|Year : 2016 | Volume
| Issue : 5 | Page : 565-576
Shigellosis: Epidemiology in India
Neelam Taneja1, Abhishek Mewara2
1 Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
2 Department of Medical Parasitology, Postgraduate Institute of Medical Education & Research, Chandigarh, India
|Date of Submission||12-Mar-2014|
|Date of Web Publication||28-Jul-2016|
Dr Neelam Taneja
Department of Medical Microbiology, Postgraduate Institute of Medical Education & Research, Chandigarh 160 012
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Shigellosis is one of the major causes of diarrhoea in India. The accurate estimates of morbidity and mortality due to shigellosis are lacking, though it is endemic in the country and has been reported to cause many outbreaks. The limited information available indicates Shigella to be an important food- borne pathogen in India. S. flexneri is the most common species, S. sonnei and non-agglutinable Shigellae seem to be steadily surfacing, while S. dysenteriae has temporarily disappeared from the northern and eastern regions. Antibiotic-resistant strains of different Shigella species and serotypes have emerged all over the world. Especially important is the global emergence of multidrug resistant Shigellae, notably the increasing resistance to third generation cephalosporins and fluoroquinolones, and also azithromycin. This calls for a continuous and strong surveillance of antibiotic resistance across the country for periodic updation of the local antibiograms. The prevention of shigellosis is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country. Public health measures like provision of safe water and adequate sanitation are of immense importance to reduce the burden of shigellosis, however, the provision of resources to develop such an infrastructure in India is a complex issue and will take time to resolve. Thus, the scientific thrust should be focused towards development of a safe and affordable multivalent vaccine. this review is focused upon the epidemiology, disease burden and the therapeutic challenges of shigellosis in Indian perspective.
Keywords: Epidemiology - India - MDR Shigella - molecular epidemiology - shigellosis
|How to cite this article:|
Taneja N, Mewara A. Shigellosis: Epidemiology in India. Indian J Med Res 2016;143:565-76
| Introduction|| |
Shigella species, members of the family Enterobacteriaceae, are responsible for causing acute gastroenteritis which is one of the most common causes of morbidity and mortality in children in developing countries. Shigellosis is ubiquitous in impoverished populations of Asian and African countries and antibiotic-resistant strains of different Shigella species and serotypes have emerged all over the world. Although shigellosis is associated with a few medical complications only, adequate control of this disease may reduce the overall diarrhoea burden globally. The diagnosis of shigellosis is made by culture isolation of Shigella from faeces or rectal swabs. Antibiotic treatment is usually recommended to in patients with moderate or severe symptoms as it can reduce the duration and severity of symptoms, excretion of organisms, and prevent complications. However, empiric antimicrobial therapy requires knowledge of the local antibiogram of circulating Shigella strains. Especially important is the awareness of the global emergence of multidrug resistant (MDR) Shigellae, notably the increasing resistance to third generation cephalosporins and fluoroquinolones, and most recently azithromycin,,. In this review, we will focus upon shigellosis in Indian perspective, mainly addressing the epidemiological parameters, disease burden, molecular epidemiology and the therapeutic challenges of emerging MDR Shigellae.
| History|| |
Hippocrates used the term dysentery to indicate a condition characterized by the frequent passage of stool containing blood and mucus, accompanied by straining and painful defecation. At the end of the 19thcentury, epidemics of bacillary dysentery occurred periodically in Japan, when Kiyoshi Shiga examined dysenteric stools of patients and isolated a bacterium that was agglutinated by serum from convalescent patients but not with acute disease. Later, to honour Shiga, this bacterium was christened as Shigella dysenteriae type 1, the first organism of the genus Shigella. Following this discovery, the next few decades witnessed additional groups of related organisms being discovered and placed in this genus and named to honour the lead workers, Flexner, Sonne, and Boyd,,.
| Classification|| |
The genus Shigella belongs to family Enterobacteriaceae. It comprises four species, S. dysenteriae, S. flexneri, S. sonnei, and S. boydii, which are further classified into serotypes based on biochemical differences and variations in their O-antigen. Thus, S. dysenteriae (group A) has 17 serotypes, S. flexneri (group B) has 14 classical serotypes and subserotypes, S. sonnei (group C) has a single serotype and S. boydii (group D) has 20 serotypes.
Serogroup distribution: S. dysenteriae usually presents in epidemic and outbreak forms of the disease. S. flexneri and S. sonnei are mainly responsible for endemic disease in developing and developed nations, respectively, while S. boydii is restricted to India and neighbouring countries. S. flexneri was found to be the most commonly isolated species (68%) in a multi-centric study from six Asian countries including China, Vietnam, Thailand, Bangladesh, Pakistan, and Indonesia, except in Thailand where S. sonnei was the commonest (84%), while S. dysenteriae, which is most often seen in southern Asia and sub-Saharan Africa, constituted only 4 per cent of the isolates. From India, we have observed temporal shifts in prevalent serogroups of Shigellae at our tertiary care referral centre which caters to patients from eight adjoining states (Chandigarh, Punjab, Haryana, Himachal Pradesh, Jammu and Kashmir, western parts of Uttar Pradesh, Uttaranchal, and some parts of Rajasthan) thus representing a large geographical area. S. flexneri stood as the most common serogroup from 1994-2002, followed by S. dysenteriae type 1 emerging as the predominant serogroup after a decade in 2003. S. flexneri again emerged as the predominant serogroup since 20044,,,,. Such cyclical changes have also been reported from National Institute of Cholera and Enteric Disease (NICED), Kolkata, in eastern India where epidemics caused by S. dysenteriae periodically occur after a gap of a decade or so. Overall the authors have shown S. flexneri (60%) as the most prevalent serogroup, followed by S. sonnei (23.8%), S. dysenteriae (9.8%) and S. boydii (5.7%). Similarly, from Manipal and Puducherry in south India, S. flexneri figures as the predominant serogroup representing >90 per cent of the isolates,. Interestingly, a lesser prevalence of S. sonnei has been reported from these two centres (3.9-5.4%) in south India as compared to eastern India (23.8%),,. This observation was corroborated by data from Kolkata where again higher rates of S. sonnei (16.2%) were reported. Overall, S. flexneri was most common (74.7%), with serotypes 2a (51%) and 3a (28.7%) being predominant among children less than 5 years. In Global Enteric Multicenter Study, serogroups 2a (26.4%), 3a (12.1%), 6 (5.5%), 4a (5.5%), 7 (5.5%) and 1b (1.1%) were found in 91 Shigella isolates from Kolkata. Another important feature was the emergence of untypeable Shigellae. At our centre, over nine years, around 4 per cent isolates were untypaeble. Similar trends of emergence of untypaeble Shigella strains (13%) have been reported from Kolkata. A peculiar observation from Kolkata was the absence of S. dysenteriae which was similar to our centre. In contrast, in Andaman islands in the Bay of Bengal over a period of seven years from 2006-2012, S. dysenteriae (12%) was recorded to be third most common, followed after S. flexneri (68%) and S. sonnei (20%). The heterogenous distribution of Shigella species and serogroups across the country implicates that multivalent or cross-protective Shigella vaccines are required to address the burden of shigellosis in India.
| Host|| |
Though humans and primates are the primary reservoir of Shigella, it has been isolated from various sources viz. aquatic bodies (rivers, surface waters as well as coastal waters), free living amoebae, insects, birds and wild animals,,,,,,,. For a continuous transmission in humans, however, the bacterium must be passed from one person to another, as it does not survive in planktonic phase for long outside the body.
| Routes of transmission/reservoirs and meteorological factors|| |
The primary mode of transmission is by faeco-oral route and as low as 10-100 bacteria can cause infection. Such a low infective dose enables Shigella to cause large outbreaks. The high incidence of Shigella in the developing world is generally attributed to lack of clean water, poor hygiene, malnutrition and close personal contact. Outbreaks have been associated with person-to-person transmission in crowded or unhygienic environments like prisons and asylums. Environmental factors such as rainfall and temperature have been shown to affect the transmission. The expression of virulence genes is activated when bacteria are shifted from 30 to 37°C, in medium of moderate osmotic stress and pH 7.433. Shigella infections can occur round the year, but peak prevalence in summer months has been reported. In most communities the incidence is highest in hot and dry weather, possibly because the scarcity of water in such conditions limits hand-washing and other hygiene measures that reduce person-to-person transfer of the bacteria. From Bay of Bengal islands, shigellosis is reported to occur mainly during rainy seasons, while low numbers of cases are recorded in winters.
Less commonly known route of transmission is through contaminated food and water or fomites. The ready-to-eat foods and beverages prepared by street-vendors can also be a source of shigellosis. In a study from Odisha in India, panipuri (a street food) samples examined for disease causing bacteria showed around 80 per cent to be coliform-positive with isolation of pathogenic bacteria like Escherichia More Details coli (13.6%), Klebsiella sp. (10.6%), Enterobacter sp. (28.8%), Bacillus sp. (3%), Enterococcus sp. (6.1%), Micrococcus tetragenus (3%), Salmonella More Details paratyphi B (1.5%), S. dysenteriae (4.5%) and Vibrio sp. (6.1%)35. Similarly, food handlers in large food service establishments often carry pathogenic microorganisms and may be a source of infection to a huge number of people. At a tertiary care centre in north India, amongst asymptomatic food handlers, Shigella was the most common bacteria isolated36.
In settings where disposal of human faeces is inadequate, flies, particularly Musca domestica, the common housefly, may serve as a vector for transmission of shigellosis. When guts of houseflies collected from various public places including a garden, public park, garbage/dump area, hospital, restaurant/canteen, and human habitation in Pune, Maharashtra, India, were cultured, 102 bacterial strains were isolated, majority of which were known potential pathogens including Shigella, along with Klebsiella, Aeromonas, Morganella, Providencia, and Staphylococcus. Also, animals in contact with human faeces may transiently harbour diarrhoeogenic bacteria as observed in Mumbai where Shigella as well as Salmonella, Pseudomonas, Streptococcus, Proteus and Pasteurella species were isolated from 200 pigs slaughtered at an organized slaughter house. Shigellae have also been found in avian reservoirs in a zoological garden in Madagascar, and muscle tissue of several wild animal carcasses from wildlife species in Canada.
Several aquatic bodies have been found to show presence of Shigellae and thus another potential source of infection may be aquatic food which may play a role in transmission of Shigella if such food is harvested from sewage-contaminated water. The distribution of major groups of enteric bacteria was explored in sediments from coastal areas in south India from different depths (5, 15, 25 and 35 meter), and the flora was found to constitute Vibrio parahaemolyticus, Shigella, Vibrio cholerae, Salmonella and E. coli with higher bacterial populations in monsoon and pre-monsoon seasons. Water samples of the river Narmada in Madhya Pradesh in India have been found to harbour S. flexneri, S. sonnei and S. dysenteriae. The virulence gene encoding the invasive plasmid antigen H (ipaH) was found in all the isolates, while the plasmid encoded invasion-associated genes (ipaBCD) were present only in S. flexneri, and the Shiga toxin (stx1) gene was found only in S. dysenteriae, thus demonstrating not only the existence of Shigella in the river but also the presence of an environmental reservoir of virulence genes. Similarly, Shigellae have been isolated from surface waters in Bangladesh. Shigella species have also been found to grow symbiotically inside Acanthamoeba castellanii implicating that free-living amoebae may serve as a transmission reservoir for Shigella in water. Such environmental gene pool may contribute to horizontal transfer of genes among strains and emergence of virulent strains leading to outbreaks, and may also help the bacteria to survive in odd conditions and re-emerge in favourable conditions.
| Risk groups|| |
No individual is immune to shigellosis, but certain individuals are at increased risk. Worldwide, the incidence of shigellosis is highest among children less than five years of age, but it has been observed that during S. dysenteriae type 1 epidemics all age groups are affected. The incidence of shigellosis has been reported to increase steadily after the age of 40, along with bacterial load as determined by semi-quantitative real-time PCR. This suggests that young children and old people shed the highest bacterial load and may be responsible for disproportional transmission of shigellosis. In children who are malnourished, Shigella may cause a vicious cycle of further impaired nutrition, recurrent infection and growth retardation. In the United States of America (USA) and Europe, children in day-care centers, migrant population, travellers to developing countries, persons in custodial institutions, prisoners and military personnel, and homosexual men are infected most often.
In HIV infected patients, intestinal parasitic pathogens are more common in antiretroviral therapy naive patients, however, the association of Shigella with HIV has not been properly studied in all patient groups. Association of shigellosis in men who have sex with men (MSM) has been implicated for a long time. In the 1970s and 1980s, shigellosis was identified as a potentially sexually transmitted disease among MSM41, and increased incidence in men was attributed to the sexual practices of MSM. A correlation between HIV infection and increased incidence of shigellosis from San Francisco area in 1996 suggested HIV as an important risk factor for shigellosis. Another study from San Francisco in 1998-1999 linked the sexual practices of direct oral-anal contact in MSM to confer the highest risk and HIV infection likely contributing to increased host susceptibility. Similar outbreaks of shigellosis among MSM have been reported from Canada, Australia, London, and Chicago,,,.
The data for higher incidence of Shigella in association with HIV infection are not so convincing from India. The common enteric pathogens detected in 331 HIV infected patients presenting with diarrhoea in Pune were Cystoisospora belli (28%) and Cryptosporidium parvum (12%), whereas in HIV uninfected individuals S. flexneri (4.9%) was the second most common pathogen, only after Entamoeba histolytica (7.1%)49. In another study from New Delhi, Shigella was only found in 2 per cent cases of diarrhoea in HIV infected patients showing a similar incidence as in immunocompetent individuals. in Senegal, Shigella was implicated as the most common cause (12.4%) of diarrhoea in immunocompetent adults but in immunocompromised individuals Shigella was fifth most common (7.6%)51. Shigellosis, presents as a more severe infection in HIV infected individuals, may cause bacteraemia and unusual features like keratitis and pneumonia, fail to respond to appropriate therapy thus requiring prolonged treatment, and may recur after completion of treatment,,.
| Clinical features and complications|| |
The clinical presentation ranges from watery, loose stools to severe symptoms such as fever, abdominal pain, tenesmus, and bloody diarrhoea. Severity of the disease varies by the infecting species - S. dysenteriae infections usually cause dysentery, which may also occur in infections caused by S. flexneri, whereas S. boydii and S. sonnei generally often self-limited watery diarrhoea. Acute complications such as toxic megacolon, peritonitis, and septicaemia are mostly observed in severely malnourished children, though may occur in absence of early antibiotic treatment. Shigella dysentery may also lead to dangerous complications such as persistent diarrhoea, severe anorexia, weight loss and malnutrition, dilation of the large intestine, seizures, kidney damage, and haemolytic-uremic syndrome. Bacteraemia may be reported in infants and immunocompromised adults. Pneumonia associated with S. sonnei has also been described in malnourished children, in HIV infected patients, and in patients with chronic diseases,.
| Mortality|| |
The advent of oral rehydration therapy to correct dehydration due to diarrhoea has greatly decreased the number of deaths due to diarrhoea of any aetiology. Severe dehydration is uncommon in shigellosis, and with proper hydration, shigellosis is generally a self-limiting disease. However, in severe cases, without antimicrobial treatment the mortality of shigellosis is greatly increased. The availability of age-specific estimates of case fatality due to shigellosis is limited. The death rate due to Shigella infection in developed countries is low (0.05 to 0.4%)58. The earlier data from developing countries over a period (1974-1988) have indicated that 13.9 per cent of infants and 9.4 per cent of 1-4 year-olds die annually due to shigellosis as estimated in admitted patients at the International Centre for Diarrhoeal Disease Research (ICDDRB), Bangladesh. However, there is a change in this situation in recent years where a decrease in mortality due to shigellosis has been observed as compared to the previous reports. In a multi-centric study from six Asian countries, no deaths were recorded in 845 patients. The authors suggested adequate treatment to study participants and absence of S. dysenteriae type 1 as possible reasons for unexpectedly low morbidity and mortality in the survey.
| Epidemiology|| |
Shigellosis occurs worldwide, in endemic and epidemic forms. Majority of cases are children <5 yr of age. The annual number of shigellosis episodes throughout the world is estimated to be 164.7 million, with 69 per cent of all episodes and 61 per cent of all deaths attributable to shigellosis involving children <5 yr of age. The multi-centric study from six Asian countries estimated Shigella as the causative agent in 5 per cent of the diarrhoeal cases, indicating an overall incidence of treated shigellosis to be 2.1 episodes per 1,000 residents per year in all ages, with higher rates in children and people more than 40 yr of age. Among children <5 yr old, the incidence was 13 new cases per 1,000 children per year. From Bangladesh a trend of increasing number of patients ≥60 yr has been reported in an analysis of patients from 2001-2012 than children <5 yr and adults aged 5-5959. Reports of shigellosis from various parts of the country have shown an overall isolation rate of Shigellae varying from 3-6 per cent of all stool samples with diarrhoea,. At our tertiary care centre in north India, Shigellae have been detected from 3 per cent of diarrhoeal stool samples, whereas in Kolkata, Nair et al isolated 6.1 per cent Shigella spp. from hospitalized diarrhoeal patients. In paediatric age group, again, higher isolation rates have been reported, 9.5 per cent in Bay of Bengal islands and 11.5 per cent in Kolkata,.
Several epidemics have been reported from many Asian countries such as Bangladesh (1972-1978, 2003), Sri Lanka (1976), Maldives (1982), Nepal (1984-1985), Bhutan (1984-1985) and Myanmar (1984-1985),,,. In India, epidemics have been reported from southern India, Vellore (1972-1973, 1997-2001),, eastern India (1984),, Andaman and Nicobar islands (1986), and Chandigarh (2003) in northern India. Epidemic dysentery caused by MDR S. dysenteriae serotype 1 has been a recurrent challenge.
Outbreaks: Shigellae have the ability to cause outbreaks involving a large number of people. In the 1984 outbreak in West Bengal and Tripura, 3, 50, 000 people were affected with 3500 deaths. In the 2002 outbreak, which occurred in West Bengal and tea gardens of Siliguri, the overall attack rate was 25.6 per cent. The death rate among those admitted to hospital was 6 per cent and the overall case-fatality ratio was 0.9 per cent. All these outbreaks were due to S. dysenteriae serotype 1. The re-emergence of S. dysenteriae type 1 with added resistance to ciprofloxacin which has epidemic potential, has also been reported from our centre. Outbreaks caused by S. flexneri and S. sonnei have also been reported recently from various parts of the country like West Bengal (2007), Kerela (2009) and Maharashtra (2010)72,73. In 2007, in a municipality in West Bengal, S. flexneri serotypes 2a and 3a caused water borne outbreak affecting 461 persons. The sources associated with the illness were drinking, washing utensils and bathing in tap water contaminated with Shigella, and the outbreak subsided following repair of the pipeline. Food-borne outbreaks of S. sonnei have also been reported. More than 300 people suffered in Kerala in south India in 2009 where local food made of rice, lentils, milk, and water was implicated as the source. In Maharashtra in 2010, about 150 persons suffered from shigellosis after eating in a madrasa (a religious place)73. These reports support the extension of S. sonnei into India. These outbreaks indicate that in India, food- and water-borne routes for transmission of shigellosis may not be so uncommon, and thus reinforces the need to provide adequate sanitation.
Shigellae are also important agents of diarrhoeal disease in travellers from developed world to other countries. As per an estimate, 15-20 million travellers to developing countries experience diarrhoea annually. Of the 64,039 enteric infections reported to FoodNet with information about travel, 8270 (13%) were travel associated, and amongst the bacterial agents, Shigella (13%) was the third most common, after Campylobacter (42%), and non-typhoidal Salmonella (32%). The most common travel destinations were Mexico, India, Peru, Dominican Republic, and Jamaica.
| Therapeutic challenge of multidrug resistant Shigellae|| |
The emergence of MDR Shigella has been reported from all over the world, including the USA, Iran, China, Indonesia, Vietnam, Bangladesh and India,,,. The progressive development of antibiotic resistance in Shigella isolates, as in all other bacteria, is not a new phenomenon. Sulphonamides were the first drugs of choice when introduced in the early 1940s and all the Shigella strains were sensitive to this drug. In late 1940s sulphonamides became ineffective, and tetracycline followed by chloramphenicol were recommended for shigellosis. Soon, resistance to these two drugs was also observed and ampicillin and co-trimoxazole came to the rescue. These were clinically highly effective. However, during the epidemic in eastern India in 1980s, the S. dysenteriae type 1 isolates were found to be resistant to most of the antibiotics except nalidixic acid which was found to be clinically effective,. Later, resistance to nalidixic acid appeared in S. dysenteriae type 1 isolates from an outbreak in Tripura in 1988. In the late 1980s, fluoroquinolones (norfloxacin, ciprofloxacin and ofloxacin) were introduced in India and were found to be very effective for shigellosis, including MDR S.dysenteriae type 181.
In 1990, ciprofloxacin was recommended as the drug of choice for empiric treatment of shigellosis in view of the existing high level resistance to agents like chloramphenicol, ampicillin, co-trimoxazole and nalidixic acid. Ciprofloxacin proved to be highly effective in the treatment of shigellosis, but possibly due to overuse and misuse of this agent promoted by the easy over-the-counter availability of antibiotics without prescription, resistance emerged against this agent also. Outbreak investigations in India (Chandigarh, Siliguri, Aizawl and Diamond Harbour, Kolkata) showed high level resistance to ciprofloxacin, norfloxacin and ofloxacin,. At our centre, an outbreak of ciprofloxacin-resistant S. dysenteriae serotype 1 occurred in 2003. There was no mortality associated with these cases and they were managed by cefotaxime and amikacin. Thereafter, high levels of resistance to nalidixic acid (S. dysenteriae 81.8%, S. flexneri 74.1%) and ciprofloxacin (S. dysenteriae 54.5%, S. flexneri 45.6%) have consistently been noted in various serogroups of Shigellae,. From north eastern region, an outbreak of bacillary dysentery caused by quinolone resistant S. dysenteriae type 1 was reported. Another study from Kolkata reported MDR Shigellae most of which were found resistant to fluoroquinolones viz. ciprofloxacin (90%), norfloxacin (83%), and ofloxacin (81%), however, majority were still susceptible to ceftriaxone (94%)20. At another hospital in Kolkata, majority of Shigella isolates (81%) were MDR and emergence of fluoroquinolone-resistant S. dysenteriae type 1 (100%) in 2002-2003 was followed by frequent isolation (>25%) of fluoroquinolone resistant S. flexneri 2a and 3a in 2004, which restricted use of fluoroquinolones for treatment of shigellosis. Fluoroquinolones are thus no longer the preferred group of drugs for managing shigellosis in India.
World Health Organization (WHO) now recommends ceftriaxone, pivmecillinam and azithromycin as alternative drugs to fluroquinolone-resistant Shigellae. We found 15.1 per cent of S. flexneri isolates collected over a period of nine years (2000-2009) resistant to at least one of the third-generation cephalosporins (ceftriaxone/cefotaxime)4. The first isolate showing ceftriaxone resistance was obtained in 2001 and an increase in number of isolates resistant to third generation cephalosporins was observed 2005 onwards. This situation has now become a therapeutic challenge in this region. The minimum inhibitory concentration (MIC) values for Shigella isolates revealed a rise for ceftriaxone (MIC90: 12 mg/l) and cefepime (MIC90: 8 mg/l). MIC values for S. dysenteriae remained below 1 mg/l for ceftriaxone, however, for cefepime the MIC90 has raised to 4 mg/l. These infections caused by ceftriaxone resistant S. flexneri isolates were successfully treated by azithromycin at our center. Emerging resistance to cephalosporins has also been reported from Puducherry and Manipal in south India,. azithromycin has also now joined the exhaustive list of drugs to which Shigella has developed resistance.
MDR Shigellae have also been reported from travellers who have visited India. At Kansai Airport Quarantine Station in Japan, stool samples were collected from overseas travellers with a history of diarrhoea over the period 2001-2005, and 53-106 Shigella strains were isolated per year (average 82.4), about 80 per cent of which were S. sonnei, and the most frequent country of origin was India. Such widespread resistance to almost all classes of drugs presently in use for Shigellae narrows down the choice of effective antimicrobial agents for shigellosis and is a matter of concern.
| Molecular epidemiology|| |
There has been an upsurging interest in exploring the molecular epidemiology of genetically encoded virulence factors and antimicrobial resistance markers of Shigella. Such insights may be valuable in understanding the transmission patterns, severity of clinical presentations and response of Shigella to antimicrobial drugs.
Molecular epidemiology of virulence genes: Several virulence factors have been reported in Shigella. virulent genes of Shigella may be present in isolates from both symptomatic and asymptomatic people. In Kolkata, all 91 Shigella isolates from both cases and controls were positive for ipaH gene. Other virulence genes such as virulence regulator (VirF), secreted autotransporter toxin (sat), Shigella enterotoxin 1 subunit A (setA), Shigella enterotoxin 1 subunit B (setB), Shigella enterotoxin 2 (sen) and epithelial cell penetration encoded by invasion associated locus (ial) were detected in Shigella isolates in 80.2, 49.4, 27.4, 27.4, 80.2 and 79.1 per cent of cases and in 64.7, 52.9, 17.6, 17.6, 64.7 and 64.7 per cent of controls, respectively. The Shigella pathogenicity island (SH-PAI) was detected exclusively in serotype 2a. Such asymptomatic carriers may play a crucial role in the transmission of Shigellae in endemic communities.
Molecular epidemiology of antimicrobial resistance:
Shigella has adapted well to many antimicrobial agents due to its ability to carry mobile genetic elements that may facilitate inter- and intra-species dissemination of antimicrobial resistance genes. In Kolkata, integron carriage has been detected in high numbers in Shigella isolates from cases (76.9%) than from controls (3505%). Of these, atypical class 1 integron has been exclusively detected in S. flexneri from cases but not from the controls. The main mechanism of quinolone resistance involves accumulation of sequential mutations in DNA gyrase and DNA topoisomerase IV. The plasmid-mediated quinolone resistance (PMQR) has been described due to mutations in the aac(60)-Ib-cr gene that encodes for a variant of aminoglycoside acetyltransferase, also known to reduce ciprofloxacin activity,. PMQR genes in Shigellae have been reported from USA, Japan, China and India,,,. From north India, we screened S. flexneri (n=139) and S. dysenteriae serotype 1 (n=38) isolated over the period 2001-2011 for PMQR determinants, and found 6.2 per cent Shigellae to harbour PMQR determinants, of which two were positive for the qnrS1 gene while nine were positive for aac(60)-Ib-cr gene. A high MIC for ciprofloxacin (32 mg/l) was shown by four of the 11 PMQR-positive isolates, while majority of isolates with a ciprofloxacin MIC 1 mg/l were negative for PMQR determinants. Although qnrB is the most common gene belonging to the qnr family, we detected qnrS1-positive Shigella from the Indian subcontinent in two strains from 2010, indicating a relatively new appearance of this PMQR determinant among Shigella in India. After the description of qnrS1-harbouring Shigella in Japan, China and the USA, appearance of qnrS1-positive Shigella in India is a matter of concern. We also detected at least two mutations in the QRDRs of each of the 11 PMQR-positive strains by sequencing of gyrA and parC indicating that PMQR determinants may have provided selection advantage by contributing to reduced susceptibility to quinolones and thus facilitating the selection of gyrA/parC mutants. Besides, four of the PMQR-positive isolates were positive for blaCTX-M-15, one of which was also positive for blaCMY-285. A close association of aac(60)-Ib-cr with blaCTX-M-15 has been detected in Shigella and is of great concern as blaCTX-M-15 has emerged worldwide in recent years. From Andaman and Nicobar Islands also, presence of aac(60)-Ib-cr and qnrB in Shigella has been reported, indicating a widespread presence of these resistance determinants in the country.
Resistance to cephalosporins is mediated by extended-spectrum beta lactamases (ESBLs) which hydrolyze a wide variety of penicillins and cephalosporins. The ESBL mediated resistance to third-generations cephalosporins arises from mutations which broadens the spectrum of native beta-lactamases like TEM-1, TEM-2, and SHV-1. Another resistance mechanism includes overproduction of chromosomal or plasmid-derived AmpC beta-lactamases. We investigated the presence of antimicrobial resistance genes in 119 S. flexneri and 24 S. dysenteriae isolates over a period of nine years (2001-2009), and found 20 S. flexneri isolates with high MICs for cephalosporins. Nine of the 20 isolates were found to be positive for ESBL and six for AmpC production by phenotypic tests, and among the resistance determinants blaTEM closely resembling blaTEM-116 was the most common ESBL gene present in all 20 isolates, followed by blaCTX-M-15 in 10, blaOXA in eight, and blaCMY-2 in seven, while none was positive for blaSHV. In contrast, of the 88 isolates from Bay of Bengal islands, 2 per cent showed the presence of the blaSHV gene, while all 15 third generation cephalosporins-resistant isolates showed the presence of the blaTEM, blaOXA1, and blaCTX-M3 genes. a high ESBL prevalence in members of the Enterobacteriaceae family has been reported in India with blaCTX-M-15 being the most common ESBL gene. The finding of a high prevalence of ESBL producing genes like blaCTX-M-15 which spread by horizontal transfer and/or mobilization of genetic mobile elements by orofaecal route, has serious implications in terms of further spread of resistance to third generation cephalosporins to other regions. overcrowding and poor sanitation, and the selective pressure due to overuse of antibiotics have been considered responsible for such widespread dispersal of blaCTX-M-1596.
From south India in Bay of Bengal islands, other resistance determinants were analyzed in 88 isolates and MDR was found to be associated with various drug-resistant genes. Ampicillin resistance was largely associated with TEM β-lactamase genes (100% isolates), the most prevalent resistance gene in ampicillin-resistant Enterobacteriaceae while gentamicin resistance was associated with aac2 gene in 22 per cent of the isolates. Plasmid mediated resistance was commonly found for tetracycline (tetB in 92% and tetA efflux genes in 90%), chloramphenicol (catI gene in 32%) and co-trimoxazole (dfrA1 in 81% and dfrA5 in 78%)22. Thus, there is a widespread emergence of MDR Shigella in the face of rampant injudicious antimicrobial use which reinforces the need for continuous surveillance of antimicrobial resistance determinants across the country to know the molecular epidemiology of resistance, which is further essential for implementing timely intervention steps to control the disease as well as spread of these resistance genes to other parts of the world.
| Prevention and control|| |
The most effective measure to decrease transmission of shigellosis is proper washing of hands, especially after defaecation. Community health education must emphasize upon good personal hygiene, adequate disposal of faeces, as well as the imminent threat of MDR pathogens. The widespread practice of misuse of antibiotics in viral diarrhoea should be discouraged by means of education as well as legislation. Better awareness about general measures such as washing, peeling and cooking of all fruits and vegetables, avoidance of food preparation by personnel who change diapers in daycare centres, proper handling and refrigeration of food, encouraging prolonged breastfeeding in infants, and appropriate case reporting to health authorities may be helpful to prevent further transmission. Though public health measures to reduce exposure and transmission are highly effective, the establishment of such infrastructure in developing countriesis resource intensive and thus remains challenging.
Vaccines: There is a strong need for an effective, safe and cheap vaccine against shigellosis. The high disease burden of shigellosis in developing countries, children <5 yr of age as the main victims, difficulty in achieving adequate sanitation and personal hygiene in these regions and scarce therapeutic alternatives for emerging MDR Shigella point towards vaccination as a hope for effective and sustainable strategy against shigellosis. Shigellosis is targeted by WHO as one of those enteric infections for which new vaccines are most needed, the target populations being travellers from developed countries and military service personnel, as well as children living in endemic areas,.
Although the need for a Shigella vaccine is urgent, not much progress has been done due to the antigenic complexity, lack of inter-species cross-protective epitopes, and gaps in understanding of the protective immune response. Several different types of vaccines against Shigella have been experimentally tested in animal models and in volunteer trials,. Various live attenuated vaccines such as CVD103, CVD104, CVD107, CVD108, SC602 and WRSS1 have been developed in the past, however, most were serotype-specific with no cross-protectivity. These vaccines progressed into phase 1/2 trials but none could go beyond. (Ipa, B, C) subunit vaccine approach has been used for Invaplex (Shigella invasion complex) containing invasion plasmid antigens B and C, and lipopolysaccharide (LPS), which was found to induce protective immunity in experimental animals. Similarly, outer membrane proteins are being developed as attractive vaccine options. However, apart from a live, non-invasive S. flexneri 2a-S. sonnei bivalent vaccine used in China, there are currently no licensed vaccines available. The current vaccine candidates are either not sufficiently attenuated or not properly immunogenic. Thus, the goal for an effective, safe and successful multivalent vaccine targeting prevalent species and serotypes is yet to be achieved,. Livio et al have shown that a quadrivalent vaccine with O antigens from S. sonnei, S. flexneri 2a, S. flexneri 3a, and S. flexneri 6 may be effective against these most common serotypes.
| Conclusion|| |
Shigellosis is one of the major causes of diarrhoea in India. S. flexneri is the most common species present in the country, S. sonnei and non-agglutinable Shigellae are steadily surfacing, while S. dysenteriae has temporarily disappeared from northern and eastern regions. Though shigellosis appears to be endemic and has been reported to cause many outbreaks, the accurate estimates of morbidity and mortality are lacking. The limited information available indicates Shigella to be an important food-borne pathogen in India. There is a nationwide presence of MDR Shigellae developing rapid resistance to most antibiotics available. Thus, judicious use of antibiotics for Shigella is amongst the most essential measures to combat shigellosis. This calls for a continuous and strong surveillance of antibiotic resistance across the country for periodic updation of the local antibiograms. The prevention of shigellosis is desirable as it will substantially reduce the morbidity associated with diarrhoea in the country. Public health measure like provision of safe water and adequate sanitation are of immense importance to reduce the burden of shigellosis, however, the provision of resources to develop such infrastructure to the huge population of a country like India is a complex issue and will take time to resolve, hence focusing the scientific thrust towards development of a safe and affordable multivalent vaccine may be the need of the hour.
| References|| |
DuPont HL. Shigella
species (bacillary dysentery). In: Mandell GL, Bennett JE, Dolin R, editors. Principles and practice of infectious diseases. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 2905-10.
von Seidlein L, Kim DR, Ali M, Hyejon Lee H, Wang X, Thiem VD, et al.
A multicentre study of Shigella
diarrhoea in six Asian countries: disease burden, clinical manifestations, and microbiology. PLoS Med
2006;3 : e353.
Kuo CY, Su LH, Perera J, Carlos C, Tan BH, Kumarasinghe G, et al.
Antimicrobial susceptibility of Shigella
isolates in eight Asian countries, 2001-2004. J Microbiol Immunol Infect
2008; 41 : 107-11.
Taneja N, Mewara A, Kumar A, Verma G, Sharma M. Cephalosporin-resistant Shigella
flexneri over 9 years (2001-09) in India. J Antimicrob Chemother
2012; 67 : 1347-53.
Li YL, Tewari D, Yealy CC, Fardig D, M'ikanatha NM. Surveillance for travel and domestically acquired multidrug-resistant human Shigella
infections-Pennsylvania, 2006-2014. Health Secur
2016;14 : 143-51.
Nüesch-Inderbinen M, Heini N, Zurfluh K, Althaus D, Hächler H, Stephan R. Shigella
antimicrobial drug resistance mechanisms, 2004-2014. Emerg Infect Dis
2016; 22 : 1083-5.
Shiga K. About the causative agent of dysentery in Japan: Preliminary communication. Zentralbal Bakteriol Microbiol Hyg
1898; 23 : 599-600.
Flexner S. On the etiology of tropical dysentery. Bull Johns Hopkins Hosp
1900; 11 : 231-42.
Kruse W. About the dysentry as a widespread disease and its pathogens. Dtsch Med Wochenschr
1900; 26 : 637-9.
Venkatesan M, Fernandez-Prada C, Buysse JM, Formal SB, Hale TL. Virulence phenotype and genetic characteristics of the T32-ISTRATI Shigella
flexneri 2a vaccine strain. Vaccine
1991; 9 : 358-63.
Wei J, Goldberg MB, Burland V, Venkatesan MM, Deng W, Fournier G, et al.
Complete genome sequence and comparative genomics of Shigella
flexneri serotype 2a strain 2457T. Infect Immun
2003;71 : 2775-86.
Venkatesan MM, Ranallo RT. Live-attenuated Shigella
vaccines. Expert Rev Vaccines
2006; 5 : 669-86.
Taneja N, Khurana S, Verma AD, Sharma M. Changing trends in shigellosis at a tertiary care centre. Indian J Pathol Microbiol
2003; 46 : 280-1.
Taneja N, Lyngdoh V, Vermani A, Mohan B, Rao P, Singh M, et al.
Re-emergence of multi-drug resistant Shigella
dysenteriae with added resistance to ciprofloxacin in north India & their plasmid profiles. Indian J Med Res
2005; 122 : 348-54.
Taneja N, Lyngdoh VW, Sharma M. Haemolytic uraemic syndrome due to ciprofloxacin-resistant Shigella
dysenteriae serotype 1. J Med Microbiol
2005; 54 : 997-8.
Taneja N. Changing epidemiology of shigellosis and emergence of ciprofloxacin-resistant Shigellae in India. J Clin Microbiol
2007; 45 : 678-9.
Pazhani GP, Ramamurthy T, Mitra U, Bhattacharya SK, Niyogi SK. Species diversity and antimicrobial resistance of Shigella
spp. isolated between 2001 and 2004 from hospitalized children with diarrhoea in Kolkata (Calcutta), India. Epidemiol Infect
2005;133 : 1089-95.
Mamatha B, Rituparna C. Decreased susceptibility to antimicrobials among Shigella
flexneri isolates in Manipal, South India - a 5 year hospital based study. Southeast Asian J Trop Med Public Health 2012; 43 : 1447-51.
Mandal J, V G, Emelda J, S M, Parija SC. The recent trends of Shigellosis: A JIPMER perspective. J Clin Diagn Res
2012; 6 : 1474-7.
Nair GB, Ramamurthy T, Bhattacharya MK, Krishnan T, Ganguly S, Saha DR, et al.
Emerging trends in the etiology of enteric pathogens as evidenced from an active surveillance of hospitalized diarrhoeal patients in Kolkata, India. Gut Pathog
2010;2 : 4.
Livio S, Strockbine NA, Panchalingam S, Tennant SM, Barry EM, Marohn ME, et al. Shigella
isolates from the Global Enteric Multicenter Study Inform Vaccine Development. Clin Infect Dis
2014; 59 : 933-41.
Bhattacharya D, Bhattacharya H, Thamizhmani R, Sayi DS, Reesu R, Anwesh M, et al.
Shigellosis in Bay of Bengal Islands, India: clinical and seasonal patterns, surveillance of antibiotic susceptibility patterns, and molecular characterization of multidrug-resistant Shigella
strains isolated during a 6-year period from 2006 to 2011. Eur J Clin Microbiol Infect Dis
2014; 33 : 157-70.
Niyogi SK. Shigellosis. J Microbiol
2005;43 : 133-43.
Sharma A, Singh SK, Bajpai D. Phenotypic and genotypic characterization of Shigella
spp. with reference to its virulence genes and antibiogram analysis from river Narmada. Indian J Microbiol
2009; 49 : 259-65.
Faruque SM, Khan R, Kamruzzaman M, Yamasaki S, Ahmad QS, Azim T, et al.
Isolation of Shigella
dysenteriae type 1 and S. flexneri
strains from surface waters in Bangladesh: comparative molecular analysis of environmental Shigella
isolates versus clinical strains. Appl Environ Microbiol
2002; 68 : 3908-13.
Murugesan P, Revathi K, Elayaraja S, Vijayalakshmi S, Balasubramanian T. Distribution of enteric bacteria in the sediments of Parangipettai and Cuddalore coast of India. J Environ Biol
2012; 33 : 705-11.
Saeed A, Abd H, Edvinsson B, Sandström G. Acanthamoeba castellanii an environmental host for Shigella
dysenteriae and Shigella
sonnei. Arch Microbiol
2009;191 : 83-8.
Gupta AK, Nayduch D, Verma P, Shah B, Ghate HV, Patole MS, et al.
Phylogenetic characterization of bacteria in the gut of house flies (Musca domestica L.). FEMS Microbiol Ecol
2012; 79 : 581-93.
Vicens R, Richard C, Coulanges P, Rasoamamunjy MA. A reservoir of Shigella
of avian origin: herons and birds of prey of the zoological garden in Tananarive. Bull Soc Pathol Exot Filiales
1987;80 : 295-300.
Kalai K, Nehete RS, Ganguly S, Ganguli M, Dhanalakshmi S, Mukhopadhayay SK. Investigation of parasitic and bacterial diseases in pigs with analysis of hematological and serum biochemical profile. J Parasit Dis
2012; 36 : 129-34.
Bachand N, Ravel A, Onanga R, Arsenault J, Gonzalez JP. Public health significance of zoonotic bacterial pathogens from bushmeat sold in urban markets of Gabon, Central Africa. J Wildl Dis
2012; 48 : 785-9.
Torres AG. Current aspects of Shigella
pathogenesis. Rev Latinoam Microbiol
2004; 46 : 89-97.
Dorman CJ, Porter ME. The Shigella
virulence gene regulatory cascade: a paradigm of bacterial gene control mechanisms. Mol Microbiol
1998;29 : 677-84.
Thapa BR, Ventkateswarlu K, Malik AK, Panigrahi D. Shigellosis in children from north India: a clinicopathological study. J Trop Pediatr
1995; 41 : 303-7.
Das M, Rath CC, Mohapatra UB. Bacteriology of a most popular street food (Panipuri) and inhibitory effect of essential oils on bacterial growth. J Food Sci Technol
2012; 49 : 564-71.
Khurana S, Taneja N, Thapar R, Sharma M, Malla N. Intestinal bacterial and parasitic infections among food handlers in a tertiary care hospital of North India. Trop Gastroenterol
2008;29 : 207-9.
Iwamoto M, Ayers T, Mahon BE, Swerdlow DL. Epidemiology of seafood-associated infections in the United States. Clin Microbiol Rev
2010; 23 : 399-411.
Weissman JB, Gangorosa EJ, Schmerler A, Marier RL, Lewis JN. Shigellosis in day-care centres. Lancet
1975; 1 : 88-90.
DuPont HL, Gangarosa EJ, Reller LB, Woodward WE, Armstrong RW, Hammond J, et al.
Shigellosis in custodial institutions. Am J Epidemiol
1970; 92 : 172-9.
Wanyiri JW, Kanyi H, Maina S, Wang DE, Ngugi P, O'Connor R, et al.
Infectious diarrhoea in antiretroviral therapy-naive HIV/AIDS patients in Kenya. Trans R Soc Trop Med Hyg
2013; 107 : 631-8.
Dritz SK, Back AF. Shigella
enteritis venereally transmitted. N
Engl J Med 1974; 291 : 1194.
Tauxe RV, McDonald RC, Hargrett-Bean N, Blake PA. The persistence of Shigella
flexneri in the United States: increasing role of adult males. Am J Public Health
1988; 78 : 1432-5.
Baer JT, Vugia DJ, Arthur L, Aragon T, Angulo FJ, Bradford WZ. HIV infection as a risk factor for Shigellosis. Emerg Infect Dis1999; 5 : 820-3.
Aragon TJ, Vugia DJ, Shallow S, Samuel MC, Reingold A, Angulo FJ, et al.
Case-control study of Shigellosis in San Francisco: The role of sexual transmission and HIV infection. Clin Infect Dis
2007; 44 : 327-34.
Strauss B, Kurzac C, Embree G, Sevigny R, Paccagnella A, Fyfe M. Clusters of Shigella
sonnei in men who have sex with men, British Columbia, 2001. Can Commun Dis Rep
2001; 27 : 109-14.
O'Sullivan B, Delpech V, Pontivivo G, Karagiannis T, Marriott D, Harkness J, et al.
Shigellosis linked to sex venues, Australia. Emerg Infect Dis
2002; 8 : 862-4.
Centers for Disease Control and Prevention. Shigella
flexneri serotype 3 infections among men who have sex with men-Chicago, Illinois, 2003-2004. MMWR Morb Mortal Wkly Rep
2005;54 : 820-2.
Morgan O, Crook P, Cheasty T, Jiggle B, Giraudon I, Hughes H, et al. Shigella
sonnei outbreak among homosexual men, London. Emerg Infect Dis
2006; 12 : 1458-60.
Kulkarni S, Patsute S, Sane S, Chandane M, Vidhate P, Risbud A. Enteric pathogens in HIV infected and HIV uninfected individuals with diarrhea in Pune. Trans R Soc Trop Med Hyg
2013; 107 : 648-52.
Uppal B, Kashyap B, Bhalla P. Enteric pathogens in HIV/AIDS from a tertiary care hospital. Indian J Community Med
2009; 34 : 237-42.
Gassama A, Thiaw B, Dia NM, Fall F, Camara P, Hovette P, et al
. Infective etiology of diarrhea in adults with HIV infection in Dakar: a case-control study on 594 patients. Dakar Med
2001;46 : 46-50.
Kristjansson M, Viner B, Maslow JN. Polymicrobial and recurrent bacteremia with Shigella
in a patient with AIDS. Scand J Infect Dis
1994; 26 : 411-6.
Freeman N, Newman H, Abrahams R. Shigella
keratitis in an HIV-exposed infant. Pediatr Infect Dis J
2013; 32 : 426-7.
Miller RF, Symeonidou C, Shaw PJ. Pneumonia complicating Shigella
sonnei dysentery in an HIV-infected adult male. Int J STD AIDS
2005; 16 : 763-5.
Sur D, Ramamurthy T, Deen J, Bhattacharya SK. Shigellosis: challenges & management issues. Indian J Med Res
2004; 120 : 454-62.
Mandell W, Neu H. Shigella
bacteremia in adults. JAMA
1986; 255 : 3116-7.
Raffensperger EC. Combined bacillary and amebic ulcerative colitis associated with atypical pneumonitis and Shigella
-positive sputum. Am J Med
1956; 20 : 964-7.
Kotloff KL, Winickoff JP, Ivanoff B, Clemens JD, Swerdlow DL, Sansonetti PJ, et al.
Global burden of Shigella
infections: implications for vaccine development and implementation of control strategies. Bull World Health Organ
1999; 77 : 651-66.
Das SK, Rahman A, Chisti MJ, Ahmed S, Malek MA, Salam MA, et al.
Changing patient population in Dhaka Hospital and Matlab Hospital of icddr, B. Trop Med Int Health
2014; 19 : 240-3.
Nandy S, Mitra U, Rajendran K, Dutta P, Dutta S. Subtype prevalence, plasmid profiles and growing fluoroquinolone resistance in Shigella
from Kolkata, India (2001-2007): a hospital-based study. Trop Med Int Health
2010; 15 : 1499-507.
Rahaman MM, Khan MM, Aziz KM, Islam MS, Kibriya AK. An outbreak of dysentery caused by Shigella
dysenteriae type 1 on a coral island in the Bay of Bengal. J Infect Dis
1975; 132 : 15-9.
Sheriff MHR. Lessons to learn from my Maldivian experience with the Shigella
dysentery. Sri Lankan Family Physician
1982; 5 : 117-20.
Pal SC, Sengupta PG, Sen D, Bhattacharya SK, Deb BC. Epidemic shigellosis due to Shigella
dysenteriae type 1 in south Asia. Indian J Med Res
1989; 89 : 57-64.
Naheed A, Kalluri P, Talukder KA, Faruque AS, Khatun F, Nair GB, et al.
dysenteriae type 1 in northeastern Bangladesh. Lancet Infect Dis
2004; 4 : 607-8.
Mathan VI, Bhat P, Kapadia CR, Ponniah J, Baker SJ. Epidemic dysentery caused by the Shiga bacillus in a southern Indian village. J Diarrhoeal Dis Res
1984; 2 : 27-32.
Jesudason MV. Shigella
isolation in Vellore, south India (1997-2001). Indian J Med Res
2002; 115 : 11-3.
Pal SC. Epidemic bacillary dysentery in West Bengal, India, 1984. Lancet
1984; 1 : 1462.
Dutta P, Bhattacharya SK, Dutta D, Sen D, Saha MR, Nair GB, et al.
Clinical presentation of shigellosis during the 1984 epidemic of bacillary dysentery in West Bengal. J Assoc Physicians India
1987; 35 : 195-7.
Sen D, Sengupta PG, Bhattacharya SK, Sinha AK, Pal SC, Lall R. Epidemic Shiga bacillus dysentery in Port Blair, Andaman and Nicobar Islands, India. J Diarrhoeal Dis Res
1986; 4 : 161-2.
Bhattacharya SK, Sinha AK, Sen D, Sengupta PG, Lall R, Pal SC. Extraintestinal manifestations of Shigellosis during an epidemic of bacillary dysentery in Port Blair, Andaman & Nicobar Island (India). J Assoc Physicians India
1988; 36 : 319-20.
Sarkar K, Ghosh S, Niyogi SK, Bhattacharya SK. Shigella
dysenteriae type 1 with reduced susceptibility to fluoroquinolones. Lancet
2003; 361 : 785.
Saha T, Murhekar M, Hutin YJ, Ramamurthy T. An urban, water-borne outbreak of diarrhoea and shigellosis in a district town in eastern India. Natl Med J India
2009; 22 : 237-9.
Nandy S, Dutta S, Ghosh S, Ganai A, Rajahamsan J, Theodore RB, et al.
sonnei, India, 2009 and 2010. Emerg Infect Dis
2011; 17 : 2072-4.
Steffen R. Epidemiology of traveler's diarrhea. Clin Infect Dis
2005; 41 : S536-40.
Kendall ME, Crim S, Fullerton K, Han PV, Cronquist AB, Shiferaw B, et al.
Travel-associated enteric infections diagnosed after return to the United States, Foodborne Diseases Active Surveillance Network (FoodNet), 2004-2009. Clin Infect Dis
2012; 54 : S480-7.
Sivapalasingam S, Nelson JM, Joyce K, Hoekstra M, Angulo FJ, Mintz ED. High prevalence of antimicrobial resistance among Shigella
isolates in the United States tested by the National Antimicrobial Resistance Monitoring System from 1999 to 2002. Antimicrob Agents Chemother
2006; 50 : 49-54.
Dutta D, Bhattacharya MK, Dutta S, Datta A, Sarkar D, Bhandari B, et al.
Emergence of multidrug-resistant Shigella
dysenteriae type 1 causing sporadic outbreak in and around Kolkata, India. J Health Popul Nutr
2003; 21 : 79-80.
Ross S, Controni G, Khan W. Resistance of Shigellae to ampicillin and other antibiotics. Its clinical and epidemiological implications. JAMA
1972; 221 : 45-7.
Bhattacharya SK, Datta P, Datta D, Bhattacharya MK, Sen D, Saha MR, et al.
Relative efficacy of trimethoprim-sulfamethoxazole and nalidixic acid for acute invasive diarrhea. Antimicrob Agents Chemother
1987; 31 : 837.
Datta P, Sen D. Outbreak of dysentery due to nalidixic acid resistant S. dysenteriae 1 at Agartala, Tripura: a hospital based study. Indian J Public Health
1990; 34 : 11-4.
Chunder N, Bhattacharya SK, Biswas D, Niyogi SK, Kumar R. Isolation of a fluoroquinolone resistant Shigella
dysenteriae 1 strain from Calcutta. Indian J Med Res
1997; 106 : 494-6.
Niyogi SK. Increasing antimicrobial resistance-an emerging problem in the treatment of shigellosis. Clin Microbiol Infect
2007; 13 : 1141-3.
Taneja N, Kumar A, Appannanavar S, Verma G, Sharma M. Plasmid-mediated quinolone resistance in Shigella
isolates over a decade in India. J Glob Antimicrob Resist
2014; 2 : 59-60.
Niyogi SK, Sarkar K, Lalmalsawma P, Pallai N, Bhattacharya SK. An outbreak of bacillary dysentery caused by quinolone-resistant Shigella
dysenteriae type 1 in a northeastern state of India. J Health Popul Nutr
2004; 22 : 97.
Arai Y, Nakano T, Katayama Y, Aoki H, Hirayama T, Ooi Y, et al.
Epidemiological evidence of multidrug-resistant Shigella
sonnei colonization in India by sentinel surveillance in a Japanese quarantine station. Kansenshogaku Zasshi
2008;82 : 322-7.
Ghosh S, Pazhani GP, Niyogi SK, Nataro JP, Ramamurthy T. Genetic characterization of Shigella
spp. isolated from diarrhoeal and asymptomatic children. J Med Microbiol
2014; 63 : 903-10.
Ke X, Gu B, Pan S, Tong M. Epidemiology and molecular mechanism of integron-mediated antibiotic resistance in Shigella
. Arch Microbiol
2011;193 : 767-74.
Jacoby GA, Gacharna N, Black TA, Miller GH, Hooper DC. Temporal appearance of plasmid-mediated quinolone resistance genes. Antimicrob Agents Chemother
2009; 53 : 1665-6.
Robicsek A, Strahilevitz J, Jacoby GA, Macielag M, Abbanat D, Park CH, et al.
Fluoroquinolone-modifying 127 enzyme: a new adaptation of a common aminoglycoside acetyltransferase. Nat Med
2006;12 : 83-8.
Kim HB, Park CH, Kim CJ, Kim EC, Jacoby GA, Hooper DC. Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period. Antimicrob Agents Chemother
2009; 53 : 639-45.
Pu XY, Pan JC, Wang HQ, Zhang W, Huang ZC, Gu YM. Characterization of fluoroquinolone-resistant Shigella
flexneri in Hangzhou area of China. J Antimicrob Chemother
2009; 63 : 917-20.
Bhattacharya D, Bhattacharjee H, Thamizhmani R, Sayi DS, Bharadwaj AP, Singhania M, et al.
Prevalence of the plasmid-mediated quinolone resistance determinants among clinical isolates of Shigella
sp. in Andaman & Nicobar Islands, India. Lett Appl Microbiol
2011; 53 : 247-51.
Pfaller MA, Segreti J. Overview of epidemiological profile and laboratory detection of extended-spectrum beta-lactamases. Clin Infect Dis
2006; 42 : S153-63.
Hawser SP, Bouchillon SK, Hoban DJ, Badal RE, Hsueh PR, Paterson DL. Emergence of high levels of extended-spectrum-beta-lactamase-producing Gram-negative bacilli in the Asia-Pacific region: data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) program, 2007. Antimicrob Agents Chemother
2009; 53 : 3280-4.
Ensor VM, Shahid M, Evans JT, Hawkey PM. Occurrence, prevalence and genetic environment of CTX-M beta-lactamases in Enterobacteriaceae
from Indian hospitals. J Antimicrob Chemother 2006; 58 : 1260-3.
Levine MM, Kotloff KL, Barry EM, Pasetti MF, Sztein MB. Clinical trials of Shigella
vaccines: two steps forward and one step back on a long, hard road. Nat Rev Microbiol
2007; 5 : 540-53.
Turbyfill KR, Kaminski RW, Oaks EV. Immunogenicity and efficacy of highly purified invasin complex vaccine from Shigella
flexneri 2a. Vaccine
2008; 26 : 1353-64.
Mukhopadhaya A, Mahalanabis D, Chakrabarti MK. Role of Shigella
flexneri 2a 34 kDa outer membrane protein in induction of protective immune response. Vaccine
2006; 24 : 6028-36.
Barnoy S, Jeong KI, Helm RF, Suvarnapunya AE, Ranallo RT, Tzipori S, et al.
Characterization of WRSs2 and WRSs3, new second-generation virG(icsA)-based Shigella
sonnei vaccine candidates with the potential for reduced reactogenicity. Vaccine
2010; 28 : 1642-54.
Kotloff KL, Noriega FR, Samandari T, Sztein MB, Losonsky GA, Nataro JP, et al. Shigella
flexneri 2a strain CVD 1207, with specific deletions in virG, sen, set, and guaBA, is highly attenuated in humans. Infect Immun
2000;68 : 1034-9.
Levine MM, Noriega F. A review of the current status of enteric vaccines. P N G Med J
1995; 38 : 325-31.
|This article has been cited by|
||Virulence-associated genes and toxin-antitoxin system genes of Shigella flexneri: Presence and expression in normal and thermal stress conditions
| ||Abbas Maleki,Mehrnoush Safikhani Moslem,Ebrahim Kouhsari,Iraj Pakzad,Zahra Ghafouri,Soheila Khaghani,Nourkhoda Sadeghifard |
| ||Meta Gene. 2021; 27: 100825 |
|[Pubmed] | [DOI]|
||Coupling the high-resolution LC–MS characterisation of the phenolic compounds with the antimicrobial and antibiofilm properties of helencha (Enydra fluctuans Lour.)
| ||Tanmay Kumar Koley,Zareen Khan,Dasharath Oulkar,Tuhina Banerjee,Aradhana Singh,Suhas Gorakh Karkute,Kaushik Banerjee |
| ||Journal of Food Science and Technology. 2021; |
|[Pubmed] | [DOI]|
||Phylogenetic and Evolutionary Analysis Reveals the Recent Dominance of Ciprofloxacin-Resistant Shigella sonnei and Local Persistence of S. flexneri Clones in India
| ||Dhiviya Prabaa Muthuirulandi Sethuvel,Ankur Mutreja,Agila Kumari Pragasam,Karthick Vasudevan,Dhivya Murugan,Shalini Anandan,Joy Sarojini Michael,Kamini Walia,Balaji Veeraraghavan,Krishna Rao |
| ||mSphere. 2020; 5(5) |
|[Pubmed] | [DOI]|
||Epidemiological characteristics and transmissibility of shigellosis in Hubei Province, China, 2005 – 2017
| ||Qi Chen,Jia Rui,Qingqing Hu,Ying Peng,Hao Zhang,Zeyu Zhao,Yeqing Tong,Yang Wu,Yanhua Su,Benhua Zhao,Xuhua Guan,Tianmu Chen |
| ||BMC Infectious Diseases. 2020; 20(1) |
|[Pubmed] | [DOI]|
||Shigella sonnei: virulence and antibiotic resistance
| ||Ahtesham Ahmad Shad,Wajahat Ahmed Shad |
| ||Archives of Microbiology. 2020; |
|[Pubmed] | [DOI]|
||Functional Annotation and Curation of Hypothetical Proteins Present in A Newly Emerged Serotype 1c of Shigella flexneri: Emphasis on Selecting Targets for Virulence and Vaccine Design Studies
| ||Tanuka Sen,Naresh K. Verma |
| ||Genes. 2020; 11(3): 340 |
|[Pubmed] | [DOI]|
||Designing and evaluation of an antibody-targeted chimeric recombinant vaccine encoding Shigella flexneri outer membrane antigens
| ||Ada Kazi,Che Muhammad Khairul Hisyam Ismail,Amy Amilda Anthony,Candy Chuah,Chiuan Herng Leow,Boon Huat Lim,Kirnpal Kaur Banga Singh,Chiuan Yee Leow |
| ||Infection, Genetics and Evolution. 2020; 80: 104176 |
|[Pubmed] | [DOI]|
||Virtual high-throughput screening and simulation studies of compounds from selected traditionally important medicinal plants for the identification of potential inhibitors of AcrB
| ||Minakshi Puzari,Pankaj Chetia |
| ||Journal of Biomolecular Structure and Dynamics. 2020; : 1 |
|[Pubmed] | [DOI]|
||High rate of resistance to ceftriaxone and azithromycin among Shigella spp. isolates at three childrenæs referral hospitals in Northeast Iran
| ||Kobra Salimiyan rizi,Hadi Farsiani,Mohammad Saeed Sasan |
| ||Journal of Infection and Chemotherapy. 2020; |
|[Pubmed] | [DOI]|
||Shigella flexneri: an emerging pathogen
| ||Iqbal Nisa,Muhammad Qasim,Nusrat Yasin,Rafi Ullah,Anwar Ali |
| ||Folia Microbiologica. 2020; |
|[Pubmed] | [DOI]|
||Antibacterial Use of Macroalgae Compounds against Foodborne Pathogens
| ||Aurora Silva,Sofia A. Silva,C. Lourenço-Lopes,C. Jimenez-Lopez,M. Carpena,P. Gullón,M. Fraga-Corral,V. F. Domingues,M. Fátima Barroso,J. Simal-Gandara,M. A. Prieto |
| ||Antibiotics. 2020; 9(10): 712 |
|[Pubmed] | [DOI]|
||Dynamic comparison of gut microbiota of mice infected with Shigella?flexneri via two different infective routes
| ||Jinsong Yang,Wei Chen,Pinchang Xia,Wenchang Zhang |
| ||Experimental and Therapeutic Medicine. 2020; |
|[Pubmed] | [DOI]|
||Factors Associated With Mortality in Toxic Encephalopathy Due to Shigellosis in Children
| ||Machinary Puthenpurayil Jayakrishnan,Madathil Govindaraj Geeta,Padinharath Krishnakumar,V. K. Gireeshan,Biju George,P. Prathiksha,Govindakarnavar Arunkumar,P. M. Anitha |
| ||Indian Pediatrics. 2020; 57(11): 1029 |
|[Pubmed] | [DOI]|
||Antimicrobial resistance: Call for rational antibiotics practice in India
| ||Shivani Chandra,PP R Prithvi,K Srija,Shalini Jauhari,Alka Grover |
| ||Journal of Family Medicine and Primary Care. 2020; 9(5): 2192 |
|[Pubmed] | [DOI]|
||Prevalence and antimicrobial profile of Shigella isolates in a tertiary care hospital of North Karnataka: A 12-year study
| ||PavithraAmrath Jain,RD Kulkarni,S Dutta,AjantaS Ganavali,AnuradhaS Kalabhavi,PraveenC Shetty,C Shubhada,ManjunathA Hosamani,SumaB Appannanavar,DeepaR Hanamaraddi |
| ||Indian Journal of Medical Microbiology. 2020; 38(1): 101 |
|[Pubmed] | [DOI]|
||Evaluation of in vitro and in vivo antibiotic efficacy against a novel bioluminescent Shigella flexneri
| ||Molly C. McCloskey,Shareef Shaheen,Lesley Rabago,Matthew A. Hulverson,Ryan Choi,Lynn K. Barrett,Samuel L. M. Arnold |
| ||Scientific Reports. 2019; 9(1) |
|[Pubmed] | [DOI]|
||Epidemiologic features of shigellosis and associated climatic factors in Taiwan
| ||Chian-Ching Chen,Chuan-Yao Lin,Kow-Tong Chen |
| ||Medicine. 2019; 98(34): e16928 |
|[Pubmed] | [DOI]|
||Relationship of Sanitation Parameters with Microbial Diversity and Load in Raw Meat from the Outlets of the Metropolitan City Biratnagar, Nepal
| ||Sanjay Mahato |
| ||International Journal of Microbiology. 2019; 2019: 1 |
|[Pubmed] | [DOI]|
||Effects of Crinum jagus Water/Ethanol Extract on Shigella flexneri-Induced Diarrhea in Rats
| ||Paul Aimé Noubissi,Michel Archange Fokam Tagne,Gaëtan Olivier Fankem,Joseph Ngakou Mukam,Henri Wambe,René Kamgang |
| ||Evidence-Based Complementary and Alternative Medicine. 2019; 2019: 1 |
|[Pubmed] | [DOI]|
||Hemolytic uremic syndrome in a developing country: Consensus guidelines
| ||Arvind Bagga,Priyanka Khandelwal,Kirtisudha Mishra,Ranjeet Thergaonkar,Anil Vasudevan,Jyoti Sharma,Saroj Kumar Patnaik,Aditi Sinha,Sidharth Sethi,Pankaj Hari,Marie-Agnes Dragon-Durey |
| ||Pediatric Nephrology. 2019; |
|[Pubmed] | [DOI]|
||Is perturbation in the quaternary structure of bacterial CysE, another regulatory mechanism for cysteine synthesis?
| ||Deepali Verma,Sunita Gupta,Kanwal J. Kaur,Vibha Gupta |
| ||International Journal of Biological Macromolecules. 2018; |
|[Pubmed] | [DOI]|
||Antimicrobial resistance profiles of Shigella dysenteriae isolated from travellers returning to the UK, 2004–2017
| ||Lauren M. Terry,Clare R. Barker,Martin R. Day,David R. Greig,Timothy J. Dallman,Claire Jenkins |
| ||Journal of Medical Microbiology. 2018; |
|[Pubmed] | [DOI]|
||Closed Genome and Comparative Phylogenetic Analysis of the Clinical Multidrug Resistant Shigella sonnei Strain 866
| ||Anna Allué-Guardia,Sara S K Koenig,Pablo Quirós,Maite Muniesa,James L Bono,Mark Eppinger,Howard Ochman |
| ||Genome Biology and Evolution. 2018; 10(9): 2241 |
|[Pubmed] | [DOI]|
||Correlation Between the Crude Extracellular Secretion by Shigella dysenteriae and Destruction of RD and L20B Cell Lines, A Simple Sign as Alternative Treatments for Cancer Tumors through Cytotoxicity
| ||Nagham Sh. Alattar,Tahreer H. Saleh,Bahaa A.L. AL-Rubai |
| ||Journal of Pure and Applied Microbiology. 2018; 12(4): 2165 |
|[Pubmed] | [DOI]|
||An Outbreak of Foodborne infection caused by Shigella sonnei in West Bengal, India
| ||Falguni Debnath,Asish K. Mukhopadhyay,Goutam Choudhury,Rudra Narayan Saha,Shanta Dutta |
| ||Japanese Journal of Infectious Diseases. 2018; |
|[Pubmed] | [DOI]|
||Antimicrobial sensitivity trends and virulence genes in Shigella spp. from the Oceania region
| ||Elisheba Malau,Rebecca Ford,Mary Valcanis,Amy V. Jennison,Jenny Mosse,David Bean,Mition Yoannes,William Pomat,Paul F. Horwood,Andrew R. Greenhill |
| ||Infection, Genetics and Evolution. 2018; 64: 52 |
|[Pubmed] | [DOI]|
||The effect of environmental parameters on the incidence of
outbreaks in Yazd province, Iran
| ||Farzaneh Aminharati,Mohammad Mehdi Soltan Dallal,Mohammad Hassan Ehrampoush,Abbasali Dehghani-Tafti,Mehdi Yaseri,Mojtaba Memariani,Zahra Rajabi |
| ||Water Science and Technology: Water Supply. 2018; 18(4): 1388 |
|[Pubmed] | [DOI]|
||Functional Prediction of Hypothetical Proteins from Shigella flexneri and Validation of the Predicted Models by Using ROC Curve Analysis
| ||Md. Amran Gazi,Sultan Mahmud,Shah Mohammad Fahim,Mohammad Golam Kibria,Parag Palit,Md. Rezaul Islam,Humaira Rashid,Subhasish Das,Mustafa Mahfuz,Tahmeed Ahmeed |
| ||Genomics & Informatics. 2018; 16(4): e26 |
|[Pubmed] | [DOI]|
||Comparison of phenotypic and WGS-derived antimicrobial resistance profiles of Shigella sonnei isolated from cases of diarrhoeal disease in England and Wales, 2015
| ||Zahra Sadouki,Martin R. Day,Michel Doumith,Marie A. Chattaway,Timothy J. Dallman,Katie L. Hopkins,Richard Elson,Neil Woodford,Gauri Godbole,Claire Jenkins |
| ||Journal of Antimicrobial Chemotherapy. 2017; |
|[Pubmed] | [DOI]|
||Effects of Oxalis barrelieri
L. (Oxalidaceae) aqueous extract on diarrhea induced by Shigella dysenteriae
type 1 in rats
| ||Michel Archange Fokam Tagne,Paul Aimé Noubissi,Gaëtan Olivier Fankem,René Kamgang |
| ||Health Science Reports. 2017; : e20 |
|[Pubmed] | [DOI]|
||Emergence of antibiotic resistant Shigella species: A matter of concern
| ||Minakshi Puzari,Mohan Sharma,Pankaj Chetia |
| ||Journal of Infection and Public Health. 2017; |
|[Pubmed] | [DOI]|