africa closely parallels the story of human strife and suffering, of warfare and of climatic disasters in my troubled continent. It shows also how management policies impact on evolving patterns of drug resistance in what is rapidly becoming an untreatable infection in many parts of the world.
This study was designed to study the in vivo prevalence and the heterogeneity of H. pylori in patients with gastroduodenal diseases in central Taiwan. H. pylori infection was detected in 74.1% (575/776) of the symptomatic population studied. The prevalence of H. pylori infection increased from 11.1% in those between the ages of one to 20, to 82.9% in those between the ages of 41 and 50, and to 84% in those between the ages of 51 and 60. There was no significant difference in the prevalence of H. pylori infection between men and women. Among different blood types, the prevalence and relative risk of H. pylori infection was significantly higher in blood group O patients (90.3%) than in blood group A (41%), blood group B (27.4%), or blood group AB (62%) patients. Metronidazole resistance was found in 6.7% of the primary isolates. The prevalence of metronidazole-resistant H. pylori strains was higher in women (7.69%) than in men (6.25%), but this difference was not significant. A total of 88% of H. pylori strains were cagA-positive. CagA gene-positive strains were present in 90.1% of duodenal ulcers, 90% of duodenal ulcers combined with gastric ulcer, 85.8% of gastric ulcers, and 69.2% of gastritis patients, and was significantly higher in peptic ulcer disease groups than in the gastritis group. In conclusion, there was a low incidence (6.7%) of metronidazole-resistant H. pylori strains and a high prevalence (88%) of H. pylori cagA-positive strains in central Taiwan. This study also demonstrated a significant in vivo correlation between active H. pylori infection and blood group O-positive patients, and showed a significant association between cagA gene-positive H. pylori strains and the development of peptic ulcers.
INTRODUCTION A fascinating aspect of Shigella pathogenesis is the small inoculum required to cause shigellosis. DuPont et. al. (5) summarized data from volunteer studies in which subjects were administered Shigella species in milk. The results of these studies showed that 500 S. flexneri, S. dysenteriae, or S. sonnei were sufficient to cause shigellosis and in some cases ingestion of as few as 10 organisms resulted in disease. This is an infective dose far lower than that reported in similar studies for most other enteric pathogens. The parameters involved in determining the infective dose of a pathogen are likely to be numerous. The route of infection, the specific virulence determinants encoded by the pathogen, the ability of the organism to avoid host immune defenses as well as the innate resistance of the host would all be expected to play a role. In general however, diarrheal disease is associated with a high infective dose for most pathogens, presumably because the low pH of the stomach provides a major barrier to intestinal colonization. Although a good deal of evidence supports the concept of a gastric barrier to intestinal colonization (4, 9, 11, 15), the mechanisms by which enteric pathogens survive exposure to pH have only been addressed in detail in the last few years. To begin dissecting determinants of low infective dose in shigellosis in vitro assays have been used to dissect the genetics and bacterial physiology of survival at low pH. Most enteric bacteria are neutrophiles able to grow only within a fairly narrow pH range between 5.5-and 8.0. The pH of the intestines generally falls within this range and thus provides a good habitat for neutrophiles such as Shigella species, Salmonella species and Escherichia coli. Very few of the large and diverse population of oral bacteria reach the intestines despite the fact that they are being constantly swallowed (4, 9, 11) It is
INTRODUCTION By the end of the 19 th century, the fruits of the new science of microbiology began to be realized and one discovery followed another with rapid succession. This year, 1998, celebrates the 100th anniversary of one of these important discoveries by the Japanese microbiologist Kiyoshi Shiga, who identified the etiologic agent of epidemic dysentery in Japan in 1898 (1, 2). Shiga called this organism Bacillus dysenteriae, however its genus name was subsequently changed to Shigella to honor its discoverer and S. dysenteriae type 1 is still often referred to as Shiga's bacillus.
INTRODUCTION There has been a dramatic increase in the incidence of EHEC O157: H7 infections in Japan since 1996. Infections with this organism are closely associated with hemolytic uremic syndrome (HUS) due to the production of Shiga toxin (Stx) as it known by the new nomenclature. Infections with EHEC O157: H7 have been associated with both sporadic cases and outbreaks of HUS. Several risk factors and predictive factors for progression of the O157 infection into HUS have been proposed such as 1) young or old age, 2 ) high level of leucocytosis, 3) high fever, 4) crampy abdominal pain, 5 ) nausea, and 6) copious bloody stool. We think all of these should be considered important. Furthermore, we want to add 7) hematuria, and 8 ) delayed diagnosis as risk factors (Table 1). Delayed diagnosis is one of the chief risk factor because delayed diagnosis means delayed administration of appropriate prevention strategy and also means that the disease has progressed to a stage where it may be difficult to revert. The basic approach to prevent serious illness caused by toxigenic enteropathogens would be to rapidly eliminate the etiologic agent and thereby prevent toxin accumulation in the host gut. However, antibiotic treatment of patients infected with EHEC O157:H7 has been documented to be a risk factor for the progression of enteritis to HUS 1, 2). To address the issue of the role of antibiotic use, we conducted a retrospective nation-wide survey of EHEC infection diagnosed in 1996 by questionnaires sent to 3908 hospitals all over Japan. In 1996 we had a deluge of EHEC infections 3, 4). Chief physicians from 1682 hospitals and returned the questionnaires through April 30, 1997 (response rate was
